The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case–Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.     

Childhood attention deficit hyperactivity disorder features in adult mood disorders

A significant overlap between childhood mood disorders and many aspects of attention deficit hyperactivity disorder (ADHD) has been established. High rates of co-occurrence, familial aggregation, and more severe clinical manifestations of the illnesses when they are comorbid suggest that common genetic and environmental factors may contribute to the development of both disorders. Research on the co-occurrence of childhood ADHD and mood disorders in childhood has been conducted. We retrospectively investigated childhood ADHD features in adults with mood disorders. Childhood ADHD features were measured with the Korean version of the Wender Utah Rating Scale (WURS). The sample consisted of 1305 subjects: 108 subjects were diagnosed with bipolar disorder type I, 41 with bipolar disorder type II, 101 with major depressive disorder, and 1055 served as normal controls. We compared total WURS scores as well as scores on 3 factors (impulsivity, inattention, and mood instability and anxiety) among the 4 different diagnostic groups. The 4 groups differed significantly from one another on all scores. The group with bipolar disorder type II obtained the highest total scores on the WURS. The impulsivity and inattention associated with childhood ADHD were more significantly related to bipolar disorder type II than with bipolar disorder type I. The mood instability and anxiety associated with childhood ADHD seem to be significantly related to major depressive disorder in adulthood. In conclusion, multifactorial childhood ADHD features were associated with mood disorders of adulthood.     

Affective instability and impulsivity in borderline personality and bipolar II disorders: similarities and differences

Objectives: many studies have reported a high degree of comorbidity between mood disorders, among which are bipolar disorders, and borderline personality disorder and some studies have suggested that these disorders are co-transmitted in families. However, few studies have compared personality traits between these disorders to determine whether there is a dimensional overlap between the two diagnoses. The aim of this study was to compare impulsivity, affective lability and intensity in patients with borderline personality and bipolar II disorder and in subjects with neither of these diagnoses. Methods: patients with borderline personality but without bipolar disorder (n=29), patients with bipolar II disorder without borderline personality but with other personality disorders (n=14), patients with both borderline personality and bipolar II disorder (n=12), and patients with neither borderline personality nor bipolar disorder but other personality disorders (OPD; n=93) were assessed using the Affective Lability Scale (ALS), the Affect Intensity Measure (AIM), the Buss–Durkee Hostility Inventory (BDHI) and the Barratt Impulsiveness Scale (BIS-7B). Results: borderline personality patients had significantly higher ALS total scores (P<0.05) and bipolar II patients tended to have higher ALS scores than patients with OPD (P<0.06). On one of the ALS subscales, the borderline patients displayed significant higher affective lability between euthymia and anger (P<0.002), whereas patients with bipolar II disorder displayed affective lability between euthymia and depression (P<0.04), or elation (P<0.01) or between depression and elation (P<0.01). A significant interaction between borderline personality and bipolar II disorder was observed for lability between anxiety and depression (P<0.01) with the ALS. High scores for impulsiveness (BISTOT, P<0.001) and hostility (BDHI, P<0.05) were obtained for borderline personality patients only and no significant interactions between diagnoses were observed. Only borderline personality patients tended to have higher affective intensity (AIM, P<0.07). Conclusions: borderline personality disorder and bipolar II disorder appear to involve affective lability, which may account for the efficacy of mood stabilizers treatments in both disorders. However, our results suggest that borderline personality disorder cannot be viewed as an attenuated group of affective disorders.     

Bipolar disorder and comorbid attention deficit hyperactivity disorder. A distinct clinical phenotype? Clinical characteristics and temperamental traits1

Abstract

Objectives. It has been suggested that bipolar disorder (BD) with comorbid ADHD represents a distinct clinical phenotype of BD. There are no data regarding potential heterogeneity between BD subjects with a diagnosis of ADHD in childhood whose ADHD remitted in adulthood (cADHD-BD) vs. BD patients with persistent ADHD diagnosis in adulthood (aADHD-BD). This heterogeneity may constitute a confounder in investigations of the nature of the co-occurrence between BD and ADHD. The aim of this paper is to compare BD patients without ADHD, to those with aADHD-BD, and those with cADHD-BD on clinical and temperamental characteristics, hypothesizing that maladaptive temperament will be increased in BD subjects with a stable diagnosis of ADHD in adulthood compared to those whose ADHD remitted. We further hypothesize that maladaptive temperament will be associated with the severity of both illnesses. Methods. A total of 100 outpatients (aged 18–30 years) with BD in remission were included. The assessment of ADHD was made according to a procedure aimed to reduce potential recall biases. Subjects had to have a parent available and had never been treated with stimulants. Temperamental traits were assessed with the California Child Q-sort (CCQ) and the Early Adolescent Temperament Questionnaire (EATQ). Results. Rate of co-occurrence of ADHD-BD was 18% lifetime and 10% current diagnosis. Patients with ADHD-BD (aADHD-BD+cADHD-BD) reported a significantly earlier onset of mood disorder, higher number of previous mood episodes, and significantly higher impulsivity than BD patients without ADHD. aADHD-BD showed a significantly earlier BD onset, higher number of previous mood episodes, higher impulsivity, decreased Reactive Control and higher Negative Emotionality temperamental scores than cADHD patients. Conclusion. Findings suggest that patients with aADHD-BD present a clinical phenotype distinct from that of patients with BD without ADHD or with a childhood ADHD diagnosis that remitted with the age. This appealing hypothesis of a BD-distinct phenotype that can be detected early due to its associated maladaptive temperamental traits requires further investigation in larger samples, supported by neuropsychological, genetic and imaging data.     

A functional dopamine-β-hydroxylase gene promoter polymorphism is associated with impulsive personality styles,but not with affective disorders

Dopamine-beta-hydroxylase (DbetaH) catalyzes the conversion of dopamine to norepinephrine in central noradrenergic and adrenergic neurons and thus is critically involved in the biosynthesis of catecholamines. There are equivocal findings concerning the question whether or not DssH activity levels are altered in affective disorders or in subtypes of affective disorders. Moreover, information about the role of dopamine beta-hydroxylase (DBH) genotype, which explains a large part of the variance of enzymatic activity, in affective disorders and personality dimensions is limited. To resolve these inconsistencies, association tests were performed using four independent samples, healthy volunteers (N = 387), patients with affective disorders (N = 182), adult attention deficit hyperactivity disorder (ADHD) patients (N = 407), and patients with personality disorders (N = 637). In the latter two samples, the revised NEO personality inventory (NEO-PI-R) was administered. All participants were genotyped for a putatively functional single nucleotide polymorphism (C-1021T, rs1611115). No differences in DBH C-1021T genotype distribution were observed between patients with affective disorders and healthy control subjects. Also when the patient sample was divided into uni- and bipolar patients versus controls, no significant differences emerged. Furthermore, no clear-cut association was detected between the TT genotype and personality disorder clusters while there was a significant association with adult ADHD. However, personality disorder patients carrying the DBH TT genotype exhibited higher neuroticism and novelty seeking scores as compared to individuals with the CC or CT genotype. Analyses on the level of the neuroticism and novelty seeking subscales revealed that the DBH TT genotype was primarily associated with personality features related to impulsiveness and aggressive hostility. Also adult ADHD patients carrying the homozygous TT genotypes displayed by significantly increased neuroticism scores; when both personality disorder and adult ADHD patient were analyzed together, TT carriers also displayed by significantly lower conscientiousness levels. Our results thus do not implicate the DBH C-1021T polymorphism in the pathophysiology of depressive disorders or personality disorders, yet homozygosity at this locus appears to increase the risk towards personality traits related to impulsiveness, aggression and related disease states, namely adult ADHD. These data argue for a dimensional rather than categorical effect of genetic variance in DBH activity; accordingly, the inconsistency of previous findings concerning DbetaH levels in affective disorders might be caused by the underlying association of the TT genotype at DBH-1021 with impulsive personality traits.     

Bipolar obsessive-compulsive disorder and personality disorders

OBJECTIVES: Relatively few systematic data exist on the clinical impact of bipolar comorbidity in obsessive-compulsive disorder (OCD) and no studies have investigated the influence of such a comorbidity on the prevalence and pattern of Axis II comorbidity. The aim of the present study was to explore the comorbidity of personality disorders in a group of patients with OCD and comorbid bipolar disorder (BD). METHODS: The sample consisted of 204 subjects with a principal diagnosis of OCD (DSM-IV) and a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score>or=16 recruited from all patients consecutively referred to the Anxiety and Mood Disorders Unit, Department of Neuroscience, University of Turin over a period of 5 years (January 1998-December 2002). Diagnostic evaluation and Axis I comorbidities were collected by means of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Personality status was assessed by using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). Socio-demographic and clinical features (including Axis II comorbidities) were compared between OCD patients with and without a lifetime comorbidity of BD. RESULTS: A total of 21 patients with OCD (10.3%) met DSM-IV criteria for a lifetime BD diagnosis: 4 (2.0%) with BD type I and 17 (8.3%) with BD type II. Those without a BD diagnosis showed significantly higher rates of male gender, sexual and hoarding obsessions, repeating compulsions and lifetime comorbid substance use disorders, when compared with patients with BD/OCD. With regard to personality disorders, those with BD/OCD showed higher prevalence rates of Cluster A (42.9% versus 21.3%; p=0.027) and Cluster B (57.1% versus 29.0%; p=0.009) personality disorders. Narcissistic and antisocial personality disorders were more frequent in BD/OCD. CONCLUSIONS: Our results point towards clinically relevant effects of comorbid BD on the personality profiles of OCD patients, with higher rates of narcissistic and antisocial personality disorders in BD/OCD patients.     

Comorbidity of adult attention-deficit hyperactivity disorder and bipolar disorder: prevalence and clinical correlates

The aim of this study was to determine the frequency of adult attention deficit hyperactivity disorder (ADHD) comorbidity with lifetime bipolar disorder, and the influence of this comorbidity on various demographic and clinical variables in patients. Patients (n = 159) with a previous diagnosis of bipolar disorder (79 female, 80 male) were included in this study. All patients were interviewed for the presence of current adult and childhood ADHD diagnosis and other axis I psychiatric disorder comorbidities using the structured clinical interview for DSM-IV (SCID) and the Schedule for Affective Disorders and Schizophrenia for School Age Children—Present and Lifetime Version (K-SADS-PL). The subjects also completed a Wender Utah rating scale (WURS-25) and a Current Symptoms Scale for ADHD symptoms. In particular, patients’ clinical characteristics, the age of onset of bipolar disorder, and the number of episodes were noted. Twenty-six of the 159 bipolar patients (16.3%) were diagnosed with adult ADHD, while another subgroup of patients (n = 17, 10.7%) received a diagnosis of childhood ADHD but did not fulfill criteria for adult ADHD. Both of these two subgroups (patients with adult ADHD, and patients with only childhood ADHD) had an earlier age of onset of the disease and a higher number of previous total affective or depressive episodes than those without any lifetime ADHD comorbidity. However only bipolar patients with adult ADHD comorbidity had higher lifetime comorbidity rates for axis I psychiatric disorders, such as panic disorder and alcohol abuse/dependence, compared to patients without lifetime ADHD. Bipolar patients with comorbid adult ADHD did not differ from bipolar patients with comorbid childhood ADHD in terms of any demographic or clinical variables except for adult ADHD scale scores. In conclusion, ADHD is a common comorbidity in bipolar patients, and it adversely affects the course of the disease and disrupts the social adjustment of the patients. Regular monitoring of ADHD will help to prevent problems and complications that could arise in the course of the disease, particularly in patients with early onset bipolar disorder.     

A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders

Mantere O, Isometsä E, Ketokivi M, Kiviruusu O, Suominen K, Valtonen HM, Arvilommi P, Leppämäki S. A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders.
Bipolar Disord 2010: 12: 271–284. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood. Methods: In the Jorvi Bipolar Study (JoBS), 191 secondary‐care outpatients and inpatients with DSM‐IV bipolar I disorder (BD‐I) or bipolar II disorder (BD‐II) were evaluated with the Structured Clinical Interview for DSM‐IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD‐I, 79 BD‐II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM‐IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM‐IV‐based scales of substance use and eating disorders. Results: In the SEM, depression and anxiety exhibited strong cross‐sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16–0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15–0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001). Conclusions: Depression and anxiety covary strongly cross‐sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.     

Concomitants of family histories of mood disorders and alcoholism in a clinical cohort of patients with bipolar I and II disorder

We diagnosed 191 secondary-care outpatients and inpatients with DSM-IV BD I or II. Sociodemographic and clinical characteristics, including axis I and II comorbidity, neuroticism, and prospective life-chart were evaluated at intake and at 6 and 18 months. The family history (FH) of mood disorders, alcoholism, or any major psychiatric disorders among first-degree relatives was investigated in a semistructured interview. Most (74%) patients had some positive FH; 55% of mood disorder, 36% of alcoholism. Positive FH was associated with psychiatric comorbidity and depressive course in the proband. Based on a multinomial logistic regression model, patients with an FH of mood disorder and alcoholism had an odds ratio of 4.8 (p = 0.001) for having an anxiety disorder. Overall, the first-degree relatives of patients with BD have multiple types of mental disorders, which correlate with bipolar patients' course of illness and psychiatric comorbidity. The strongest associations are between FH of mood disorders and presence of comorbid anxiety disorders.     

Comparison of clinical characteristics of bipolar and depressive disorders in Korean clinical sample of youth: a retrospective chart review

The purpose of this study was to compare the clinical characteristics of bipolar disorder I, II (BD I and II) and not otherwise specified (BD NOS) to those of major depressive disorder (MDD) in a clinical sample of Korean children and adolescents. This study was a cross-sectional review of longitudinal observational data. Two psychiatrists retrospectively reviewed the medical records of 198 children and adolescents (age 6–18) that were diagnosed as having bipolar or depressive disorders from March 2010 to February 2012 at Department of Psychiatry of Asan Medical Center, Seoul, Korea. Every subject’s diagnoses were reviewed and confirmed. BD I, II and MDD were assessed according to the Diagnostic and Statistical Manual-IV criteria. BD NOS was defined based on the criteria for the Course and Outcome of Bipolar Youth study. Comparisons were made in demographic information, clinical characteristics, family history, and psychiatric comorbidities at baseline and during observation. Among 198 subjects, 20 (10.1 %) subjects were diagnosed as having BD I, 10 (5.1 %) as BD II, 25 (12.6 %) as BD NOS and 143 (73.7 %) as MDD. BD depression was associated with mood change while taking an antidepressant, familial bipolarity, aggressive behaviors, and atypical features. Comorbid obsessive–compulsive disorder tended to be higher in BD NOS than in MDD. Presence of psychosocial stressors was more common in MDD than in BD depression. In children and adolescents, bipolar depression is distinct from unipolar depression in family history, comorbidity, and clinical characteristics.     

Bipolar disorder risk alleles in children with ADHD

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a ‘genome-wide significance’ level of α = 5 × 10^?8. A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.     

Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period

Bipolar disorders are usually defined by alternative mood states, but a more precise characterization of the euthymic period could provide further insights into the pathophysiology of bipolar disorders. Surprisingly, few studies have investigated core affective dimensions in euthymic bipolar patients. In this study, we assessed 179 euthymic bipolar patients (score < 12 on the Montgomery-Åsberg Depression Scale and a score < 6 on the Bech–Rafaelsen Mania Scale) compared with 86 control subjects using French versions of the Affective Lability Scale (ALS) and the Affect Intensity Measure (AIM). Data were analyzed by logistic regression. Our results showed that euthymic bipolar subjects reported having more intense emotions than controls and also had a higher affective lability. High scores in both affective dimensions were associated with a significantly higher risk for psychiatric axis I comorbidity. Moreover, a high affective lability score was associated with an earlier age of onset for bipolar disease. Affective lability and affect intensity might be two core dimensions of bipolar disorder during euthymic periods, suggesting that bipolar disorder is not circumscribed to mood episodes but also affects emotional reactivity between episodes. Both dimensions could account for the stress reactivity of bipolar patients that may lead to relapses.     

Chemokines in bipolar disorder: Trait or state?

Recent evidence has suggested that inflammatory and immune mechanisms may play a role in the pathophysiology of bipolar disorder (BD). Only a few studies have assessed the profile of chemokines, a family of chemotactic cytokines related to the recruitment of leukocytes, in BD. The objective of our study was to evaluate the plasma levels of chemokines in BD patients in different mood states in comparison with healthy controls. Seventy BD type I patients (35 in euthymia and 35 in mania), and 50 healthy controls matched by age, gender, and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001), CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic regression stressed the main effect of increased plasma levels of CXCL10 (OR = 1.009, 95 % CI = 1.000–1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001–1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI = 0.990–0.999, p = 0.013) to BD. This study reinforces the view that BD is associated with an immune dysfunction.     

Juvenile bipolar disorder in Brazil: clinical and treatment findings.

BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.     

Can Psychological,Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia?

Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5–1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.     

The role of white matter in personality traits and affective processing in bipolar disorder

BackgroundBipolar 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.Methods24 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.ResultsIn 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.ConclusionsOur 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.     

Externalizing disorders in consecutively referred children and adolescents with bipolar disorder

We describe a consecutive clinical sample of children and adolescents with bipolar disorder (BD), in order to define the pattern of comorbid externalizing disorders and to explore the possible influence of such a comorbidity on their cross-sectional and longitudinal clinical characteristics. The sample consisted of 59 bipolar patients: 35 males and 24 females, with a mean age 14.6 +/- 3 years (range, 7 to 18 years), diagnosed as either type I or II according to DSM-IV. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). Severity and subsequent outcome of the symptomatology were recorded with the Clinical Global Impression (CGI), Severity and Improvement Scales, at the baseline and thereafter monthly for a period up to 48 months. BD disorder type I was present in 37 (62.7%) of the patients; 14 (23.7%) were affected by attention deficit-hyperactivity disorder (ADHD) and 10 (16.9%) by conduct disorder (CD). Comorbid ADHD was associated with an earlier onset of BD, while CD was highly associated with BD type I. Anxiety disorders appeared more represented in patients without CD. At the end of the observation, a lower clinical improvement was recorded in patients with CD. In our children and adolescents with BD, comorbidity with externalizing disorders such as ADHD and CD is common. The clinical implications of comorbid ADHD and CD are rather different. ADHD can be viewed as a precursor of a child-onset subtype of BD, while CD might represent a prodromal or a concomitant behavioral complication that identifies a more malignant and refractory form of BD.