Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring

Background. A consistent association between paternal age and their offspring`s risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring`s risk of BPAD, whereas maternal age is not. Method. This population-based cohort study was conducted with individuals born in Sweden during 1973-1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox`s proportional hazard regression. Results. After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (Cl) 1.11-1.48], but this fell to 1.20 (95% CI 0.97-1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08-1.56) before adjustment for paternal age, HR 1.12 (95% Cl 0.86-1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01-1.57) and it was 1.45 (95%, CI 1.16-1.81) if both parents were >30 years. Conclusions. Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.

Assessment of Personality Dimensions in Children and Adolescents with Bipolar Disorder Using the Junior Temperament and Character Inventory

Objective: We compared temperament and character traits in children and adolescents with bipolar disorder (BP) and healthy control (HC) subjects. Method: Sixty nine subjects (38 BP and 31 HC), 8-17 years old, were assessed with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime. Temperament and character traits were measured with parent and child versions of the Junior Temperament and Character Inventory. Results: BP subjects scored higher on novelty seeking, harm avoidance, and fantasy subscales, and lower on reward dependence, persistence, self-directedness, and cooperativeness compared to HC(all p < 0.007), by child and parent reports. These findings were consistent in both children and adolescents. Higher parent-rated novelty seeking, lower self-directedness, and lower cooperativeness were associated with co-morbid attention-deficit/hyperactivity disorder (ADHD). Lower parent-rated reward dependence was associated with co-morbid conduct disorder, and higher child-rated persistence was associated with co-morbid anxiety. Conclusions: These findings support previous reports of differences in temperament in BP children and adolescents and may assist in a greater understating of BP children and adolescents beyond mood symptomatology.

Clinical correlates of eating disorder comorbidity in women with bipolar disorder type I

Objective: To report on the presence of current and lifetime eating disorders (ED) in a well-defined sample of 137 female individuals with bipolar disorder type I. Methods: Trained psychiatrists interviewed the patients, and the diagnoses of BD and comorbidities were confirmed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis I Disorders. Clinical and demographic characteristics of both groups (group with ED vs. group without ED) were compared. Results: Female patients with ED had an earlier onset of BD and an increased number of mood episodes, predominantly depressive. Women in the ED group also had higher rates of comorbidity with substance use disorders and anxiety disorders and reported a history of suicide attempts more frequently than women without ED. Conclusion: The presence of ED is a correlate of severity of BD type 1, and interventions should be developed to minimize distress and suicide risk and to improve treatment outcome. (C) 2010 Elsevier B.V. All rights reserved.

Morphology of the subgenual prefrontal cortex in pediatric bipolar disorder

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 = 003 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 (C) 2010 Elsevier Ltd All rights reserved

Latent class analysis of manic and depressive symptoms in a population-based sample in Sao Paulo, Brazil

Background: Current diagnostic criteria cannot capture the full range of bipolar spectrum. This study aims to clarify the natural co-segregation of manic-depressive symptoms occurring in the general population. Methods: Using data from the Sao Paulo Catchment Area Study, latent class analysis (LCA) was applied to eleven manic and fourteen depressive symptoms assessed through CIDI 1.1 in 1464 subjects from a community-based study in Sao Paulo, Brazil. All manic symptoms were assessed, regardless of presence of euphoria or irritability, and demographics, services used, suicidality and CIDI/DSM-IIIR mood disorders used to external validate the classes. Results: The four obtained classes were labeled Euthymics (EU; 49.1%), Mild Affectives (MA; 31.1%), Bipolars (BIP; 10.7%), and Depressives (DEP; 9%). BIP and DEP classes represented bipolar and depressive spectra, respectively. Compared to DEP class, BIP exhibited more atypical depressive characteristics (hypersomnia and increase in appetite and/or weight gain), risk of suicide, and use of services. Depressives had rates of atypical symptoms and suicidality comparable to oligosymptomatic MA class subjects. Limitations: The use of lay interviewers and DSM-IIIR diagnostic criteria, which are more restrictive than the currently used DSM-IV TR. Conclusions: Findings of high prevalence of bipolar spectrum and of atypical symptoms and suicidality as indicators of bipolarity are of great clinical importance, due to different treatment needs, and higher severity. Lifetime sub-affective and syndromic manic symptoms are clinically significant, arguing for the need Of revising DSM bipolar spectrum categories. (C) 2009 Elsevier B.V. All rights reserved.

Family Environment and Pediatric Major Depressive Disorder

Background: The risks for depression broadly include biological and environmental factors. Furthermore, having a family member suffering from major depression is also likely to have consequences for the family environment. Further research aimed at understanding the effects of having a child with major depression on family interaction patterns is warranted. Methods: We studied 31 families with an 8- to 17-year-old child (mean age +/- SD = 12.9 +/- 2.7 years) who met the DSM-IV criteria for major depressive disorder (MDD) and 34 families with no mentally ill children (mean age 8 SD = 12.6 +/- 2.9 years) or parents. Children and their parents were assessed with the K-SADS-PL (Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version) interview. Parents completed the Moos Family Environment Scale (FES) to assess their perceptions of current family functioning. Data were analyzed using the nonparametric Wilcoxon-Mann-Whitney test. Results: Families of MDD children showed significantly different patterns of family functioning on FES subscales representing relationships and personal growth dimensions. The families with MDD children showed higher levels of conflict (p < 0.001) and lower levels of cohesion (p < 0.001), expressiveness (p = 0.003) and active-recreational orientation (p = 0.02) compared to the families without mentally ill children. Conclusion: Families with MDD children show a lower degree of commitment, provide less support to one another, provide less encouragement to express feelings and have more conflicts compared to families with no mentally ill children or parents. Interventions aimed at improving family dynamics may be beneficial to MDD children and their families. Copyright (C) 2010 S. Karger AG, Basel

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BID individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD. (C) 2009 Elsevier B.V. All rights reserved.

Amygdala hyperactivation in untreated depressed individuals

The amygdala participates in the detection and control of affective states, and has been proposed to be a site of dysfunction in affective disorders. To assess amygdala processing in individuals with unipolar depression, we applied a functional MRI (fMRI) paradigm previously shown to be sensitive to amygdala function. Fourteen individuals with untreated DSM-IV major depression and 15 healthy subjects were studied using fMRI with a standardized emotion face recognition task. Voxel-level data sets were subjected to a multiple-regression analysis, and functionally defined regions of interest (ROI), including bilateral amygdala, were analyzed with MANOVA. Pearson correlation coefficients between amygdala activation and HAM-D score also were performed. While both depressed and healthy groups showed increased amygdala activity when viewing emotive faces compared to geometric shapes, patients with unipolar depression showed relatively more activity than healthy subjects, particularly on the left. Positive Pearson correlations between amygdala activation and HAM-D score were found for both left and right ROIs in the patient group. This study provides in vivo imaging evidence to support the hypothesis of abnormal amygdala functioning in depressed individuals. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A Neuropsychological Study Comparing Patients Infected With HCV and HBV Without Psychiatric Comorbidities

Hepatitis C is one of the most common chronic infectious diseases worldwide, with well-documented extra-hepatic manifestations, such as a broad number of cognitive deficits. These impairments may be explained by psychiatric comorbidities, which have not been investigated properly in the literature. In order to elucidate a specific hepatitis C virus (HCV) induced cognitive impairment not related to mental disorders, neuropsychological performance of patients infected with HCV was compared with that of patients infected with hepatitis B virus cognitive impairment, especially psychiatric comorbidities. A total of 33 patients infected with HCV and 22 patients infected with HBV were included in the study. There were no significant differences between the two groups with regard to age or years of education. The group of patients infected with HCV performed significantly worse on visuo-spatial memory tasks after adjusting for years of education and age. There were no significant differences between patients infected with HCV and patients infected with HBV with regards to other neuropsychological functions. The data indicate that patients infected with HCV patients have poorer visuo-spacial memory performance than patients infected with HBV, suggesting that the cognitive deficit may be specific to HCV infection and not to secondary comorbid psychiatric disorders. J. Med. Virol. 81: 1184-1188, 2009. (C) 2009 Wiley-Liss, Inc.

Suicide behavior and neuropsychological assessment of type I bipolar patients

Background: Neuropsychological deficits are often described in patients with bipolar disorder (BID). Some symptoms and/or associated characteristics of BD can be more closely associated to those cognitive impairments. We aimed to explore cognitive neuropsychological characteristics of type I bipolar patients (BPI) in terms Of lifetime Suicide attempt history. Method: We studied 39 BPI Outpatients compared with 53 healthy controls (HC) matched by age, educational and intellectual level. All Subjects were submitted to a neuropsychological assessment of executive functions, decision-making and declarative episodic memory. Results: When comparing BD1 patients, regardless of suicide attempt history or HC, we observed that bipolar patients performed worse than controls oil measures of memory, attention, executive functions and decision-making, Patients with a history of suicide attempt performed worse than non-attempters on measures of decision-making and there were a significant negative correlation between the number of suicide attempts and decision-making results (block 3 and net score). We also found significant Positive correlation between the number Of Suicide attempts and amount Of errors in Stroop Color Word Test (part 3). Limitations: The sample Studied call be considered small and a potentially confounding variable - medication status - were not controlled. Conclusion: Our results show the presence of neuropsychological deficits in memory, executive functions, attention and decision-making in BPI patients. Suicide attempts BPI scored worse than non-suicide attempt Bill oil measures of decision-making. More suicide attempts were associated with a worse decision-making process. Future research should explore the relationship between the association between this specific cognitive deficits in BPIs, serotonergic function and suicide behavior in bipolar patients as well other diagnostic groups. (C) 2009 Elsevier B.V. All rights reserved.

Brain structure and symptom dimension relationships in obsessive-compulsive disorder: A voxel-based morphometry study

Background: Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. Methods: GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. Results: Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls > patients), and bilateral midbrain (patients > controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. Limitations: The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. Conclusions: These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples. (C) 2008 Elsevier B.V. All rights reserved.

Abnormal corpus callosum myelination in pediatric bipolar patients

Background: Decreased signal intensity in the corpus callosum, reported in adult bipolar disorder patients, has been regarded as an indicator of abnormalities in myelination. Here we compared the callosal signal intensity of children and adolescents with bipolar disorder to that of matched healthy subjects, to investigate the hypothesis that callosal myelination is abnormal in pediatric bipolar patients. Methods: Children and adolescents with DSM-lV bipolar disorder (n=16, mean age +/- S.D. = 15.5 +/- 3.4 y) and matched healthy comparison subjects (n=21, mean age +/- S.D.=16.9 3.8 y) underwent a 1.5 T MRI brain scan. Corpus callosuin signal intensity was measured using an Apple Power Mac G4 running NIH Image 1.62 software. Results: Bipolar children and adolescents had significantly lower corpus callosum signal intensity for all callosal sub-regions (genu, anterior body, posterior body, isthmus and splenium) compared to healthy subjects (ANCOVA, all p < 0.05, age and gender as covariates). Limitations: Relatively small sample size. Conclusions: Abnormalities in corpus callosum, probably due to altered myelination during neurodevelopment, may play a role in the pathophysiology of bipolar disorder among children and adolescents. (c) 2007 Elsevier B.V All rights reserved.

Family environment patterns in families with bipolar children

Background: We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). Methods: We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Results: Parents of bipolar children reported lower levels of family cohesion (p<0.001), expressiveness (p=0.005), active-recreational orientation (p<0.001), intellectual-cultural orientation (p=0.04) and higher levels of conflict (p<0.001) compared to parents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.03 1) and cohesion (p=0.014) in families where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Limitations: Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Conclusion: Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder. (C) 2007 Elsevier B.V. All rights reserved.

Effect of antidepressants on melatonin metabolite in depressed patients

Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients - most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo (n = 12) or antidepressant (n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 +/- 1.4 vs. 9.0 +/- 2.8, P = 0.007 for placebo, and 18.6 +/- 1.1 vs. 11.8 +/- 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants (P < 0.01), but not after placebo (P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.

Symptomatic expression of depression among Jewish adolescents: effects of gender and age

Background Depression symptomatology was assessed with the Beck Depression Inventory (BDI) in a sample of Jewish adolescents, in order to compare the frequency and severity of depression with non-Jewish adolescents as well as examine gender difference of the expression of depressive symptomatology. Method Subjects comprised 475 students from Jewish private schools, aged 13-17 years, who were compared with an age-matched non-Jewish sample (n = 899). Kendall`s definition was adopted to classify these adolescents according to level of depressive symptoms. The frequency of depression was calculated for ethnicity, gender and age strata. Discriminant analysis and principal component analysis were performed to assess the importance of depression-specific and non-specific items, along with the factor structure of the BDI, respectively. Results The overall mean score on the BDI in the Jewish and the non-Jewish sample was 9.0 (SD = 6.4) and 8.6 (SD = 7.2), respectively. Jewish girls and boys had comparable mean BDI scores, contrasting with non-Jewish sample, where girls complained more of depressive symptoms than boys (p < 0.001). The frequency of depression, adopting a BDI cutoff of 20, was 5.1% for the Jewish sample and 6.3% for the non-Jewish sample. The frequency of depression for Jewish girls and boys was 5.5% (SE = 1.4) and 4.6% (SE = 1.5), respectively. On the other hand, the frequency of depression for non-Jewish girls and boys was 8.4% (SE = 1.2) and 4.0% (SE = 1.0), respectively. The female/male ratio of frequency of BDI-depression was 1.2 in the Jewish sample, but non-Jewish girls were twice (2.1) as likely to report depression as boys. Discriminant analysis showed that the BDI highly discriminates depressive symptomatology among Jewish adolescents, and measured specific aspects of depression. Factor analysis revealed two meaningful factors for the total sample and each gender (cognitive-affective dimension and somatic dimension), evidencing a difference between Jewish boys and Jewish girls in the symptomatic expression of depression akin to non-Jewish counterparts. Conclusions Ethnic-cultural factor might play a role in the frequency, severity and symptomatic expression of depressive symptoms in Jewish adolescents. The lack of gender effect on depression, which might persist from adolescence to adulthood among Jewish people, should be investigated in prospective studies.