Mood disorders, including major depressive disorder (MDD), bipolar disorder (BD), and seasonal affective disorder (SAD), exhibit significant heterogeneity, with disturbances in biological rhythms playing a central role. These disturbances not only contribute to the onset and progression of mood disorders but also serve as important predictors of relapse (Chronos syndrome) and treatment response. Circadian disruptions, influenced by factors such as seasonality, jet lag, shift work, and childbirth, are hallmarks of mood episodes and pivotal in transitions between mood states. Longitudinal studies reveal a bidirectional relationship between circadian dysregulation and mood disorders, suggesting that biological clock abnormalities may both signal and predispose individuals to mood episodes. Despite their significance, no single circadian biomarker has demonstrated sufficient specificity or sensitivity for diagnostic precision. This underscores the urgent need for multimodal approaches that integrate circadian markers with other physiological and behavioral dimensions. Advancing mood disorder care requires biomarkers that capture individualized biological signatures, revealing circadian dysregulation and its interactions with multiple other physiological systems to enable precise subtyping and improved interventions. This review emphasizes the potential of integrating biological rhythms into a dimensional framework, leveraging advanced digital tools and mathematical models to provide ecologically valid insights into mood disorder mechanisms. Such approaches aim to bridge the gap between clinical observations and biological underpinnings, paving the way for biologically informed classifications and personalized treatment strategies. By addressing the complexity of circadian disruptions and their interplay with other systems, this paradigm shift offers a promising path to enhancing mood disorder diagnostics and therapeutics.

Major depressive disorder represents a complex heterogeneous syndrome with significant public health impact. This pictorial review explores the multifaceted pathophysiology of depression through the case of an individual suffering from depression. Genetic vulnerability and environmental etiological factors, including early life adversity, and their interactions create a biological diathesis through alterations in stress response systems and neural circuitry. We review current evidence for several interconnected pathophysiological mechanisms underlying depression, including monoamine neurotransmission, hypothalamic-pituitary-adrenal axis dysfunction, chronic inflammation, and reduced neuroplasticity. Using the Research Domain Criteria framework, we connect these mechanisms across multiple levels of analysis-from genes, circuits to behavior. Neuroimaging findings highlight disruptions in key networks including the default mode, salience, and executive control circuits. The effectiveness of pharmacological, psychotherapeutic and other non-pharmacological interventions in depression underscores the importance of targeting multiple biological systems. This review emphasizes depression's complex etiology involving dynamic interactions between genetic predisposition, environmental stressors, and neurobiological alterations, suggesting the need for personalized, multimodal therapeutic approaches.

Major depressive disorder (MDD) is a prevalent psychiatric disorder with a complex pathogenesis influenced by various factors. Recent research has highlighted a significant connection between psychological stress and MDD, with inflammation playing a central role in this relationship. Studies have demonstrated that peripheral immune changes in patients with MDD and in mouse models of social stress are closely linked to depressive symptoms. These findings suggest that targeting peripheral immune factors could represent a novel approach for treating stress-related neuropsychiatric disorders. Stress triggers a cascade of inflammatory responses, leading to disruptions in neurotransmitter metabolism and reduced synaptic plasticity. These changes exacerbate depression and contribute to cognitive decline. This study examines the bidirectional relationship between MDD and stress, focusing on the role of inflammation in this complex interplay. Recent studies have identified specific immune factors that are elevated in the serum of patients with MDD and stress-exposed mice, indicating a mechanism by which peripheral immune responses can affect central nervous system function and behavior. Furthermore, proteins, such as nuclear factor kappa-B (NF-κB), reportedly play a critical role in the regulation of stress hormones and are associated with depressive behaviors. Understanding these mechanisms is essential for advancing diagnostic, intervention, and treatment strategies for MDD.

A strict association exists between mood disorders and endogenous hypercortisolism, namely Cushing's syndrome (CS). Indeed, CS is characterized by a wide range of mood disorders, such as major depression, generalized anxiety, panic disorders, bipolar disorders up to psychosis, with major depression being the most frequent, with a prevalence of 50-80%, and potentially representing the clinical onset of disease. Despite this observation, the exact prevalence of hypercortisolism in patients with mood disorders is unknown and who/how to screen for endogenous hypercortisolism among patients with mood disorders is still unclear. In this context, an accurate anamnestic and clinical examination are crucial in order to identify those patients who may benefit from CS screening. In particular, the presence of specific signs and symptoms of CS, comorbidities typically associated with CS, and lack of improvement of depressive symptoms with standard treatments can further guide the decision to screen for CS. Anyhow, it is noteworthy that mood disorders represent a cause of functional activation of hypothalamic-pituitary-adrenal (HPA) axis, a condition formerly known as non-neoplastic hypercortisolism (NNH). The differential diagnosis between CS and NNH is challenging. Beyond anamnestic and clinical features, various tests, including measurement of daily urinary cortisol and late-night salivary cortisol, together with low dose-dexamethasone suppression test, are used for initial screening. However, considering their low accuracy, a definitive diagnosis may require a longitudinal follow-up along with second-line dynamic tests like combined dexamethasone-CRH test and desmopressin test. In conclusion, available data suggest the need for a comprehensive assessment and follow-up of individuals with mood disorders to detect possible underlying CS, considering the pitfalls in diagnosis and the overlap of symptoms with other conditions like NNH. Specialized centers with expertise in CS diagnosis and differential testing are recommended for accurate evaluation and management of these patients.

Adults with symptoms of anxiety, depression, or PTSD and a history of adverse childhood experiences (ACEs) may experience more severe symptoms than those without ACEs. The identification of mechanisms linking ACEs to later mental health problems may provide salient treatment targets to improve outcomes. Several biological markers (cortisol, inflammation, allostatic load, DNA methylation, and telomere length) that are indicative of functional variation in stress response systems, have been hypothesized as potential mechanisms linking ACEs to later mental health outcomes. Much of the evidence supporting this hypothesis examines isolated pairwise associations between variables and it is unclear whether statistical tests of mediation support these conclusions. It is also unclear how much of the extant research has used theory to guide mediation analyses, which may be a salient factor in the recognition of a mechanism. This scoping review surveyed research conducting mediation analysis examining the indirect effect of any of these five biological markers on the relationship between ACEs and anxiety, depression, or PTSD. It further surveyed the use of theory in these analyses. Pubmed and seven electronic databases were searched: (1) APA PsychInfo (2) CINAHL Plus (3) Health Source: Nursing/Academic Edition (4) MEDLINE (5) Psychology and Behavioral Sciences Collection (6) Science and Technology Collection, and (7) SocINDEX. A total of 16 articles were identified. The majority of studies examined depression as an outcome and the statistical significance of indirect effects were mixed across mediators. Common theoretical models and frameworks were consistent with life course theory and evolutionary or developmental perspectives.

Persistently poor sleep quality in young adults is linked to a higher risk of depression. However, the impact of changes in sleep quality on depression risk in middle-aged and older adults remain unclear. This study investigates the association between sleep quality, its changes, and the risk of depression in middle-aged and elderly people.

We included 4007 participants (mean age 63.0 ± 7.6 years, 53.0 % women) from the English Longitudinal Study of Ageing. Sleep quality was assessed using the Jenkins Sleep Problems Scale and a global sleep quality question. Depression was evaluated with the Center for Epidemiological Studies Depression Scale and self-reported doctor-diagnosed depression. Multivariable logistic regression, restricted cubic spline curve, and mediation analysis was employed.

After 10 years of follow-up, 777 individuals developed depression. Sleep quality scores positively correlated with depression risk. Among those with good sleep quality, worsening sleep quality increased depression risk (OR = 1.67, 95 % CI: 1.21-2.31). For those with intermediate sleep quality, improved sleep quality reduced depression risk (OR = 0.70, 95 % CI: 0.50-0.98). Conversely, worsening sleep quality increased depression risk (OR = 2.11, 95 % CI: 1.47-3.02). Pain and functional disability partially mediated the association between intermediate/poor sleep quality and depression (9.8 % and 4.2 %, respectively).

Sleep quality is based on self-reported.

Intermediate, poor, and worsening sleep quality are linked to higher depression risk. Improving sleep quality mitigates depression risk in those with intermediate sleep quality. Sleep quality may influence depression indirectly through pain and functional disability.

The circadian rhythm of cortisol, a key hormone essential for maintaining metabolic balance and stress homeostasis, is profoundly disrupted by night-shift work. This narrative review examines the physiological mechanisms underlying cortisol regulation, the effects of shift work on its circadian rhythm, the associated health risks, and potential mitigation strategies. Night-shift work alters the natural secretion pattern of cortisol, leading to dysregulation of the hypothalamic-pituitary-adrenal axis, which in turn can contribute to metabolic disorders, cardiovascular diseases, and impaired cognitive function. Understanding the physiological pathways mediating these changes is crucial for developing targeted interventions to mitigate the adverse effects of circadian misalignment. Potential strategies, such as controlled light exposure, strategic napping, and personalized scheduling, may help to stabilize cortisol rhythms and improve health outcomes. This review aims to provide insights that can guide future research and inform occupational health policies for night-shift workers by addressing these challenges.

Breast cancer is a significant traumatic experience that often leads to chronic stress and mental health challenges. Research has consistently shown that physical activity-especially exercise-can alleviate depressive symptoms; however, the specific biological mechanisms underlying these antidepressant effects remain unclear. In this review, we comprehensively summarize the biological mechanisms of depression and the antidepressant mechanisms of physical activity and explore the biological processes through which exercise exerts its antidepressant effects in breast cancer patients. We focus on the impact of physical activity on inflammation, the endocrine system, glutamate, and other aspects, all of which play crucial roles in the pathophysiology of depression. Moreover, we discuss the heterogeneity of depression in breast cancer patients and the complex interactions between its underlying mechanisms. Additionally, we propose that a deeper understanding of these mechanisms in the breast cancer population can guide the design and implementation of exercise-based interventions that maximize the antidepressant benefits of physical activity. Finally, we summarize the current research and propose future research directions.

Peripartum depression is a global health concern, characterized by mood disturbances inclusive of pregnancy through up to 12-months postpartum. Hormones play a vital role in pregnancy maintenance, fetal development, and labor and delivery and change significantly as a function of pregnancy and childbirth. However, such life sustaining changes may have consequences related to risk for peripartum depression. To date, most studies that have examined hormones in relation to peripartum depression have focused on blood or saliva sampling approaches, though hair analysis offers unique information on trajectories of hormone concentrations over more sustained periods of time (i.e., over months). The aim of this systematic review was to provide a comprehensive review of the association between hair measures of hormones (i.e., cortisol, progesterone, estrogen, and testosterone) and depression during the peripartum period. Forty-one studies were identified for inclusion. A majority of studies reported statistically null associations. Between-person studies varied widely in reported direction and magnitude of hair hormone-depression associations, most likely attributable to a wide range of methodological approaches including timing of assessments and sample size. Studies using within-person approaches observed positive coupling of cortisol concentration and symptoms across time. Most studies focused exclusively on cortisol. We recommend future research consider both stress and reproductive hormones, prioritize within-person change in hormone levels given this is a period of dramatic change, and include contextual (e.g., social support, adverse and benevolent childhood experiences, physical and psychiatric conditions) features that may modify both changes in hormones and the association between hormone levels and depression in the peripartum period.

Mood and anxiety disorders are complex psychiatric conditions shaped by the multifactorial interplay of genetic, epigenetic, and neuropeptide factors. This review aims to elucidate the intricate interactions among these factors and their potential in advancing personalized medicine. We examine the genetic underpinnings, emphasizing key heritability studies and specific gene associations. The role of epigenetics is discussed, focusing on how environmental factors can modify gene expression and contribute to these disorders. Neuropeptides, including substance P, CRF, AVP, NPY, galanin, and kisspeptin, are evaluated for their involvement in mood regulation and their potential as therapeutic targets. Additionally, we address the emerging role of the gut microbiome in modulating neuropeptide activity and its connection to mood disorders. This review integrates findings from genetic, epigenetic, and neuropeptide research, offering a comprehensive overview of their collective impact on mood and anxiety disorders. By highlighting novel insights and potential clinical applications, we underscore the importance of a multi-omics approach in developing personalized treatment strategies. Future research directions are proposed to address existing knowledge gaps and translate these findings into clinical practice. Our review provides a fresh perspective on the pathophysiology of mood and anxiety disorders, paving the way for more effective and individualized therapies.

This study introduces StressFit, a novel hybrid wearable sensor system designed to simultaneously monitor electromyogram (EMG) signals and sweat cortisol levels. Our approach involves the development of a noninvasive skin patch capable of monitoring skin temperature, sweat pH, cortisol levels, and corresponding EMG signals using a combination of physical and electrochemical sensors integrated with EMG electrodes. StressFit was optimized by enhancing sensor output and mechanical resilience for practical application on curved body surfaces, ensuring accurate acquisition of cortisol, pH, body temperature, and EMG data without sensor interference. In addition, we integrated an onboard data processing unit with Internet of Things (IoT) capabilities for real-time acquisition, processing, and wireless transmission of sensor measurements. Sweat cortisol and EMG signals were measured during cycling exercises to evaluate the sensor suite's performance. Our results demonstrate an increase in sweat cortisol levels and decrease in the EMG signal's power spectral density following exercise. These findings suggest that combining sweat cortisol levels with EMG signals in real-time could serve as valuable indicators for stress assessment and early detection of abnormal physiological changes.

To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.

Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled.

Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, -7.4%/-4.9%, -6.0%/-5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, -5.0%, -4.8%, and 1.9%; glycated hemoglobin, -5.1%, -4.8%, and -1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL.

In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes.

NCT02180217 (LINC 3); NCT02697734 (LINC 4).

Many studies have moved toward saliva and peripheral blood sampling for studying cortisol, even in relation to disorders of the brain. However, the degree to which peripheral cortisol reflects central cortisol levels has yet to be comprehensively described. Data describing the effect that biological characteristics such as age and sex have on cortisol levels across compartments is also limited.

To assess the relationships of cortisol levels across cerebrospinal fluid (CSF), saliva, and plasma (total and free) compartments and describe the effects of age and sex on these relationships.

Multisite cross-sectional observation study.

Samples collected in academic outpatient settings in 2001-2004.

Healthy community volunteers (n = 157) of both sexes, aged 20-85 years.

None.

This study was a secondary analysis of data collected from a previously published study.

CSF cortisol correlated more strongly with plasma (r = 0.49, P < .0001) than with saliva cortisol levels. Sex but not age was a significant modifier of these relationships. CSF cortisol levels trended higher with older age in men (R2 = 0.31, P < .001) but not women. Age-related cortisol binding globulin trends differed by sex but did not correlate with sex differences in cortisol levels in any compartment.

Variability in the correlations between central and peripheral cortisol discourages the use of peripheral cortisol as a direct surrogate for central cortisol measures. Further investigation of how mechanistic drivers interact with biological factors such as sex will be necessary to fully understand the dynamics of cortisol regulation across fluid compartments.

Background/Objectives: Animal models can help understand human physiological responses, including the response to exercise and physical activity. However, many of these models incorporate noxious stimuli for various scientific purposes. We propose a noxious stimuli-free treadmill running training program for Rattus norvegicus species to study adaptations to aerobic exercise. Methods: In this study, rats were randomly allocated to training (n = 20) and sedentary (n = 20) groups. The training group underwent a program consisting of 30-50 min of treadmill running at 60% intensity, three times per week for 8 weeks. Maximum speed tasks (Tmax) were conducted to determine, adjust, and evaluate changes in fitness conditions. The rats had one week of familiarization with the treadmill, and a rubber ball was used at the back wall of the lane as a painless stimulus to encourage running. All assessments were conducted by two independent researchers in a double-blind manner, with data analysis conducted by a third-blind investigator. Results: A significant effect of time (η2p = 0.430, p < 0.001, large effect) could be found, showing differences between Tmax1 and Tmax2, and between Tmax1 and Tmax3 in both groups. The training group significantly outperformed the sedentary group (η2p = 0.266, p < 0.001, large effect). There was a significant interaction between time and condition (η2p = 0.152, p < 0.001, large effect). Conclusions: The proposed moderate-intensity treadmill running program could effectively differentiate between trained and sedentary conditions within both the short period of 4 weeks and the extended period of 8 weeks. This protocol can be used as a model for running on a treadmill for Rattus norvegicus species without the use of noxious stimuli.

Major Depressive Disorder affects 8.4 % of the U.S. population, particularly women during perimenopause. This study implemented a chronic corticosterone manipulation (CORT, a major rodent stress hormone) using middle-aged, ovariectomized female rats to investigate depressive-like behavior, anxiety-like symptoms, and cognitive ability. CORT (400 μg/ml, in drinking water) was administered for four weeks before behavioral testing began and continued throughout all behavioral assessments. Compared to vehicle-treated rats, CORT significantly intensified depressive-like behaviors: CORT decreased sucrose preference, enhanced immobility on the forced swim test, and decreased sociability on a choice task between a novel conspecific female rat and an inanimate object. Moreover, CORT enhanced anxiety-like behavior on a marble bury task by reducing time investigating tabasco-topped marbles. No effects were observed on novelty suppressed feeding or the elevated plus maze. For spatial working memory using an 8-arm radial arm maze, CORT did not alter acquisition but disrupted performance during retention. CORT enhanced the errors committed during the highest working memory load following a delay and during the last trial requiring the most items to remember; this cognitive metric positively correlated with a composite depressive-like score to reveal that as depressive-like symptoms increased, cognitive performance worsened. This protocol allowed for the inclusion of multiple behavioral assessments without stopping the CORT treatment needed to produce a MDD phenotype and to assess a battery of behaviors. Moreover, that when middle-age was targeted, chronic CORT produced a depressive-like phenotype in ovariectomized females, who also comorbidly expressed aspects of anxiety and cognitive dysfunction.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Depression is one of the most disabling diseases globally, with a high disease burden that generates high direct and indirect costs. The incidence of depression is twofold higher in adult women than in men. Biological and psychosocial factors constitute the pathophysiological bases of the condition and due to the complexity of the condition, current understanding is that the "treatment strategy must be multimodal". The objective of this study was to measure the effect of introducing the frequent use of makeup on improving depressive symptoms in adult women of medium-low purchasing power METHODS: Participants with the targeted profile who did not frequently use makeup were selected and randomised to receive (test group) or not (control group) stimuli and makeup products intended for encouraging the frequent use of makeup. The Zung Depression Self-Assessment Scale was used to assess depressive symptoms, with additional assessments on self-image perception using the mirror test and salivary cortisol level.

The results demonstrated a sustained reduction in depressive symptoms (8.3 percentage points reduction in the Average Zung Index; P < 0.05), with a significant improvement in self-image perception (25% increase in the average score obtained in the mirror test; P < 0.05) and a specific influence on salivary cortisol levels (55% reduction in salivary cortisol concentration; P < 0.05) after the first makeup application.

The results show that encouraging the frequent use of makeup, a practice that can be achieved by most people and which is simple and inexpensive to implement, can contribute to effective and sustainable improvement in the well-being and mental health of a significant portion of the population.

The significant anatomical changes in large intestine of germ-free (GF) mice provide excellent material for understanding microbe-host crosstalk. We observed significant differences of GF mice in anatomical and physiological involving in enlarged cecum, thinned mucosal layer and enriched water in cecal content. Furthermore, integration analysis of multi-omics data revealed the associations between the structure of large intestinal mesenchymal cells and the thinning of the mucosal layer. Increased Aqp8 expression in GF mice may contribute to enhanced water secretion or altered hydrodynamics in the cecum. In addition, the proportion of epithelial cells, nutrient absorption capacity, immune function and the metabolome of cecum contents of large intestine were also significantly altered. Together, this is the first systematic study of the transcriptome and metabolome of the cecum and colon of GF mice, and these findings contribute to our understanding of the intricate interactions between microbes and the large intestine.

Background: Antenatal depression is common and associated with detrimental impacts on women and their families. Disrupted neuroendocrine functioning is reported in women experiencing perinatal mental health disturbances. Preliminary randomized controlled trial (RCT) evidence suggests acupuncture may provide a safe and effective adjunct treatment; however, underlying mechanisms of effect are unclear. We conducted an RCT examination of acupuncture for the management of antenatal depressive symptomologies, which included oxytocinergic and hypothalamic pituitary adrenal (HPA) axis system evaluations. This article reports postintervention changes to cortisol: dehydroepiandrosterone (DHEA) ratios, and oxytocin (OT) hormone concentrations. Methods: Fifty-seven women with Edinburgh Postnatal Depression Scale (EPDS) scores ≥13 were randomized to receive individually tailored depressed specific acupuncture, progressive muscle relaxation (PMR) attention comparator, or treatment as usual (TAU). Weekly 1-h sessions were conducted for 8 weeks (24-31 of pregnancy). Preintervention and postintervention saliva samples were collected. Results: Postintervention mean cortisol: DHEA ratio differences were not significantly predicted by group allocation (n = 46, p = 0.065). Two-group comparisons demonstrated cortisol: DHEA ratios were significantly increased and predicted by group allocation when acupuncture was compared to TAU (p = 0.039); however, not between acupuncture and PMR (p = 0.179), or PMR and TAU (p = 0.421). Postintervention OT concentrations were not significantly predicted by group allocation. Limitations: Small sample size and posthoc analysis Conclusion: Findings suggest positive regulation of the HPA axis may be an underlying mechanism by which acupuncture provided the significant improvements to antenatal depression, stress, and distress observed in this cohort. Trial Registration: Registered on March 19, 2015, with the Australian New Zealand Clinical Trials Registry (ACTRN12615000250538).

Sleep duration has been associated with depression. However, mean regression, such as linear regression or logistic regression, may not capture relationships that occur mainly in the tails of outcome distribution. This study aimed to evaluate the associations between sleep duration and depression along the entire distribution of depression using quantile regression approach.

This study included 55,954 adults aged 18 to 80 years from the National Health and Nutrition Examination Survey (N = 34,156) and the Korea National Health and Nutrition Examination Survey (N = 21,798). The coefficients corresponding to cross-group differences in PHQ-9 scores were estimated when comparing short or long sleep duration with normal sleep duration on deciles of PHQ-9 score distribution.

At lower quantiles, either short or long sleep duration was not associated with depression. At higher quantiles, the association of both short and long sleep duration with depression became much more pronounced. Compared with normal sleep duration, short and long sleep duration were associated with increases of 1.34 (95 % CI: 1.16, 1.51) and 0.28 (95 % CI: 0.04, 0.52) in PHQ-9 scores at the 50th quantile, while the corresponding increases were 3.27 (95 % CI: 2.83, 3.72) and 1.65 (95 % CI: 0.86, 2.45) at the 90th quantile, respectively. We also found that the magnitude of association between short sleep duration and depression was stronger among females and individuals with chronic diseases.

The beneficial effect of sufficient sleep in decreasing depression severity may be more evident among individuals with severe depression. Further studies could explore whether these heterogeneous associations can be generalized to populations with different characteristics.

Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers.

This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated.

The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms.

High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.

The article presents a case of a long-term mental disorder in a 35-year-old woman with a persistent laboratory-confirmed increase in cortisol levels, without clinical manifestations of hypercortisolism. The first signs of mental illness appeared at the age of 14; over the past 8 years, the disease has been continuous and manifests itself in the form of a predominantly depressive state with increasing severity and complication of symptoms. Throughout all the years of the disease, active psychopharmacotherapy was carried out, combinations of antidepressants with antipsychotics and mood stabilizers were used, but no pronounced effect was achieved. Inpatient treatment in the clinic of the Mental Health Research Center for 5 months using several methods of enhancing antidepressant therapy had a good therapeutic effect and made it possible to achieve complete remission of the disease. There was a normalization of laboratory parameters of cortisol along with a decrease in the severity of pathopsychological symptoms, which indicates the genesis of hypercortisolism secondary to mental illness and its functional nature. It is assumed that hypercortisolism in this patient contributed to the formation of atypical clinical symptoms and resistance to antidepressant therapy. The discussion substantiates the need to consult a psychiatrist in case of persistent hypercortisolism in the absence of clinical manifestations of Cushing's syndrome. The detection of persistent hypercortisolism in patients with depression determines the advisability of active therapy using several tactics to enhance the effect of antidepressants.

In concert with neuropeptides and transmitters, the end products of the hypothalamus-pituitary-adrenal (HPA) axis, the glucocorticoid hormones cortisol and corticosterone (CORT), promote resilience: i.e., the ability to cope with threats, adversity, and trauma. To exert this protective action, CORT activates mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) that operate in a complementary manner -as an on/off switch- to coordinate circadian events, stress-coping, and adaptation. The evolutionary older limbic MR facilitates contextual memory retrieval and supports an on-switch in the selection of stress-coping styles at a low cost. The rise in circulating CORT concentration after stress subsequently activates a GR-mediated off-switch underlying recovery of homeostasis by providing the energy for restraining the primary stress reactions and promoting cognitive control over emotional reactivity. GR activation facilitates contextual memory storage of the experience to enable future stress-coping. Such complementary MR-GR-mediated actions involve rapid non-genomic and slower gene-mediated mechanisms; they are time-dependent, conditional, and sexually dimorphic, and depend on genetic background and prior experience. If coping fails, GR activation impairs cognitive control and promotes emotional arousal which eventually may compromise resilience. Such breakdown of resilience involves a transition to a chronic stress construct, where information processing is crashed; it leads to an imbalanced MR-GR switch and hence increased vulnerability. Novel MR-GR modulators are becoming available that may reset a dysregulated stress response system to reinstate the cognitive flexibility required for resilience.

Prior studies found increased hair cortisol concentration (a surrogate marker for hypothalamic-pituitary-adrenal axis activation) in users of the levonorgestrel intrauterine device (LNG 52 mg IUD). We evaluated change in hair cortisol and psychometric tests in women initiating a copper (CuT380 IUD) or LNG 52 mg IUD.

We prospectively enrolled healthy women initiating an LNG 52 mg IUD or CuT380 IUD. Participants provided hair and blood samples and completed psychometric inventories (Patient Health Questionnaire-9, Positive and Negative Affect Schedule, and Psychological General Well-Being Index) after IUD insertion and at 6 and 12 months. We used liquid chromatography with tandem mass spectrometry to measure hair cortisol concentrations. We compared hair cortisol concentrations and psychometric test changes from baseline to 6 and 12 months using independent two-sample t tests.

We enrolled 39 of our targeted 86 participants (LNG 52 mg IUD 26, CuT380 IUD 13). Thirty-eight subjects (LNG 52 mg IUD 25, CuT380 IUD 13) completed 6 months of follow-up. We found no difference between cohorts in the mean change in hair cortisol concentrations at 6 months (LNG 52 mg IUD n = 21 [-0.01 pg/mg (95% CI -1.26, 1.23); CuT380 IUD n = 13 [-1.31 pg/mg (-3.36, 0.73)]). While psychometric inventory results remained within normal ranges, LNG 52 mg IUD users reported a trend toward more favorable changes over time.

We did not find clinically important differences in hair cortisol concentrations following initiation of a CuT380 IUD or LNG 52 mg IUD; psychometric inventories demonstrated no adverse effect of hormonal IUDs on mood.

Our findings of similar hair cortisol concentrations following the initiation of either the LNG 52 mg IUD or CuT380 IUD suggest that hormonal IUDs do not increase cortisol concentrations or alter stress reactivity, and favorable effects on psychometric inventories provide further reassurance that the LNG 52 mg IUD has no adverse impact on mood.

ClinicalTrials.gov NCT03499379.

Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal (HPA) axis activity, which is related to emotion regulation. We compare hair cortisol concentrations (HCC), in clinically referred children with disruptive mood dysregulation disorder (DMDD) (n = 19), children with other types of psychological disorders (n = 48), and healthy subjects (n = 36). We also investigate the association between HCC and irritability, age, and sex. Our results show that children with DMDD or other types of psychological disorders have higher HCC than healthy subjects, p < .001, ηp2 = .39. No difference between children with DMDD and those with other types of psychological disorders was found, p = .91, nor an association between HCC and irritability in the clinical sample, p = .32. We found a significant negative correlation between HCC and age in those with DMDD, r = -0.54, p < .05, but not in the normative sample, r = -0.20, p = .25. No differences in HCC between girls and boys were found in the normative sample, p = .49. Children in need of psychological treatment, including those with DMDD, seem to have dysregulated HPA-axis activity over time. Excessive accumulated cortisol concentrations in hair could be an indicator of a psychological disorder in children.

Social jetlag is associated with physical and mental health problems. With the increased popularity of telework, we investigated a specific form of social jetlag that we termed "telework jetlag". This study aimed to clarify the relationship between telework jetlag-the difference in sleep and wake-up times between in-office and telework days-and mental health problems among Japanese hybrid workers. A cross-sectional study was conducted with 1789 participants from October to December 2021 using an online-based questionnaire. Telework jetlag, defined as the difference in the midsleep point between in-office and telework days, was investigated using two groups according to telework jetlag-those lagging <1 h versus ≥1 h. We used the six-item Kessler Scale as a nonspecific psychological distress scale for the outcome. Telework jetlag was significantly associated with psychological distress, and the ≥1 h group had a higher risk (odds ratio: 1.80) of developing high psychological distress (HPD) than the <1 h group in the multivariate analysis. Since most teleworkers are forced to have a hybrid work style that mixes going to work and teleworking, telework jetlag must be addressed to maintain the health of teleworkers.

Loneliness is a distressful feeling that can affect mental and physical health, particularly among older adults. Cortisol, the primary hormone of the Hypothalamic-Pituitary-Adrenal axis (HPA-axis), may act as a biological transducer through which loneliness affects health. While most previous studies have evaluated the association between loneliness, as a unidimensional construct, and diurnal cortisol pattern, no research has examined this relationship discriminating between social and emotional loneliness in older adults. As sex differences in the negative mental health outcomes of loneliness have been reported, we also investigated whether diurnal cortisol indices and loneliness associations occur in a sex-specific manner.

We analyzed the diurnal cortisol- pattern in 142 community-dwelling, non-depressed, Caucasian older adults (55,6% female) aged 60-90. Social and emotional (family and romantic) loneliness scores were assessed using the Spanish version of the Social and Emotional Loneliness Scale for Adults (SELSA). Five salivary cortisol samples were used to capture key features of the diurnal cortisol pattern, including: awakening and bedtime cortisol levels, awakening response (CAR), post-awakening cortisol output (post-awakening cortisol [i.e., the area under the curve with reference to the ground: AUCG]), total diurnal cortisol release (AUCG), and diurnal cortisol slope (DCS).

After controlling for sociodemographic variables, the hierarchical linear multiple regression analyses revealed that in male older adults, higher scores on social and family loneliness were associated with elevated awakening cortisol levels, total diurnal cortisol output, and a steeper diurnal cortisol slope (DCS). However, these associations were not observed in female older adults. In addition, feelings of romantic loneliness were positively associated with bedtime cortisol levels and AUCG in older males. Multilevel growth curve modeling showed that experiencing more social and emotional loneliness predicted higher diurnal cortisol output throughout the day in older male adults.

The presence of sex differences in the relationship between cortisol indices and loneliness among older adults holds particular significance for diagnostic and screening procedures. Combining loneliness scales as screening tools with diurnal cortisol measures has the potential to be an effective and cost-efficient approach in identifying higher-risk individuals at early stages.

Current treatments modalities for major depressive disorder (MDD) mainly target the monoaminergic neurotransmission. However, the therapeutic inadequacy and adverse effects confine the use of these conventional antidepressants to a limited subset of MDD patients. The classical antidepressants are increasingly proving unsatisfactory in tackling the treatment-resistant depression (TRD). Hence, the focus of treatment is shifting to alternative pathogenic pathways involved in depression. Preclinical and clinical evidences accumulated across the last decades have unequivocally affirmed the causative role of immuno-inflammatory pathways in the progression of depression. There is an upsurge in the clinical evaluations of the drugs having anti-inflammatory effects as antidepressants. This review highlights the molecular mechanisms connecting the inflammatory pathways to the MDD and current clinical status of inflammation modulating drugs in the treatment of MDD.

The lack of biomarkers to monitor and predict the efficacy of electroconvulsive therapy (ECT) has hindered its optimal use. To establish metabolomic markers for monitoring and predicting the treatment efficacy of ECT, we comprehensively evaluated metabolite levels in patients with major depressive disorder (MDD) by performing targeted and non-targeted metabolomic analyses using plasma samples before and after the first, third, and final ECT sessions, and 3-7 days after the final session. We compared the plasma metabolomes of age- and sex-matched healthy controls (HCs). Thirteen hospitalized patients with MDD and their corresponding HCs were included in this study. We observed that patients with MDD exhibited lower levels of amino acids, including gamma-aminobutyric acid (GABA), and metabolites involved in tryptophan metabolism and the kynurenine pathway, and higher levels of cortisol at baseline. Furthermore, we investigated the relationship between metabolite levels and depression severity across seven measurement timepoints along with one correlation analysis and found that amino acids, including GABA and tryptophan catabolites, were significantly correlated with the severity of depression. Despite the exploratory nature of this study due to the limited sample size necessitating further validation, our findings suggest that the blood metabolic profile has potential as a biomarker for ECT.

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro-immuno-metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host's circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness.

The current study assesses whether the association between diagnosis of Bipolar Disorder (BD) in mothers and emotional and behavioral problems (EBP) in their offspring is mediated by a disruption in the offspring's biological rhythms.

A probabilistic sample of 492 public school children (ages 7-8, 48 % female) were assessed for biological rhythms disruption and EBP using the Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids and the Strengths and Difficulties Questionnaire, respectively. Mothers' mental health (BD = 64) was evaluated using a standardized clinical interview. A mediation analysis was conducted to assess the effect of the mother's diagnosis of BD on the EBP of their offspring in relation to the offspring's biological rhythms disruptions.

When compared to offspring of mothers without BD, offspring of mothers with BD showed greater difficulty in maintaining biological rhythms and higher prevalence of EBP. Using the presence of EBP as the outcome, 75 % of the effect of mother's BD diagnosis was mediated by offspring's biological rhythms disruption.

Biological rhythms disruption in children fully mediates the effect of the mother's diagnosis of BD on the child's EBP. These data encourage the development of further studies to find effective strategies to prevent and treat biological rhythms disruption in offspring of mothers with BD.

Depression is a mental health disorder that develops as a result of complex psycho-neuro-immuno-endocrinological disturbances. This disease presents with mood disturbances, persistent sadness, loss of interest and impaired cognition, which causes distress to the patient and significantly affects the ability to function and have a satisfying family, social and professional life. Depression requires comprehensive management, including pharmacological treatment. Because pharmacotherapy of depression is a long-term process associated with the risk of numerous adverse drug effects, much attention is paid to alternative therapy methods, including phytopharmacotherapy, especially in treating mild or moderate depression. Preclinical studies and previous clinical studies confirm the antidepressant activity of active compounds in plants, such as St. John's wort, saffron crocus, lemon balm and lavender, or less known in European ethnopharmacology, roseroot, ginkgo, Korean ginseng, borage, brahmi, mimosa tree and magnolia bark. The active compounds in these plants exert antidepressive effects in similar mechanisms to those found in synthetic antidepressants. The description of phytopharmacodynamics includes inhibiting monoamine reuptake and monoamine oxidase activity and complex, agonistic or antagonistic effects on multiple central nervous system (CNS) receptors. Moreover, it is noteworthy that the anti-inflammatory effect is also important to the antidepressant activity of the plants mentioned above in light of the hypothesis that immunological disorders of the CNS are a significant pathogenetic factor of depression. This narrative review results from a traditional, non-systematic literature review. It briefly discusses the pathophysiology, symptomatology and treatment of depression, with a particular focus on the role of phytopharmacology in its treatment. It provides the mechanisms of action revealed in experimental studies of active ingredients isolated from herbal antidepressants and presents the results of selected clinical studies confirming their antidepressant effectiveness.

Studies suggest associations between cortisol and sleep, and cortisol shows a profound diurnal rhythm. The evidence about the relationship between chronic insomnia and cortisol is mixed. Chronic insomnia is associated with the risk of mental health disorders. The aim of this study was to evaluate the association of insomnia severity and objective sleep pattern with morning cortisol level and psychological health. The instruments used were the Insomnia Severity Index (ISI), polysomnography, Beck Depression Inventory (BDI), and Profile of Mood States (POMS). Serum cortisol was analyzed by chemiluminescence. The data revealed significant positive correlations of ISI with morning cortisol level (r = 0.37, p  = 0.03), BDI score (r = 0.44, p  < 0.01), and POMS-tension anxiety (r = 0.39, p  = 0.02). Sleep stages N2 and N3 were correlated with POMS-fatigue (r = 0.46, p  < 0.01; r = -0.37, p  = 0.04). Sleep stage N3 was also negatively correlated with POMS-tension-anxiety (r = -0.36, p  = 0.04). Higher insomnia severity was associated with higher morning cortisol, depression, and tension-anxiety. Sleep stage N2 was associated with higher fatigue and N3 was associated with lower tension-anxiety and fatigue.

Considering that the classical categorical approach to mental disorders does not allow a clear identification of at-risk conditions, the dimensional approach provided by the Research Domain Criteria (RDoC) is useful in the exploration of vulnerability to psychopathology. In the RDoC era, psychophysiological models have an important role in the reconceptualization of mental disorders. Indeed, progress in the study of depression vulnerability has increasingly been informed by psychophysiological models. By adopting an RDoC lens, this narrative review focuses on how psychophysiological models can be used to advance our knowledge of the pathophysiological mechanisms underlying depression vulnerability. Findings from psychophysiological research that explored multiple RDoC domains in populations at-risk for depression are reviewed and discussed. Future directions for the application of psychophysiological research in reaching a more complete understanding of depression vulnerability and, ultimately, improving clinical utility, are presented.

Pregnancy is a sensitive period when women experience major hormonal and psychological changes. A high prevalence of the symptoms of depression and manifested major depression rates have been reported during this period, leading to negative outcomes both for mothers and the offspring. Despite its prevalence, the aetiology of depression is not yet fully understood. Nonetheless, alterations in cortisol levels have been proposed as a reliable biomarker to identify pregnant women at risk of perinatal depression. Hair cortisol has recently been extensively used in bio-psychological studies as a suitable non-invasive biomarker for several neuropsychiatric disorders. Various studies have published evidence regarding the relationship between cortisol fluctuations during the perinatal period, measured both in hair and in other substrates, and the onset of perinatal symptoms of depression. This current review provides an overview of cortisol level changes measured in women's hair during pregnancy or the postpartum period and its association with perinatal symptoms of depression. Further studies, including repetitive measurement of both hair cortisol and depression throughout the prenatal period, must be performed to clarify the relationship between cortisol levels and perinatal symptoms of depression.

The objective of this study was to investigate how cortisol levels and appraisals of daily hassles differ across tripartite dimensions of depression and anxiety in emerging adults. Data collected from a sample of undergraduate students at a large Midwestern university was used to investigate these aims. This included salivary cortisol data collected over four days, scores on a measure of the tripartite model of anxiety and depression, and scores on a measure of daily hassles administered everyday for two weeks. Generalized estimating equations and multilevel modeling techniques were used to analyze data. Elevated cortisol levels during the awakening period and the evening period, lower total levels across the day, steeper diurnal slopes, and elevated levels of negative affect and physiological hyperarousal predicted experiences of daily hassles. Tripartite dimensions were unrelated to cortisol indices. The present study demonstrates the utility of modeling multiple cortisol indices and provides evidence of differential associations between physiological and phenomenological indices of stress.

The inflammatory potential of unhealthy diets can lead to the development of chronic diseases and also exacerbating their complications. Therefore, the present systematic review aimed to evaluate the association of dietary inflammatory index (DII) and quality of life (QOL) in human subjects.

A systematic search was conducted in PubMed, Web of Science, and Scopus databases, using the combination of all search terms related to DII and QOL until May 2022. All eligible human studies published in English were included.

Three hundred twenty-seven studies were obtained from the first systematic search of the databases although, only eight studies were eligible for the evaluation. Seven studies reported that there was a significant reverse association between DII scores and overall QOL and/or its subscales in different populations including patients with asthma, osteoarthritis, hemodialysis patients, multiple sclerosis, obese women, and also in healthy subjects. While, one study on postmenopausal women found no evidence of this association.

This systematic review demonstrated that an anti-inflammatory diet might be associated with better QOL. However, future well-designed clinical trials can provide better conclusions especially regarding the quantifying of this relationship.

Depression is a common mental disorder that occurs all over the world with treatment resistance commonly seen in clinical practice. Ketamine exhibits an antidepressant that is more often used in the case of treatment-resistant depression (TRD) in MDD and BP. Research emphasizes that a healthy diet and the nutrients it contains can lower the risk of developing depression and form a strategy that supports conventional treatment. The aim of the study was to evaluate the patients' diet and to analyze the effect of ketamine on food intake among patients with TRD. The study involved 15 patients suffering from treatment-resistant depression and 15 healthy volunteers. The data required for the analysis were collected using the food frequency questionnaire (FFQ) and 4-day food diaries. The study group was statistically significantly less likely to consume milk and plain milk beverages, plain white cheese, wholemeal bread, various vegetables, wine, and drinks. Our results show several disorders in the eating habits of patients with treatment-resistant depression. After the administration of ketamine, the patients consumed significantly less protein, fats, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), fiber, tryptophan, vitamins, and minerals compared to the control group. There is a lack of research describing the effects of ketamine on nutrition. In order to confirm the results of the study, more participants are required, and the assessment of food diaries filled in at the patient's home with a longer interval after the last dose of ketamine as well.

The hypothalamic-pituitary-adrenal axis function in depression has been the subject of considerable interest, and its function has been tested with a variety of methods. We investigated associations between saliva cortisol at awakening and the 24-h urine cortisol output, both measured at study baseline, with endpoint depression scores.

Patients were admitted to a psychiatric inpatient ward with a major depressive episode and were started on fixed duloxetine treatment. They delivered saliva samples at awakening and 15, 30, and 60 min post-awakening and sampled urine for 24 h. Subsequently, they started a daily exercise program maintained for a 9-week period. Clinician-rated depression severity was blindly assessed with the Hamilton Depression Rating 6-item subscale (HAM-D6). The cortisol awakening response was quantified by the area under the curve with respect to the ground (AUCG) and with respect to the rise (AUCI) using saliva cortisol levels in the 1-h period after awakening. Analysis of expected associations between depression severity, AUCG, AUCI, exercise, and 24-h cortisol output was performed in a general linear model.

In all, 35 participants delivered saliva or 24-h urine samples. The mean age was 49.0 years (SD = 11.0) with 48.6% females with a mean baseline HAM-D6 score of 12.2 (SD = 2.3). In a statistical model investigating the association between HAM-D6 at week 9 as a dependent variable and AUCI, concurrent HAM-D6, gender, smoking, and exercise volume as covariates, we found a significant effect of AUCI, concurrent HAM-D6, and exercise. The following statistics were found: AUCI (regression coefficient 0.008; F value = 9.1; p = 0.007), concurrent HAM-D6 (regression coefficient 0.70; F value = 8.0; p = 0.01), and exercise (regression coefficient -0.005; F value = 5.7; p = 0.03). The model had an R2 of 0.43. The association between HAM-D6 endpoint scores and the AUCI showed that higher AUCI values predicted higher HAM-D6 endpoint values. The association between HAM-D6 endpoint scores and the exercise level showed that a high exercise level was associated with lower HAM-D6 endpoint values.

The results thus showed that high AUCI values predicted less improvement of depression and high exercise levels predicted more improvement of depression. These findings need to be confirmed in larger samples to test if more covariates can improve prediction of depression severity.