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The hippocampus has been implicated in various mood disorders, with global volume deficits consistently found in patient populations. The hippocampus, however, consists of anatomically distinct subfields, and examination of specific subfield differences may elucidate the possible molecular mechanisms behind psychiatric pathologies. Indeed, adult studies have reported smaller hippocampal subfield volumes in regions within the cornu ammonis (CA1 and CA4), dentate gyrus (DG), and hippocampal tails in both patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) compared to healthy controls. Subfield differences in pediatric patients with mood disorders, on the other hand, have not been extensively investigated. In the current study, magnetic resonance imaging scans were acquired for 141 children and adolescents between the ages of eight and eighteen (57 with BD, 30 with MDD, and 54 healthy controls). An automated segmentation method was then used to assess differences in hippocampal subfield volumes. Children and adolescents with BD were found to have significantly smaller volumes in the right CA1, CA4, and right subiculum, as well as the bilateral granule cell layer (GCL), molecular layer (ML), and hippocampal tails. The volume of the right subiculum in BD patients was also found to be negatively correlated with illness duration. Overall, the findings from this cross-sectional study provide evidence for specific hippocampal subfield volume differences in children and adolescents with BD compared to healthy controls and suggest progressive reductions with increased illness duration., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Previous proton magnetic resonance spectroscopy ((1)H MRS) studies have reported elevated glycerophosphocholine plus phosphocholine (GPC+PC) in the basal ganglia of patients with bipolar disorders (BD), which implicates an imbalance between synthesis and degradation activity of neuronal and glia membrane phospholipids (MPLs). However, the full extent of altered metabolites of MPLs in subareas within the basal ganglia, such as caudate and putamen, as well as anterior cingulate cortex (ACC) of BD patients is poorly understood., Methods: Multi-voxel (1)H MRS measurements were acquired in 50 type-one BD (BD-I) and 44 healthy controls (HC) on a 3-T MRI scanner. Four different anatomically defined voxels covering ACC, caudate and putamen were systematically extracted and quantified using LCModel. Group differences in absolute GPC+PC and other metabolites were tested with age and gender as covariates., Results: BD-I patients had higher GPC+PC levels in the anterior-dorsal ACC (p = 0.037), caudate (p = 0.005) and putamen (p = 0.004) compared to HC. GPC+PC levels in the caudate were elevated most significantly in currently unmediated BD-I patients (p = 0.022) and were positively correlated with HAM-D scores (r = 0.51, p = 0.005). PCr+Cr and myo-inositol levels were also significantly higher in the caudate head (F(1,45) = 6.010, p = 0.018) of patients compared to HC. NAA and glutamate levels were not significantly different between BD-I and HC in these regions (p > 0.05)., Conclusion: The increased GPC+PC in BD-I patients may reflect an imbalance in the MPL metabolism. Caudate GPC+PC levels may be a potential biomarker for depressive symptoms in BD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Bipolar disorder (BD) is characterized by affective processing bias and variations in personality traits. It is still unknown whether these features are linked to the same structural brain alterations. The aim of this study was to investigate relationships between specific personality traits, white matter (WM) properties, and affective processing in BD and HC., Methods: 24 healthy controls (HC) and 38 adults with BDI (HC: 29.47 ± 2.23 years, 15 females; BDI: 32.44 ± 1.84 years, 20 females) completed clinical scales and the Big Five Inventory. They were also administered the Affective Go/No-Go (AGN) and the Rapid Visual Processing (RVP) tasks of the Cambridge Neuropsychological Test Automated Battery. Diffusion Tensor Imaging (DTI) assessed the microstructure of WM tracts., Results: In BDI measures of WM properties were reduced across all major brain white matter tracts. As expected, individuals with BDI reported greater neuroticism, lower agreeableness and conscientiousness, and made a greater number of errors in response to affective stimuli in the AGN task compared to HC. High neuroticism scores were associated with faster AGN latency, and overall reduced AGN accuracy in both HC and BDI. Elevated FA values were associated with reduced neuroticism and increased cognitive processing in HC but not in BDI., Conclusions: Our findings showed important potential links between personality, affective processing and WM integrity in BD. In the future therapeutic interventions for BD using brain stimulation protocols might benefit from the use of DTI to target pathways underlying abnormal affective processing., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Bipolar disorder (BD) is a serious mental illness associated with a high risk of medical comorbidities, long-term disability and premature death. This systematic review examined the current literature on therapeutic interventions targeting nutrition, physical activity and wellness in BD and collecting health-related measures such as mood and course of illness., Methods: Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to June 2015, for studies focusing on lifestyle interventions in BD. Search terms were related to bipolar disorder, nutrition, physical activity, wellbeing, psychosocial interventions and course of illness. We hand searched content pages of Bipolar Disorders and Journal of Affective Disorders and checked references of relevant reviews and dissertations to identify additional papers., Results: After applying inclusion and exclusion criteria to identified hits, this literature search retrieved six papers. Overall findings point towards a beneficial role of lifestyle interventions on mood, weight, blood pressure, lipid profile, physical activity and overall wellbeing. Methodological limitations include small sample size, gender ratio imbalance, inconsistencies in terms of laboratory measures, and lack of randomized controlled trials and absence of follow-up and longitudinal studies to determine the benefits of these factors on clinical and functional outcomes over time, Conclusions: Lifestyle interventions in BD targeting nutrition, exercise, wellbeing alongside beliefs, coping strategies and attitudes towards health show promise in reducing the risk of comorbid ailments in BD. There is still a strong need for studies a) developing interventions which are informed by the patient's input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials., (Published by Elsevier Ltd.)

Studies about changes in hippocampal volumes in subjects with bipolar disorder (BD) have been contradictory. Since the number of manic episodes and hospitalization has been associated with brain changes and poor cognitive outcomes among BD patients, we have hypothesized that these variables could clarify this issue. We stratified subjects with BD in early (BD-Early), intermediate (BD-intermediate) and late (BD-Late) stages as a function of number of manic episodes and prior hospitalization. Then, we compared their hippocampal volumes and California Verbal Learning Test-II (CVLT-II) scores with healthy controls (HC) using the general linear model. A total of 173 subjects were included in the study (112 HC, 15 BD-Early, 30 BD-Intermediate, and 16 BD-Late). We found a significant group effect on hippocampus volume (F(3,167) = 3.227, p = 0.024). Post-hoc analysis showed that BD-Late subjects had smaller hippocampus than HC (p = 0.017). BD-Early and BD-Intermediate subjects showed no significant difference in hippocampus volume compared to HC and BD-Late subjects. The CVLT trial 1 to 5 scores were significantly different across the groups (F(3,167) = 6.371, p < 0.001). Post-hoc analysis showed that BD-Intermediate (p = 0.006) and BD-Late (p = 0.017) subjects had worse memory performance during immediate recall than HC, while the performance difference between BD-Early subjects and HC was not significant (p = 0.208). These findings add to the notion that BD is a neuroprogressive disorder with brain changes and cognitive impairment according to prior morbidity (number of manic episodes and hospitalization). Also, they suggest that hippocampus is a brain marker and a potential therapeutic target for patients at late stage., (Published by Elsevier Ltd.)

Accumulating evidence shows abnormal glucose metabolism in schizophrenia, even at the onset of psychosis. This study aims to examine the glucose and lipid metabolism in first-episode and drug naïve (FEDN) patients with schizophrenia and to explore their relationships with psychopathology, which have been under-investigated. Fasting glucose and lipid profiles, as well as homeostasis model of assessment-insulin resistance (HOMA-IR) index were determined in 120 never-medicated first-episode and 31 healthy control subjects matched for gender and age. The schizophrenia symptomatology was assessed by the positive and negative syndrome scale (PANSS). Our results showed that schizophrenia patients had a significantly higher level of fasting plasma glucose (p<0.0001) and insulin (p=0.038). HOMA, an indicator of insulin resistance was higher in the patients than in the healthy controls (p=0.008). No differences were found between the patients and healthy subjects in the levels of plasma triglycerides, high-density lipoprotein, and low-density lipoprotein, except that the cholesterol level was higher in the patients than health subjects (p=0.016). A significant negative association between plasma glucose levels and the PANSS positive symptom subscores was observed (p=0.013). Stepwise multiple regression analysis identified insulin resistance, insulin and the PANSS positive symptom subscore as significant predictor factors for glucose level. These results suggest that abnormal glucose metabolism may be associated with the pathogenesis and psychopathology of schizophrenia in the early phases of the disease process., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Diagnosis of pediatric neuropsychiatric disorders such as unipolar depression is largely based on clinical judgment - without objective biomarkers to guide diagnostic process and subsequent therapeutic interventions. Neuroimaging studies have previously reported average group-level neuroanatomical differences between patients with pediatric unipolar depression and healthy controls. In the present study, we investigated the utility of multiple neuromorphometric indices in distinguishing pediatric unipolar depression patients from healthy controls at an individual subject level., Methods: We acquired structural T1-weighted scans from 25 pediatric unipolar depression patients and 26 demographically matched healthy controls. Multiple neuromorphometric indices such as cortical thickness, volume, and cortical folding patterns were obtained. A support vector machine pattern classification model was 'trained' to distinguish individual subjects with pediatric unipolar depression from healthy controls based on multiple neuromorphometric indices and model predictive validity (sensitivity and specificity) calculated., Results: The model correctly identified 40 out of 51 subjects translating to 78.4% accuracy, 76.0% sensitivity and 80.8% specificity, chi-square p-value = 0.000049. Volumetric and cortical folding abnormalities in the right thalamus and right temporal pole respectively were most central in distinguishing individual patients with pediatric unipolar depression from healthy controls., Conclusions: These findings provide evidence that a support vector machine pattern classification model using multiple neuromorphometric indices may qualify as diagnostic marker for pediatric unipolar depression. In addition, our results identified the most relevant neuromorphometric features in distinguishing PUD patients from healthy controls., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Clinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning., Methods: 49 adult BD patients ((M±SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M±SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity - MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A)., Results: BD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities., Conclusions: The reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Some recent studies show an association between a functional polymorphism of BDNF gene (Val66Met) and the susceptibility to nicotine dependence and we hypothesized that this polymorphism was associated with smoking in both schizophrenia patients and healthy controls. The BDNF Val66Met gene polymorphism was genotyped in 690 chronic male schizophrenia patients (smoker/nonsmoker = 522/169) and 628 male controls (smoker/nonsmoker = 322/306) using a case-control design. Nicotine dependence (ND) was assessed by the cigarettes smoked per day (CPD), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for ND (FTND). Patients also were rated on the Positive and Negative Syndrome Scale (PANSS). The results showed no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls or between smokers and nonsmokers in either patients or healthy controls alone. In patient groups, however, the smokers with the Met allele had significantly higher HSI scores (Met/Met: 2.8 ± 1.7 vs. Met/Val: 2.2 ± 1.7 vs. Val/Val: 2.0 ± 1.6, p < 0.01) and a trend toward a significantly higher FTND score (p = 0.09) than those with the Val/Val genotype. In addition, the smokers showed significantly lower PANSS negative symptom and total scores, longer duration of illness and more hospitalizations (all p < 0.05). In the control group, the smokers with the Met allele started smoking significantly earlier than those with the Val/Val genotype (both p < 0.05). These results suggest that the BDNF Val66Met polymorphism may affect a smoker's response to nicotine in both schizophrenia and healthy controls from a Chinese Han population, but with differential effects in different aspects of smoking behaviors., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Neurodegenerative processes may be involved in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin and oxidative stress (OS) may be critical for several pathological manifestations of neurodegenerative disorders. Accumulating evidence suggests that both BDNF and OS may be involved in the pathophysiology of schizophrenia. However, the possible interaction between BDNF and OS has been under-investigated. Serum BDNF, plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 164 chronic medicated schizophrenia and 50 healthy controls. Schizophrenic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive and depressive factors derived from the five factor model of the PANSS. Compared to the control group, the patients exhibited a significant decrease in BDNF levels, in the activities of SOD and GSH-Px but a significant increase in MDA levels. In patients, but not in controls, we observed a significant negative correlation between BDNF and SOD. Furthermore, the interaction between BDNF and CAT was associated with the PANSS cognitive factor, and the interaction between BDNF and GSH-Px with the PANSS depressive factor. Both decreased BDNF levels and OS may be implicated in the pathophysiology of chronic schizophrenia. Their inverse association only in the schizophrenia group may reflect a pathological mechanism involving an interaction of oxidative damage and neurotrophin dysfunction. Moreover, OS may interact with the BDNF system to influence the clinical symptoms and cognitive impairment in schizophrenia, which is line with the neurodevelopmental hypothesis of schizophrenia., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Bipolar disorder (BD) is a devastating disorder with a strong genetic component. While the frontolimbic profile of individuals suffering from BD is relatively well-established, there is still disagreement over the neuroanatomical features of unaffected BD offspring., Material and Methods: Brain volumetric measures were obtained for 82 children and adolescents including 18 unaffected BD offspring (10.50 ± 3.37 years), 19 BD offspring suffering from psychiatric disorders (12.87 ± 3.28 years) and 45 healthy controls (HC-10.50 ± 3.37 years). Clinical diagnoses were established according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis suite. Profile analyses compared frontolimbic volumes across groups. Age, gender, testing site, ethnicity and intracranial volume were entered as covariates., Results: The right amygdala was significantly larger in unaffected BD offspring compared to BD offspring with psychiatric disorders and HC. Volumes of striatal, hippocampal, cingulate, and temporal regions were comparable across groups., Discussion: The size of the amygdala may be a marker of disease susceptibility in offspring of BD parents. Longitudinal studies are needed to examine rates of conversion to BD as related to specific pre-morbid brain abnormalities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Bipolar disorder (BD) patients present a 3-5 fold greater risk of developing type 2 diabetes (T2D) compared to general population. The underlying mechanisms for the increased prevalence of T2D in BD population are poorly understood., Objectives: The purpose of this review is to critically review evidence suggesting that inflammation may have an important role in the development of both BD and T2D., Results: The literature covered in this review suggests that inflammatory dysregulation take place among many BD patients. Such dysregulated and low grade chronic inflammatory process may also increase the prevalence of T2D in BD population. Current evidence supports the hypothesis of dysregulated inflammatory processes as a critical upstream event in BD as well as in T2D., Conclusions: Inflammation may be a factor for the development of T2D in BD population. The identification of inflammatory markers common to these two medical conditions will enable researchers and clinicians to better understand the etiology of BD and develop treatments that simultaneously target all aspects of this multi-system condition., (Copyright © 2014. Published by Elsevier Inc.)

While numerous studies have reported that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia, very few studies have explored its association with cognitive impairment or gender differences in schizophrenia which we explored. We compared gender differences in 248 chronic schizophrenic patients (male/female=185/63) to 188 healthy controls (male/female=98/90) on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Our results showed that schizophrenic patients performed worse than normals on most of the cognitive tasks, and male patients had significantly lower immediate memory and delayed memory scores than female patients. BDNF levels were significantly lower in patients than controls, and male patients had significantly lower BDNF levels than female patients. For the patients, BDNF was positively associated with immediate memory and the RBANS total score. Furthermore, these associations were only observed in female not male patients. Among healthy controls, no gender difference was observed in cognitive domains and BDNF levels, or in the association between BDNF and cognition. Our results suggest gender differences in cognitive impairments, BDNF levels and their association in chronic patients with schizophrenia. However, the findings should be regarded as preliminary due to the cross-sectional design and our chronic patients, which need replication in a first-episode and drug naïve patients using a longitudinal study., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: The subgenual prefrontal cortex (SGPFC) is an important brain region involved in emotional regulation and reward mechanisms. Volumetric abnormalities in this region have been identified in adults with bipolar disorder but thus far not in pediatric cases. We examined the volume of this brain region in subjects with pediatric bipolar disorder (PBD) and compared them to healthy controls., Methods: Fifty one children and adolescents (mean age ± SD; 13.2 ± 2.9 y) with DSM-IV PBD and 41 (mean age ± SD; 13.7 ± 2.7 y) healthy comparison subjects (HC) underwent 1.5 T structural magnetic resonance imaging (MRI) brain scans. We traced the SGPFC manually and compared SGPFC gray matter volumes using analysis of covariance with age, gender, and intracranial volume as covariates. We also examined the relationship of family history of affective disorders and medication status to SGPFC volumes., Results: SGPFC volumes were not significantly different in PBD and HC subjects. However, exploratory analysis showed PBD subjects who had one or more first degree relatives with mood disorders (n = 33) had significantly smaller left hemisphere SGPFC compared to HC (p = 0.03 Sidak corrected). Current usage of a mood stabilizer was significantly associated with larger right SGPFC volume in PBD (F = 4.82, df = 1/41, p = 0.03)., Conclusion: Subjects with PBD and a close family history of mood disorders may have smaller left SGPFC volumes than HC. Mood stabilizing medication may also impact SGPFC size and could have masked more subtle abnormalities overall., (Copyright © 2010 Elsevier Ltd. All rights reserved.)