(1) The prevalence of depression is two times higher in women than men. Black women have an increased risk of depression due to stressors such as low socioeconomic status and perceived discrimination. Depression is likely influenced by both genetic and environmental factors. Psychosocial stressors can influence DNA methylation (DNAm), leading to changes in gene expression and ultimately, depression. The objective of this study was to examine associations between DNAm and depressive symptoms in Black women. (2) This study was a secondary analysis of data from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) Study. Perceived discrimination was assessed using Krieger's Experiences of Discrimination and Waelde's Race-Related Events Scale, and participants were screened for depressive symptoms with the Beck Depression Inventory. Raw data from saliva samples were analyzed using the Illumina Infinium Epic (850 K) BeadChip and then preprocessed in RStudio. (3) Differential methylation analysis identified DNAm sites and regions associated with depressive symptoms. Six DNAm sites had a q-value less than 0.05. Additionally, of the 25 regions identified, 12 were associated with neurological diseases or disorders. (4) These findings suggest that there is a neurological component to depression, which should be considered during treatment.

Mainstream psychiatric practice requires a solid grounding in neuroscience, an important part of the biopsychosocial model, allowing for holistic person-centred care. There have been repeated calls for better integration of neuroscience into training, although so far with less focus on implementation for life-long learning. We suggest that such training should be accessible and utilised by all psychiatrists, not solely those with a special interest in neuropsychiatry. By considering recent positive developments within the general psychiatry curricula and neuropsychiatric resource implementation, we propose strategies for how this can be progressed, minimising regional disparities within the growing world of virtual learning.

Depression is a significant public health issue that needs to be taken care of, as it poses a great economic burden on the society at large. Early identification and treatment of the patients will reduce mental morbidity and disability.

The aim is to study the prevalence and functional status of subjects with major depressive disorder in the community.

After identification of the sample population, the sociodemographic details were recorded. Subsequently, assessment was carried out by General Health Questionnaire (GHQ), Patient Health Questionnaire-9 (PHQ-9), Functional Status Questionnaire (FSQ), and Mini Mental State examination (MMSE).

A total of 2000 subjects were screened using the GHQ and PHQ and 544 subjects were selected. These 544 subjects were further assessed with FSQ and MMSE. Out of the 544 subjects, 65.1% had a GHQ score of <14, 22.1% had a score between 15 and 19, and 12.9% had a score of >20. The PHQ-9 score was found to be <5 in 28.9% subjects, 5-14 in 64.3% subjects, and >14 in 6.8% subjects. Majority of the sample population was in the warning zone according to the FSQ. The MMSE scores were ≥23 in 86% and ≤22 in 14% of the patients. Over 65% of the subjects were relatively mentally healthy. Out of the remaining 35%, 22% of the subjects required screening for psychiatric disorders and 13% of them did require active psychiatric intervention.

It would be beneficial to the community if a database is created regarding the psychiatric disorders such as depression prevalent in the community and their functional status so that the effective measures can be implemented to minimize the suffering by providing effective psychiatric care at the earliest and follow them up in the long run.

This article focuses on some common dilemmas facing clinicians, patients, and families in managing the treatment of complicated mood disorders. Specifically, this article reviews the interaction of depressive states, including unipolar, bipolar, and mixed, with other adversities, including comorbid physical and psychological disorders, personality vulnerabilities, misuse of drugs and alcohol, and social and family problems. These issues are not always clearly differentiated from the depressive illness. Each of these adversities can worsen an existing mood disorder and influence the patient's resolve to persist with a treatment plan. Although this article is not focused strictly on treatment-resistant depression, these coexisting issues make depressive states harder to manage therapeutically. For brevity, the aim of this article has been limited to discussion of some complex situations that psychiatrists in general practice may encounter.

Mapping different structural forms of serotonin subtypes 5-HT1A-5-HT7 using a selective-specific ligand with good pharmacokinetics and brain permeability can open avenues for personalized medication in depressed population. Herein, the selective 5-HT1A/7 antagonist, modified for enhanced brain permeation, is developed as a homobivalent ligand, (6-AcBTZ)2DTPA. After in-depth computational studies to probe the binding mechanism, two-step synthesis lead to (6-AcBTZ)2DTPA. Biocompatibility studies indicated cytocompatibility with 3.6-1.64% cell death (0.1 mM-1 pM) and hemocompatibility with 2.33% hemolysis of human erythrocytes. When 99mTc-radiolabeled in a quantitative yield (98%), a stable preparation was obtained with 7.4 and 3.5% dissociation upon incubation with human serum and excess cysteine. The single-photon-emission computed tomography (SPECT) tracer 99mTc-(6-AcBTZ)2DTPA showed biphasic clearance (t 1/2, distribution = 0.5 min and t 1/2, elimination = 482 min) and maximum brain uptake of 0.42 ± 0.02% ID/g with the regional localization (hippocampus: 11.38% ID/g; cortex: 26.42% ID/g; cerebellum: 25.23% ID/g). Thus, the 99mTc-metal-based SPECT neurotracer holds potential for neuroreceptor mapping.

Parkinson's disease (PD) is a progressive and multifactorial neurodegenerative disease. It has been suggested that a dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) occurs in PD. Furthermore, this dysregulation may be involved in triggering, exacerbation or progression of disease. The objective of this study was to systematically review the literature regarding cortisol levels and their relation with motor, cognitive and behavioral symptoms in patients with PD. A systematic search was performed in PubMed and Embase databases, according to PRISMA norms. Twenty-one studies were included, which evaluated baseline levels of cortisol and motor, cognitive, behavioral symptoms, drugs administration or deep brain stimulation to PD treatment. Sample size ranged from 7 to 249 individuals. In 14 studies that assessed cortisol levels in PD patients, seven showed elevation of cortisol levels. In relation to symptomatology, high levels of cortisol were associated with worst functional scores evaluated by UPDRS, depression and behavior in risk preference. Medication interactions showed an influence on the regulation of cortisol release, mainly, conventional drugs used in the PD's treatment, such as levodopa. The results found in this review point to a possible relationship between cortisol levels and symptoms in PD, indicating that an HPA axis dysfunction related to cortisol level occurs in PD.

Mood disorders associated with epilepsy are very common and overrepresented compared with other chronic medical conditions. Depression is a particularly common and worrisome comorbidity, especially because suicidality seems to be increased significantly in the context of epilepsy. Although psychosocial stressors commonly are associated, intrinsic characteristics of seizure disorders may contribute to the expression of depressive symptoms. Depression and epilepsy may exacerbate each other. Epilepsy with seizure foci in the temporal lobe may represent a higher risk of developing depression, especially if the seizures do not generalize. Treatment of depression is multifaceted and includes psychotherapy and sophisticated regimens of anticonvulsants. Most antidepressants may be used safely and effectively in the context of depression, although high-quality evidence is lacking. Ultimately, treatment of comorbid mood disorder has important implications for outcome and quality of life, perhaps even more than treatment of epilepsy itself.

Despite the strong association between epilepsy and psychiatric comorbidities, data on clinicopathologic correlations are scant. We previously reported differential mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (MTLE) patients with psychosis (MTLE + P) and major depression (MTLE + D). Because neurotrophins (NTs) can promote MFS, here, we investigated MFS, neuronal density and immunoreactivity for the NT nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in hippocampi of 14 MTLE patients without a psychiatric history, 13 MTLE + D, 13 MTLE + P, and 10 control necropsies. Mossy fiber sprouting correlated with granular layer NGF immunoreactivity and seizure frequency. Patients with secondarily generalized seizures exhibited less NGF immunoreactivity versus patients with complex partial seizures. There was greater NT immunoreactivity in MTLE versus control groups but lesser NT immunoreactivity in MTLE + P versus MTLE patients; these findings correlated with neuropsychologic scores. Patients with MTLE + D taking fluoxetine showed greater BDNF immunoreactivity than those not taking fluoxetine; MTLE + P patients taking haloperidol had decreased neuronal density and immunoreactivity for NGF and BDNF in specific subfields versus those not taking haloperidol. There were no differences in NT3 immunoreactivity among the groups. These findings support a close association between MFS and NT expression in the hippocampi of MTLE patients and suggest that distinct structural and neurochemical milieu may contribute to the genesis or maintenance of psychiatric comorbidities in MTLE.

Depression is recognized as a serious comorbidity of epilepsy, but treatment of depression and anxiety in people with epilepsy is challenging. The aim of this article was to review published controlled clinical treatment studies of depression and anxiety in patients with epilepsy. The PubMed, Cochrane and PsycINFO databases were searched for controlled clinical trials, or controlled psychosocial or behavioral trials published in English before June 2012. Search terms were: seizures, epilepsy, depression, psychotherapy, cognitive therapy/treatment, behavioral therapy/treatment and nonpharmacologic therapy/treatment, education and stress management. Seven studies were included in this review. Interventions included antidepressant medications, antiepileptic medications, and cognitive behavioral therapy. Despite the methodological limitations in the studies identified by this review, both medications and psychotherapy improved depression and anxiety in patients with epilepsy. However, further research is needed in the form of randomized controlled clinical trials to establish appropriate pharmacological and psychosocial co-management of depression and epilepsy.

Children and adolescents with epilepsy have an overrepresentation of psychiatric illness. However, few studies in pediatrics have characterized specific psychiatric conditions associated with seizure localization. In addition, degree to which psychiatric illness may be more prominent in children refractory to standard medical treatment for epilepsy is not known. The aim of this study was to assess psychiatric symptoms in children with medically refractory epilepsy and ascertain whether symptoms were associated with specific localization.

Case records were reviewed for 40 children with medically refractory epilepsy at the time of their referral for presurgical evaluation. Patients received a clinical psychiatric evaluation and parents completed the Child Behavioral Checklist (CBCL). Seizure localization was verified by pediatric epileptologists, and suitability for surgical procedures was verified by neurosurgical specialists. Groups were compared based on localization of seizure foci, either in the temporal lobe or predominantly extratemporal.

The majority of the sample had psychiatric diagnoses and behavior problems, well beyond the level reported in chronic epilepsy populations. In addition, children with temporal lobe seizure foci had more CBCL behavioral problem categories rated in the clinically significant range, and also were more likely to have clinical diagnoses of depression.

Routine psychiatric evaluation prior to epilepsy surgery may be important for pediatric patients with medically refractory epilepsy. Psychiatric illness, particularly depression, may be especially prominent for those with temporal lobe seizure foci.

Poststroke depression (PSD) is the most common neuropsychiatric consequence of stroke. A large number of studies have focused on the pathogenesis of PSD, but only a few aimed to characterize its psychopathology; these studies yielded results that are difficult to compare because of the different methods utilized. The current study aimed to characterize the symptom profile of PSD in an attempt to better understand the disease and allow a more accurate diagnosis.

The study sample comprised 64 patients divided into three groups: stroke patients without diagnosis of depression (n = 33), stroke patients diagnosed with PSD (PSD group, n = 14) and patients diagnosed with major depression (MD) but with no clinical comorbidity (MD group, n = 17). All patients were diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The initial diagnostic interview was complemented by the Mini Mental State Examination (MMSE), the Rankin Scale, and four scales for the assessment of the intensity of symptoms of anxiety and depression: the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression General Scale (HADS), the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A). The Star Plot, a graphical method of data visualization, was used to analyze the results. The t test was used for independent samples (two-tailed analysis).

As measured by the BDI, HAM-D and HAM-A scales and HADS depression subscale, the average total scores of symptoms for the sample of patients diagnosed with MD without clinical comorbidity was significantly higher than that of the PSD patients (p < 0.05). Similar results were obtained by plotting the BDI data on Star Plot. The PSD patients showed mild typical depressive symptoms such as less depressed mood, anhedonia, disinterest, guilt, negative thoughts, depreciation, suicidal ideation and anxiety, when evaluated by the HAM-A scale. Moreover, the somatic symptoms of depression did not lead to increased diagnosis of major depression in stroke patients.

The results indicate that the PSD clinical picture comprised, in general, symptoms of mild/moderate intensity, especially those considered as pillars for the diagnosis of depression: depressed mood, loss of pleasure and lack of interest. Given the imprecision of boundaries that separate the clinical forms of depression from subclinical and nonpathological forms, or even from the concepts of demoralization and adjustment disorders, we situate PSD in a complex biopsychosocial context in which a better understanding of its psychopathological profile could provide diagnostic and therapeutic alternatives best suited to the difficult reality experienced by stroke patients.

The purpose of this study was to determine the nature and extent of depressive symptoms among patients with epilepsy.

Ninety patients were investigated over a three-month period: 42 were suffering from generalized epilepsy, 29 from focal epilepsy and 19 from undetermined epilepsy. All completed the Zung self-rating scale for assessment of the depressive symptoms.

Sixty-seven patients felt stigmatized because of epilepsy (67%): 73.6% in the undetermined epilepsy group, 55.1% in the focal epilepsy group and 88% in the generalized epilepsy group. Moreover, among the 90 epileptic patients studied, symptoms of irritability, indecisiveness, personal devaluation and emptiness showed a constant increasing trend for their presence from the undetermined epilepsy group through the generalized epilepsy group to the focal epilepsy group.

These findings indicate that although the focal epilepsy patients felt less stigmatized, they did not differ greatly in terms of depressive symptoms, in relation to the undetermined epilepsy and generalized epilepsy patients.

In this review, we focus on the relationship among Parkinson's disease (PD), stress and depression. Parkinson's disease patients have a high risk of developing depression, and it is possible that stress contributes to the development of both pathologies. Stress dysfunction may have a role in the etiology of preclinical non-motor symptoms of PD (such as depression) and, later in the course of the disease, may worsen motor symptoms. However, relatively few studies have examined stress or depression and the injured nigrostriatal system. This review discusses the effects of stress on neurodegeneration and depression, and their association with the symptoms and progression of PD.

People with epilepsy (PWE) are at increased risk of experiencing suicidal ideation, displaying suicidal behavior, and committing suicide than the general population. The relationship between suicidality and epilepsy is complex and multifactorial in which operant pathogenic mechanisms include epilepsy-related variables, personal and familial psychiatric history, and iatrogenic effects. Furthermore, a bidirectional relationship between suicidality and epilepsy has suggested the existence of common neurobiological pathogenic mechanisms operant in both conditions and including disturbances of several neurotransmitters, in particular, serotonin (5HT), norepinephrine (NE), glutamate (GTE), and γ-aminobutyric acid (GABA), and disturbances of the hypothalamic-pituitary-adrenal axis (HPAA), which, in turn, can result in abnormal secretion of some of these neurotransmitters. The purpose of this article is to review these common neurobiological pathogenic mechanisms.

People with epilepsy frequently present with bitter memory complaints. Previous research variously attributes this to symptoms of mood disturbance or objective memory deficits. To investigate the influence of the epileptogenic region on this variability, we examined interrelationships between mood, objective memory, and memory complaints in a sample of patients with refractory focal epilepsy and controls (N = 96). Patients had either mesial temporal (MT, n = 39) or non mesial-temporal (NMT, n = 21) foci. In contrast to controls (n = 36), both patient groups were highly concerned about their memory (P<0.001) and were more likely to have a history of depression (P = 0.005). Multiple regression showed that objective memory dysfunction and current depressive symptoms predicted the memory complaints of patients with MT epilepsy (P = 0.005), whereas a history of depression predicted the complaints of patients with NMT epilepsy (P = 0.008). These findings suggest that patients have concerns about their memory underpinned by distinct psychological and neurobiological factors depending on the location of their epileptogenic focus.

To develop a functional MRI (fMRI) signal based model that can evaluate depression severity in a numeric form; therefore, depressed patients can be identified during the course of illness, independent from symptoms.

Data from 20 medication-free depressed patients and 16 healthy subjects were analyzed. The event-related fMRI scanning features under sad facial emotional stimuli were extracted as model inputs. Fuzzy logic and a genetic algorithm were used to provide suitable model outputs for numeric estimations of depression.

The correlation value r between the model estimations and the professional Hamilton Depression Rating Scales (HAMD) was 0.7886 with P < 0.00016. A typical tracking history for a particular subject has also promised the possibility for early disease warning, when the clinal symptoms are ambiguous or recessive.

A numeric and objective estimation for the course of illness can be provided. The model can be used by psychiatrists to track the recovery process. As a simple extended application, the proposed model can be applied to classify subjects into different patterns: major depression, moderate depression, or healthy.

Mood-related phenotypes are commonly comorbid with, and have been implicated in the development of, neurological disorders. APOE is a major susceptibility gene for neurodegeneration. Recent evidence from case-control studies has suggested that the apoE 2 allele is associated with major depressive disorder (MDD). However, evidence from large-scale community-based studies is limited. APOE was genotyped for 17,507 men and women, aged 41-80 years, participating in the European Prospective Investigation into Cancer-Norfolk study, who had also completed a psychosocial assessment that included measures of emotional health status defined by MDD, psychological distress (as represented by the Mental Health Inventory, MHI-5), and by an assessment of neuroticism. No associations were found between APOE genotypes and measures either of past-year or lifetime MDD, or of emotional health defined according to the MHI-5 or by neuroticism. Data from this large-scale, community-based, study are not supportive of an association between either MDD or associated measures of emotional state and APOE genotype. These findings suggest that the association between APOE and MDD risk is more modest than has been previously reported.

Alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Glutamic acid decarboxylase (GAD) is the key enzyme of GABA synthesis.

Immunohistochemical staining of GAD 65/67 was performed in the orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex (DLC), the entorhinal cortex (EC), the hippocampal formation, and the medial dorsal and lateral dorsal thalamic nuclei, with consecutive determination of GAD-immunoreactive (-ir) neuropil relative density. The study was performed on paraffin-embedded brains from 21 depressed patients (14 of whom had committed suicide) and 18 matched controls. The data were tested using Kruskal-Wallis, Mann-Whitney (U) and Spearman statistical procedures.

As shown by post-hoc U-tests, an increase in the relative density of GAD-ir neuropil was present in the hippocampal formation, specific for suicidal patients. The EC was the only area where non-suicidal patients also revealed an increase compared with controls. On the contrary, the DLC was the only area where a significant decrease existed, specific for non-suicidal patients. Numerous negative correlations were found between the investigated parameter and psychotropic medication.

A major limitation of this study is the relatively small case number. A further limitation is given by the lack of data on drug exposure across the whole life span. The possible impact of unipolar-bipolar dichotomy of mood disorders on the obtained results should also be considered.

The study, revealing predominantly an increased relative density of GAD-ir neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients.

Resumption of hazardous drinking after treatment is common in alcohol use disorders (AUD). This study examined the ability of multimodality magnetic resonance, neurocognitive, psychiatric and demographic, to predict alcohol consumption after treatment for AUD.

Seventy treatment-seeking participants completed 1.5T magnetic resonance studies, yielding regional gray matter (GM) and white matter (WM) surrogate markers of neuronal integrity (N-acetylaspartate: NAA) and cell membrane turnover/synthesis (choline: Cho), assessment of major psychiatric disorders and comprehensive neurocognitive assessment after approximately 1 month of abstinence. Participants were followed up 6-12 months after treatment and classified as Abstainers (no alcohol consumption; n=26) and Resumers (any alcohol consumption; n=44). Abstainers and Resumers were contrasted on various outcome measures, and those that significantly differed between groups were entered as factors in a logistical regression model to predict drinking status at follow-up.

The following variables were independent predictors of resumption of drinking: temporal GM NAA, frontal WM NAA, frontal GM Cho, processing speed and comorbid unipolar mood disorder. With each standard deviation unit decrease in temporal GM NAA, frontal WM NAA, frontal GM Cho and processing speed, the odds of resumption of drinking were increased 3.1, 3.3, 6.4 and 14.2 times, respectively. Diagnosis of a unipolar mood disorder was associated with 14.5-fold increased odds of resumed drinking.

The findings suggest that Resumers, relative to Abstainers, demonstrated greater abnormalities in anterior frontal-subcortical circuits involved in mood and behavioral regulation, and development and maintenance of alcohol use disorders, The magnetic resonance-derived variables used in this study may provide additional information regarding the prediction and neurobiological correlates of resumption of hazardous drinking.

Co-morbidities that commonly accompany those afflicted with an alcohol use disorder (AUD) may promote variability in the pattern and magnitude of neurocognitive abnormalities demonstrated. The goal of this study was to investigate the influence of several common co-morbid medical conditions (primarily hypertension and hepatitis C), psychiatric (primarily unipolar mood and anxiety disorders), and substance use (primarily psychostimulant and cannabis) disorders, and chronic cigarette smoking on the neurocognitive functioning in short-term abstinent, treatment-seeking individuals with AUD. Seventy-five alcohol-dependent participants (ALC; 51+/-9 years of age; three females) completed comprehensive neurocognitive testing after approximately 1 month of abstinence. Multivariate multiple linear regression evaluated the relationships among neurocognitive variables and medical conditions, psychiatric, and substance-use disorders, controlling for sociodemographic factors. Sixty-four percent of ALC had at least one medical, psychiatric, or substance-abuse co-morbidity (excluding smoking). Smoking status (smoker or nonsmoker) and age were significant independent predictors of cognitive efficiency, general intelligence, postural stability, processing speed, and visuospatial memory after age-normed adjustment and control for estimated pre-morbid verbal intelligence, education, alcohol consumption, and medical, psychiatric, and substance-misuse co-morbidities. Results indicated that chronic smoking accounted for a significant portion of the variance in the neurocognitive performance of this middle-aged AUD cohort. The age-related findings for ALC suggest that alcohol dependence, per se, was associated with diminished neurocognitive functioning with increasing age. The study of participants who demonstrate common co-morbidities observed in AUD is necessary to fully understand how AUD, as a clinical syndrome, affects neurocognition, brain neurobiology, and their changes with extended abstinence.

Despite a growing interest in this area, we continue to lack an understanding of the pathophysiology of depression and of treatment-resistant depression (TRD) in particular. The role of the medial temporal lobe, particularly the hippocampus, has been widely implicated in the aetiology of depression. However, related structures such as the entorhinal cortex have not been systematically examined. This research study aimed to examine possible abnormalities in the volume of the entorhinal cortex (ERC) in TRD patients. A group of 45 TRD patients and 30 healthy age- and sex-matched controls underwent magnetic resonance imaging (MRI). ERC volumes were manually traced from MRI data using ANALYZE software. An analysis of variance was conducted between subject groups and in the sexes separately while controlling for the effects of brain size via intracranial volume (ICV). Results revealed significant reductions in the volume of the left ERC of female patients. Although preliminary, our findings suggest that anatomical abnormalities in the ERC may confer vulnerability to treatment resistance. Confirmatory longitudinal studies are required to determine whether these abnormalities predate the onset of depression or are the result of a more chronic, treatment-resistant course of illness.

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.

As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema.

We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD).

A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided.

While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD.

Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.

Psychiatric and psychosocial complications with pediatric epilepsy are more common than with other chronic medical illnesses. Epilepsy is a disorder of hyperexcitable neurons and may have direct neurophysiologic effects leading to psychiatric comorbidity. Epilepsy also requires significant lifestyle adjustment, and the psychosocial impact on children and their families may be severe. The scientific literature is underrepresented in terms of diagnosis and management of psychiatric and psychosocial comorbidity associated with pediatric epilepsy. However, recent scientific efforts have assisted in highlighting the impact of these comorbidities and in bringing them to greater clinical attention. This review incorporates the available evidence with an aim to describe effective strategies for diagnosis and management.

Refractory temporal lobe epilepsy (TLE) is often associated with hippocampal sclerosis (HS). Patients with major depression (MD) may also show structural abnormalities in the limbic system. Co-occurrence of TLE with HS and MD is not uncommon. We have investigated the clinical and morphological characteristics of TLE patients in relation to MD.

34 TLE patients with HS were assessed at a Comprehensive Epilepsy Programme. All relevant clinical data were obtained, including the history of antecedent events to epilepsy. MD was diagnosed based on detailed psychiatric investigation. MRI was used to measure the volume and tissue signal (T2 relaxometry) of the hippocampus and amygdala. The imaging data were expressed as a percentage of the values obtained in a series of 55 controls.

A history of MD was present in 15 (44%) of 34 patients. Patients with MD had a longer duration of their epilepsy (p<0.05) and a lower frequency of antecedent events (13% with MD, 58% without MD, p<0.05). Both groups had a similar degree of ipsilateral HS (small hippocampal volume, increased hippocampal T2 relaxation time) and demonstrated bilateral amygdaloid atrophy. However, the contralateral amygdala showed lower signal in the presence of MD (97 (9) ms; no MD 103 (8) ms; ANCOVA, p = 0.02).

The integrity of the amygdala may influence mood disturbances in TLE patients with HS, as depression was associated with a relative preservation of the contralateral amygdala. In contrast, hippocampal abnormalities were not related to the presence of depression.

A number of studies have demonstrated that affective disorders in epilepsy represent a common psychiatric comorbidity; however, most of the classic neuropsychiatric literature focuses on depression, which is actually prominent, but little is known about bipolar depression, and very little about mania, in epilepsy. Biochemical, structural, and functional abnormalities in primary bipolar disorder could also occur secondary to seizure disorders. The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. In bipolar patients, changes in second-messenger systems, such as G-proteins, phosphatidylinositol, protein kinase C, myristoylated alanine-rich C kinase substrate, or calcium activity have been described, along with changes in c-fos expression. Common mechanisms at the level of ion channels might include the antikindling and the calcium-antagonistic and potassium outward current-modulating properties of antiepileptic drugs. All these lines of research appear to be converging on a richer understanding of neurobiological underpinnings between bipolar disorder and epilepsy. Mania, which is the other side of the coin in affective disorders, may represent a privileged window into the neurobiology of mood regulation and the neurobiology of epilepsy itself. Future research on intracellular mechanisms might become decisive for a better understanding of the similarities between these two disorders.

Our primary objective was to test whether negatively biased response to neutral physical or visual stimuli was associated with antidepressant nonadherence.

We surveyed 22 primary care adults receiving pharmacological treatment for depression. Somatoform complaints, in addition to interpretation of and response to neutral facial expressions (NFEs), were assessed with surveys. Seven response anchors to NFE were classified as "negative" or "neutral/positive." Antidepressant adherence was ascertained after 3 months by self-report and pharmacy refill records.

Elevated somatoform complaints were associated with early antidepressant discontinuation (P=.01). Exclusively negative emotional response to NFE, reported by 55% (12/22) of subjects, was associated with clinically significant missed antidepressant doses (R=-.69, P=.0004). Two multivariate models adjusted for depressive symptoms demonstrated that exclusively positive or neutral emotional response to NFE was associated with improved adherence relative to an exclusively negative response (beta=34.0, t=3.7, P=.002); the somatoform complaints subscale "health concerns" adversely influenced depressive symptom improvement (beta=-.3, t=-3.0, P=.008).

Negatively biased responses to neutral stimuli in the physical and visual axes were associated with early antidepressant discontinuation and missed doses, respectively. If substantiated, these initial findings might contribute to improved understanding and treatment of antidepressant nonadherence.

Referral patterns for on-site psychological services were tracked in a pediatric epilepsy clinic at a university medical center. Results revealed that 84 children treated for seizures were referred to an on-site pediatric psychologist. Behavior problems were the overall most common reason for referral; however, boys were more likely to be referred for disruptive behaviors, and girls were more likely to be referred for internalizing symptoms. Following psychological assessment, brief cognitive-behavioral intervention services were provided on-site in the epilepsy clinic to 39% of children and families. Finally, referral rates for psychological assessment/intervention were likely far below the estimated prevalence rates for psychosocial maladjustment in children with epilepsy. Results, therefore, highlight the necessity of facilitating increased referrals to mental health providers and provide support for the feasibility of on-site mental health services.

The main purpose of the present article is to review the possible risk factors for suicidal behaviour in epilepsy with a special emphasis on the different antiepileptic drugs (AEDs). Epidemiological data show that, in general, the suicide rate among patients with epilepsy is 5-fold higher than that in the general population, while in temporal lobe epilepsy and complex partial seizures it is approximately 25-fold higher. A certain psychiatric comorbidity may provoke suicidality in patients with epilepsy, and depression and cognitive impairment seem to be the main risk factors for suicidality in epilepsy. In addition, depression and cognitive deterioration in epilepsy may share common neuropsychological mechanisms in terms of hypofrontality. This may cause similar psychopathological signs in both diagnostic categories, including suicidality. Analysis of the literature has shown that serotonin metabolism disturbances are involved in the pathogenesis of suicidal behaviour irrespective of primary diagnosis. Serotonin disturbances also seem to be a common link between depression, suicidality and even epilepsy itself. The various AEDs differ not only in their mechanisms of action, but also in influences on cognition and mood in epileptic patients and suicidality, respectively. Until now, only Ketter's hypothesis has been proposed to explain the psychotropic effects of different AEDs, although it does not explain the positive psychotropic effects of some AEDs, such as carbamazepine and oxcarbazepine. According to this model, all psychotropic effects of AEDs may be the result of effects on the function of two types of receptor functions: gamma-aminobutyric acid (GABA) ergic and antiglutamatergic; other possible mechanisms have not been incorporated. Presumably, other neurochemical mechanisms, and a serotonergic mechanism in particular, should also be taken into account when explaining the psychotropic effects of different AEDs. Based on these data, it has been suggested that AEDs with certain serotonergic properties should reduce the suicidality risk because they exert effects similar to antidepressants (i.e. selective serotonin reuptake inhibitors), whereas AEDs that lack serotonergic mechanisms would not be effective in suicidality prevention. In line with this paradigm, phenobarbital and phenytoin seem to be the only drugs with proven suicidality risk. On the other hand, carbamazepine, oxcarbazepine, valproate and lamotrigine could be regarded as drugs with antisuicidal properties because they all improve cognitive functions and mood in epileptic patients, and possess serotonergic mechanisms of action. The other AEDs, including topiramate, tiagabine, vigabatrin, levetiracetam and zonisamide, all exert negative effects on mood and cognition, although their influence on suicidality has not been proven in evidence-based studies yet. Although zonizamide has serotonergic properties, it exerts negative psychotropic effects, whereas gabapentin is devoid of serotonergic properties but has positive psychotropic effects on mood and cognition. To more fully explain the positive and negative psychotropic effects and influence on suicidality of AEDs, Ketter's paradigm should be supplemented by an understanding of the serotonergic mechanisms of different AEDs. Further trials are required to prove or refute this model.

Anticonvulsant drugs are first-line treatments for both bipolar mood disorder and epilepsy; however, few studies have explored treatment options when these disorders co-occur. The aim of this study was to identify bipolar disorder symptoms common in pediatric epilepsy and to determine whether anticonvulsant monotherapy might be a practical treatment consideration. A retrospective chart review identified 38 children with bipolar spectrum disorder and epilepsy comorbidity. Two mental health clinicians independently assessed psychiatric diagnoses, symptoms, and assigned retrospective CGI-I ratings for psychiatric symptoms. Common bipolar symptoms included impulsivity, psychomotor agitation, and explosive rage. Forty-two medication trials with 11 different anticonvulsants were identified. Of the 30 instances in which anticonvulsant monotherapy was attempted, carbamazepine, divalproex sodium, lamotrigine, and oxcarbazepine were associated with better psychiatric CGI-I ratings than other monotherapies (P<0.01). Results suggest that in many cases, selected anticonvulsants appeared to simultaneously treat both epilepsy and mood disorder. Controlled trials are necessary to further ascertain optimal anticonvulsant usage.

This research is based on previous publications that have analyzed certain neuropsychological phenomena that always have the same characteristic clinical features: a vivid experience of sudden onset and automatic development, accompanied by an intense sensation of strangeness. When these automatisms are accompanied by only mental symptoms, the designation paroxysmal psychic automatisms (PPAs) is proposed, and they should be interpreted as partial seizures (PSs) with a psychic content whenever they clearly exhibit the four features of suddenness, passivity, intensity, and strangeness. This interpretation is based on the existence of a wealth of scientific literature indicating an overlap between PPAs and PSs; moreover, bibliographic reviews indicate that the clinical signs just defined as characterizing PPAs are precisely those defining the epileptic consciousness.

To examine the effect of gender on regional brain activity, we utilized functional magnetic resonance imaging (fMRI) during a motor task and three cognitive tasks; a word generation task, a spatial attention task, and a working memory task in healthy male (n = 23) and female (n = 10) volunteers. Functional data were examined for group differences both in the number of pixels activated, and the blood-oxygen-level-dependent (BOLD) magnitude during each task. Males had a significantly greater mean activation than females in the working memory task with a greater number of pixels being activated in the right superior parietal gyrus and right inferior occipital gyrus, and a greater BOLD magnitude occurring in the left inferior parietal lobe. However, despite these fMRI changes, there were no significant differences between males and females on cognitive performance of the task. In contrast, in the spatial attention task, men performed better at this task than women, but there were no significant functional differences between the two groups. In the word generation task, there were no external measures of performance, but in the functional measurements, males had a significantly greater mean activation than females, where males had a significantly greater BOLD signal magnitude in the left and right dorsolateral prefrontal cortex, the right inferior parietal lobe, and the cingulate. In neither of the motor tasks (right or left hand) did males and females perform differently. Our fMRI findings during the motor tasks were a greater mean BOLD signal magnitude in males in the right hand motor task, compared to females where males had an increased BOLD signal magnitude in the right inferior parietal gyrus and in the left inferior frontal gyrus. In conclusion, these results demonstrate differential patterns of activation in males and females during a variety of cognitive tasks, even though performance in these tasks may not vary, and also that variability in performance may not be reflected in differences in brain activation. These results suggest that in functional imaging studies in clinical populations it may be sensible to examine each sex independently until this effect is more fully understood.

In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P < 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly affecting white matter, basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences in brain development may partially underpin behavioural differences. We suggest that there is preliminary evidence for specific vulnerability of the frontostriatal and cerebellar-cortical networks in 22qDS.

Stress can profoundly affect memory and alter the functioning of the hippocampus and amygdala. Studies have also shown that the antidepressant tianeptine can block the effects of stress on hippocampal and amygdala morphology and synaptic plasticity. We examined the effects of acute predator stress and tianeptine on long-term potentiation (LTP; induced by 100 pulses in 1 s) and primed burst potentiation (PB; a low threshold form of LTP induced by only five physiologically patterned pulses) in CA1 and in the basolateral nucleus (BLA) of the amygdala in anesthetized rats. Predator stress blocked the induction of PB potentiation in CA1 and enhanced LTP in BLA. Tianeptine blocked the stress-induced suppression of PB potentiation in CA1 without affecting the stress-induced enhancement of LTP in BLA. In addition, tianeptine administered under non-stress conditions enhanced PB potentiation in the hippocampus and LTP in the amygdala. These findings support the hypothesis that acute stress impairs hippocampal functioning and enhances amygdaloid functioning. The work also provides insight into the actions of tianeptine with the finding that it enhanced electrophysiological measures of plasticity in the hippocampus and amygdala under stress, as well as non-stress, conditions.

There are many challenges facing epidemiologists wishing to investigate relationships between physical activity, obesity, diabetes, dementia and depression, all of which are complex fields in their own right. There is a large literature investigating the relationship between diabetes and dementia but less, as yet, on the other exposures and outcomes. In this literature there is a diversity of definitions making rigorous systematic review problematic. There is a need to define hypotheses in this area very clearly and to identify studies that have addressed the specific question. Such exercises have not been carried out to date but would enlighten the research area and point more clearly to questions which remain to be answered. Our own research group has examined the specific question of risk of development of dementia in relation to levels of HbA(1)c, as a marker of glycaemic control and showed that although not related to dementia, it is related to incidence of severe cognitive impairment.

Comorbidity with depression is an important determinant of the quality of life for patients with epilepsy. Antidepressant medications can effectively treat depression in epileptic patients, but drug-drug interactions and epileptogenic effects of these drugs pose therapeutic challenges. The mood-stabilizing effects of antiepileptic medications may not be sufficient to treat depression. Therefore, treatments that alleviate the burden of depression without increasing seizure risk or, better yet, with the possibility of improving seizure control are worth exploring. Neuroimaging techniques, such as functional magnetic resonance imaging, are providing novel insights into the pathophysiology of depression in epilepsy. For example, there appears to be prominent brain prefrontal hypoactivity, which may be sustained by the hyperactivity of the seizure focus. If so, neuromodulatory approaches that suppress epileptic focus hyperactivity and concurrently enhance prefrontal activity may be ideally suited. Indeed, vagus nerve stimulation has been shown to yield simultaneous antiseizure and mood effects. Another neuromodulatory technique, transcranial magnetic stimulation (TMS), can also modulate brain activity, but in a noninvasive, painless, and focal manner. Depending on the stimulation parameters, it is possible to enhance or reduce activity in the targeted brain region. Furthermore, TMS has been shown to be effective in treating depression, and preliminary data suggest that this treatment may also be effective for epilepsy treatment. This article reviews these data and explores further the question of whether depression and epilepsy can be simultaneously treated with TMS for optimal therapeutic impact.

Neuroplasticity contributes to both normal and pathological brain function. A recent hypothesis links depression to lack of adaptive responses to stress or other aversive stimuli, and effects of antidepressant treatments on adult neurogenesis are more and more extensively studied because of the structural changes involved in the pathophysiology of depression. Indeed, neuronal remodelling in hippocampal formation is associated with chronic stress and is reversed by antidepressant treatments in animals. Decrease in hippocampal volume has also been associated to cognitive deficits in patients with major depression. Interestingly, serotonergic (5-HT) systems play a major role both as antidepressants and by increasing hippocampal neurogenesis through various receptor subtypes. Recently, we have also demonstrated that agomelatine, a new antidepressant drug having serotonergic and melatonergic properties, can increase proliferation and survival of newly formed hippocampal cells. Although the mechanisms underlying such effects are still unknown, these data reinforce the view that changes in hippocampal neurogenesis might belong to the cellular correlates of mood disorders.

This study analyzes diverse psychic phenomena which, although always occurring with very characteristic clinical features, are sometimes diagnosed as epilepsy and sometimes as symptoms of different psychiatric disorders depending on the availability of an electroencephalogram. It is posited that these phenomena, whenever they are accompanied by the features characteristic of an epileptic consciousness (suddenness, automatic nature, great intensity and a strong sensation of strangeness) should be diagnosed as partial seizures with a psychic content, regardless of the availability of an EEG. The co-occurrence of these four clinical signs, which are relatively simple to objectivize, is a more reliable clinical criterion for diagnosis than a transcraneal electroencephalogram, which, as is known, is of little value in measuring the electrical activity of partial seizures. Moreover, an interpretation of this type makes it possible to reconcile scientific data from various neurosciences which thus far have seemed contradictory.