|
1
|
Vella VR, Ainsworth-Cruickshank G, Luft C, Wong KE, Parfrey LW, Vogl AW, Holman PJ, Bodnar TS, Raineki C. Dysregulation of immune system markers, gut microbiota and short-chain fatty acid production following prenatal alcohol exposure: A developmental perspective. Neurochem Int 2025; 185:105952. [PMID: 39988283 DOI: 10.1016/j.neuint.2025.105952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/25/2025] [Accepted: 02/19/2025] [Indexed: 02/25/2025]
Abstract
Prenatal alcohol exposure (PAE) can severely impact fetal development, including alterations to the developing immune system. Immune perturbations, in tandem with gut dysbiosis, have been linked to brain and behavioral dysfunction, but this relationship is poorly understood in the context of PAE. This study takes an ontogenetic approach to evaluate PAE-induced alterations to brain and serum cytokine levels and both the composition and metabolic output of the gut microbiota. Using a well-established rat model of PAE, cytokine levels in the serum, prefrontal cortex, amygdala, and hypothalamus as well as gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed at three postnatal (P) timepoints: P8 (infancy), P22 (weaning), and P38 (adolescence). Male PAE rats had increased cytokine levels in the amygdala and hypothalamus, but not prefrontal cortex, at P8. This altered neuroimmune function was not seen in the PAE females. The effect of PAE on central cytokine levels was reduced at P22/38, the same age at which PAE-induced alterations in serum cytokine levels emerge in both sexes. PAE reduced bacterial diversity in both sexes at P8, but only in females at P38, where a PAE-induced unique community composition emerged. Both sexes had alterations to specific bacterial taxa (e.g., Firmicutes), some of which are important in producing the SCFA butyric acid, which was decreased in PAE animals at P22. These results demonstrate that PAE leads to sex- and age-specific alterations in immune function, gut microbiota and SCFA production, highlighting the need to consider both age and sex in future work.
Collapse
Affiliation(s)
- Victoria R Vella
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | | | - Carolina Luft
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | - Kingston E Wong
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | - Laura W Parfrey
- Department of Botany, University of British Columbia, British Columbia, Canada
| | - A Wayne Vogl
- Life Sciences Centre, Department of Cellular and Physiological Sciences, University of British Columbia, British Columbia, Canada
| | - Parker J Holman
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | - Tamara S Bodnar
- Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
| | - Charlis Raineki
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada.
| |
Collapse
|
|
2
|
Thomas KN, Basel A, Reitz H, Toler R, Thomas KR, Dotson LJ, Brown T, Pham AN, Rouzer SK, Miranda RC, Golding MC. Maternal, paternal, and dual-parental alcohol exposures result in both overlapping and distinct impacts on behavior in adolescent offspring. Alcohol 2025; 124:65-77. [PMID: 39855492 DOI: 10.1016/j.alcohol.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 01/07/2025] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
Emerging research reveals that alcohol use by fathers before conception can affect the growth and development of their offspring. Here, we used a C57BL/6J mouse model to study the effects of alcohol exposure on the behavior of the first-generation (F1) offspring, comparing the impacts of alcohol exposure by mothers, fathers, and both parents. Our goal was to determine how alcohol exposure by each parent or both parents influences the behavior of the offspring. We found that adolescent male offspring of alcohol-exposed fathers showed reduced anxiety-like behaviors as they spent more time in the center of the testing arena during the open field test. Both maternal and paternal alcohol exposure caused sex-specific increases in the nestlet shredding test while decreasing the number of buried marbles in the marble burying test. Interestingly, dual-parental alcohol exposure did not produce any significant changes in these same tests. However, during novel object recognition testing, we found that dual-parental male and female offspring exhibit an increased preference for novel objects, suggesting an increased risk preference. Finally, at sixteen weeks, male offspring of dual-exposed parents exhibited decreased voluntary physical activity on running wheels during the active phase, suggesting alterations in their circadian rhythms. Although differences in parental exposure histories between treatment groups make interpretation challenging, our findings suggest that exposure to alcohol by both parents may have unique effects on behavior and that studying both maternal and paternal alcohol use is essential for understanding the full range of factors influencing the penetrance and severity of alcohol-related phenotypes.
Collapse
Affiliation(s)
- Kara N Thomas
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Alison Basel
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Hayden Reitz
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Rachel Toler
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Kelly R Thomas
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Luke J Dotson
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Tyler Brown
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Alan Nguyen Pham
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - Siara K Rouzer
- Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University, USA
| | - Rajesh C Miranda
- Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University, USA
| | - Michael C Golding
- Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA.
| |
Collapse
|
|
3
|
Felicicchia RJ, Hyland MT, Roesch SC, Mattson SN. Identifying family environment profiles in families of children with prenatal alcohol exposure. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2025; 49:771-782. [PMID: 40070079 PMCID: PMC12012878 DOI: 10.1111/acer.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 02/09/2025] [Indexed: 03/28/2025]
Abstract
BACKGROUND Individuals with prenatal alcohol exposure (PAE) may face unique family environments that potentially influence adaptive functioning and behavioral challenges. This study aimed to identify profiles of families of children with PAE based on family characteristics, including cohesion, conflict, and organization, and to examine the relationship between family environment profiles and child outcomes. METHODS Data were collected from caregivers of 283 youth (5-17 years) with histories of PAE. Caregivers completed several questionnaires, including the Child Behavior Checklist (CBCL), Vineland Adaptive Behavior Scales (VABS), and Family Environment Scale (FES). Latent profile analysis (LPA) was used to identify profiles in the family environment using three subscales from the FES (Cohesion, Conflict, and Organization). Model fit was determined by comparing 1-, 2-, 3-, 4-, and 5-profile solutions. One-way ANCOVA follow-up tests were conducted to explore differences in adaptive and behavioral functioning across family environment profiles. RESULTS The 4-profile solution was considered the best fit for the data. Interpretation of conditional response probabilities indicated that Profile 1 was defined by low cohesion; Profile 2 was defined by low organization; Profile 3 was defined as high cohesion and organization; and Profile 4 was defined as high conflict. After controlling for race, sex, age, and ethnicity, there were significant profile differences on the Internalizing, Externalizing, and Total Problem Behavior scales of the CBCL. There were no significant differences in adaptive functioning across profiles. CONCLUSIONS The results of this study highlight the importance of the family environment in understanding the strengths and challenges experienced by children with PAE. Four unique profiles of family environments emerged in families of children with PAE. The high-conflict profile was associated with increased behavioral problems in children. These findings can be used to support families of children with PAE and to identify treatment targets for interventions for children with PAE and their caregivers.
Collapse
Affiliation(s)
- Riley J. Felicicchia
- Center for Behavioral Teratology and Department of PsychologySan Diego State UniversitySan DiegoCaliforniaUSA
| | - Matthew T. Hyland
- Center for Behavioral Teratology and Department of PsychologySan Diego State UniversitySan DiegoCaliforniaUSA
| | - Scott C. Roesch
- Department of PsychologySan Diego State UniversitySan DiegoCaliforniaUSA
| | - Sarah N. Mattson
- Center for Behavioral Teratology and Department of PsychologySan Diego State UniversitySan DiegoCaliforniaUSA
| |
Collapse
|
|
4
|
Rouzer SK, Domen M, George A, Bowring A, Miranda RC. Early Life Outcomes of Prenatal Exposure to Alcohol and Synthetic Cannabinoids in Mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.27.635118. [PMID: 39975197 PMCID: PMC11838379 DOI: 10.1101/2025.01.27.635118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
This study explores the effects of prenatal co-exposure to alcohol and synthetic cannabinoids on offspring viability, physical development, and neurobehavioral outcomes in young adulthood. The aim is to identify distinct outcomes of co-exposure compared to single-drug exposures and to examine potential sex-specific vulnerabilities in motor coordination and exploratory behaviors. Pregnant C57Bl/6J mice were assigned to one of four treatment groups: Control, Alcohol-exposed, Cannabinoid-exposed, or Alcohol+Cannabinoid-exposed, with drug administration occurring between Gestational Days 12-15. Offspring were first evaluated at birth for survival, physical malformations, and developmental delays. Subsequently, young adult offspring were assessed for motor coordination using rotarod tests and exploratory behavior using open field tests. Our results indicate that alcohol and cannabinoid co-exposure significantly reduced offspring survival and litter sizes compared to controls. Non-viable offspring displayed craniofacial abnormalities, limb malformations, and developmental delays. Behavioral assessments in young adulthood demonstrated that all forms of prenatal drug exposure impaired motor coordination in males, while alcohol and cannabinoid exposures independently produced impairments in females. In the open field test, co-exposed male offspring exhibited reduced center exploration, indicative of anxiety-like behavior. Co-exposed offspring, regardless of sex, demonstrated hyperactivity, characterized by increased speed and distance traveled. Together, these findings underscore the heightened risks associated with prenatal polysubstance exposure, which exacerbates offspring mortality and induces sex-specific neurobehavioral deficits. This study highlights the distinct outcomes associated with prenatal co-exposure, and the need for future research to investigate underlying mechanisms driving these developmental disruptions and sex-specific susceptibilities.
Collapse
Affiliation(s)
- Siara K. Rouzer
- Department of Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, 8447 John Sharp Parkway, Bryan, TX 77807, United States
| | - McKay Domen
- Department of Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, 8447 John Sharp Parkway, Bryan, TX 77807, United States
| | - Aisley George
- Department of Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, 8447 John Sharp Parkway, Bryan, TX 77807, United States
| | - Abigail Bowring
- Department of Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, 8447 John Sharp Parkway, Bryan, TX 77807, United States
| | - Rajesh C. Miranda
- Department of Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, 8447 John Sharp Parkway, Bryan, TX 77807, United States
| |
Collapse
|
|
5
|
Aghamohammadi-Sereshki A, McMorris CA, Gibbard WB, Tortorelli C, Pike GB, Lebel C. Properties of the prefrontal tracts and cingulum bundle in children with prenatal alcohol exposure. J Affect Disord 2025; 369:164-173. [PMID: 39341291 DOI: 10.1016/j.jad.2024.09.165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 09/23/2024] [Accepted: 09/25/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Prenatal alcohol exposure (PAE) significantly impacts brain structure and function, including cognition and behavior. The cingulum bundle and frontal lobe mediate social-, emotional- and cognitive-related functioning that are affected by PAE. However, the neurobehavioural development of the cingulum and intra-frontal tracts has not been examined in people with PAE. METHODS We recruited 29 children and adolescents with PAE and 42 age- and gender-matched unexposed controls. Diffusion magnetic resonance imaging (MRI) data were acquired on a 3 T scanner. The rostral, dorsal and parahippocampal cingulum as well as medio-orbitofrontal, lateral-orbitofrontal, dorsolateral-prefrontal and medial-prefrontal tracts, were delineated and their fractional anisotropy and mean (MD), radial (RD), and axial (AD) diffusivities were calculated using constrained spherical deconvolution and deterministic tractography. We measured behavioural and emotional difficulties using the Behavior Assessment System for Children, 2nd Edition, Parent Rating Scale, and then explored their associations with diffusion metrics that differed between groups. RESULTS We found lower MD, RD, and AD in the right parahippocampal cingulum and multiple intra-frontal tracts in youth with PAE compared to controls; however, these differences did not withstand correction for multiple comparisons. While, youth with PAE showed significantly more emotional and behavioural difficulties compared to unexposed controls, these challenges were not associated with differences in diffusion metrics between groups. CONCLUSION PAE may be weakly associated with restricted diffusion in the right parahippocampal cingulum and multiple intra-frontal tracts. However, diffusivity changes related to PAE might not be the primary contributor to emotional and behavioural challenges in children and adolescents with PAE.
Collapse
Affiliation(s)
| | - Carly A McMorris
- Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Werklund School of Education, University of Calgary, Calgary, Alberta, Canada
| | - W Ben Gibbard
- Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
| | - Christina Tortorelli
- Department of Child Studies and Social Work, Mount Royal University, Calgary, Alberta, Canada
| | - G Bruce Pike
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
| | - Catherine Lebel
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
| |
Collapse
|
|
6
|
Cunningham LA, Tunc-Ozcan E, Rodriguez AM. Adult Hippocampal Neurogenesis as a Therapeutic Target in Fetal Alcohol Spectrum Disorder. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1473:93-109. [PMID: 40128476 DOI: 10.1007/978-3-031-81908-7_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
This review is focused on adult hippocampal neurogenesis as a potential therapeutic target in fetal alcohol spectrum disorder (FASD). Adult hippocampal neurogenesis refers to the production of new hippocampal dentate granule cells (DGCs) from a replenishable pool of neural stem and progenitor cells throughout life. Adult-generated DGCs have been shown to exert a profound influence on hippocampal network activity in experimental animals and have been implicated in the regulation of many hippocampal-dependent behaviors and emotional states, including certain forms of learning and memory, anxiety, mood, and stress resilience. While adult hippocampal neurogenesis in humans remains controversial, many studies support its existence and impact on hippocampal function in human health and disease. Here, we review mechanisms of adult hippocampal neurogenesis under physiological conditions, as described primarily in rodent brain, its impact on network activity and behavior, and the negative effects of developmental alcohol exposure on this process. We then explore hippocampal neurogenesis as a potential target for FASD therapy using pharmacological and neurophysiological approaches known to stimulate adult hippocampal neurogenesis, currently available for clinical use in FASD patients.
Collapse
Affiliation(s)
- Lee Anna Cunningham
- Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
| | - Elif Tunc-Ozcan
- Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Arasely M Rodriguez
- Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| |
Collapse
|
|
7
|
Vella VR, Holman PJ, Bodnar TS, Raineki C. Ontogenetic Neuroimmune Changes Following Prenatal Alcohol Exposure: Implications for Neurobehavioral Function. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1473:15-39. [PMID: 40128473 DOI: 10.1007/978-3-031-81908-7_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
This chapter reviews the enduring effects of prenatal alcohol exposure (PAE) on neuroimmune function across the lifespan, including discussion of associated neurobehavioral alterations. Alcohol has potent teratogenic effects, with a large body of work linking PAE to perturbations in neuroimmune function. These PAE-related neuroimmune disturbances may have downstream effects on neurobehavioral function given the critical role of the neuroimmune system in central nervous system development. The neuroimmune system matures over time, playing distinct roles depending on the developmental processes occurring within that maturational stage. This chapter thus takes an ontogenetic approach to understanding how PAE induces unique neuroimmune changes across the lifespan, beginning with a review of changes in early life before moving into adolescence and ending in adulthood. The focus will be on work utilizing rodent models, which allow for more tightly controlled conditions than are possible in human research. The chapter concludes with a discussion of possible mechanisms underlying the developmental changes in neuroimmune function following PAE, with a specific focus on the role of the gut microbiota.
Collapse
Affiliation(s)
- Victoria R Vella
- Department of Psychology, Brock University, St. Catharines, ON, Canada
| | - Parker J Holman
- Department of Psychology, Brock University, St. Catharines, ON, Canada
| | - Tamara S Bodnar
- Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute, Calgary, AB, Canada
- Hotchkiss Brain Institute, Calgary, AB, Canada
| | - Charlis Raineki
- Department of Psychology, Brock University, St. Catharines, ON, Canada.
- Centre for Neuroscience, Brock University, St. Catharines, ON, Canada.
| |
Collapse
|
|
8
|
Acosta G, Rico KT, Madden JT, LaCour A, Wang E, Sanchez LM, Davies S, Maestas-Olguin C, Cox KB, Reyna NC, Hogeveen J, Savage DD, Pentkowski NS, Clark BJ. The effects of moderate prenatal alcohol exposure on performance in hippocampal-sensitive spatial memory and anxiety tasks by adult male and female rat offspring. Alcohol 2024; 121:75-86. [PMID: 39122134 PMCID: PMC11637952 DOI: 10.1016/j.alcohol.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 07/24/2024] [Accepted: 08/04/2024] [Indexed: 08/12/2024]
Abstract
Moderate prenatal alcohol exposure (mPAE) results in structural alterations to the hippocampus. Previous studies have reported impairments in hippocampal-sensitive tasks, but have not compared performance between male and female animals. In the present study, performance in hippocampal-sensitive spatial memory and anxiety behavior tests were compared across adult male and female saccharin (SACC) control mPAE Long-Evans rat offspring. Two tests of spatial memory were conducted that were aimed at assessing memory for recently acquired spatial information: A delayed spatial alternation task using an M-shaped maze and a delayed match-to-place task in the Morris water task. In both tasks, rats in SACC and mPAE groups showed similar learning and retention of a spatial location even after a 2-h interval between encoding and retention. A separate group of adult male and female SACC and mPAE rat offspring were tested for anxiety-like behaviors in the elevated plus-maze paradigm. In this test, both male and female mPAE rats exhibited a significantly greater amount of time and a greater number of head dips in the open arms, while locomotion and open arm entries did not differ between groups. The results suggest that mPAE produces a reduction in anxiety-like behaviors in both male and female rats in the elevated plus-maze.
Collapse
Affiliation(s)
- Gabriela Acosta
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Kehiry Trejo Rico
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - John T Madden
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Ariyana LaCour
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Enhui Wang
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Lilliana M Sanchez
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Suzy Davies
- Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA
| | | | - Kayla B Cox
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Nicole C Reyna
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Jeremy Hogeveen
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Daniel D Savage
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA; Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA
| | | | - Benjamin J Clark
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA; Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.
| |
Collapse
|
|
9
|
Wilson DA, Sullivan RM, Smiley JF, Saito M, Raineki C. Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development. Neurosci Biobehav Rev 2024; 158:105567. [PMID: 38309498 PMCID: PMC10923002 DOI: 10.1016/j.neubiorev.2024.105567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/25/2024] [Accepted: 01/29/2024] [Indexed: 02/05/2024]
Abstract
Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.
Collapse
Affiliation(s)
- Donald A Wilson
- Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, USA.
| | - Regina M Sullivan
- Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, USA
| | - John F Smiley
- Division of Neurochemistry, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Psychiatry, New York University Medical Center, New York, NY, USA
| | - Mariko Saito
- Division of Neurochemistry, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Psychiatry, New York University Medical Center, New York, NY, USA
| | - Charlis Raineki
- Department of Psychology, Brock University, St. Catharines, ON, Canada; Centre for Neuroscience, Brock University, St. Catharines, ON, Canada
| |
Collapse
|
|
10
|
Roetner J, Van Doren J, Maschke J, Kulke L, Pontones C, Fasching PA, Beckmann MW, Lenz B, Kratz O, Moll GH, Kornhuber J, Eichler A. Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide. Eur Arch Psychiatry Clin Neurosci 2024; 274:343-352. [PMID: 37532863 PMCID: PMC10914883 DOI: 10.1007/s00406-023-01657-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 07/17/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND Prenatal alcohol exposure (PAE) has been linked to severe, adverse child outcomes. However, little is known regarding subclinical outcomes of low/moderate PAE and its longitudinal consequences, especially regarding neurophysiological and neurocognitive development. A newborn biomarker of PAE, meconium ethyl glucuronide (EtG), has been shown to predict cognitive impairments in primary-school-aged children. The current study investigated the ongoing effects of subclinical PAE in adolescence. METHODS A sample of n = 96 mother-child dyads of the FRAMES/FRANCES cohort were classified into PAE/no PAE using EtG with a 10 ng/g cutoff. Mothers were recruited during pregnancy and children were assessed during primary-school age (M = 7.57, SD = 0.65, range: 6.00-9.92 years) and adolescence (M = 13.26, SD = 0.31, range: 12.79-14.20 years) on three levels: clinical (ADHD rating), neuropsychological (IQ score and performance in a go/nogo task), and neurophysiological (analysis of P3 event-related potentials (ERP) during said go/nogo task). Developmental outcomes and courses following PAE were assessed using rmANCOVAs, controlling for relevant confounders (socioeconomic status (SES), birth weight, and maternal psychopathology). RESULTS Neurophysiological impairments emerged for exposed children in the form of diminished attentional resource recruiting in childhood and adolescence (reduced go-P3 amplitudes) with no differences in performance. Neuropsychological testing showed a reduced IQ score for both time points with dose-dependent effects in childhood. Clinical ADHD symptoms were not significantly affected. CONCLUSION Subclinical PAE, as determined by meconium EtG, has negative developmental consequences on cognitive function that persist from childhood to adolescence. These findings suggest that there is no safe limit for alcohol consumption during pregnancy and that more thorough screening of alcohol consumption during pregnancy is necessary for early identification and treatment of at-risk children.
Collapse
Affiliation(s)
- Jakob Roetner
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany
- Department of Psychology I - Developmental Psychology, Otto-Friedrich-University Bamberg, Bamberg, Germany
| | - Jessica Van Doren
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany
| | - Janina Maschke
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany
| | - Louisa Kulke
- Department of Neurocognitive Developmental Psychology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Constanza Pontones
- Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Peter A Fasching
- Department of Psychology I - Developmental Psychology, Otto-Friedrich-University Bamberg, Bamberg, Germany
| | - Matthias W Beckmann
- Department of Psychology I - Developmental Psychology, Otto-Friedrich-University Bamberg, Bamberg, Germany
| | - Bernd Lenz
- Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Oliver Kratz
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany
| | - Gunther H Moll
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany
| | - Johannes Kornhuber
- Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Anna Eichler
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054, Erlangen, Germany.
| |
Collapse
|
|
11
|
Bethmann D, Cho JI. How are they doing? The academic performance and mental wellbeing of world cup babies. SSM Popul Health 2024; 25:101579. [PMID: 38156293 PMCID: PMC10753079 DOI: 10.1016/j.ssmph.2023.101579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/02/2023] [Accepted: 12/03/2023] [Indexed: 12/30/2023] Open
Abstract
In June 2002, South Korea cohosted the 17th FIFA World Cup. Unexpected wins carried the Korean National Football Team to the semi-finals and sparked an unprecedented euphoria among Koreans. Die-hard fans and occasional football viewers, young and old, women and men flocked the streets side by side, cheered for their team, and partied through the nights. In the subsequent spring of 2003, the country experienced a temporary and significant increase in its fertility rate. Using a difference-in-differences design, we exploit the quasi-experimental nature of this episode to investigate the Beckerian trade-off between the quantity and quality of children born to parents in South Korea. Our results support the notion of an adverse effect on child quality. Students born approximately ten months after the World Cup tend to perform significantly worse in school. Moreover, our results uncover a hitherto overlooked aspect: the same students exhibit significantly higher degrees of mental wellbeing.
Collapse
Affiliation(s)
- Dirk Bethmann
- Department of Economics, Korea University, South Korea
| | - Jae Il Cho
- Department of Economics, Vanderbilt University, 005 Calhoun Hall, Nashville, TN, 37240, United States
| |
Collapse
|
|
12
|
Ritfeld GJ, Wang M, Shapiro Z, Kable JA, Coles CD. Parenting by individuals with fetal alcohol spectrum disorders and neurobehavioral outcomes in their offspring. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:400-408. [PMID: 38149361 PMCID: PMC10922647 DOI: 10.1111/acer.15256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND The neurobehavioral health impairments associated with prenatal alcohol exposure are now known to persist through adulthood. However, little is known about how these impairments affect individuals' parenting abilities and the neurobehavioral health of their offspring. This study compares parents with fetal alcohol spectrum disorder (FASD) with socioeconomically matched, nonexposed parents on measures of parenting and family support and assesses the neurobehavioral health of the children in both groups. METHODS Forty-nine parent-child dyads were recruited from a longitudinal cohort of low socioeconomic status. Measures included the Parenting Styles and Dimensions Questionnaire, Family Support Scale, an in-depth psychosocial history, the Pediatric Symptom Checklist (PSC; parent and child reports), the Achenbach Child Behavior Checklist (CBCL), a screening psychiatric evaluation of the child, the NIH Toolbox Cognition Battery for Children, The Vineland Adaptive Behavior Scales-Third Edition caregiver rating form, and the Traumatic Events Screening Inventory (parent and child reports). RESULTS Cognitive functioning was impaired for both offspring of parents with FASD (x ¯ = 81.1, SD = 13.0) and control parents (x ¯ = 79.9, SD = 16.1), but despite similar impairments, children of parents with FASD were less likely to have an Individualized Education Plan than controls. Adaptive functioning was adequate for both groups (x ¯ = 92.1, SD = 15.4 in exposed vs.x ¯ = 94.3, SD = 12.3 in controls) and CBCL and PSC scores in both groups were within normal limits. Parents in both groups showed a predominantly authoritative parenting style. Despite a similar frequency of adverse childhood experiences in both groups, parents with FASD were less likely to recognize their child's adverse experiences. CONCLUSION Parents with FASD display notable strengths including a predominantly authoritative parenting style. However, parents with FASD underrecognize child trauma and underutilize developmental services compared to socioeconomically matched controls, despite similar neurocognitive impairments. Impairments in adaptive functioning in parents with FASD may translate into difficulties with child-parent communication and limit both insight into neurobehavioral problems and advocacy skills. There is a need to identify and support parents with FASD to optimize their parenting abilities in the context of their individual strengths and difficulties.
Collapse
Affiliation(s)
- Gaby J Ritfeld
- Barrow Neurological Institute at Phoenix Children's, Phoenix, Arizona, USA
- Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA
- Department of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
- Department of Psychiatry, Creighton University School of Medicine, Phoenix, Arizona, USA
| | - Michael Wang
- Department of Psychiatry, Creighton University School of Medicine, Phoenix, Arizona, USA
| | - Zvi Shapiro
- Department of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Julie A Kable
- Department of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Claire D Coles
- Department of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
| |
Collapse
|
|
13
|
Weinmann T, Ordenewitz LK, Schlüter JA, Jung J, Kerber K, Finkeldey L, Heinen F, Landgraf MN. Establishing a multidisciplinary specialist centre for fetal alcohol spectrum disorders-Lessons learned from a model project in Germany. Child Care Health Dev 2024; 50:e13143. [PMID: 37317477 DOI: 10.1111/cch.13143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 05/22/2023] [Accepted: 05/30/2023] [Indexed: 06/16/2023]
Abstract
BACKGROUND Inadequate coordination between relevant professionals hampers the provision of appropriate care for individuals with fetal alcohol spectrum disorder (FASD). Integrated, multidisciplinary care is thus urgently required. Hence, we aimed at establishing the first university-bound, interdisciplinary specialist centre for FASD in Germany, systematically collecting data on its utilisation and evaluation by attendees. METHODS After our centre started to provide consultation and support services in July 2019 until May 2021, we collected 233 questionnaires on the centre's utilisation (including attendees' sociodemographic characteristics and the topics on which they requested consultation, e.g., general information about FASD, consultation on therapy options, and educational consultation). Ninety-four of 136 individuals who received consultation at our centre submitted an evaluation questionnaire that recorded attendees' satisfaction with the support they had received (e.g., the extent to which the consultation met their needs). RESULTS Of 233 participants who completed the utilisation questionnaire, 81.8% were female, and 56.7% were aged 40 to 60 years. Moreover, 42% were foster parents, while 38% were professionals. Most attendees had questions on FASD in general as well as on a specific child or adolescent with FASD. Almost three quarters of the attendees requested consultation on adequate therapies for FASD patients, while 64% had questions on parenting issues. The overall quality of the consultation was rated very well. DISCUSSION Our service was used by both caregivers and professionals who reported numerous and complex concerns and needs. Professionally sound and multidisciplinary services are viable instruments to meet those needs, bearing the potential for quick and notable relief among individuals affected. We propose further advancement of networking and coordination between care providers, the expansion of multidisciplinary services, and securing early diagnosis and consistency of care as relevant steps to even better support children and adolescents with FASD and their families in the future.
Collapse
Affiliation(s)
- Tobias Weinmann
- Institute and Clinic for Occupational, Social and Environmental Medicine, LMU University Hospital, LMU Munich, Munich, Germany
| | - Lisa K Ordenewitz
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| | - Julia A Schlüter
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| | - Jessica Jung
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| | - Katharina Kerber
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| | - Lukas Finkeldey
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| | - Florian Heinen
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| | - Mirjam N Landgraf
- Department of Pediatric Neurology and Developmental Medicine, LMU Center for Development and Children with Medical Complexity, German FASD Competence Centre Bavaria, Dr. von Hauner Children's Hospital, LMU University Hospital, LMU Munich, Munich, Germany
| |
Collapse
|
|
14
|
Poth LD, Love T, Mattson SN. Profiles of language and communication abilities in adolescents with fetal alcohol spectrum disorders. J Int Neuropsychol Soc 2023; 29:724-733. [PMID: 36325639 PMCID: PMC10154428 DOI: 10.1017/s1355617722000789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Language and communication are largely understudied among youth with fetal alcohol spectrum disorders (FASD). Findings have been mixed, and have generally focused on more severely affected (i.e., children with FAS alone) or younger children. This study aimed to elucidate the profiles of language (i.e., receptive, expressive, general language) and communication (i.e., functional, social) abilities in adolescents with FASD. METHOD Participants aged 12-17 years with (AE = 31) and without (CON = 29) prenatal alcohol exposure were included. Receptive and expressive language were measured by the Clinical Evaluation of Language Fundamentals - Fifth Edition (CELF-5). Parents or caregivers completed the Children's Communication Checklist - Second Edition as a subjective measure of general language skills. Functional communication was measured by the Student Functional Assessment of Verbal Reasoning and Executive Strategies and parents or caregivers completed the Social Skills Improvement System Rating Scales as a measure of social communication. Multivariate analysis of variance determined the overall profiles of language and communication and whether they differed between groups. RESULTS The AE group performed significantly lower than the CON group on receptive language and parent report of general language while groups did not significantly differ on expressive language. Groups did not significantly differ on functional communication while social communication was significantly lower in the AE group. CONCLUSIONS Results of this study provide important information regarding the overall profile of basic language abilities and higher-level communication skills of adolescents with FASD. Ultimately, improving communication skills of youth with FASD may translate to better overall functioning.
Collapse
Affiliation(s)
- Lauren D. Poth
- Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, CA 92120
| | - Tracy Love
- School of Speech, Language and Hearing Sciences, San Diego State University, San Diego, CA 92120
| | - Sarah N. Mattson
- Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, CA 92120
| |
Collapse
|
|
15
|
Przybysz KR, Spodnick MB, Johnson JM, Varlinskaya EI, Diaz MR. Moderate prenatal alcohol exposure produces sex-specific social impairments and attenuates prelimbic excitability and amygdala-cortex modulation of adult social behaviour. Addict Biol 2023; 28:e13252. [PMID: 36577734 PMCID: PMC10509785 DOI: 10.1111/adb.13252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 09/23/2022] [Accepted: 10/21/2022] [Indexed: 11/19/2022]
Abstract
Lifelong social impairments are common in individuals with prenatal alcohol exposure (PAE), and preclinical studies have identified gestational day (G)12 as a vulnerable timepoint for producing social deficits following binge-level PAE. While moderate (m)PAE also produces social impairments, the long-term neuroadaptations underlying them are poorly understood. Activity of the projection from the basolateral amygdala to the prelimbic cortex (BLA → PL) leads to social avoidance, and the PL is implicated in negative social behaviours, making each of these potential candidates for the neuroadaptations underlying mPAE-induced social impairments. To examine this, we first established that G12 mPAE produced sex-specific social impairments lasting into adulthood in Sprague-Dawley rats. We then chemogenetically inhibited the BLA → PL using clozapine N-oxide (CNO) during adult social testing. This revealed that CNO reduced social investigation in control males but had no effect on mPAE males or females of either exposure, indicating that mPAE attenuated the role of this projection in regulating male social behaviour and highlighting one potential mechanism by which mPAE affects male social behaviour more severely. Using whole-cell electrophysiology, we also examined mPAE-induced changes to PL pyramidal cell physiology and determined that mPAE reduced cell excitability, likely due to increased suppression by inhibitory interneurons. Overall, this work identified two mPAE-induced neuroadaptations that last into adulthood and that may underlie the sex-specific vulnerability to mPAE-induced social impairments. Future research is necessary to expand upon how these circuits modulate both normal and pathological social behaviours and to identify sex-specific mechanisms, leading to differential vulnerability in males and females.
Collapse
Affiliation(s)
- Kathryn R. Przybysz
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA
| | - Mary B. Spodnick
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA
| | - Julia M. Johnson
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA
| | - Elena I. Varlinskaya
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA
| | - Marvin R. Diaz
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA
| |
Collapse
|
|
16
|
Rouzer SK, Diaz MR. Moderate prenatal alcohol exposure modifies sex-specific CRFR1 activity in the central amygdala and anxiety-like behavior in adolescent offspring. Neuropsychopharmacology 2022; 47:2140-2149. [PMID: 35478009 PMCID: PMC9556708 DOI: 10.1038/s41386-022-01327-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 02/08/2023]
Abstract
Anxiety disorders are highly prevalent among individuals with a history of prenatal alcohol exposure (PAE), and adolescent rodents demonstrate anxiety-like behavior following moderate PAE on Gestational Day (G) 12. A likely systemic target of PAE is the stress peptide corticotropin-releasing factor (CRF), as activation of CRF receptor 1 (CRFR1) in the medial nucleus of the central amygdala (CeM) is known to increase anxiety-like behavior in adults. To determine if CRF-CRFR1 interactions underly PAE-induced anxiety, functional changes in CRF system activity were investigated in adolescent male and female Sprague Dawley rats following G12 PAE. Compared to air-exposed controls, PAE increased basal spontaneous (s) inhibitory postsynaptic current (IPSC) frequency in the CeM of males, but not females. Furthermore, PAE blunted CRFR1-regulated miniature (m) IPSCs in a sex- and concentration-specific manner, and only PAE males demonstrated tonic CRFR1 activity in the CeM. It was further determined that G12 PAE decreased CRFR1 mRNA in the CeM of males while increasing regional expression in females. Finally, infusion of a CRFR1 agonist into the CeM of adolescents produced a blunted expression of CRFR1-induced anxiety-like behavior exclusively in PAE males, mirroring the blunted physiology demonstrated by PAE males. Cumulatively, these data suggest that CRFR1 function within the CeM is age- and sex-specific, and PAE not only increases the expression of anxiety-like behavior, but may reduce the efficacy of treatment for PAE-induced anxiety through CRFR1-associated mechanisms. Therefore, future research will be necessary to develop targeted treatment of anxiety disorders in individuals with a history of PAE.
Collapse
Affiliation(s)
- Siara Kate Rouzer
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA
| | - Marvin R Diaz
- Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, 13902, USA.
- Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY, 13902, USA.
| |
Collapse
|
|
17
|
Binge-like Prenatal Ethanol Exposure Causes Impaired Cellular Differentiation in the Embryonic Forebrain and Synaptic and Behavioral Defects in Adult Mice. Brain Sci 2022; 12:brainsci12060793. [PMID: 35741678 PMCID: PMC9220802 DOI: 10.3390/brainsci12060793] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/10/2022] [Accepted: 06/15/2022] [Indexed: 11/30/2022] Open
Abstract
An embryo’s in-utero exposure to ethanol due to a mother’s alcohol drinking results in a range of deficits in the child that are collectively termed fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is one of the leading causes of preventable intellectual disability. Its neurobehavioral underpinnings warrant systematic research. We investigated the immediate effects on embryos of acute prenatal ethanol exposure during gestational days (GDs) and the influence of such exposure on persistent neurobehavioral deficits in adult offspring. We administered pregnant C57BL/6J mice with ethanol (1.75 g/kg) (GDE) or saline (GDS) intraperitoneally (i.p.) at 0 h and again at 2 h intervals on GD 8 and GD 12. Subsequently, we assessed apoptosis, differentiation, and signaling events in embryo forebrains (E13.5; GD13.5). Long-lasting effects of GDE were evaluated via a behavioral test battery. We also determined the long-term potentiation and synaptic plasticity-related protein expression in adult hippocampal tissue. GDE caused apoptosis, inhibited differentiation, and reduced pERK and pCREB signaling and the expression of transcription factors Pax6 and Lhx2. GDE caused persistent spatial and social investigation memory deficits compared with saline controls, regardless of sex. Interestingly, GDE adult mice exhibited enhanced repetitive and anxiety-like behavior, irrespective of sex. GDE reduced synaptic plasticity-related protein expression and caused hippocampal synaptic plasticity (LTP and LTD) deficits in adult offspring. These findings demonstrate that binge-like ethanol exposure at the GD8 and GD12 developmental stages causes defects in pERK–pCREB signaling and reduces the expression of Pax6 and Lhx2, leading to impaired cellular differentiation during the embryonic stage. In the adult stage, binge-like ethanol exposure caused persistent synaptic and behavioral abnormalities in adult mice. Furthermore, the findings suggest that combining ethanol exposure at two sensitive stages (GD8 and GD12) causes deficits in synaptic plasticity-associated proteins (Arc, Egr1, Fgf1, GluR1, and GluN1), leading to persistent FASD-like neurobehavioral deficits in mice.
Collapse
|
|
18
|
Ritfeld GJ, Kable JA, Holton JE, Coles CD. Psychopharmacological Treatments in Children with Fetal Alcohol Spectrum Disorders: A Review. Child Psychiatry Hum Dev 2022; 53:268-277. [PMID: 33502703 DOI: 10.1007/s10578-021-01124-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/13/2021] [Indexed: 10/22/2022]
Abstract
Psychiatric symptoms in children with Fetal Alcohol Spectrum Disorders (FASD) present with high prevalence and morbidity, often across symptom domains, e.g. ADHD-like symptoms, emotional dysregulation and sleep problems. Polypharmacy is often used, but no empirically-based guidelines exist regarding optimal treatment for these children. Moreover, stimulant use in these children is controversial as their responsiveness may be different due to altered neural circuitry associated with prenatal alcohol exposure. The objective of this review is to give an overview of existing data on pharmacological treatments of neurobehavioral symptoms in FASD. Our literature review yielded limited and conflicting clinical data on the effectiveness of pharmacological treatments for psychiatric symptoms in children with FASD, with some symptom domains lacking data altogether. We emphasize the need for clinical trials to guide pharmacological treatments in this complex population.
Collapse
Affiliation(s)
- Gaby J Ritfeld
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Suite 200, Atlanta, GA, USA.
| | - Julie A Kable
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Suite 200, Atlanta, GA, USA
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Jennifer E Holton
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Suite 200, Atlanta, GA, USA
| | - Claire D Coles
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Suite 200, Atlanta, GA, USA
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| |
Collapse
|
|
19
|
Fan P, Wang Y, Xu M, Han X, Liu Y. The Application of Brain Organoids in Assessing Neural Toxicity. Front Mol Neurosci 2022; 15:799397. [PMID: 35221913 PMCID: PMC8864968 DOI: 10.3389/fnmol.2022.799397] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/05/2022] [Indexed: 11/17/2022] Open
Abstract
The human brain is a complicated and precisely organized organ. Exogenous chemicals, such as pollutants, drugs, and industrial chemicals, may affect the biological processes of the brain or its function and eventually lead to neurological diseases. Animal models may not fully recapitulate the human brain for testing neural toxicity. Brain organoids with self-assembled three-dimensional (3D) structures provide opportunities to generate relevant tests or predictions of human neurotoxicity. In this study, we reviewed recent advances in brain organoid techniques and their application in assessing neural toxicants. We hope this review provides new insights for further progress in brain organoid application in the screening studies of neural toxicants.
Collapse
Affiliation(s)
- Pan Fan
- State Key Laboratory of Reproductive Medicine, School of Pharmacy, Institute for Stem Cell and Neural Regeneration, Nanjing Medical University, Nanjing, China
| | - YuanHao Wang
- State Key Laboratory of Reproductive Medicine, School of Pharmacy, Institute for Stem Cell and Neural Regeneration, Nanjing Medical University, Nanjing, China
| | - Min Xu
- State Key Laboratory of Reproductive Medicine, School of Pharmacy, Institute for Stem Cell and Neural Regeneration, Nanjing Medical University, Nanjing, China
| | - Xiao Han
- State Key Laboratory of Reproductive Medicine, School of Pharmacy, Institute for Stem Cell and Neural Regeneration, Nanjing Medical University, Nanjing, China
| | - Yan Liu
- State Key Laboratory of Reproductive Medicine, School of Pharmacy, Institute for Stem Cell and Neural Regeneration, Nanjing Medical University, Nanjing, China
- Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
20
|
Brown J, Spiller V, Carter M, Osmonson K, Porth D, Bishop-Deaton D, Jozan A. Fetal alcohol spectrum disorders (FASD) and youth firesetting: A call on criminal justice, emergency responder, and fire prevention specialists to become informed. BEHAVIORAL SCIENCES & THE LAW 2022; 40:186-217. [PMID: 34961964 DOI: 10.1002/bsl.2553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 10/08/2021] [Accepted: 11/20/2021] [Indexed: 06/14/2023]
Abstract
Central nervous system damage resulting from prenatal exposure to alcohol, often referred to as fetal alcohol spectrum disorders (FASD), commonly manifests as lacking cognitive functioning, problem solving, impulsivity, memory, executive functioning, and social skill deficits. For individuals with FASD, these brain-based deficits translate into impulsive behaviors and poorly thought-out decision-making, coupled with an inability to anticipate and recognize the sometimes very severe consequences of their behaviors. Not unexpectedly, individuals with FASD frequently find themselves disproportionately involved in the criminal justice system and mental health services. For some individuals with FASD, these behaviors can also include firesetting. First responders, like other health and legal professionals, are often unable to recognize the behavioral indicators of FASD, primarily due to a lack of training. As a result, firesetting behaviors are often attributed to deliberate, willful acts of delinquency, a desire to damage property, thrill seeking, or as attempts for personal gain, rather than being viewed as maladaptive attempts to solve problems by individuals who lack the tools to do this in more appropriate ways. These same skill deficits also present when individuals with FASD are interviewed about their involvement in such behaviors, sometimes resulting in confabulation, suggestibility, and false confessions. Further education and training in FASD are vital for first responders if they are to better support individuals with FASD and minimize their chances of becoming involved in firesetting behaviors. Furthermore, this training and education will help ensure that first responders can intervene in more appropriately when crisis situations do occur. This article will outline key behavioral symptoms of FASD as well as provide first responders with suggestions as to how to best support individuals when FASD is suspected. The brief quote that follows highlights some of the key challenges facing individuals with FASD and how poor decision-making and impulsiveness can result in severe consequences for the individual and those around them.
Collapse
Affiliation(s)
- Jerrod Brown
- American Institute for the Advancement of Forensic Studies, St. Paul, Minnesota, USA
| | - Vanessa Spiller
- JumpStart Psychology, Brisbane, Queensland, Australia
- Benchmark Psychology, Brisbane, Queensland, Australia
| | - Megan Carter
- University of Washington, Seattle, Washington, USA
- Department of Social and Health Services, Special Commitment Center, Steilacoom, Washington, USA
| | - Kathi Osmonson
- Minnesota State Fire Marshal Division, Walden University, Minneapolis, Minnesota, USA
| | - Don Porth
- American Institute for the Advancement of Forensic Studies, St. Paul, Minnesota, USA
| | - Deanna Bishop-Deaton
- School of Forensic Psychology, College of Social and Behavioral Sciences, Walden University, Minneapolis, Minnesota, USA
| | - Amy Jozan
- American Institute for the Advancement of Forensic Studies, St. Paul, Minnesota, USA
| |
Collapse
|
|
21
|
Coles CD, Grant T, Kable JA, Stoner S, Perez A, CIFASD. Prenatal alcohol exposure and mental health at midlife: A preliminary report on two longitudinal cohorts. Alcohol Clin Exp Res 2022; 46:232-242. [PMID: 35157325 PMCID: PMC8867925 DOI: 10.1111/acer.14761] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/09/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND Although the effects of prenatal alcohol exposure (PAE) have been studied extensively, there is relatively little information available on adult mental health functioning among exposed individuals. The current study compares the self-reported midlife mental health status of individuals who were prenatally exposed to alcohol and diagnosed in childhood with the effects of this exposure with that of unexposed individuals. METHODS Participants (N = 292) were recruited from two longitudinal cohorts in Atlanta and Seattle and asked to complete an Adult Health Questionnaire that surveyed their current health and mental health status. The questionnaire was completed either in-person or remotely and included questions about current symptoms of depression and anxiety and mental health disorder diagnoses. The analysis compared a Nonexposed Contrast group to those in two exposure groups: (1) Alcohol Exposed with Fetal Alcohol Effect but not meeting criteria for Fetal Alcohol Syndrome (FAS) and (2) Alcohol Affected and meeting criteria for FAS. RESULTS Both alcohol-exposed groups reported higher levels of current depressive symptoms and a higher prevalence of diagnoses of depression, anxiety, bipolar disorder, and/or attention deficit/hyperactivity disorder. No differences were noted for psychotic disorders. PAE was also associated with greater environmental stressors, including higher levels of adverse childhood events and lower current socioeconomic status. Path analyses suggested that PAE was indirectly related to mood disorders with its effects being mediated by other environmental factors. CONCLUSIONS PAE is associated with greater rates of mental health disorders in middle adulthood. These outcomes appear to result from multiple stressors that affect individuals made vulnerable by their early alcohol exposure. Clinical outcomes could be improved by prevention efforts directed at preventing prenatal alcohol use and reducing environmental stressors later in life, and by the early identification of PAE and its effects.
Collapse
Affiliation(s)
- Claire D. Coles
- Departments of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - Therese Grant
- Fetal Alcohol and Drug Unit, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington
| | - Julie A. Kable
- Departments of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - Susan Stoner
- Fetal Alcohol and Drug Unit, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington
| | - Alexandra Perez
- Departments of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - CIFASD
- Collaborative Initiative on Fetal Alcohol Spectrum Disorders
| |
Collapse
|
|
22
|
Carloni E, Ramos A, Hayes LN. Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk. Int J Mol Sci 2021; 22:13035. [PMID: 34884841 PMCID: PMC8657756 DOI: 10.3390/ijms222313035] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/25/2021] [Indexed: 12/26/2022] Open
Abstract
Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting. Immune activation is a shared pathophysiology across several different developmental stressors and may thus be a targetable treatment to mitigate the later behavioral deficits. In this review, we explore different types of prenatal and perinatal stressors and their contribution to disease risk and underlying molecular mechanisms. We highlight the impact of developmental stressors on microglia biology because of their early infiltration into the brain, their critical role in brain development and function, and their long-lived status in the brain throughout life. Furthermore, we introduce innate immune memory as a potential underlying mechanism for developmental stressors' impact on disease. Finally, we highlight the molecular and epigenetic reprogramming that is known to underlie innate immune memory and explain how similar molecular mechanisms may be at work for cells to retain a long-term perturbation after exposure to developmental stressors.
Collapse
Affiliation(s)
- Elisa Carloni
- Department of Molecular and Cellular Biology, Dartmouth College, Hanover, NH 03755, USA;
| | - Adriana Ramos
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA;
| | - Lindsay N. Hayes
- Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| |
Collapse
|
|
23
|
Shili I, Hamdi Y, Marouani A, Ben Lasfar Z, Ghrairi T, Lefranc B, Leprince J, Vaudry D, Olfa MK. Long-term protective effect of PACAP in a fetal alcohol syndrome (FAS) model. Peptides 2021; 146:170630. [PMID: 34481915 DOI: 10.1016/j.peptides.2021.170630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/13/2021] [Accepted: 08/14/2021] [Indexed: 12/29/2022]
Abstract
Prenatal ethanol exposure provokes teratogenic effects, due to oxidative stress and massive neuronal apoptosis in the developing brain that result in lifelong behavioral abnormalities. PACAP exerts anti-oxidative and neuroprotective activities on neuronal cells, and prevents ethanol neurotoxicity. The present study focused on the ability of PACAP to protect the brain of 30-day-old mice (P30) from prenatal alcohol exposure induced oxidative damage and toxicity. Pregnant mice were divided randomly into 4 groups, i.e. control group, ethanol group (1.5 g/kg ip daily injection), PACAP group (5 μg intrauterine daily injection) and an ethanol plus PACAP group. Offspring prenatally exposed to ethanol had decreased body weight and reduced cell survival. Moreover, production of ROS was sharply enhanced in the brain of prenatal ethanol-exposed animals, associated with an elevation in the activity of the antioxidant enzymes, and an increase of oxidative damages as shown by the accumulation of the lipid oxidation marker malondialdehyde and of protein carbonyl compounds. Intrauterine administration of PACAP during the gestational period restored the endogenous antioxidant system, prevented ROS overproduction and promoted the survival of dissociated cells from animals prenatally exposed to ethanol. Behavioral tests revealed that P30 animals exposed to ethanol during the prenatal period exhibited reduced motor activity, altered exploratory interest and increased anxiety. However, PACAP treatment significantly attenuated these behavioral impairments. This study demonstrates that PACAP exerts a potent neuroprotective effect against alcohol toxicity during brain development, and indicates that PACAP and/or PACAP analogs might be a useful tool for treatment of alcohol intoxication during pregnancy.
Collapse
Affiliation(s)
- Ilhem Shili
- University Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03, Laboratory of Neurophysiology, Cellular Physiopathology and Biomelcules Valorisation, 2092 Tunis, Tunisia; Normandie Univ, UNIROUEN, Inserm, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Neuropeptides, Neuronal Death and Cell Plasticity Team, 76000 Rouen, France
| | - Yosra Hamdi
- University Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03, Laboratory of Neurophysiology, Cellular Physiopathology and Biomelcules Valorisation, 2092 Tunis, Tunisia
| | - Ammar Marouani
- Institut Pasteur Tunisia, Laboratory of Venins and Toxines, B.P. 74, 1002 Tunis-Belvédère, Tunisia
| | - Zakaria Ben Lasfar
- Institut Pasteur Tunisia, Laboratory of Venins and Toxines, B.P. 74, 1002 Tunis-Belvédère, Tunisia
| | - Taoufik Ghrairi
- University Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03, Laboratory of Neurophysiology, Cellular Physiopathology and Biomelcules Valorisation, 2092 Tunis, Tunisia
| | - Benjamin Lefranc
- Normandie Univ, UNIROUEN, Inserm, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Neuropeptides, Neuronal Death and Cell Plasticity Team, 76000 Rouen, France; Normandie Univ, UNIROUEN, Regional Cell Imaging Platform of Normandy (PRIMACEN), 76000 Rouen, France
| | - Jérôme Leprince
- Normandie Univ, UNIROUEN, Inserm, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Neuropeptides, Neuronal Death and Cell Plasticity Team, 76000 Rouen, France; Normandie Univ, UNIROUEN, Regional Cell Imaging Platform of Normandy (PRIMACEN), 76000 Rouen, France
| | - David Vaudry
- Normandie Univ, UNIROUEN, Inserm, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Neuropeptides, Neuronal Death and Cell Plasticity Team, 76000 Rouen, France; Normandie Univ, UNIROUEN, Regional Cell Imaging Platform of Normandy (PRIMACEN), 76000 Rouen, France.
| | - Masmoudi-Kouki Olfa
- University Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03, Laboratory of Neurophysiology, Cellular Physiopathology and Biomelcules Valorisation, 2092 Tunis, Tunisia.
| |
Collapse
|
|
24
|
Arzua T, Jiang C, Yan Y, Bai X. The importance of non-coding RNAs in environmental stress-related developmental brain disorders: A systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections. Neurosci Biobehav Rev 2021; 128:633-647. [PMID: 34186153 PMCID: PMC8357057 DOI: 10.1016/j.neubiorev.2021.06.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 05/23/2021] [Accepted: 06/23/2021] [Indexed: 12/11/2022]
Abstract
Brain development is a dynamic and lengthy process that includes cell proliferation, migration, neurogenesis, gliogenesis, synaptogenesis, and pruning. Disruption of any of these developmental events can result in long-term outcomes ranging from brain structural changes, to cognitive and behavioral abnormality, with the mechanisms largely unknown. Emerging evidence suggests non-coding RNAs (ncRNAs) as pivotal molecules that participate in normal brain development and neurodevelopmental disorders. NcRNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are transcribed from the genome but not translated into proteins. Many ncRNAs have been implicated as tuners of cell fate. In this review, we started with an introduction of the current knowledge of lncRNAs and miRNAs, and their potential roles in brain development in health and disorders. We then reviewed and discussed the evidence of ncRNA involvement in abnormal brain development resulted from alcohol, anesthetic drugs, nicotine, and viral infections. The complex connections among these ncRNAs were also discussed, along with potential overlapping ncRNA mechanisms, possible pharmacological targets for therapeutic/neuroprotective interventions, and potential biomarkers for brain developmental disorders.
Collapse
Affiliation(s)
- Thiago Arzua
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Congshan Jiang
- Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Yasheng Yan
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Xiaowen Bai
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
| |
Collapse
|
|
25
|
Chatterjee D, Mahabir S, Chatterjee D, Gerlai R. Lasting effects of mild embryonic ethanol exposure on voltage-gated ion channels in adult zebrafish brain. Prog Neuropsychopharmacol Biol Psychiatry 2021; 110:110327. [PMID: 33864849 DOI: 10.1016/j.pnpbp.2021.110327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 02/28/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023]
Abstract
The zebrafish is increasingly well utilized in alcohol research, particularly in modeling human fetal alcohol spectrum disorders (FASD). FASD results from alcohol reaching the developing fetus intra utero, a completely preventable yet prevalent and devastating life-long disorder. The hope with animal models, including the zebrafish, is to discover the mechanisms underlying this disease, which may aid treatment and diagnosis. In the past, we developed an embryonic alcohol exposure regimen that is aimed at mimicking the milder, and most prevalent, forms of FASD in zebrafish. We have found numerous lasting alterations in behavior, neurochemistry, neuronal markers and glial cell phenotypes in this zebrafish FASD model. Using the same model (2 h long bath immersion of 24 h post-fertilization old zebrafish eggs into 1% vol/vol ethanol), here we conduct a proof of concept analysis of voltage-gated cation channels, investigating potential embryonic alcohol induced changes in L-, T- and N- type Ca++ and the SCN1A Na+ channels using Western blot followed by immunohistochemical analysis of the same channels in the pallium and cerebellum of the zebrafish brain. We report significant reduction of expression in all four channel proteins using both methods. We conclude that reduced voltage-gated cation channel expression induced by short and low dose exposure to alcohol during embryonic development of zebrafish may contribute to the previously demonstrated lasting behavioral and neurobiological changes.
Collapse
Affiliation(s)
| | - Samantha Mahabir
- Department of Psychology, University of Toronto, Mississauga, Ontario, Canada
| | | | - Robert Gerlai
- Department of Psychology, University of Toronto, Mississauga, Ontario, Canada.
| |
Collapse
|
|
26
|
Maschke J, Roetner J, Bösl S, Plank AC, Rohleder N, Goecke TW, Fasching PA, Beckmann MW, Kratz O, Moll GH, Lenz B, Kornhuber J, Eichler A, IMAC-Mind-Consortium. Association of Prenatal Alcohol Exposure and Prenatal Maternal Depression with Offspring Low-Grade Inflammation in Early Adolescence. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18157920. [PMID: 34360212 PMCID: PMC8345560 DOI: 10.3390/ijerph18157920] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/15/2021] [Accepted: 07/20/2021] [Indexed: 12/27/2022]
Abstract
(1) This longitudinal study aimed to investigate the link between prenatal alcohol exposure and prenatal maternal depression with the offspring’s low-grade inflammatory status. (2) Prenatal alcohol exposure was determined via maternal self-report during the 3rd trimester of pregnancy (self-report+: n = 29) and the meconium alcohol metabolite Ethyl Glucuronide (EtG), collected at birth (≥30 ng/g: n = 23). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for prenatal maternal depressive symptoms during the 3rd trimester (≥10: n = 35). Fifteen years later, 122 adolescents (M = 13.32 years; 48.4% female) provided blood samples for the analysis of high sensitivity C-reactive protein (hsCRP; M = 0.91; SD = 1.28). (3) Higher hsCRP levels were found in EtG positive adolescents (p = 0.036, ηp2 = 0.04) and an inverse non-significant dose–response relation with hsCRP (r = −0.35, p = 0.113). For maternal self-reported prenatal alcohol consumption (p = 0.780, ηp2 = 0.00) and prenatal depressive symptoms (p = 0.360, ηp2 = 0.01) no differences for hsCRP levels between the affected and unaffected groups were found. (4) Adolescents with prenatal alcohol exposure are at risk for low-grade systemic inflammation. The EtG biomarker may be more accurate compared to self-reports. The findings suggest that prenatal maternal depression does not evoke low-grade systemic inflammation.
Collapse
Affiliation(s)
- Janina Maschke
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
- Correspondence: ; Tel.: +49-9131-8544657
| | - Jakob Roetner
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
| | - Sophia Bösl
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
| | - Anne-Christine Plank
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
| | - Nicolas Rohleder
- Department of Psychology, Friedrich-Alexander University Erlangen-Nürnberg, 91052 Erlangen, Germany;
| | - Tamme W. Goecke
- Department of Obstetrics and Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (T.W.G.); (P.A.F.); (M.W.B.)
- Department of Obstetrics and Gynecology, RoMed Klinikum Rosenheim, 83022 Rosenheim, Germany
| | - Peter A. Fasching
- Department of Obstetrics and Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (T.W.G.); (P.A.F.); (M.W.B.)
| | - Matthias W. Beckmann
- Department of Obstetrics and Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (T.W.G.); (P.A.F.); (M.W.B.)
| | - Oliver Kratz
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
| | - Gunther H. Moll
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
| | - Bernd Lenz
- Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (B.L.); (J.K.)
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
| | - Johannes Kornhuber
- Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (B.L.); (J.K.)
| | - Anna Eichler
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (J.R.); (S.B.); (A.-C.P.); (O.K.); (G.H.M.); (A.E.)
| | | |
Collapse
|
|
27
|
Effects of prenatal alcohol and cannabis exposure on neurodevelopmental and cognitive disabilities. HANDBOOK OF CLINICAL NEUROLOGY 2021. [PMID: 32958186 DOI: 10.1016/b978-0-444-64150-2.00028-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/23/2025]
Abstract
Substance use during pregnancy and the short- and long-term impacts of different substances on maternal, fetal, and longer-term health outcomes of individuals prenatally exposed have been the subject of much investigation. Alcohol has been recognized as harmful during pregnancy and has been clearly recognized as a neurobehavioral teratogen, and the pattern of effects has been termed fetal alcohol spectrum disorder. More recently, the effects of prenatal cannabis exposure have been vigorously explored as a priority research area following decriminalization/legalization of cannabis in Canada and the United States. As the data become more and more robust, we are learning that cannabis during pregnancy can have negative effects on maternal and fetal outcomes and on longer-term neurodevelopmental and cognitive functions.
Collapse
|
|
28
|
Zaso MJ, Youngentob SL, Park A. Characterizing the role of early alcohol reexposure in associations of prenatal alcohol exposure with adolescent alcohol outcomes. Alcohol Clin Exp Res 2021; 45:1436-1447. [PMID: 33977545 PMCID: PMC8295222 DOI: 10.1111/acer.14632] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 04/09/2021] [Accepted: 05/05/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Prenatal alcohol exposure has been linked to a host of negative outcomes, although it is largely unknown whether prenatal exposure leads to an earlier age of initiation of alcohol use or exacerbates early alcohol initiation. The current study examined whether adolescents exposed to heavy drinking during gestation began drinking earlier than their nonexposed peers and whether an earlier age of alcohol reexposure in adolescence exacerbated associations with adverse alcohol outcomes. METHODS Adolescents (17 years of age; 57% female; 96% White) from a longitudinal, population-based cohort study, the Avon Longitudinal Study of Parents and Children, reported on the age they first consumed a whole drink and other alcohol behaviors. Adolescents' mothers also reported on their own heavy drinking during pregnancy (i.e., any consumption of 4+ U.K. units in a drinking day at either 18 or 32 weeks of gestation). RESULTS Survival analyses indicated that prenatal heavy drinking exposure was not associated with an earlier initiation of alcohol use after controlling for potential demographic and parental mental health and substance use confounds. Generalized negative binomial models demonstrated that prenatal heavy drinking exposure moderated associations of the age of alcohol initiation with alcohol quantity and heavy drinking frequency (but not alcohol frequency or Alcohol Use Disorders Identification Test score), after controlling for the same demographic and parental confounds. Specifically, earlier alcohol initiation was associated with more adverse alcohol outcomes regardless of prenatal exposure. However, the protective associations of delayed alcohol initiation were lower among adolescents exposed to prenatal heavy drinking. CONCLUSIONS This study provides evidence for the interplay between prenatal and postnatal alcohol exposures. Importantly, adolescents who were prenatally exposed to heavy drinking appeared to be less protected by later alcohol initiation than those who were not exposed in utero.
Collapse
Affiliation(s)
- Michelle J. Zaso
- Syracuse University, Department of Psychology, Syracuse, NY, USA
- Clinical and Research Institute on Addictions, University at Buffalo – The State University of New York, Buffalo, NY, USA
| | | | - Aesoon Park
- Syracuse University, Department of Psychology, Syracuse, NY, USA
| |
Collapse
|
|
29
|
Day DB, Collett BR, Barrett ES, Bush NR, Swan SH, Nguyen RHN, Szpiro AA, Sathyanarayana S. Phthalate mixtures in pregnancy, autistic traits, and adverse childhood behavioral outcomes. ENVIRONMENT INTERNATIONAL 2021; 147:106330. [PMID: 33418196 PMCID: PMC9291724 DOI: 10.1016/j.envint.2020.106330] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/28/2020] [Accepted: 12/07/2020] [Indexed: 05/22/2023]
Abstract
BACKGROUND Prenatal exposure to multiple phthalates is ubiquitous, and yet few studies have evaluated these exposures as a mixture in relation to child autistic traits and behavioral problems. OBJECTIVES To assess cumulative associations between prenatal phthalate mixtures and child behaviors, including effect modification by exposure timing and child sex. METHODS Analyses included 501 mother/child pairs from the multicenter pregnancy cohort The Infant Development and Environment Study (TIDES). Nine maternal urinary phthalate metabolites were measured in early and late pregnancy, and behavior was assessed at ages 4-5 years using composite T scores for the Behavioral Assessment System for Children (BASC-2), which measures several dimensions of child behavior, and the Social Responsiveness Scale (SRS-2), which measures social impairment consistent with autistic traits. We utilized weighted quantile sum (WQS) regressions to examine pregnancy period-specific associations between phthalate mixtures and behavioral outcomes. Full-sample 95% WQS confidence intervals are known to be anti-conservative, so we calculated a confirmatory p-value using a permutation test. Effect modification by sex was examined with stratified analyses. RESULTS A one-quintile increase in the early pregnancy phthalate mixture was associated with increased SRS-2 total score (coefficient = 1.0, confirmatory p = 0.01) and worse adaptive skills (coefficient = -1.0, confirmatory p = 0.06) in both sexes. In sex-stratified analyses, the early pregnancy phthalate mixture was associated with increased SRS-2 total score in boys (coefficient = 1.2, confirmatory p = 0.04) and girls (coefficient = 1.0, confirmatory p = 0.10) and worse BASC-2 adaptive skills score in girls (coefficient = -1.5, confirmatory p = 0.06), while the late pregnancy phthalate mixture was associated with increased BASC-2 externalizing score in boys (coefficient = 1.3, confirmatory p = 0.03). CONCLUSION Our results suggest cumulative adverse associations between prenatal phthalate mixtures and multiple facets of childhood behavior.
Collapse
Affiliation(s)
- Drew B Day
- Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, 1920 Terry Ave, Seattle, WA 98101, USA.
| | - Brent R Collett
- Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, 1920 Terry Ave, Seattle, WA 98101, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
| | - Emily S Barrett
- Department of Epidemiology, Environmental and Occupational Health Sciences Institute, Rutgers School of Public Health, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
| | - Nicole R Bush
- Center for Health and Community, Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, Department of Pediatrics, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143, USA.
| | - Shanna H Swan
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 17 E. 102nd Street, CAM Building, 3 West, One Gustave L. Levy Place, New York, NY 10029, USA.
| | - Ruby H N Nguyen
- Department of Epidemiology and Community Health, University of Minnesota, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
| | - Adam A Szpiro
- Department of Biostatistics, University of Washington, 1705 Northeast Pacific Street, Seattle, WA 98195, USA.
| | - Sheela Sathyanarayana
- Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, 1920 Terry Ave, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.
| |
Collapse
|
|
30
|
Popova S, Temple V, Dozet D, O'Hanlon G, Toews C, Rehm J. Health, social and legal outcomes of individuals with diagnosed or at risk for fetal alcohol spectrum disorder: Canadian example. Drug Alcohol Depend 2021; 219:108487. [PMID: 33385689 DOI: 10.1016/j.drugalcdep.2020.108487] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 11/17/2020] [Accepted: 11/18/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Fetal Alcohol Spectrum Disorder (FASD) is a leading cause of lifelong developmental and physical disabilities and behavioural problems. This study describes the characteristics of individuals diagnosed with or at risk for FASD in British Columbia, Canada. METHODS A retrospective chart review and cross-sectional analysis were conducted on records of individuals diagnosed or at risk for FASD at the Asante Centre from January 2015 to July 2019. Descriptive statistics results were stratified by age, sex, and involvement with the criminal justice and child welfare systems. Logistic regression was used to investigate potential associations. RESULTS 161 individuals with diagnosed or at risk for FASD, (53 % male; mean age = 15.7 years, SD = 9.1) were included in the analysis. High levels of psychological/developmental disabilities (78 %), physical comorbidities (38 %), substance use (50 %), and involvement in child welfare (75 %) and criminal justice systems (30 %) were found across the entire group. Individuals over 20 reported the greatest proportion of any past substance (60.9 %), alcohol use (39.1 %) and stimulant use (30.4 %), compared to individuals aged 10-19 (41.3 %; 12.0 %; 14.1 %, respectively). Involvement with the child welfare system was associated with higher chances of having anxiety (OR 4.1; 95 % CI: 1.25-15.00). Involvement with the criminal justice system was associated with higher rates of past substance and cannabis use. CONCLUSION Individuals with FASD demonstrate a significant need for access to mental health and addiction services, especially among those with involvement in the child welfare and criminal justice systems. These findings point to the importance of improving policies to support the unique needs of individuals with FASD.
Collapse
Affiliation(s)
- Svetlana Popova
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research, 33 Ursula Franklin Street, Toronto, ON, M5S 2S1, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada; Factor-Inwentash Faculty of Social Work, University of Toronto, 246 Bloor Street W, Toronto, ON, M5S 1V4, Canada; Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Valerie Temple
- Surrey Place, 2 Surrey Place, Toronto, ON, M5S 2C2, Canada.
| | - Danijela Dozet
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research, 33 Ursula Franklin Street, Toronto, ON, M5S 2S1, Canada; Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Graham O'Hanlon
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research, 33 Ursula Franklin Street, Toronto, ON, M5S 2S1, Canada.
| | - Caitlin Toews
- The Asante Centre, 103-22356 McIntosh Ave., Maple Ridge, BC, V2X 3C1, Canada.
| | - Jurgen Rehm
- Centre for Addiction and Mental Health, Institute for Mental Health Policy Research, 33 Ursula Franklin Street, Toronto, ON, M5S 2S1, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada; Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies, Technische Universität Dresden, Chemnitzer Str. 46, 01187, Dresden, Germany; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada.
| |
Collapse
|
|
31
|
Flannigan K, Kapasi A, Pei J, Murdoch I, Andrew G, Rasmussen C. Characterizing adverse childhood experiences among children and adolescents with prenatal alcohol exposure and Fetal Alcohol Spectrum Disorder. CHILD ABUSE & NEGLECT 2021; 112:104888. [PMID: 33388606 DOI: 10.1016/j.chiabu.2020.104888] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/28/2020] [Accepted: 12/09/2020] [Indexed: 06/12/2023]
Abstract
BACKGROUND Individuals with Fetal Alcohol Spectrum Disorder (FASD) and prenatal alcohol exposure (PAE) face elevated rates of postnatal environmental adversity across the lifespan. OBJECTIVE We explored early adversity among children and adolescents with PAE. PARTICIPANTS AND SETTING Our sample included 333 children and adolescents with PAE assessed at a Canadian FASD diagnostic clinic, 66% of whom were diagnosed with FASD. METHODS Data were collected retrospectively via record review, and adversity was measured using the Adverse Childhood Experiences Questionnaire (ACE-Q). RESULTS Participants experienced high levels of adversity (mean ACE score of 3.4), which increased with age, mental health comorbidity, and number of living placements. Common ACEs included: not being raised by both biological parents (97.3%), caregiver disruption (88.5%), and exposure to household substance use (69.7%). Females had significantly higher rates of sexual abuse than males (p < .001, ø = -0.18). There was no difference in total ACE scores between participants diagnosed with FASD versus those not diagnosed, but participants with FASD were less likely to live with both biological parents (p < .001, ø = .19) or to have been exposed to household mental health problems (p = .007, ø = -0.15). CONCLUSIONS Children and adolescents with PAE experience high rates of early adversity. Practice and policy initiatives are needed to improve early detection of ACEs among children with PAE, and of PAE among children with ACEs. Targeted supports are needed to strengthen the early caregiving environment and mitigate the risks of adversity to support healthy outcomes for individuals with PAE and FASD.
Collapse
Affiliation(s)
- Katherine Flannigan
- Canada Fetal Alcohol Spectrum Disorder Research Network, PO Box 11364 Wessex PO, Vancouver BC, V5R 0A4, Canada.
| | - Aamena Kapasi
- University of Alberta, Educational Psychology, 6-131 Education North, 116 Street and 85 Avenue, Edmonton AB, T6G 2R3, Canada
| | - Jacqueline Pei
- Canada Fetal Alcohol Spectrum Disorder Research Network, PO Box 11364 Wessex PO, Vancouver BC, V5R 0A4, Canada; University of Alberta, Educational Psychology, 6-131 Education North, 116 Street and 85 Avenue, Edmonton AB, T6G 2R3, Canada
| | - Isabel Murdoch
- University of Alberta, Educational Psychology, 6-131 Education North, 116 Street and 85 Avenue, Edmonton AB, T6G 2R3, Canada
| | - Gail Andrew
- Glenrose Rehabilitation Hospital, 10230 111 Avenue, Edmonton AB, T5G 0B7, Canada
| | - Carmen Rasmussen
- University of Alberta, Educational Psychology, 6-131 Education North, 116 Street and 85 Avenue, Edmonton AB, T6G 2R3, Canada
| |
Collapse
|
|
32
|
Chatterjee D, Mahabir S, Chatterjee D, Gerlai R. Lasting alterations induced in glial cell phenotypes by short exposure to alcohol during embryonic development in zebrafish. Addict Biol 2021; 26:e12867. [PMID: 31919968 DOI: 10.1111/adb.12867] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 12/04/2019] [Accepted: 12/05/2019] [Indexed: 12/13/2022]
Abstract
Despite the known teratogenic effects of alcohol (ethanol) on the developing human fetus, the prevalence of fetal alcohol spectrum disorder (FASD) is not decreasing. Appropriate treatment for this life-long disease has not been developed, and even diagnostic biomarkers are unavailable. FASD remains a large unmet medical need. Numerous animal models have been developed to mimic FASD and study potential underlying biological mechanisms. However, most of these models focused on neuronal phenotypes. Given that glial cells represent the majority of cells in the vertebrate brain, and given the increasingly appreciated roles they play in a myriad of neuronal functions as well as CNS disorders, we decided to investigate potential embryonic alcohol exposure induced changes in them. Building upon a previously introduced zebrafish model of milder and most prevalent forms of FASD, we investigated the effect of a 2-hour-long exposure to alcohol (1% vol/vol bath concentration) employed at the 24th hour postfertilization stage of development of zebrafish on a number of glial cell-related phenotypes. We studied oligodendrocyte, astrocyte as well as microglia-related phenotypes using immunohistochemistry, lipid, and enzyme activity analyses. We report significant changes in wide-spread glial cell phenotypes induced by embryonic alcohol exposure in the zebrafish brain and conclude that the zebrafish will advance our understanding of the mechanisms of this devastating disorder.
Collapse
Affiliation(s)
| | - Samantha Mahabir
- Department of Cell and Systems Biology University of Toronto Toronto Canada
| | - Diptendu Chatterjee
- Department of Psychology University of Toronto Mississauga Mississauga Canada
| | - Robert Gerlai
- Department of Cell and Systems Biology University of Toronto Toronto Canada
- Department of Psychology University of Toronto Mississauga Mississauga Canada
| |
Collapse
|
|
33
|
Gustus K, Li L, Newville J, Cunningham LA. Functional and Structural Correlates of Impaired Enrichment-Mediated Adult Hippocampal Neurogenesis in a Mouse Model of Prenatal Alcohol Exposure. Brain Plast 2020; 6:67-82. [PMID: 33680847 PMCID: PMC7902980 DOI: 10.3233/bpl-200112] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Fetal alcohol spectrum disorders (FASDs) are associated with a wide range of cognitive deficiencies. Objective: We previously
found that gestational exposure to moderate levels of alcohol in mice throughout the 1st-2nd human trimester-equivalents
for brain development results in profound impairment of the hippocampal neurogenic response to enriched environment
(EE) in adulthood, without altering baseline neurogenesis rate under standard housing (SH). However, the functional and
structural consequences of impaired EE-mediated neurogenesis in the context of prenatal alcohol exposure (PAE) have
not been determined. Results: Here, we demonstrate that PAE-EE mice display impaired performance on a neurogenesis-dependent
pattern discrimination task, broadened behavioral activation of the dentate gyrus, as assessed by expression of the immediate
early gene, c-Fos, and impaired dendritic branching of adult-generated dentate granule cells (aDGCs). Conclusions: These studies further underscore the impact of moderate gestational alcohol exposure on adult hippocampal plasticity and support adult hippocampal neurogenesis as a potential therapeutic target to remediate certain neurological outcomes in FASD.
Collapse
Affiliation(s)
- Kymberly Gustus
- Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Lu Li
- Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Jessie Newville
- Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Lee Anna Cunningham
- Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA
| |
Collapse
|
|
34
|
Aglawe MM, Kale MB, Rahangdale SR, Kotagale NR, Umekar MJ, Taksande BG. Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats. Brain Res Bull 2020; 167:37-47. [PMID: 33242522 DOI: 10.1016/j.brainresbull.2020.11.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 10/28/2020] [Accepted: 11/19/2020] [Indexed: 12/30/2022]
Abstract
Chronic maternal ethanol exposure leads to poor intelligence, impaired cognition and array of neurological symptoms in offsprings and commonly referred as fetal alcohol spectrum disorder (FASD). Despite high prevalence and severity, the neurochemical basis of FASD remains largely unexplored. The present study evaluated the pharmacological effects of agmatine in cognitive deficits associated with FAS in rat's offsprings prenatally exposed to alcohol. Pregnant rats received ethanol in liquid modified diet during the entire gestational period of 21 days. Offsprings were treated with agmatine (20-80 mg/Kg, i.p.) during early postnatal days (PND: 21-35) and subsequently evaluated for anxiety in elevated plus maze (EPM), depression in forced swim test (FST) and learning and memory in Morris's water maze (MWM) during post adolescent phase. Hippocampal agmatine, BDNF, TNF-α and IL-6 levels were also analyzed in prenatally ethanol exposed pups. Offsprings prenatally exposed to ethanol demonstrated delayed righting reflex, reduced exploratory behavior along with anxiety, depression-like behavior and impaired memory. These behavioral abnormalities were correlated with a significant reduction in hippocampal agmatine and BDNF levels and elevation in TNF-α and IL-6 immunocontent. Chronic agmatine (40 and 80 mg/Kg, i.p.) administration for 15 days (PND: 21-35), improved entries and time spent in open arm of EPM, decreased immobility time in FST. It also reduced latency to reach the platform location; increased the number of entries, time spent in platform quadrant and also number of crossing over platform quadrant when subjected to MWM test in prenatally ethanol exposed offsprings. This study provides functional evidences for the therapeutic potential of agmatine in cognitive impairment and other neurological complications associated with FASD.
Collapse
Affiliation(s)
- Manish M Aglawe
- Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India
| | - Mayur B Kale
- Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India
| | - Sandip R Rahangdale
- Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India
| | | | - Milind J Umekar
- Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India
| | - Brijesh G Taksande
- Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, 441 002, India.
| |
Collapse
|
|
35
|
Flannigan K, Coons-Harding KD, Anderson T, Wolfson L, Campbell A, Mela M, Pei J. A Systematic Review of Interventions to Improve Mental Health and Substance Use Outcomes for Individuals with Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder. Alcohol Clin Exp Res 2020; 44:2401-2430. [PMID: 33119894 PMCID: PMC7839542 DOI: 10.1111/acer.14490] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 10/18/2020] [Indexed: 12/25/2022]
Abstract
Individuals with fetal alcohol spectrum disorder (FASD) experience remarkably high rates of mental health and substance use challenges, beginning early in life and extending throughout adulthood. Proactive intervention can help to mitigate some of these negative experiences. Although the literature on FASD intervention is growing, there is currently a lack of consolidated evidence on interventions that may improve mental health and substance use outcomes in this population. Informed by a life course perspective, we undertook a systematic review of the literature to identify interventions that improve mental wellness through all developmental stages for people with prenatal alcohol exposure (PAE) and FASD. A total of 33 articles were identified, most of which were focused on building skills or strategies that underlie the well‐being of children with PAE and FASD and their families. Other interventions were geared toward supporting child and family wellness and responding to risk or reducing harm. There was a notable lack of interventions that directly targeted mental health and substance use challenges, and a major gap was also noted in terms of interventions for adolescents and adults. Combined, these studies provide preliminary and emerging evidence for a range of intervention approaches that may support positive outcomes for individuals with FASD across the life course.
Collapse
Affiliation(s)
- Katherine Flannigan
- (KF, KDC-H, LW, MM, JP), Canada FASD Research Network, Vancouver, British Columbia, Canada
| | - Kelly D Coons-Harding
- (KF, KDC-H, LW, MM, JP), Canada FASD Research Network, Vancouver, British Columbia, Canada.,Psychology Department, (KDC-H), Laurentian University, Sudbury, Ontario, Canada
| | - Tara Anderson
- (TA), Saskatchewan Health Authority, Saskatoon, Saskatchewan, Canada
| | - Lindsay Wolfson
- (KF, KDC-H, LW, MM, JP), Canada FASD Research Network, Vancouver, British Columbia, Canada.,(LW), Centre of Excellence for Women's Health, Vancouver, British Columbia, Canada
| | - Alanna Campbell
- (AC), Northern Ontario School of Medicine, Sudbury, Ontario, Canada
| | - Mansfield Mela
- (KF, KDC-H, LW, MM, JP), Canada FASD Research Network, Vancouver, British Columbia, Canada.,Department of Psychiatry, College of Medicine, (MM), University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Jacqueline Pei
- (KF, KDC-H, LW, MM, JP), Canada FASD Research Network, Vancouver, British Columbia, Canada.,Department of Educational Psychology, (JP), University of Alberta, Edmonton, Alberta, Canada.,Department of Pediatrics, (JP), University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
36
|
Arzua T, Yan Y, Jiang C, Logan S, Allison RL, Wells C, Kumar SN, Schäfer R, Bai X. Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids. Transl Psychiatry 2020; 10:347. [PMID: 33051447 PMCID: PMC7553959 DOI: 10.1038/s41398-020-01029-4] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 09/11/2020] [Accepted: 09/22/2020] [Indexed: 02/07/2023] Open
Abstract
Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.
Collapse
Affiliation(s)
- Thiago Arzua
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
- Department of Physiology, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Yasheng Yan
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Congshan Jiang
- Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Sarah Logan
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
- Department of Physiology, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Reilly L Allison
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Clive Wells
- Department of Microbiology, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Suresh N Kumar
- Department of Pathology, Children's Research Institute Imaging Core, Neuroscience Imaging Facility, Medical College of Wisconsin, Milwaukee, 53226, WI, USA
| | - Richard Schäfer
- Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, 60438, Frankfurt am Main, Germany
| | - Xiaowen Bai
- Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, 53226, WI, USA.
| |
Collapse
|
|
37
|
Longitudinal associations between inhibitory control and externalizing and internalizing symptoms in school-aged children. Dev Psychopathol 2020; 33:843-855. [PMID: 32662373 DOI: 10.1017/s0954579420000176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Inhibitory control (IC) deficits have been associated with psychiatric symptoms in all ages. However, longitudinal studies testing the direction of the associations in childhood are scarce. We used a sample of 2,874 children (7 to 9 years old) to test the following three hypotheses: (a) IC deficits are an underlying risk factor with a potentially causal role for psychopathology, (b) IC deficits are a complication of psychopathology, and (c) IC deficits and psychopathology are associated at the trait level but not necessarily causally related. We used the go/no-go task to assess IC, the parent-rated Strengths and Difficulties Questionnaire to evaluate externalizing/internalizing symptoms, and the random intercepts cross-lagged panel model to test the hypotheses. The results showed no support for the underlying risk factor hypothesis, suggesting that IC unlikely has a causal role in this age group's psychopathology. The complication hypothesis received support for externalizing symptoms, suggesting that externalizing symptoms may hamper the normal development of IC. IC deficits and both externalizing and internalizing symptoms were correlated at the trait level, indicating a possible common origin. We suggest that it may be useful to support children with externalizing symptoms to promote and protect their IC development.
Collapse
|
|
38
|
Madarnas C, Villalba NM, Soriano D, Brusco A. Anxious Behavior of Adult CD1 Mice Perinatally Exposed to Low Concentrations of Ethanol Correlates With Morphological Changes in Cingulate Cortex and Amygdala. Front Behav Neurosci 2020; 14:92. [PMID: 32636737 PMCID: PMC7319189 DOI: 10.3389/fnbeh.2020.00092] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 05/14/2020] [Indexed: 01/12/2023] Open
Abstract
Perinatal ethanol (EtOH) exposure is associated with high incidence of behavioral disorders such as depression and anxiety. The cerebral areas related with these consequences involve the corticolimbic system, in particular the prefrontal cortex, hippocampus, amygdala, and cingulate cortex, although the latter has not been thoroughly studied yet. Different animal models of prenatal or perinatal EtOH exposure have reported morphofunctional alterations in the central nervous system, which could explain behavioral disorders along life; these results focus on youth and adolescents and are still controversial. In the light of these inconclusive results, the aim of this work was to analyze adult behavior in CD1 mice perinatally exposed to low concentrations of EtOH (PEE) during gestation and lactation, and describe the morphology of the cingulate cortex and amygdala with a view to establishing structure/function/behavior correlations. Primiparous CD1 female mice were exposed to EtOH 6% v/v for 20 days prior to mating and continued drinking EtOH 6% v/v during pregnancy and lactation. After weaning, male pups were fed food and water ad libitum until 77 days of age, when behavioral and morphological studies were performed. Mouse behavior was analyzed through light–dark box and open field tests. Parameters related to anxious behavior and locomotor activity revealed anxiogenic behavior in PEE mice. After behavioral studies, mice were perfused and neurons, axons, serotonin transporter, 5HT, CB1 receptor (CB1R) and 5HT1A receptor (5HT1AR) were studied by immunofluorescence and immunohistochemistry in brain sections containing cingulate cortex and amygdala. Cingulate cortex and amygdala cytoarchitecture were preserved in adult PEE mice, although a smaller number of neurons was detected in the amygdala. Cingulate cortex axons demonstrated disorganized radial distribution and reduced area. Serotonergic and endocannabinoid systems, both involved in anxious behavior, showed differential expression. Serotonergic afferents were lower in both brain areas of PEE animals, while 5HT1AR expression was lower in the cingulate cortex and higher in the amygdala. The expression of CB1R was lower only in the amygdala. In sum, EtOH exposure during early brain development induces morphological changes in structures of the limbic system and its neuromodulation, which persist into adulthood and may be responsible for anxious behavior.
Collapse
Affiliation(s)
- Catalina Madarnas
- Instituto de Biología Celular y Neurociencia (IBCN), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
| | - Nerina Mariel Villalba
- Instituto de Biología Celular y Neurociencia (IBCN), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
| | - Delia Soriano
- Instituto de Biología Celular y Neurociencia (IBCN), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.,Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Alicia Brusco
- Instituto de Biología Celular y Neurociencia (IBCN), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.,Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Universidad de Buenos Aires, Buenos Aires, Argentina
| |
Collapse
|
|
39
|
Diaz MR, Johnson JM, Varlinskaya EI. Increased ethanol intake is associated with social anxiety in offspring exposed to ethanol on gestational day 12. Behav Brain Res 2020; 393:112766. [PMID: 32535179 DOI: 10.1016/j.bbr.2020.112766] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 06/05/2020] [Accepted: 06/07/2020] [Indexed: 01/21/2023]
Abstract
Prenatal alcohol exposure (PAE) can result in physical, cognitive, and neurological deficits termed Fetal Alcohol Spectrum Disorder (FASD). Deficits in social functioning associated with PAE are frequently observed and persist throughout the lifespan. Social impairments, such as social anxiety, are associated with increased alcohol abuse, which is also highly pervasive following PAE. Yet, the relationship between PAE-induced social alterations and alcohol intake later in life is not well understood. In order to test this relationship, we exposed pregnant female Sprague Dawley rats to a single instance of PAE on gestational day 12, a period of substantial neural development, and tested offspring in adulthood (postnatal day 63) in a modified social interaction test followed by alternating alone and social ethanol intake sessions. Consistent with our previous findings, we found that, in general, PAE reduced social preference (measure of social anxiety-like behavior) in female but not male adults. However, ethanol intake was significantly higher in the PAE group regardless of sex. When dividing subjects according to level of social anxiety-like behavior (low, medium, or high), PAE males (under both drinking contexts) and control females (under the social drinking context) with a high social anxiety phenotype showed the highest level of ethanol intake. Taken together, these data indicate that PAE differentially affects the interactions between social anxiety, ethanol intake, and drinking context in males and females. These findings extend our understanding of the complexity and persistence of PAE's sex-dependent effects into adulthood.
Collapse
Affiliation(s)
- Marvin R Diaz
- Department of Psychology, Center for Development and Behavioral Neuroscience Binghamton University, Binghamton, NY13902, United States; Developmental Exposure Alcohol Research Center, Baltimore MD21201, Binghamton NY 13902, Syracuse NY13210, United States.
| | - Julia M Johnson
- Developmental Exposure Alcohol Research Center, Baltimore MD21201, Binghamton NY 13902, Syracuse NY13210, United States
| | - Elena I Varlinskaya
- Department of Psychology, Center for Development and Behavioral Neuroscience Binghamton University, Binghamton, NY13902, United States; Developmental Exposure Alcohol Research Center, Baltimore MD21201, Binghamton NY 13902, Syracuse NY13210, United States
| |
Collapse
|
|
40
|
May PA, Hasken JM, Baete A, Russo J, Elliott AJ, Kalberg WO, Buckley D, Brooks M, Ortega MA, Hedrick DM, Tabachnick BG, Abdul-Rahman O, Adam MP, Jewett T, Robinson LK, Manning MA, Hoyme HE. Fetal Alcohol Spectrum Disorders in a Midwestern City: Child Characteristics, Maternal Risk Traits, and Prevalence. Alcohol Clin Exp Res 2020; 44:919-938. [PMID: 32293735 DOI: 10.1111/acer.14314] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 12/16/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To determine the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers in a Midwestern city. METHODS Case-control samples were drawn from 2 separate first-grade cohorts (combined N = 4,047) in every city school using different methods. In Cohort Sample 1, all consented small children (≤25th centile on height, weight, and/or head circumference) entered the study along with a random sample from all enrolled students. Cohort Sample 2 was drawn totally at random. Child growth, dysmorphology, and neurobehavior were assessed using the Collaboration on FASD Prevalence (CoFASP) criteria, and mothers were interviewed. RESULTS For the samples combined, 891 children received dysmorphology examinations, and 692 were case-conferenced for final diagnosis. Forty-four children met criteria for FASD. Total dysmorphology scores differentiated diagnostic groups: fetal alcohol syndrome (FAS), 16.7; partial FAS, 11.8; alcohol-related neurodevelopmental disorder (ARND), 6.1; and typically developing controls, 4.2. Neurobehavioral tests distinguished children with FASD from controls, more for behavioral problems than cognitive delay. Children with ARND demonstrated the poorest neurobehavioral indicators. An adjusted regression model of usual prepregnancy drinking indicated that maternal reports of 3 drinks per drinking day (DDD) were significantly associated with a FASD diagnosis (p = 0.020, OR = 10.1, 95% CI = 1.44 to 70.54), as were 5 or more DDD (p < 0.001, OR = 26.47, 95% CI = 4.65 to 150.62). Other significant maternal risk factors included the following: self-reported drinking in any trimester; smoking and cocaine use during pregnancy; later pregnancy recognition and later and less prenatal care; lower maternal weight, body mass index (BMI), and head circumference; and unmarried status. There was no significant difference in FASD prevalence by race, Hispanic ethnicity, or socioeconomic status at this site, where the prevalence of FASD was 14.4 to 41.2 per 1,000 (1.4 to 4.1%). CONCLUSION This city displayed the lowest prevalence of FASD of the 4 CoFASP sites. Nevertheless, FASD were common, and affected children demonstrated a common, recognizable, and measurable array of traits.
Collapse
Affiliation(s)
- Philip A May
- Department of Nutrition, Nutrition Research Institute, University of North Carolina, Chapel Hill, North Carolina.,Center on Alcoholism, Substance Abuse and Addictions (CASAA), University of New Mexico, Albuquerque, New Mexico
| | - Julie M Hasken
- Department of Nutrition, Nutrition Research Institute, University of North Carolina, Chapel Hill, North Carolina
| | - Amy Baete
- Sanford Research, Sioux Falls, South Dakota
| | | | - Amy J Elliott
- Avera Research, Sioux Falls, South Dakota.,Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota
| | - Wendy O Kalberg
- Center on Alcoholism, Substance Abuse and Addictions (CASAA), University of New Mexico, Albuquerque, New Mexico
| | - David Buckley
- Center on Alcoholism, Substance Abuse and Addictions (CASAA), University of New Mexico, Albuquerque, New Mexico
| | - Marita Brooks
- Center on Alcoholism, Substance Abuse and Addictions (CASAA), University of New Mexico, Albuquerque, New Mexico
| | - Marian A Ortega
- Center on Alcoholism, Substance Abuse and Addictions (CASAA), University of New Mexico, Albuquerque, New Mexico
| | - Dixie M Hedrick
- Department of Nutrition, Nutrition Research Institute, University of North Carolina, Chapel Hill, North Carolina
| | | | - Omar Abdul-Rahman
- Department of Pediatrics, University of Nebraska College of Medicine, Omaha, Nebraska
| | - Margaret P Adam
- Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington
| | - Tamison Jewett
- Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Luther K Robinson
- Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York
| | - Melanie A Manning
- Departments of Pathology and Pediatrics, Stanford University School of Medicine, Stanford, California
| | - H Eugene Hoyme
- Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota.,Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona.,Sanford Health, Sanford Children's Genomic Medicine Consortium, Sioux Falls, South Dakota
| |
Collapse
|
|
41
|
Day DB, Collett BR, Barrett ES, Bush NR, Swan SH, Wang C, Sathyanarayana S. Prenatal sex hormones and behavioral outcomes in children. Psychoneuroendocrinology 2020; 113:104547. [PMID: 31901731 PMCID: PMC7759302 DOI: 10.1016/j.psyneuen.2019.104547] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 12/12/2019] [Accepted: 12/12/2019] [Indexed: 01/07/2023]
Abstract
Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95 % CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.
Collapse
Affiliation(s)
- Drew B Day
- Seattle Children's Research Institute, Seattle, WA, United States.
| | - Brent R Collett
- Seattle Children’s Research Institute, Seattle, WA,University of Washington, Seattle, WA
| | | | - Nicole R Bush
- University of California, San Francisco, San Francisco, CA
| | - Shanna H Swan
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Christina Wang
- Lundquist Institute, Harbor-UCLA Medical Center, Torrance, CA
| | - Sheela Sathyanarayana
- Seattle Children’s Research Institute, Seattle, WA,University of Washington, Seattle, WA
| | | |
Collapse
|
|
42
|
Temple VK, Cook JL, Unsworth K, Rajani H, Mela M. Mental Health and Affect Regulation Impairment in Fetal Alcohol Spectrum Disorder (FASD): Results from the Canadian National FASD Database. Alcohol Alcohol 2020; 54:545-550. [PMID: 31216355 DOI: 10.1093/alcalc/agz049] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Revised: 05/10/2019] [Accepted: 05/26/2019] [Indexed: 01/23/2023] Open
Abstract
AIMS Individuals with fetal alcohol spectrum disorder (FASD) frequently have challenges with regulating emotional arousal, or affect regulation (AR), and experience high rates of mental health disorders. This study examined children and adults with FASD to investigate the relationship between AR impairment and several mental health problems and diagnoses. METHODS Data from the Canadian national FASD database was used for analysis. Seven mental health diagnoses, including attention-deficit/hyperactivity disorder, post-traumatic stress disorder, conduct disorder, attachment disorder, intellectual disability, and language disorder were examined. A history of suicidality was also examined. The prevalence of these mental health problems in individuals with and without AR impairment was compared. RESULTS Individuals with FASD and AR impairment were significantly more likely to be diagnosed with conduct disorder (OR 4.8), attachment disorder (OR 6.1), or post-traumatic stress disorder (OR 8.1) when compared to those without AR impairment. They were also more likely to have a history of suicidality (OR 8.6). AR impairment was most commonly found in those with greater overall neurodevelopmental impairment. Having AR impairment was associated with receiving a diagnosis of FASD at a later age, but was not related to gender, intellectual disability, or language disorder. CONCLUSION AR impairment is strongly related to several mental health diagnoses in those with FASD and presents some promising possibilities for targeted early intervention.
Collapse
Affiliation(s)
- Valerie K Temple
- Clinical Psychologist, Surrey Place, 2 Surrey Place, Toronto, Ontario
| | - Jocelynn L Cook
- Scientific Director, The Society of Obstetricians and Gynaecologists of Canada, 2781 Lancaster Road, Ottawa, Ontario K1B 1A7 and Adjunct Professor, Department of Obstetrics and Gynaecology, University of Ottawa, 75 Laurier Ave E, Ottawa, Ontario
| | - Kathy Unsworth
- Managing Director, The Canada FASD Research Network, PO Box 11364 Wessex PO, Vancouver, British Columbia
| | - Hasu Rajani
- Professor Department of Pediatrics, University of Alberta, Edmonton, Alberta
| | - Mansfield Mela
- Professor Department of Psychiatry, University of Saskatchewan, 103 Hospital Dr., Saskatoon, Saskatchewan
| |
Collapse
|
|
43
|
Kambeitz C, Klug MG, Greenmyer J, Popova S, Burd L. Association of adverse childhood experiences and neurodevelopmental disorders in people with fetal alcohol spectrum disorders (FASD) and non-FASD controls. BMC Pediatr 2019; 19:498. [PMID: 31842817 PMCID: PMC6912946 DOI: 10.1186/s12887-019-1878-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 12/08/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Fetal alcohol spectrum disorder (FASD) is a highly prevalent lifelong disorder with high rates of comorbid neurodevelopmental disorders. Individuals with FASD are often exposed to abuse, neglect and foster home placements which have uncertain effects on the lifelong course of FASD. In this study we compare the prevalence of adverse childhood events (ACEs) and neurodevelopmental disorders in subjects with fetal alcohol spectrum disorders (FASD) and non-FASD controls. METHODS A cross-sectional chart review of patients referred to a regional developmental center was used to identify people with FASD and non-FASD controls. We recorded the number of ACEs and neurodevelopmental disorders in each patient's chart. The most common diagnoses were attention deficit hyperactivity disorder, comprehension deficits, sleep disorders, and cognitive impairments. T-tests and a regression equation were utilized to determine significant differences between the groups. RESULTS The review identified 203 subjects, 98 with FASD and 105 non-FASD controls. Group mean age was 8.6 years and 64.5% were male. People with FASD were more likely to have any ACEs (mean 5.3) with ACE scores 3.7 points higher than non-FASD controls (mean 1.69) (t = 11.29; p < .001). Increased ACEs were associated with increased rates of neurodevelopmental disorders for people with FASD (R = .179, p = .026) but not for non-FASD controls (R = .130, p = .094). CONCLUSIONS Both FASD and subsequent exposure to ACEs are associated with increased risk for development of comorbid neurodevelopmental disorders. Prevention of ACEs during childhood may decrease risk for development of comorbid neurodevelopmental disorders.
Collapse
Affiliation(s)
- Cassondra Kambeitz
- Department of Pediatrics, University of North Dakota School of Medicine and Health Sciences, 1301 N Columbia Rd Stop 9037, Grand Forks, ND 58202-9037 USA
| | - Marilyn G. Klug
- Department of Population Health, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND USA
| | - Jacob Greenmyer
- Department of Pediatrics, University of North Dakota School of Medicine and Health Sciences, 1301 N Columbia Rd Stop 9037, Grand Forks, ND 58202-9037 USA
| | - Svetlana Popova
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario Canada
- Factor-Inwentash Faculty of Social Work, University of Toronto Graduate, Toronto, Ontario Canada
- Faculty Associate Member, Institute of Medical Science, University of Toronto, Toronto, Ontario Canada
| | - Larry Burd
- Department of Pediatrics, University of North Dakota School of Medicine and Health Sciences, 1301 N Columbia Rd Stop 9037, Grand Forks, ND 58202-9037 USA
| |
Collapse
|
|
44
|
Bosse KE, Chiu VM, Lloyd SC, Conti AC. Neonatal alcohol exposure augments voluntary ethanol intake in the absence of potentiated anxiety-like behavior induced by chronic intermittent ethanol vapor exposure. Alcohol 2019; 79:17-24. [PMID: 30385201 DOI: 10.1016/j.alcohol.2018.10.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 10/12/2018] [Accepted: 10/26/2018] [Indexed: 12/21/2022]
Abstract
Individuals fetally exposed to alcohol have a disproportionate risk for developing lifetime alcohol dependence, an association that may be confounded by the presence of comorbid conditions, such as anxiety. Anxiety is also observed following fetal alcohol exposure and is known to exacerbate ethanol consumption, highlighting the utility of animal models to assess this relationship. The present study evaluated the impact of third-trimester equivalent ethanol exposure on ethanol consumption and anxiety-like, marble burying behavior in adult, male C57BL/6 mice following exposure to chronic intermittent ethanol vapor, proposed to model dependence. Neonatal mice (P5-6, 2.5-3.0 g) were administered one injection of saline or ethanol (2.5 g/kg, subcutaneously [s.c.]). Pre-vapor marble burying and limited-access two-bottle choice ethanol intake (15% v/v, 2 h) were comparable in adults (8 weeks of age) across neonatal treatment groups. Five consecutive drinking sessions were repeated 72 h after each weekly ethanol vapor exposure procedure for a total of five vapor/drinking cycles. Consistent with prior research, an increase in voluntary ethanol drinking was observed in vapor-exposed, neonatal saline-treated mice throughout the study starting after the second vapor cycle compared to both air-exposed control groups. In neonatal ethanol-treated mice, this increase in ethanol intake and preference following vapor exposure was accelerated, being observed after the first vapor cycle, and observed at an augmented level compared to vapor-exposed, neonatal saline-treated mice and air controls for both neonatal conditions. Conversely, marble burying was enhanced equivalently in vapor-exposed mice from either neonatal treatment group relative to their respective air-exposed controls. These data recapitulate clinical observations of enhanced sensitivity for alcohol dependence following developmental alcohol exposure, which may reflect enhanced motivational drive rather than potentiated negative affect. The present model will facilitate the future exploration of mechanisms that underlie increased risk for alcohol use after early developmental exposure.
Collapse
Affiliation(s)
- K E Bosse
- Research & Development Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI, 48201, United States; Department of Neurosurgery, Wayne State University School of Medicine, 4160 John R St., Detroit, MI, 48201, United States
| | - V M Chiu
- Research & Development Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI, 48201, United States; Department of Neurosurgery, Wayne State University School of Medicine, 4160 John R St., Detroit, MI, 48201, United States
| | - S C Lloyd
- Research & Development Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI, 48201, United States; Department of Neurosurgery, Wayne State University School of Medicine, 4160 John R St., Detroit, MI, 48201, United States
| | - A C Conti
- Research & Development Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI, 48201, United States; Department of Neurosurgery, Wayne State University School of Medicine, 4160 John R St., Detroit, MI, 48201, United States.
| |
Collapse
|
|
45
|
O’Neill J, O’Connor MJ, Yee V, Ly R, Narr K, Alger JR, Levitt JG. Differential neuroimaging indices in prefrontal white matter in prenatal alcohol-associated ADHD versus idiopathic ADHD. Birth Defects Res 2019; 111:797-811. [PMID: 30694611 PMCID: PMC6650301 DOI: 10.1002/bdr2.1460] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 12/08/2018] [Accepted: 01/03/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Attention deficit-hyperactivity disorder (ADHD) is common in fetal alcohol spectrum disorders (FASD) but also in patients without prenatal alcohol exposure (PAE). Many patients diagnosed with idiopathic ADHD may actually have ADHD and covert PAE, a treatment-relevant distinction. METHODS We compared proton magnetic resonance spectroscopic imaging (MRSI; N = 44) and diffusion tensor imaging (DTI; N = 46) of the anterior corona radiata (ACR)-a key fiber tract in models of ADHD-at 1.5 T in children with ADHD with PAE (ADHD+PAE), children with ADHD without PAE (ADHD-PAE), children without ADHD with PAE (non-ADHD+PAE), and children with neither ADHD nor PAE (non-ADHD-PAE, i.e., typically developing controls). Levels of choline-compounds (Cho) were the main MRSI endpoint, given interest in dietary choline for FASD; the main DTI endpoint was fractional anisotropy (FA), as ACR FA may reflect ADHD-relevant executive control functions. RESULTS For ACR Cho, there was an ADHD-by-PAE interaction (p = 0.038) whereby ACR Cho was 26.7% lower in ADHD+PAE than in ADHD-PAE children (p < 0.0005), but there was no significant ACR Cho difference between non-ADHD+PAE and non-ADHD-PAE children. Voxelwise false-discovery rate (FDR)-corrected analysis of DTI revealed significantly (q ≤ 0.0101-0.05) lower FA in ACR for subjects with PAE (ADHD+PAE or non-ADHD+PAE) than for subjects without PAE (ADHD-PAE or non-ADHD-PAE). There was no significant effect of ADHD on FA. Thus, in overlapping samples, effects of PAE on Cho and FA were observed in the same white-matter tract. CONCLUSIONS These findings point to tract focal, white-matter pathology possibly specific for ADHD+PAE subjects. Low Cho may derive from abnormal choline metabolism; low FA suggests suboptimal white-matter integrity in PAE. More advanced MRSI and DTI-and neurocognitive assessments-may better distinguish ADHD+PAE from ADHD-PAE, helping identify covert cases of FASD.
Collapse
Affiliation(s)
- Joseph O’Neill
- Division of Child & Adolescent Psychiatry, UCLA Semel institute for Neuroscience, Los Angeles, CA
| | - Mary J. O’Connor
- Division of Child & Adolescent Psychiatry, UCLA Semel institute for Neuroscience, Los Angeles, CA
| | - Victor Yee
- Division of Child & Adolescent Psychiatry, UCLA Semel institute for Neuroscience, Los Angeles, CA
| | - Ronald Ly
- Division of Child & Adolescent Psychiatry, UCLA Semel institute for Neuroscience, Los Angeles, CA
| | | | - Jeffrey R. Alger
- Department of Neurology, UCLA Los Angeles, CA
- Neurospectroscopics, Inc., Encino, CA
| | - Jennifer G. Levitt
- Division of Child & Adolescent Psychiatry, UCLA Semel institute for Neuroscience, Los Angeles, CA
| |
Collapse
|
|
46
|
Nieto SJ, Kosten TA. Who's your daddy? Behavioral and epigenetic consequences of paternal drug exposure. Int J Dev Neurosci 2019; 78:109-121. [PMID: 31301337 DOI: 10.1016/j.ijdevneu.2019.07.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 06/11/2019] [Accepted: 07/08/2019] [Indexed: 12/11/2022] Open
Abstract
Substance use disorders (SUDs) reflect genetic and environmental factors. While identifying reliable genetic variants that predispose individuals to developing SUDs has been challenging, epigenetic factors may also contribute to the heritability of SUDs. Familial drug use associates with a wide range of problems in children, including an increased risk for developing a SUD. The implications of maternal drug use on offspring development are a well-studied area; however, paternal drug use prior to conception has received relatively little attention. Paternal exposure to several environmental stimuli (i.e. stress or diet manipulations) results in behavioral and epigenetic changes in offspring. The purpose of this review is to determine the state of the preclinical literature on the behavioral and epigenetic consequences of paternal drug exposure. Drug-sired offspring show several developmental and physiological abnormalities. These offspring also show deficits in cognitive and emotional domains. Examining sensitivity to drugs in offspring is a growing area of research. Drug-sired offspring are resistant to the rewarding and reinforcing properties of drugs. However, greater paternal motivation for the drug, combined with high drug intake, can result in addiction-like behaviors in offspring. Drug-sired offspring also show altered histone modifications and DNA methylation levels of imprinted genes and microRNAs; epigenetic-mediated changes were also noted in genes related to glutamatergic and neurotrophic factor signaling. In some instances, drug use resulted in aberrant epigenetic modifications in sire sperm, and these changes were maintained in the brains of offspring. Thus, paternal drug exposure has long-lasting consequences that include altered drug sensitivity in subsequent generations. We discuss factors (i.e. maternal behaviors) that may moderate these paternal drug-induced effects as well as ideas for future directions.
Collapse
Affiliation(s)
- Steven J Nieto
- University of Houston, Department of Psychology & Texas Institute for Measurement, Evaluation and Statistics (TIMES), Houston, TX, 77204-6022, United States
| | - Therese A Kosten
- University of Houston, Department of Psychology & Texas Institute for Measurement, Evaluation and Statistics (TIMES), Houston, TX, 77204-6022, United States
| |
Collapse
|
|
47
|
Mattson SN, Bernes GA, Doyle LR. Fetal Alcohol Spectrum Disorders: A Review of the Neurobehavioral Deficits Associated With Prenatal Alcohol Exposure. Alcohol Clin Exp Res 2019; 43:1046-1062. [PMID: 30964197 DOI: 10.1111/acer.14040] [Citation(s) in RCA: 209] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 04/03/2019] [Indexed: 11/26/2022]
Abstract
In utero alcohol exposure can disrupt the development of the fetal brain and result in a wide range of neurobehavioral outcomes collectively known as fetal alcohol spectrum disorders (FASD). This paper provides a comprehensive review of the cognitive and behavioral outcomes of prenatal alcohol exposure, including domains of general intelligence, executive functioning, language development, learning and memory, adaptive functioning, academic performance, and concurrent psychopathology. In addition, the current status of the neurobehavioral profile of FASD and its potential as a diagnostic tool will be discussed.
Collapse
Affiliation(s)
- Sarah N Mattson
- Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, California
| | - Gemma A Bernes
- Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, California
| | - Lauren R Doyle
- Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, California
| |
Collapse
|
|
48
|
Lam VYY, Raineki C, Wang LY, Chiu M, Lee G, Ellis L, Yu W, Weinberg J. Role of corticosterone in anxiety- and depressive-like behavior and HPA regulation following prenatal alcohol exposure. Prog Neuropsychopharmacol Biol Psychiatry 2019; 90:1-15. [PMID: 30367959 PMCID: PMC6449057 DOI: 10.1016/j.pnpbp.2018.10.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 10/01/2018] [Accepted: 10/14/2018] [Indexed: 12/13/2022]
Abstract
Prenatal alcohol exposure (PAE) is known to cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperresponsivity to stressors. Dysregulation of the HPA axis plays a role in vulnerability to stress-related disorders, such as anxiety and depression. Thus, the effects of PAE on HPA function may result in increased vulnerability to the effects of stress and, in turn, lead to the development of stress-related disorders. Indeed, individuals prenatally exposed to alcohol have an increased risk of developing anxiety and depression. However, it is unclear whether hypersecretion of corticosterone (CORT) in response to stress per se is involved with mediating differential effects of stress in PAE and control animals. To investigate the role of CORT in mediating effects of stress in both adult females and males following PAE, adrenalectomy with CORT replacement (ADXR) was utilized to produce similar CORT levels among prenatal treatment groups before exposure to chronic unpredictable stress (CUS). Anxiety-like behavior was evaluated using the open field and elevated plus maze, and depressive-like behavior was examined in the forced swim test. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA expression was assessed in the medial prefrontal cortex (mPFC), amygdala, and hippocampal formation. Under the non-CUS condition, PAE alone differentially altered anxiety-like behavior in sham but not ADXR females and males, with females showing decreased anxiety-like behavior but males exhibiting increased anxiety-like behavior compared to their control counterparts. There were no effects of PAE alone on depressive-like in females or males. PAE also decreased GR mRNA expression in the hippocampal formation in females but had no effects on MR or GR mRNA expression in any brain region in males. CUS had differential effects on anxiety- and depressive-like behavior in PAE and control animals, and these effects were sex dependent. Importantly, ADXR unmasked differences between PAE and control animals, demonstrating that CORT may play a differential role in modulating behavior and HPA activity/regulation in PAE and control animals, and may do so in a sex-dependent manner.
Collapse
Affiliation(s)
- Vivian YY Lam
- Corresponding author: Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
| | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Barrett CE, Kable JA, Madsen TE, Hsu CC, Coles CD, Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). The Use of Functional Near-Infrared Spectroscopy to Differentiate Alcohol-Related Neurodevelopmental Impairment. Dev Neuropsychol 2019; 44:203-219. [PMID: 30661412 PMCID: PMC6423538 DOI: 10.1080/87565641.2019.1567734] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 11/16/2018] [Accepted: 01/03/2019] [Indexed: 12/12/2022]
Abstract
Oxygenated (HBO) and deoxygenated hemoglobin (HBR) levels in the prefrontal cortex (PFC) were measured using functional near-infrared spectroscopy (fNIRS) to determine if PFC activity during a cognitive inhibition task distinguishes children with prenatal alcohol exposure (PAE, n = 26) from both typically developing controls (n = 19) and a contrast group of children with other neurobehavioral problems (n = 14). Despite showing evidence of increased PFC activity in the non-inhibitory condition relative to controls, children in the PAE group displayed reduced PFC HBO and increased HBR relative to both other groups in the inhibitory condition, suggesting reduced PFC activity but increased oxygen consumption without sufficient oxygen replacement.
Collapse
Affiliation(s)
- Catherine E. Barrett
- Department of Psychiatry and Behavioral Science, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
| | - Julie A. Kable
- Department of Psychiatry and Behavioral Science, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
- Department of Pediatrics, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
| | - Teresa E Madsen
- Department of Psychiatry and Behavioral Science, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
| | - Chia-Chun Hsu
- Department of Psychiatry and Behavioral Science, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
| | - Claire D. Coles
- Department of Psychiatry and Behavioral Science, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
- Department of Pediatrics, Emory University School of Medicine, 12 Executive Park, Atlanta, GA 30329
| | | |
Collapse
|
|
50
|
Dirks H, Francke L, Würz V, Kretschmann C, Dehghan-Sanij S, Scherbaum N. Substance use, comorbid psychiatric disorders and suicide attempts in adult FASD patients. ADVANCES IN DUAL DIAGNOSIS 2019. [DOI: 10.1108/add-10-2018-0018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose
Fetal alcohol spectrum disorders (FASD) are a group of developmental disabilities related to prenatal alcohol exposure. FASD is a life-long lasting condition with various neurocognitive impairments and deficits in daily-life functioning. Research also indicates that FASD patients have an increased prevalence for substance use, substance related disorders and other psychiatric disorders. In Germany, data on adult FASD patients and their mental health are rare. The purpose of this paper is to describe substance use and comorbid psychiatric disorders (in addition to FASD) and suicide attempts in adult FASD patients.
Design/methodology/approach
The German version of the structured “Mini International Neuropsychiatric Interview (MINI)” was administered to a convenience sample of patients attending a specialized FASD diagnostic service at a German university hospital to assess psychiatric disorders. Current and lifetime substance use were examined using sections from the German version of the “European Addiction Severity Index (EUROP-ASI-R)” interview.
Findings
In total, 31 adults with FASD were included. Two patients were diagnosed with a substance related disorder, one for alcohol and one for cannabis. Nearly half of all patients fulfilled the diagnostic criteria for mild mental retardation, a further 16 per cent fulfilled the criteria for another current comorbid psychiatric disorder. In total, 26 per cent reported at least one suicide attempt.
Originality/value
Given that the body of research literature on FASD in adulthood is sparse, even a clinical sample of thirty individuals expands knowledge on mental health and substance use in the adult FASD population. The sample was comprehensively assessed using validated structured interviews on mental health, substance use and FASD.
Collapse
|