Normalization of impaired emotion inhibition in bipolar disorder mediated by cholinergic neurotransmission in the cingulate cortex.

The muscarinic-cholinergic system is involved in the pathophysiology of bipolar disorder (BD), and contributes to attention and the top-down and bottom-up cognitive and affective mechanisms of emotional processing, functionally altered in BD. Emotion processing can be assessed by the ability to inhibit a response when the content of the image is emotional. Impaired regulatory capacity of cholinergic neurotransmission conferred by reduced M2-autoreceptor availability is hypothesized to play a role in elevated salience of negative emotional distractors in euthymic BD relative to individuals with no history of mood instability. Thirty-three euthymic BD type-I (DSM-V-TR) and 50 psychiatrically-healthy controls underwent functional magnetic resonance imaging (fMRI) and an emotion-inhibition paradigm before and after intravenous cholinergic challenge using the acetylcholinesterase inhibitor, physostigmine (1 mg), or placebo. Mood, accuracy, and reaction time on either recognizing or inhibiting a response associated with an image involving emotion and regional functional activation were examined for effects of cholinergic challenge physostigmine relative to placebo, prioritizing any interaction with the diagnostic group. Analyses revealed that (1) at baseline, impaired behavioral performance was associated with lower activation in the anterior cingulate cortex in BD relative to controls during emotion processing; (2) physostigmine (vs. placebo) affected behavioral performance during the inhibition of negative emotions, without altering mood, and increased activation in the posterior cingulate cortex in BD (vs. controls); (3) In BD, lower accuracy observed during emotion inhibition of negative emotions was remediated by physostigmine and was associated with cingulate cortex overactivation. Our findings implicate abnormal regulation of cholinergic neurotransmission in the cingulate cortices in BD, which may mediate exaggerated emotional salience processing, a core feature of BD.

Brain imaging in patients with COVID-19: A systematic review.

BACKGROUND: There is increasing evidence that SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) not only affects the respiratory tract but also influence the central nervous system (CNS), resulting in neurological symptoms such as loss of smell and taste. Growing literature indicates largely distributed brain alterations encompassing subcortical micro- and macro-bleeds, cerebral swelling and haemorrhage in gray and white matter tissue. A systematic review was performed to synthesise the potential evidence of the brain correlates of SARS-CoV-2. METHODS: A literature search was conducted using electronic databases for studies reporting neuroimaging abnormalities in SARS-CoV-2 infected individuals. Identified case series, cohort studies, and case control studies on SARS-CoV-2 effects on the brain were critically appraised for methodological quality. A narrative synthesis of the findings from the included studies is presented. RESULTS: Twenty-seven studies were included in the review, including 5 case series, 8 cohort studies and 14 case control studies. The findings revealed predominant involvement of the olfactory system with disruptions across four olfactory structures. Abnormalities also extended to the corpus callosum, cingulate cortex, and insula, jointly implicating the olfactory brain network. CONCLUSION: Alterations in olfactory areas, along with neighbouring brain regions, including prefrontal and limbic regions were associated to contraction of SARS-CoV-2. Viral infection could either trigger systemic reactions, or use the olfactory's unique anatomical organisation as an environmental entry zone to directly impact on the CNS.

An investigation of psychological responses to COVID-19 in Irish healthcare workers: longitudinal quantitative and nested qualitative study.

COVID-19 is an unprecedent occurrence in modern times and individuals who work within healthcare settings, face a broad array of challenges in responding to this worldwide event. Key information on the psychosocial responses of such healthcare workers (HCWs) in the context of COVID-19 is limited and in particular there is a need for studies that utilise longitudinal methods, an overarching theoretical model, and use of a cohort of participants within a defined geographical area across acute and community settings. The work packages making up the current research project use quantitative and qualitative methods to examine the psychological sequelae for HCWs in the context of COVID-19 in geographically adjacent healthcare areas (South and Mid-West of Ireland) across four time points (induction, 3 months, 6 months, and 1 year follow-up). The quantitative arm of the project (WP 1) utilises the Common-Sense Model of Self-Regulation (CSM-SR) and examines a number of key psychological factors pertinent to this model including perceptions about COVID-19 and infection more generally, coping, formal and informal support and a number of impact variables including mood, sleep quality, and perceptions of stigma. The qualitative study (WP 2) will address HCWs experiences of working during the pandemic, ascertain any additional areas of psychological functioning, environmental and workplace factors and resources that may be utilised by HCWs and that are not assessed by the quantitative study protocol, focusing particularly on those staff groups typically underrepresented in previous studies.

Neuroanatomical Dysconnectivity Underlying Cognitive Deficits in Bipolar Disorder.

BACKGROUND: Graph theory applied to brain networks is an emerging approach to understanding the brain's topological associations with human cognitive ability. Despite well-documented cognitive impairments in bipolar disorder (BD) and recent reports of altered anatomical network organization, the association between connectivity and cognitive impairments in BD remains unclear. METHODS: We examined the role of anatomical network connectivity derived from T1- and diffusion-weighted magnetic resonance imaging in impaired cognitive performance in individuals with BD (n = 32) compared with healthy control individuals (n = 38). Fractional anisotropy- and number of streamlines-weighted anatomical brain networks were generated by mapping constrained spherical deconvolution-reconstructed white matter among 86 cortical/subcortical bilateral brain regions delineated in the individual's own coordinate space. Intelligence and executive function were investigated as distributed functions using measures of global, rich-club, and interhemispheric connectivity, while memory and social cognition were examined in relation to subnetwork connectivity. RESULTS: Lower executive functioning related to higher global clustering coefficient in participants with BD, and lower IQ performance may present with a differential relationship between global and interhemispheric efficiency in individuals with BD relative to control individuals. Spatial recognition memory accuracy and response times were similar between diagnostic groups and associated with basal ganglia and thalamus interconnectivity and connectivity within extended anatomical subnetworks in all participants. No anatomical subnetworks related to episodic memory, short-term memory, or social cognition generally or differently in BD. CONCLUSIONS: Results demonstrate selective influence of subnetwork patterns of connectivity in underlying cognitive performance generally and abnormal global topology underlying discrete cognitive impairments in BD.

Bipolar Disorder and Gender Are Associated with Frontolimbic and Basal Ganglia Dysconnectivity: A Study of Topological Variance Using Network Analysis.

Well-established structural abnormalities, mostly involving the limbic system, have been associated with disorders of emotion regulation. Understanding the arrangement and connections of these regions with other functionally specialized cortico-subcortical subnetworks is key to understanding how the human brain's architecture underpins abnormalities of mood and emotion. We investigated topological patterns in bipolar disorder (BD) with the anatomically improved precision conferred by combining subject-specific parcellation/segmentation with nontensor-based tractograms derived using a high-angular resolution diffusion-weighted approach. Connectivity matrices were constructed using 34 cortical and 9 subcortical bilateral nodes (Desikan-Killiany), and edges that were weighted by fractional anisotropy and streamline count derived from deterministic tractography using constrained spherical deconvolution. Whole-brain and rich-club connectivity alongside a permutation-based statistical approach was used to investigate topological variance in predominantly euthymic BD relative to healthy volunteers. BP patients (n = 40) demonstrated impairments across whole-brain topological arrangements (density, degree, and efficiency), and a dysconnected subnetwork involving limbic and basal ganglia relative to controls (n = 45). Increased rich-club connectivity was most evident in females with BD, with frontolimbic and parieto-occipital nodes not members of BD rich-club. Increased centrality in females relative to males was driven by basal ganglia and fronto-temporo-limbic nodes. Our subject-specific cortico-subcortical nontensor-based connectome map presents a neuroanatomical model of BD dysconnectivity that differentially involves communication within and between emotion-regulatory and reward-related subsystems. Moreover, the female brain positions more dependence on nodes belonging to these two differently specialized subsystems for communication relative to males, which may confer increased susceptibility to processes dependent on integration of emotion and reward-related information.

The Arcuate Fasciculus Network and Verbal Deficits in Psychosis.

BACKGROUND: Verbal learning (VL) and fluency (VF) are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF) and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness. METHODS: Twenty-six individuals with recent-onset psychosis and 27 healthy controls underwent cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion-weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and volume of seven cortical regions were investigated in relation to VL and VF performance in both groups. RESULTS: Reduced right superior temporal gyrus surface area and volume related to better VF in controls. In psychosis, greater right pars opercularis volume and reduced left lateralization of this region related to better VL, while greater right long AF fractional anisotropy and right pars orbitalis volume related to better VF, these findings not present in controls. Psychosis had reduced right pars orbitalis thickness compared to controls. CONCLUSION: Anatomical substrates for normal processing of VL and VF appear altered in recent-onset psychosis. A possible aberrant role of the right hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis may contribute to deficits in VL and VF.

Anterior Cortical Development During Adolescence in Bipolar Disorder.

BACKGROUND: Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. METHODS: Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. RESULTS: Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p < .05, corrected), including greater gray matter contraction and decreased white matter expansion over time, in the BD compared with the healthy group. CONCLUSIONS: The findings support neurodevelopmental abnormalities during adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter.

Atypical right hemispheric functioning in the euthymic state of bipolar affective disorder.

Bipolar disorder (BD) has been associated with right hemisphere dysfunction. These findings usually come from studies that have not distinguished between symptomatic and euthymic states of BD. The present study aims to investigate atypical right (and left) hemispheric functioning in euthymic BD patients. We evaluated 40 participants (18 healthy controls and 22 euthymic BD patients) using an emotional prosody dichotic listening task and a linguistic dichotic listening task which have been shown to produce a strong left ear advantage (LEA) and right ear advantage (REA), indicating a right and left hemisphere superiority, respectively. The results replicate the well-known LEA in emotional prosody for healthy controls. In contrast, no ear advantage was found for emotional prosody in euthymic BD patients. Both groups revealed the well-established REA in the linguistic dichotic listening task. The patient group was heterogeneous with regard to medication, as it consisted of patients with a variety of pharmacological treatments. The results are in line with previous studies in symptomatic BD patients, and suggest that atypical LEA in emotional prosody can be interpreted as a neurobehavioral vulnerability marker of emotional dysregulation and dysfunction in the right hemispheric fronto-temporal network in both symptomatic and euthymic BD patients.

Right fronto-parietal dysfunction underlying spatial attention in bipolar disorder.

Although the neural underpinning of bipolar disorder (BD) is still unknown, recent research suggests that the right fronto-parietal cortex is particularly affected in BD patients. If this were true, we would expect atypical functional cerebral asymmetries in allocation of visuospatial attention. To test this hypothesis, euthymic BD patients and age- and gender-matched healthy controls were compared on the visual line-bisection task, a reliable measure of visuospatial attention, associated with right parietal function. Line bisection performance (i.e. absolute and directional bias) was compared between groups as a function of response hand and line position. The results showed a typical hand-use effect in healthy controls involving a larger leftward bias (i.e. pseudoneglect) with the left hand than with the right hand. Although euthymic BD patients did not differ from healthy controls in the overall accuracy (i.e. absolute bias), they differed significantly in the directional line bisection bias. In contrast to healthy controls, BD patients did not significantly deviate from the veridical center, regardless of which hand was used to bisect horizontal lines. This finding indicates an atypical functional cerebral asymmetry in visuospatial attention in euthymic BD patients, supporting the idea of a dysfunction especially in the right fronto-parietal cortex.

Models of hemispheric specialization in facial emotion perception--a reevaluation.

A considerable amount of research on functional cerebral asymmetries (FCAs) for facial emotion perception has shown conflicting support for three competing models: (i) the Right Hemisphere Hypothesis, (ii) the Valence-Specific Hypothesis, and (iii) the Approach/Withdrawal model. However, the majority of studies evaluating the Right Hemisphere or the Valence-Specific Hypotheses are rather limited by the small number of emotional expressions used. In addition, it is difficult to evaluate the Approach/Withdrawal Hypothesis due to insufficient data on anger and FCAs. The aim of the present study was (a) to review visual half field (VHF) studies of hemispheric specialization in facial emotion perception and (b) to reevaluate empirical evidence with respect to all three partly conflicting hypotheses. Results from the present study revealed a left visual field (LVF)/right hemisphere advantage for the perception of angry, fearful, and sad facial expressions and a right visual field (RVF)/left hemisphere advantage for the perception of happy expressions. Thus, FCAs for the perception of specific facial emotions do not fully support the Right Hemisphere Hypothesis, the Valence-Specific Hypothesis, or the Approach/Withdrawal model. A systematic literature review, together with the results of the present study, indicate a consistent LVF/right hemisphere advantage only for a subset of negative emotions including anger, fear and sadness, rather suggesting a "negative (only) valence model."

Atypical lateralisation in emotional prosody in men with schizotypy.

Individuals high in schizotypy have been shown to reveal reduced lateralisation in verbal processing which may be influenced by an impaired left hemisphere performance. However, little is known about schizotypy and right hemisphere functions such as emotional perception. The present study focuses on atypical lateralisation in language and emotional prosody in Impulsive Non-conformity (IMP), a specific aspect of schizotypy. A total of 41 participants (20 females) performed a dichotic listening linguistic and emotional prosody task, which typically shows a right ear advantage (REA) and left ear advantage (LEA), respectively. A median split based on the IMP scale included in the Oxford-Liverpool Inventory of Feelings and Experiences was used to divide the sample into high and low scorers. The results revealed a selective reduction of the LEA in the prosody task in high-IMP males. Females high and low in IMP revealed typical lateralisation in both tasks. The results indicate that high-IMP males are especially prone to atypical lateralisation in emotional prosody, which parallels those findings in male patients with schizophrenia. The results suggest similarities in sex-specific atypical brain organisation between schizotypy and schizophrenia.

Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: a (15)O-H(2)O PET study.

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H(2)(15)O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET-MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI-free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM-D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic-frontal structures in depressed patients compared to healthy volunteers.

Cortex and amygdala morphology in psychopathy.

Psychopathy is characterized by abnormal emotional processes, but only recent neuroimaging studies have investigated its cerebral correlates. The study aim was to map local differences of cortical and amygdalar morphology. Cortical pattern matching and radial distance mapping techniques were used to analyze the magnetic resonance images of 26 violent male offenders (age: 32±8) with psychopathy diagnosed using the Psychopathy Checklist-Revised (PCL-R) and no schizophrenia spectrum disorders, and in matched controls (age: 35± sp="0.12"/>11). The cortex displayed up to 20% reduction in the orbitofrontal and midline structures (corrected p<0.001 bilaterally). Up to 30% tissue reduction in the basolateral nucleus, and 10-30% enlargement effects in the central and lateral nuclei indicated abnormal structure of the amygdala (corrected p=0.05 on the right; and symmetrical pattern on the left). Psychopathy features specific morphology of the main cerebral structures involved in cognitive and emotional processing, consistent with clinical and functional data, and with a hypothesis of an alternative evolutionary brain development.

Co-occurring mental and substance abuse disorders: a review on the potential predictors and clinical outcomes.

This article reviews the literature on co-occurring mental disorders and substance use disorders. The co-occurrence of mental disorders with substance use disorders presents a major challenge to those who provide psychiatric services. Despite the clinical and social burdens caused by this complex problem, research in this area is still insufficient. We found 18 studies showing potential predictors of co-occurring disorders (COD). Poor outcomes have been associated with: (i) COD compared to single disorders and (ii) COD with prior mental disorder compared to COD with prior substance use disorders. Poorer outcomes were reported for substance use disorder patients with comorbid major depressive disorder, and patients with substance use disorder and post-traumatic stress disorder. Furthermore, more negative outcomes were related to COD patients with temporally prior onset of mood disorders. Comorbidity between major depressive disorder or post-traumatic stress disorder and substance use disorder is suggested in the literature as a potential predictor of COD problems.

Normal metabolite levels in the left dorsolateral prefrontal cortex of unmedicated major depressive disorder patients: a single voxel (1)H spectroscopy study.

Few proton magnetic resonance spectroscopy ((1)H spectroscopy) studies have investigated the dorsolateral prefrontal cortex (DLPFC), a key region in the pathophysiology of major depressive disorder (MDD). We used (1)H spectroscopy to verify whether MDD patients differ from healthy controls (HC) in metabolite levels in this brain area. Thirty-seven unmedicated DSM-IV MDD patients were compared with 40 HC. Subjects underwent a short echo-time (1)H spectroscopy examination at 1.5 T, with an 8-cm(3) single voxel placed in the left DLPFC. Reliable absolute metabolite levels of N-acetyl aspartate (NAA), phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol, glutamate plus glutamine (Glu+Gln), and glutamate were obtained using the unsuppressed water signal as an internal reference. Metabolite levels in the left DLPFC did not statistically differ between MDD patients and HC. We found an interaction between gender and diagnosis on PCr+Cr levels. Male MDD patients presented lower levels of PCr+Cr than male HC, and female MDD patients presented higher levels of PCr+Cr than female HC. Moreover, length of illness was inversely correlated with NAA levels. These findings suggest that there is not an effect of diagnosis on the left DLPFC neurochemistry. Possible effects of gender on PCr+Cr levels of MDD patients need to be further investigated.

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.

Temperament and character traits in major depressive disorder: influence of mood state and recurrence of episodes.

BACKGROUND: The objective of this study was to compare personality traits between major depressive disorder (MDD) patients and healthy comparison subjects (HC) and examine if personality traits in patients are associated with specific clinical characteristics of the disorder. METHODS: Sixty MDD patients (45 depressed, 15 remitted) were compared to 60 HC using the Temperament and Character Inventory. Analysis of covariance, with age and gender as covariates, was used to compare the mean Temperament and Character Inventory scores among the subject groups. RESULTS: Depressed MDD patients scored significantly higher than HC on novelty seeking, harm avoidance, and self-transcendence and lower on reward dependence, self-directedness, and cooperativeness. Remitted MDD patients scored significantly lower than HC only on self-directedness. Comorbidity with anxiety disorder had a main effect only on harm avoidance. Harm avoidance was positively correlated with depression intensity and with number of episodes. Self-directedness had an inverse correlation with depression intensity. CONCLUSIONS: MDD patients present a different personality profile from HC, and these differences are influenced by mood state and comorbid anxiety disorders. When considering patients who have been in remission for some time, the differences pertain to few personality dimensions. Cumulated number of depressive episodes may result in increased harm avoidance.

Rasgos del temperamento y carácter en pacientescon trastorno bipolar y asociaciones con elalcoholismo o trastornos de ansiedad comórbidos / Temperament and character traits in patients with bipolar disorder and associations with comorbid alcoholism or anxiety disorders

Los rasgos de temperamento y carácter pueden determinar diferencias en las presentaciones clínicas y el desenlace del trastorno bipolar. Comparamos los rasgos de personalidad en pacientes bipolares e individuos sanos utilizando el cuestionario de temperamento y carácter (Temperament and Character Inventory [TCI]) y tratamos de verificar si la comorbilidad con el alcoholismo o los trastornos de ansiedad se asocia con rasgos específicos de la personalidad. Se comparó a 73 pacientes con trastorno bipolar, basado en los criterios del Diagnostic and Statistical Manual of Mental Disorders,4.a edición (DSM-IV), con 63 individuos sanos usando el TCI. En una segunda fase, la muestra de pacientes bipolares se dividió en subgrupos según la comorbilidad psiquiátrica que tuvieran (alcoholismo, n = 10; trastornos de ansiedad, n = 23; alcoholismo más trastornos de ansiedad, n = 21; ausencia de comorbilidad, n = 19). Los pacientes bipolares obtuvieron puntuaciones significativamente más altas que los individuos sanos en la búsqueda de novedades, evitación de riesgos y autotrascendencia y puntuaciones más bajas en autodirección y cooperación. Los pacientes bipolares con alcoholismo comórbido exclusivo obtuvieron puntuaciones significativamente más bajas que aquellos sin ninguna comorbilidad en la perseverancia. Los pacientes bipolares con trastornos de ansiedad comórbidos exclusivos obtuvieron puntuaciones significativamente más altas en evitación de riesgos y más bajas en autodirección que aquellos sin ninguna comorbilidad. Las limitaciones de este estudio son el diseño transversal y el reducido tamaño de la muestra, específicamente en el análisis de subgrupos. Sin embargo, los resultados indican que los pacientes bipolares manifiestan una estructura de la personalidad diferente que los individuos sanos y quela comorbilidad psiquiátrica en este trastorno se asocia con rasgos específicos de personalidad. Estos hallazgos indican que la personalidad, al menos hasta cierto punto, media el fenómeno de la comorbilidad en el trastorno bipolar (AU)

Temperament and character traits may determine differences in clinical presentations and outcome of bipolar disorder. We compared personality traits in bipolar patients and healthy individuals using the Temperament and Character Inventory (TCI) and sought to verify whether comorbidity with alcoholism or anxiety disorders is associated with specific personality traits. Seventy-three DSM-IV bipolar patients were compared to 63 healthy individuals using the TCI. In a second step, the bipolar sample was subgrouped according to the presence of psychiatric comorbidity (alcoholism, n = 10; anxiety disorders; n = 23; alcoholism plus anxiety disorders, n = 21; no comorbidity, n = 19). Bipolar patients scored statistically higher than the healthy individuals on novelty seeking, harm avoidance and self-transcendence and lower on self-directedness and cooperativeness. Bipolar patients with only comorbid alcoholism scored statistically lower than bipolar patients without any comorbidity on persistence. Bipolar patients with only comorbid anxiety disorders scored statistically higher on harm avoidance and lower on self-directedness than bipolar patients without any comorbidity. Limitations of this study include the cross-sectional design and the small sample size, specifically in the analysis of the subgroups. However, our results suggest that bipolar patients exhibit a different personality structure than healthy individuals and that presence of psychiatric comorbidity in bipolar disorder is associated with specific personality traits. These findings suggest that personality, at least to some extent, mediates the comorbidity phenomena in bipolar disorder (AU)

Temperament and character traits in patients with bipolar disorder and associations with comorbid alcoholism or anxiety disorders.

Temperament and character traits may determine differences in clinical presentations and outcome of bipolar disorder. We compared personality traits in bipolar patients and healthy individuals using the Temperament and Character Inventory (TCI) and sought to verify whether comorbidity with alcoholism or anxiety disorders is associated with specific personality traits. Seventy-three DSM-IV bipolar patients were compared to 63 healthy individuals using the TCI. In a second step, the bipolar sample was subgrouped according to the presence of psychiatric comorbidity (alcoholism, n=10; anxiety disorders; n=23; alcoholism plus anxiety disorders, n=21; no comorbidity, n=19). Bipolar patients scored statistically higher than the healthy individuals on novelty seeking, harm avoidance and self-transcendence and lower on self-directedness and cooperativeness. Bipolar patients with only comorbid alcoholism scored statistically lower than bipolar patients without any comorbidity on persistence. Bipolar patients with only comorbid anxiety disorders scored statistically higher on harm avoidance and lower on self-directedness than bipolar patients without any comorbidity. Limitations of this study include the cross-sectional design and the small sample size, specifically in the analysis of the subgroups. However, our results suggest that bipolar patients exhibit a different personality structure than healthy individuals and that presence of psychiatric comorbidity in bipolar disorder is associated with specific personality traits. These findings suggest that personality, at least to some extent, mediates the comorbidity phenomena in bipolar disorder.

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder.

OBJECTIVES: Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD). METHODS: A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 +/- 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 +/- 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment). RESULTS: Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance. CONCLUSIONS: These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies.