Showing papers in "Psychiatry Research-neuroimaging in 2008"

The economic and social burden of compulsive hoarding.

Abstract: The aim of the present study was to determine the economic and social burden of compulsive hoarding in a large sample of individuals with self-identified hoarding, as well as a separate sample of family members of individuals who hoard. Self-identified hoarding participants ( N =864, 94% female, 65% met research criteria for clinically relevant compulsive hoarding) and family informants ( N =655, 58% described a relative who appeared to meet research criteria for compulsive hoarding), completed an internet survey. Questions were derived in part from those used in the National Comorbidity Survey (NCS), and when possible, hoarding participants were compared to NCS participants. Compulsive hoarding was associated with an average 7.0 work impairment days in the past month, equivalent to that reported by individuals with psychotic disorders and significantly greater than that reported by female NCS participants with all other anxiety, mood, and substance use disorders. Severity of hoarding predicted the degree of work impairment after controlling for age, sex, and non-psychiatric medical conditions. Hoarding participants were nearly three times as likely to be overweight or obese as were family members. Compared to female NCS participants, hoarding participants were significantly more likely to report a broad range of chronic and severe medical concerns and had a five-fold higher rate of mental health service utilization. Eight to 12% had been evicted or threatened with eviction due to hoarding, and 0.1–3.0% had a child or elder removed from the home. These results suggest that compulsive hoarding represents a profound public health burden in terms of occupational impairment, poor physical health, and social service involvement.

P50 sensory gating ratios in schizophrenics and controls: a review and data analysis.

Abstract: Many studies have found that the P50 sensory gating ratio in a paired click task is smaller in normal control subjects than in patients with schizophrenia, indicating more effective sensory gating. However, a wide range of gating ratios has been reported in the literature for both groups. The purpose of this study was to compile these findings and to compare reported P50 gating ratios in controls and patients with schizophrenia. Current data collected from individual controls in eight studies from the University of California, Irvine (UCI), Indiana University (IU), and Yale University also are reported. The IU, UCI, and Yale data showed that approximately 40% of controls had P50 ratios within 1 S.D. below the mean of means for patients with schizophrenia. The meta-analysis rejected the null hypothesis that all studies showed no effect. The meta-analysis also showed that the differences were not the same across all studies. The mean ratios in 45 of the 46 group comparisons were smaller for controls than for patients, and the observed difference in means was significant for 35 of those studies. Reported gating ratios for controls from two laboratories whose findings were reported in the literature differed from all the other control groups. Variables affecting the gating ratio included band pass filter setting, rules regarding the inclusion of P30, sex, and age. Standards of P50 collection and measurement would help determine whether the gating ratio can be sufficiently reliable to be labeled an endophenotype, and suggestions are made toward this goal.

Impulsivity is associated with behavioral decision-making deficits.

Abstract: Impaired decision-making is a key-feature of many neuropsychiatric disorders. In the present study, we examined task performance in a healthy population consisting of those whose scores indicated high and low impulsivity on several behavioral decision-making tasks reflecting orbitofrontal functioning. The measures included tasks that assess decision-making with and without a learning component and choice flexibility. The results show that subjects high on impulsivity display an overall deficit in their decision-making performance as compared with subjects low on impulsivity. More specifically, subjects with high impulsivity show weaknesses in learning of reward and punishment associations in order to make appropriate decisions (reversal-learning task and Iowa Gambling Task), and impaired adaptation of choice behavior according to changes in stimulus-reward contingencies (reversal-learning task). Simple, non-learning, components of reward- and punishment-based decision-making (Rogers Decision-Making Task) seem to be relatively unaffected. Above all, the results indicate that impulsivity is associated with a decreased ability to alter choice behavior in response to fluctuations in reward contingency. The findings add further evidence to the notion that trait impulsivity is associated with decision-making, a function of the orbitofrontal cortex.

Lifetime criminality among boys with attention deficit hyperactivity disorder: a prospective follow-up study into adulthood using official arrest records.

Abstract: This study investigates the relationship between childhood attention deficit hyperactivity disorder (ADHD) and later criminality. White boys (n = 207, ages 6–12) with ADHD, free of conduct disorder, were assessed at ages 18 and 25 by clinicians who were blind to childhood status. A non-ADHD group served as comparisons. Lifetime arrest records were obtained when subjects were 38 years old for subjects who resided in New York State throughout the follow-up interval (93 probands, 93 comparisons). Significantly more ADHD probands than comparisons had been arrested (47% vs. 24%), convicted (42% vs. 14%), and incarcerated (15% vs. 1%). Rates of felonies and aggressive offenses also were significantly higher among probands. Importantly, the development of an antisocial or substance use disorder in adolescence completely explained the increased risk for subsequent criminality. Results suggest that even in the absence of comorbid conduct disorder in childhood, ADHD increases the risk for developing antisocial and substance use disorders in adolescence, which, in turn, increases the risk for criminal behavior in adolescence and adulthood.

Reliability and validity of the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form.

Abstract: We examined the reliability and validity of the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF), a widely cited measure of mental health treatment attitudes. Data from 296 college students and 389 primary care patients were analyzed. The ATSPPH-SF evidenced adequate internal consistency. Higher scores (indicating more positive treatment attitudes) were associated with less treatment-related stigma, and greater intentions to seek treatment in the future. No associations were found for mental health impairment or depression. The ATSPPH-SF was related to the recent use of mental health treatment and recent treatment intensity (i.e., visit counts); after controlling for demographic variables associated with treatment use, this relationship held in predicting previous use from non-use, but not visit counts. Factor-analytic findings demonstrated that a two-factor model (Openness to Seeking Treatment for Emotional Problems, and Value and Need in Seeking Treatment) represented the data well. Implications for future research on mental healthcare use correlates are discussed, as well as the need for enhancing peoples' attitudes toward treatment.

Reduced auditory evoked potential component N100 in schizophrenia — A critical review

Abstract: The role of a reduced N100 (or N1) component of the auditory event related potential as a potential trait marker of schizophrenia is critically discussed in this review. We suggest that the extent of the N100 amplitude reduction in schizophrenia depends on experimental and subject factors, as well as on clinical variables: N100 is more consistently reduced in studies using interstimulus intervals (ISIs) > 1 s than in studies using shorter ISIs. An increase of the N100 amplitude by allocation of attention is often lacking in schizophrenia patients. A reduction of the N100 amplitude is nevertheless also observed when such an allocation is not required, proposing that both endogenous and exogenous constituents of the N100 are affected by schizophrenia. N100 is more consistently reduced in medicated than unmedicated patients, but a reduction of the N100 amplitude as a consequence of antipsychotic medication was shown in only two of seven studies. In line with that, the association between the N100 reduction and degree of psychopathology of patients appears to be weak overall. A reduced N100 amplitude is found in first degree relatives of schizophrenia patients, but the risk of developing schizophrenia is not reflected in the N100 amplitude reduction.

Evidence for deficient modulation of amygdala response by prefrontal cortex in bipolar mania.

Abstract: Several studies have implicated the involvement of two major components of emotion regulatory networks, the ventrolateral prefrontal cortex (VLPFC) and amygdala, in the pathophysiology of bipolar disorder In healthy subjects, the VLPFC has been shown to negatively modulate amygdala response when subjects cognitively evaluate an emotional face by identifying and labeling the emotion it expresses The current study used such a paradigm to assess whether the strength of this modulation was altered in bipolar subjects when manic During functional magnetic resonance imaging (fMRI), nine manic subjects with bipolar I disorder and nine healthy subjects either named the emotion shown in a face by identifying one of two words that correctly expressed the emotion (emotion labeling task) or matched the emotion shown in a face to one of two other faces (emotion perception task) The degree to which the VLPFC regulated amygdala response during these tasks was assessed using a psychophysiological interaction (PPI) analysis Compared with healthy subjects, manic patients had a significantly reduced VLPFC regulation of amygdala response during the emotion labeling task These findings, taken in context with previous fMRI studies of bipolar mania, suggest that reductions in inhibitory frontal activity in these patients may lead to an increased reactivity of the amygdala

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

Abstract: 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-Asberg 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.

Corpus callosum in maltreated children with posttraumatic stress disorder: A diffusion tensor imaging study

Abstract: Contrary to expectations derived from preclinical studies of the effects of stress, and imaging studies of adults with posttraumatic stress disorder (PTSD), there is no evidence of hippocampus atrophy in children with PTSD. Multiple pediatric studies have reported reductions in the corpus callosum--the primary white matter tract in the brain. Consequently, in the present study, diffusion tensor imaging was used to assess white matter integrity in the corpus callosum in 17 maltreated children with PTSD and 15 demographically matched normal controls. Children with PTSD had reduced fractional anisotropy in the medial and posterior corpus, a region which contains interhemispheric projections from brain structures involved in circuits that mediate the processing of emotional stimuli and various memory functions--core disturbances associated with a history of trauma. Further exploration of the effects of stress on the corpus callosum and white matter development appears a promising strategy to better understand the pathophysiology of PTSD in children.

Identifying differences in biased affective information processing in major depression

Abstract: This study investigates the extent to which participants with major depression differ from healthy comparison participants in the irregularities in affective information processing, characterized by deficits in facial expression recognition, intensity categorization, and reaction time to identifying emotionally salient and neutral information Data on diagnoses, symptom severity, and affective information processing using a facial recognition task were collected from 66 participants, male and female between ages 18 and 54 years, grouped by major depressive disorder (N=37) or healthy non-psychiatric (N=29) status Findings from MANCOVAs revealed that major depression was associated with a significantly longer reaction time to sad facial expressions compared with healthy status Also, depressed participants demonstrated a negative bias towards interpreting neutral facial expressions as sad significantly more often than healthy participants In turn, healthy participants interpreted neutral faces as happy significantly more often than depressed participants No group differences were observed for facial expression recognition and intensity categorization The observed effects suggest that depression has significant effects on the perception of the intensity of negative affective stimuli, delayed speed of processing sad affective information, and biases towards interpreting neutral faces as sad

Prefrontal mechanisms for executive control over emotional distraction are altered in major depression.

Abstract: A dysfunction in the interaction between executive function and mood regulation has been proposed as the pathophysiology of depression. However, few studies have investigated the alteration in brain systems related to executive control over emotional distraction in depression. To address this issue, 19 patients with major depressive disorder (MDD) and 20 healthy controls were scanned using functional magnetic resonance imaging. Participants performed an emotional oddball task in which infrequently presented circle targets required detection while sad and neutral pictures were irrelevant novel distractors. Hemodynamic responses were compared for targets, sad distractors, and for targets that followed sad or neutral distractors (Target-after-Sad and Target-after-Neutral). Patients with MDD revealed attenuated activation overall to targets in executive brain regions. Behaviorally, MDD patients were slower in response to Target-after-Sad than Target-after-Neutra stimuli. Patients also revealed a reversed activation pattern from controls in response to this contrast in the left anterior cingulate, insula, right inferior frontal gyrus (IFG), and bilateral middle frontal gyrus. Those patients who engaged the right IFG more during Target-after-Neutral stimuli responded faster to targets, confirming a role of this region in coping with emotional distraction. The results provide direct evidence of an alteration in the neural systems that interplay cognition with mood in MDD.

Reliability, validity and ability to detect change of the Personal and Social Performance scale in patients with stable schizophrenia.

Abstract: This report describes the measurement properties of the Personal and Social Performance scale (PSP), a clinician-reported measure of severity of personal and social dysfunction, in an outpatient population with stabilized schizophrenia. Pooled data from two similar antipsychotic clinical studies were analyzed (n=411). The PSP showed good test-retest reliability (intraclass correlation coefficient=0.79). The PSP was more highly correlated with the Strauss-Carpenter Level of Function, an instrument measuring a similar construct, than the Positive and Negative Syndrome Scale, an instrument measuring a different construct. There was a statistically significant difference between mean PSP scores in subjects grouped by their severity rating on the Clinical Global Impression-Severity (CGI-S) (mild or less versus at least moderate), indicating the ability to discriminate between known groups. Effect sizes for mean change in the PSP based on 1-category improvement (0.72) or worsening (-0.88) versus no change in the CGI-S were moderate to large, demonstrating the ability to detect change. Estimates of between-group minimum important difference suggest that a 7-point improvement in the PSP may be clinically meaningful in a clinical trial setting. Initial reliability and validity assessments suggest the PSP may be a useful measure of social functioning in patients with stable schizophrenia.

Abstinent adolescent marijuana users show altered fMRI response during spatial working memory

Abstract: Marijuana is the most widely used illicit substance among teenagers, yet little is known about the possible neural influence of heavy marijuana use during adolescence. We previously demonstrated an altered functional magnetic resonance imaging (fMRI) activity related to spatial working memory (SWM) among adolescents who were heavy users of after an average of 8 days of abstinence, but the persisting neural effects remain unclear. To characterize the potentially persisting neurocognitive effects of heavy marijuana use in adolescence, we examined fMRI response during SWM among abstinent marijuana-using teens. Participants were 15 MJ teens and 17 demographically similar non-using controls, ages 16-18. Teens underwent biweekly urine toxicology screens to ensure abstinence for 28 days before fMRI acquisition. Groups performed similarly on the SWM task, but MJ teens demonstrated lower activity in right dorsolateral prefrontal and occipital cortices, yet significantly more activation in right posterior parietal cortex. MJ teens showed abnormalities in brain response during a SWM task compared with controls, even after 1 month of abstinence. The activation pattern among MJ teens may reflect different patterns of utilization of spatial rehearsal and attention strategies, and could indicate altered neurodevelopment or persisting abnormalities associated with heavy marijuana use in adolescence.

Theory of mind disability in major depression with or without psychotic symptoms: a componential view.

Abstract: Previous reports have conceptualized theory of mind (ToM) as comprising two components and questioned whether ToM deficits are associated with psychotic symptoms. We investigated 33 nonpsychotic depressed inpatients, 23 psychotic depressed inpatients, and 53 normal controls with the following measures: Eyes Task, Faux pas Task, Verbal Fluency Test (VFT), Digit Span Test (DST) and WAIS-IQ. The depressed patients were also evaluated with the Beck Depression Inventory-II (BDI-II) and the Brief Psychiatric Rating Scale (BPRS). The nonpsychotic depressed patients and the psychotic depressed individuals were significantly impaired on tasks involving ToM social-perceptual and social-cognitive components, as well as the VFT. The psychotic depressed patients performed significantly worse than nonpsychotic depressed patients on ToM tasks. An association was found between ToM performances and both BPRS total and hostile-suspiciousness scores in the depressed group. Both of the ToM components were impaired in depressed patients. Similar mechanisms and neurobiological substrate may contribute to schizophrenia and major depression.

Attention Deficit in Depressed Suicide Attempters

Abstract: Attention is typically impaired in depression and may play a role in risk for suicidal behavior. In this study, 66 non-patients, 83 depressed subjects with no past history of suicide attempt, 53 depressed subjects with one or more low lethality suicide attempts, and 42 depressed subjects with at least one high lethality attempt were compared on two computerized measures of attention, a continuous performance test (CPT) and a Stroop task. All subjects were medication free at the time of assessment. Attention was impaired in all depressed subjects but worse in those with a past history of suicidal behavior. CPT performance did not differ among the groups, but Stroop interference was significantly poorer in all depressed subjects relative to non-patients, and poorer still in high lethality suicide attempters relative to all other groups. Interference scores correlated modestly with subjective depression, functional level, suicide ideation, number of past suicide attempts, and lethality of past attempts. Depression-related impairments of attention, especially susceptibility to interference, are accentuated in those with a past history of suicidal behavior. Fundamental deficits in attentional control may play a role in risk for suicidal behavior, and may contribute to a variety of cognitive deficits in suicidal patients. Brain regions subserving attentional control, which overlap considerably with regions implicated in affective disorders, may be a useful target for studies seeking to characterize neuropsychological factors associated with suicidal behavior.

Primary caregivers of schizophrenia outpatients: burden and predictor variables.

Abstract: This article explores family burden in relation to relatives' coping strategies and social networks, as well as in relation to the patients' severity of positive and negative symptoms. Data on the severity of symptoms (Positive and Negative Syndrome Scale for Schizophrenia [PANSS]), social functioning (Social Functioning Scale [SFS]), caregivers burden (Interview on Objective and Subjective Family Burden or Entrevista de Carga Familiar Objetiva y Subjetiva [ECFOS]), coping skills (Family Coping Questionnaire [FCQ]), and social support (Social Network Questionnaire [SNQ]) were gathered from a randomized sample of 101 Chilean outpatients and their primary caregivers, mostly mothers. Low levels of burden were typically found, with the exception of moderate levels on general concerns for the ill relative. A hierarchical regression analysis with four blocks showed that clinical characteristics, such as higher frequency of relapses, more positive symptoms and lower independence-performance, together with lower self-control attributed to the patient, decrease in social interests, and less affective support, predict burden. The results support the relevance of psychoeducational interventions where families' needs are addressed.

Is a neutral face really evaluated as being emotionally neutral

Abstract: Most of the functional neuroimaging studies on emotion have used neutral faces as a baseline condition. The aim of the present study was to explore whether prototypical neutral faces are evaluated as displaying neutral emotions. Twenty-one subjects performed the Extrinsic Affective Simon Task (EAST), a validated implicit task that measures the emotional evaluation of target stimuli. All stimuli consisted of two juxtaposed faces from standardized facial pictures. The attribute stimuli (positive vs. negative), which needed to be classified on the basis of extrinsic valence, were presented as black and white facial pictures. The target stimuli were color-filtered positive, negative, neutral, and positive/negative faces, and subjects were instructed to classify them on the basis of the filtered color (blue vs. green). The responses to the positive target faces were associated with the positive emotions and the responses to the negative target faces were associated with the negative emotions. For the neutral faces, the responses were similar to those of negative faces, while for the positive/negative stimuli, the responses were undifferentiated. These findings suggested that prototypical "neutral" faces may be evaluated as negative in some circumstances, which suggests that the inclusion of neutral faces as a baseline condition might introduce an experimental confound in functional neuroimaging studies.

Partial compliance in schizophrenia and the impact on patient outcomes

Abstract: This review evaluates the impact of partial compliance on treatment outcomes in schizophrenia and discusses strategies that may be implemented to enhance compliance. As such, a search of English language articles evaluating compliance in schizophrenia was performed using Medline and EMBASE, with no time limits. Abstracts and posters presented at key psychiatry congresses were also reviewed. Results demonstrated that partial compliance with antipsychotic medication is a significant barrier to achieving optimal outcomes in schizophrenia. The problem increases with the duration of treatment, and is difficult to monitor. The impact of partial compliance is significant, leading to increases in psychotic symptoms, the risk of relapse and rehospitalization, and even suicide. Compliance is a complex phenomenon, influenced by aspects of the illness itself such as cognitive impairment and patients' health beliefs. The patient's environment and therapeutic alliance also influence medication compliance. Behavioural and pharmacological measures should be used together to improve compliance. While atypical antipsychotics have demonstrated improvements in psychotic symptoms, insight and cognition, these may not be enough to ensure compliance with oral daily medication. Long-acting risperidone may therefore bring together the benefits of the atypical antipsychotics with the long-acting injection delivery system required to build a platform for improved outcomes.

Brain anatomy of persistent violent offenders: more rather than less.

Abstract: Most violent crimes in Western societies are committed by a small group of men who display antisocial behavior from an early age that remains stable across the life-span. It is not known if these men display abnormal brain structure. We compared regional brain volumes of 26 persistently violent offenders with antisocial personality disorder and substance dependence and 25 healthy men using magnetic resonance imaging volumetry and voxel-based morphometry (VBM). The violent offenders, as compared with the healthy men, had markedly larger white matter volumes, bilaterally, in the occipital and parietal lobes, and in the left cerebellum, and larger grey matter volume in right cerebellum (effect sizes up to 1.24, P<0.001). Among the offenders, volumes of these areas were not associated with psychopathy scores, substance abuse, psychotropic medication, or global IQ scores. By contrast, VBM analyses of grey matter revealed focal, symmetrical, bilateral areas of atrophy in the postcentral gyri, frontopolar cortex, and orbitofrontal cortex among the offenders as compared with the healthy men (z-scores as high as 5.06). Offenders with psychopathy showed the smallest volumes in these areas. The larger volumes in posterior brain areas may reflect atypical neurodevelopmental processes that underlie early-onset persistent antisocial and aggressive behavior.

Reduced caudate gray matter volume in women with major depressive disorder.

Abstract: Previous brain-imaging studies have reported that major depressive disorder (MDD) is characterized by decreased volumes of several cortical and subcortical structures, including the hippocampus, amygdala, anterior cingulate cortex, and caudate nucleus. The purpose of the present study was to identify structural volumetric differences between MDD and healthy participants using a method that allows a comparison of gray and white matter volume across the whole brain. In addition, we explored the relation between symptom severity and brain regions with decreased volumes in MDD participants. The study group comprised 22 women diagnosed with MDD and 25 healthy women with no history of major psychiatric disorders. Magnetic resonance brain images were analyzed using optimized voxel-based morphometry to examine group differences in regional gray and white matter volume. Compared with healthy controls, MDD participants were found to have decreased gray matter volume in the bilateral caudate nucleus and the thalamus. No group differences were found for white matter volume, nor were there significant correlations between gray matter volumes and symptom severity within the MDD group. The present results suggest that smaller volume of the caudate nucleus may be related to the pathophysiology of MDD and may account for abnormalities of the cortico-striatal-pallido-thalamic loop in MDD.

Comparison of data analysis strategies for intent-to-treat analysis in pre-test-post-test designs with substantial dropout rates

Abstract: The pre-test–post-test design (PPD) is predominant in trials of psychotherapeutic treatments. Missing data due to withdrawals present an even bigger challenge in assessing treatment effectiveness under the PPD than under designs with more observations since dropout implies an absence of information about response to treatment. When confronted with missing data, often it is reasonable to assume that the mechanism underlying missingness is related to observed but not to unobserved outcomes ( missing at random, MAR ). Previous simulation and theoretical studies have shown that, under MAR, modern techniques such as maximum-likelihood (ML) based methods and multiple imputation (MI) can be used to produce unbiased estimates of treatment effects. In practice, however, ad hoc methods such as last observation carried forward (LOCF) imputation and complete-case (CC) analysis continue to be used. In order to better understand the behaviour of these methods in the PPD, we compare the performance of traditional approaches (LOCF, CC) and theoretically sound techniques (MI, ML), under various MAR mechanisms. We show that the LOCF method is seriously biased and conclude that its use should be abandoned. Complete-case analysis produces unbiased estimates only when the dropout mechanism does not depend on pre-test values even when dropout is related to fixed covariates including treatment group ( covariate-dependent: CD ). However, CC analysis is generally biased under MAR. The magnitude of the bias is largest when the correlation of post- and pre-test is relatively low.

Regional gray matter abnormalities in panic disorder: A voxel-based morphometry study

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

Structural brain abnormalities in borderline personality disorder: A voxel-based morphometry study

Abstract: Imaging studies using region-of-interest morphometry and positron emission tomography have contributed to our understanding of structural and functional abnormalities in borderline personality disorder (BPD); however, both methods have practical limitations to their usefulness for exploratory studies of brain-behavior relationships. We used voxel-based morphometry (VBM) in 34 subjects with BPD and 30 healthy control (HC) subjects to study effects of diagnosis, gender, childhood sexual abuse, depressed mood, impulsivity and aggression on group differences. VBM is a computer-based method for whole brain analysis that combines the advantages of a functional study with a structural method. The BPD subjects, diagnosed with the Diagnostic Interview for Borderline Patients and the International Personality Disorders Examination, were compared with 30 HC subjects, with age and gender covaried. Analyses were repeated separately by gender and, in women, by histories of childhood sexual abuse. Depressed mood, impulsivity, and aggression were covaried in separate analyses. Compared with HC, BPD subjects had significant bilateral reductions in gray matter concentrations in ventral cingulate gyrus and several regions of the medial temporal lobe, including the hippocampus, amygdala, parahippocampal gyrus, and uncus. BPD women (and abused BPD women), but not BPD men, had significant reductions in medial temporal lobe, including the amygdala. BPD men, but not BPD women, showed diminished gray matter concentrations in the anterior cingulate gyrus compared with findings in HC subjects. Covarying for depressed mood rendered group differences non-significant in the ventral cingulate but had little effect on differences in medial temporal cortex. Covarying for aggression (LHA) had relatively little effect on group differences, while covarying for impulsivity, as determined by the Barratt Impulsiveness Scale, rendered all previously noted voxel-level group differences non-significant. Diminished gray matter in the prefrontal cortex and the medial temporal cortex may mediate the dysregulation of impulse and affect in BPD. Group differences varied greatly by gender, levels of depression, and impulsivity. VBM is an efficient method for exploratory study of brain-behavior relationships.

Orbitofrontal, amygdala and hippocampal volumes in teenagers with first-presentation borderline personality disorder

Abstract: It is not known whether the fronto-limbic volume reductions found in adults with established borderline personality disorder (BPD) are present early in the disorder. The aim of the study was to investigate orbitofrontal cortex (OFC), hippocampal and amygdala volumes in a first-presentation teenage BPD sample with minimal exposure to treatment. Groups of 20 BPD patients and 20 healthy control participants underwent magnetic resonance imaging. Hippocampal, amygdala, OFC and whole brain volumes were estimated and compared between the two groups. Analysis of variance revealed reversal of the normal (right>left) asymmetry of OFC grey matter volume in the BPD group, reflecting right-sided OFC grey matter loss in the BPD group compared with control participants. No significant differences were found for amygdala or hippocampal volumes comparing BPD with control participants. We identified OFC but not hippocampal or amygdala volumetric differences early in the course of BPD. Hippocampal and amygdala volume reductions observed in adult BPD samples might develop during the course of the disorder, although longitudinal studies are needed to examine this.

Further development of YBOCS dimensions in the OCD Collaborative Genetics study: symptoms vs. categories.

Abstract: Despite progress in identifying homogeneous subphenotypes of obsessive-compulsive disorder (OCD) through factor analysis of the Yale Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC), prior solutions have been limited by a reliance on presupposed symptom categories rather than discrete symptoms. Furthermore, there have been few attempts to evaluate the familiality of OCD symptom dimensions. The purpose of this study was to extend prior work by this collaborative group in category-based dimensions by conducting the first-ever exploratory dichotomous factor analysis using individual OCD symptoms, comparing these results to a refined category-level solution, and testing the familiality of derived factors. Participants were 485 adults in the six-site OCD Collaborative Genetics Study, diagnosed with lifetime OCD using semi-structured interviews. YBOCS-SC data were factor analyzed at both the individual item and symptom category levels. Factor score intraclass correlations were calculated using a subsample of 145 independent affected sib pairs. The item- and category-level factor analyses yielded nearly identical 5-factor solutions. While significant sib-sib associations were found for four of the five factors, Hoarding and Taboo Thoughts were the most robustly familial (r ICC>or=0.2). This report presents considerable converging evidence for a five-factor structural model of OCD symptoms, including separate factor analyses employing individual symptoms and symptom categories, as well as sibling concordance. The results support investigation of this multidimensional model in OCD genetic linkage studies.

A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents : Interaction with adverse childhood environment

Abstract: Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, environmental conditions play an important role in its manifestation during childhood development. Here, we report the results of an investigation on the interaction of adverse childhood environment with a functional polymorphism of the serotonin transporter promoter gene (5-HTTLPR) and its impact on ADHD psychopathology in young adult delinquents. Standardized instruments were used to assess childhood and current ADHD and adverse childhood environment in 184 male delinquents. Each subject was genotyped for 5-HTTLPR long (L) and small (S) alleles. Logistic regression analysis revealed independent effects of high childhood environmental adversity and the 5-HTTLPR LL-genotype on self-reported childhood ADHD and on persistent ADHD. In addition, a significant gene by environment interaction was found, indicating that carriers of at least one 5-HTTLPR short allele are more sensitive to childhood environment adversity than carriers of the LL-genotype. The results support prior findings of association between ADHD and 5-HTTLPR LL-genotype and adverse childhood environment, and they underline the need for further investigation of gene by environment interaction with respect to ADHD.

Gray matter changes in right superior temporal gyrus in criminal psychopaths. Evidence from voxel-based morphometry

Abstract: "Psychopathy" according to the PCL-R describes a specific subgroup of antisocial personality disorder with a high risk for criminal relapses. Lesion and imaging studies point towards frontal or temporal brain regions connected with disturbed social behavior, antisocial personality disorder (APD) and psychopathy. Morphologically, some studies described a reduced prefrontal brain volume, whereas others reported on temporal lobe atrophy. To further investigate whether participants with psychopathy according to the Psychopathy Checklist-Revised Version (PCL-R) show abnormalities in brain structure, we used voxel-based morphometry (VBM) to investigate region-specific changes in gray matter in 17 forensic male inpatients with high PCL-R scores (PCL-R>28) and 17 male control subjects with low PCL-R scores (PCL<10). We found significant gray matter reductions in frontal and temporal brain regions in psychopaths compared with controls. In particular, we found a highly significant volume loss in the right superior temporal gyrus. This is the first study to show that psychopathy is associated with a decrease in gray matter in both frontal and temporal brain regions, in particular in the right superior temporal gyrus, supporting the hypothesis that a disturbed frontotemporal network is critically involved in the pathogenesis of psychopathy.

Comprehension of metaphor and irony in schizophrenia during remission: the role of theory of mind and IQ.

Abstract: The study reported herein explored the comprehension of metaphor and irony in schizophrenia during remission, and examined the role of IQ and a theory of mind. Performance of 29 Schizophrenic patients in remission and 22 healthy controls was compared on metaphor and irony comprehension tasks and first- and second-order theory of mind tasks. Participants' IQs were measured using the Wechsler Adult Intelligence Scale-Revised, and the symptoms of individuals with schizophrenia were assessed using the Positive and Negative Syndrome Scale. The results showed that patients with schizophrenia were impaired in their comprehension of metaphor and irony as compared with healthy controls. A theory of mind deficit was found in patients with remitted schizophrenia. The comprehension of metaphor was significantly correlated with second-order false belief understanding and the comprehension of irony was not significantly related to theory of mind. IQ and verbal IQ did not explain the deficit of metaphor and irony comprehension. These findings were not explained by Happe's [Happe, F.G.E., 1993. Communication competence and theory of mind in autism: a test of relevance theory. Cognition 48, 101-119] theory and the shared semantic understanding requirement was discussed.

Neural correlates of attachment trauma in borderline personality disorder: a functional magnetic resonance imaging study.

Abstract: Functional imaging studies have shown that individuals with borderline personality disorder (BPD) display prefrontal and amygdala dysfunction while viewing or listening to emotional or traumatic stimuli. The study examined for the first time the functional neuroanatomy of attachment trauma in BPD patients using functional magnetic resonance imaging (fMRI) during the telling of individual stories. A group of 11 female BPD patients and 17 healthy female controls, matched for age and education, told stories in response to a validated set of seven attachment pictures while being scanned. Group differences in narrative and neural responses to "monadic" pictures (characters facing attachment threats alone) and "dyadic" pictures (interaction between characters in an attachment context) were analyzed. Behavioral narrative data showed that monadic pictures were significantly more traumatic for BPD patients than for controls. As hypothesized BPD patients showed significantly more anterior midcingulate cortex activation in response to monadic pictures than controls. In response to dyadic pictures patients showed more activation of the right superior temporal sulcus and less activation of the right parahippocampal gyrus compared to controls. Our results suggest evidence for potential neural mechanisms of attachment trauma underlying interpersonal symptoms of BPD, i.e. fearful and painful intolerance of aloneness, hypersensitivity to social environment, and reduced positive memories of dyadic interactions.

Response inhibition and impulsivity in schizophrenia.

Abstract: Response inhibition in schizophrenia remains controversial, with behavioral correlates largely unknown. Inpatients with schizophrenia and controls completed a stop task and an impulsiveness questionnaire. Slower inhibitory processes were evident in schizophrenia, but there was no association with impulsivity. The nature of inhibition and impulsivity in schizophrenia is complex, and could reflect schizophrenia subgroups or disease states.