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Introduction: Although comorbidity of post-traumatic stress disorder (PTSD) with borderline personality disorder (BPD) and/or cluster C personality disorders (CPD) is common, neural correlates of this comorbidity are unknown., Methods: We acquired functional MRI scans during an emotional face task in participants with PTSD + CPD (n = 34), PTSD + BPD (n = 24), PTSD + BPD + CPD (n = 18) and controls (n = 30). We used ANCOVAs and Bayesian analyses on specific ROIs in a fearful vs. scrambled faces contrast. We also investigated associations with clinical measures., Results: There were no robust differences in brain activation between the groups with ANCOVAs. Transdiagnostically, we found a negative association between severity of dissociation and right insula and right dmPFC activation, and emotion regulation problems with right dmPFC activation. Bayesian analyses showed credible evidence for higher activation in all ROIs in the PTSD + BPD + CPD group compared to PTSD + BPD and PTSD + CPD., Discussion: Our Bayesian and correlation analyses support new dimensional conceptualizations of personality disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purposes: 1. To find a difference in white matter (WM) between young adult males with narcissistic personality disorder (NPD) and healthy controls (HCs). 2. To find some correlations between white matter in the abnormal regions of NPD group and the pathological narcissism inventory (PNI)., Materials and Methods: Eighteen male participants with NPD (age M  = 18.39, SD = 0.164; education M  = 12.33, SD = 0.14) were included in our experiment. NPD participants met the DSM-IV criteria for NPD and without other personality disorders evaluated by trained clinical psychiatrists using the Structured Clinical Interview of DSM-IV for Personality Disorders (SCID-II). Moreover, healthy controls were also confirmed to be free of any axis I or II disorders and matched with education level, age and handedness (age M  = 18.83 years, SD = 0.246; education M  = 12.56, SD = 0.202; all participants were right handed). Those who have had major life events in the last six months, mental and physical illnesses, claustrophobia and oral implants have been excluded. We used tract-based spatial statistics (TBSS) on diffusion tensor images (DTI) and analysis of Pearson correlation between abnormal brain regions of white matter fibers and the pathological narcissism inventory., Results: There was no significant difference in age and education level between NPD and HCs ( p  > 0.05). There were significant differences in PNI score and its subscales between NPD group and HCs ( p  < 0.01). Fractional anisotropy (FA) values were found decreased mainly in the right superior longitudinal fasciculus and the bilateral posterior thalamic radiation (include optic radiation). Lower axial diffusivity (AD) values were identified mostly in the left retrolenticular part of internal capsule and the left posterior thalamic radiation (include optic radiation). There existed a significant correlation between DTI data and pathological narcissism inventory., Conclusions: The decreased brain white matter microstructures among three clusters were found in the association, projection/thalamic and connection pathways of white matter in young adult males with NPD. The abnormal white matter brain regions may be one of the neuropathological basis of the pathogenesis of young males with NPD, and it may be related to white matter development in early adulthood.

Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Personality disorders (PDs) have a prevalence of approximately 10% in the United States, translating to over 30 million people affected in just one country. The true prevalence of these disorders may be even higher, as the paucity of objective diagnostic criteria could be leading to underdiagnosis. Because little is known about the underlying neuropathologies of these disorders, patients are diagnosed using subjective criteria and treated nonspecifically. To better understand the neural aberrancies responsible for these patients' symptoms, a review of functional MRI literature was performed. The findings reveal that each PD is characterized by a unique set of activation changes corresponding to individual structures or specific neural networks. While unique patterns of neural activity are distinguishable within each PD, aberrations of the limbic/paralimbic structures and default mode network are noted across several of them. In addition to identifying valuable activation patterns, this review reveals a void in research pertaining to paranoid, schizoid, histrionic, narcissistic, and dependent PDs. By delineating patterns in PD neuropathology, we can more effectively direct future research efforts toward enhancing objective diagnostic techniques and developing targeted treatment modalities. Furthermore, understanding why patients are manifesting certain symptoms can advance clinical awareness and improve patient outcomes., (© 2021 American Society of Neuroimaging.)

Impulsivity is a characteristic syndromal and neurobehavioral feature of borderline personality disorder (BPD). Research suggests an important interaction between high negative emotions and low behavioral inhibition in BPD. However, knowledge about the generalizability across stimulus categories and diagnosis specificity is limited. We investigated neural correlates of hypothesized impaired response inhibition of BPD patients to negative, positive and erotic stimuli, by comparing them to non-patients and cluster-C personality disorder patients. During fMRI scanning, 53 BPD patients, 34 non-patients and 20 cluster-C personality disorder patients completed an affective go/no-go task, including social pictures. BPD patients showed more omission errors than non-patients, independent of the stimulus category. Furthermore, BPD patients showed higher activity in the inferior parietal lobule and frontal eye fields when inhibiting negative versus neutral stimuli. Activity of the inferior parietal lobule correlated positively with the BPD checklist subscale impulsivity. When inhibiting emotional stimuli, BPD patients showed an altered brain activity in the inferior parietal lobe and frontal eye fields, whereas previously shown dysfunctional prefrontal activity was not replicated. BPD patients showed a general responsivity across stimulus categories in the frontal eye fields, whereas effects in the inferior parietal lobe were specific for negative stimuli. Results of diagnosis specificity support a dimensional rather than a categorical differentiation between BPD and cluster-C patients during inhibition of social emotional stimuli. Supported by behavioral results, BPD patients showed no deficiencies in emotionally modulated response inhibition per se but the present findings rather hint at attentional difficulties for emotional information.

Background: Avoidant personality disorder (AvPD) is a condition typified by social inhibition, feelings of inadequacy, and hypersensitivity to negative evaluation. AvPD has a high comorbidity rate with other personality disorders and other psychological diagnostic categories. There is very little research investigating subcortical volumetry in AvPD. We studied subcortical brain morphometry in AvPD as compared to both healthy controls and comorbidity-matched psychiatric controls (patients in the same clinic matched for age, sex and all psychiatric diagnoses except for AvPD)., Methods: We compared volumetric measures of 9 bilateral subcortical brain regions between AvPD patients, healthy controls, and psychiatric controls (n = 100 each group). The Bonferroni correction was used to control for multiple comparisons across regions (p < 0.0028)., Results: Compared to healthy controls, AvPD patients had lower volume of the left accumbens and left thalamus. However, no significant results were found when comparing AvPD patients and psychiatric controls. An exploratory study of cortical regions showed similar results: statistically significant differences between HC and AvPD (left lateral occipital, left and right pericalcarine smaller in AvPD) but no differences between AvPD and PC., Limitations: MRI and neuroimaging provides correlational information, and no causal claims can be made., Conclusions: These results suggest there may be no overt subcortical volumetric differences specific to AvPD, and provide strong cautionary advice when comparing patients to healthy controls, a common practice in psychiatry biomarker research., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Touch, such as affective caress, can be interpreted as being pleasant. The emotional valence that is assigned to touch is related to certain bottom-up factors, such as the optimal activation of C-tactile (CT) afferents. Tactile processing with a hedonic or emotional component has been defined as affective touch-a component that CT fibers are likely to convey. Tactile deficiencies are frequent in the psychiatric population but also in healthy people with disorganized attachment; accordingly, it is likely that affective difficulties in adults with disorganized attachment are reflected in altered perception of affective touch. To test this hypothesis, we combined methods from clinical psychology, psychophysics, and neuroimaging. We found that people with a history of traumatic parental bonds and a disorganized attachment pattern perceive a "caress-like" stimulus as being unpleasant, whereas participants with organized attachment consider the same tactile stimulation to be pleasant. Further, unlike in organized adults, the responses of disorganized adults to CT and non-CT stimulation activated limbic and paralimbic structures in a fight-or-flight manner, suggesting that early experiences with parental deficiencies shape the physiological responses of peripheral CT fibers and central nervous networks.

Background: Obsessive-compulsive personality disorder (OCPD) is one of the most prevalent personality disorders in general population. However, neural mechanisms underlying OCPD remain elusive. The aim of this study is to use functional magnetic resonance imaging (fMRI) to examine whether OCPD patients will exhibit altered spontaneous brain activity as compared to healthy controls (HC)., Methods: Resting-state fMRI data were acquired in 37 OCPD patients and 37 matched HC. Amplitudes of low-frequency fluctuation (ALFF) were calculated and compared between the two groups. Correlation analysis was performed between regional ALFF values and OCPD severity scores., Results: Significant group differences in regional ALFF were found in multiple brain regions. Compared to HCs, OCPD subjects had increased ALFF in bilateral caudate, left precuneus, left insula, and left medial superior frontal gyrus, and decreased ALFF in the right fusiform gyrus and left lingual gyrus. The ALFF values in the left precuneus correlated with OCPD severity scores., Limitations: We excluded patients with comorbidity and did not conduct cognitive function assessments. Our findings are also limited to cross-sectional analysis., Conclusions: OCPD patients exhibit altered spontaneous neural activity as compared to healthy controls in multiple brain regions, which may reflect different characteristic symptoms of OCPD pathophysiology, including cognitive inflexibility, excessive self-control, lower empathy, and visual attention bias., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Neuroticism is associated with greater reactivity to stress and lifetime psychopathology. In the present study we examined the association between neuroticism and regional and total cortical thickness (CT) across the lifespan, accounting for gender. We also assessed interactions among these factors. 450 subjects between 19 and 80 years were included. Participants completed the International Personality Item Pool and a structural MRI scan. Total CT and the mean values of CT in five regions of interest were examined. We also investigated the interaction effect among age, gender and neuroticism on CT. There was no significant association between neuroticism and regional/total CT. A significant interaction between neuroticism, age, and gender on the thickness of the anterior cingulate was found. Women high in neuroticism showed a thinner anterior cingulate cortex than women low in neuroticism, with increasing age. In contrast, men high in neuroticism had a thicker anterior cingulate cortex compared to men low in neuroticism, with increasing age. Overall, high neuroticism was associated with differential cortical thickness in the anterior cingulate among men and women with increasing age., (Copyright © 2019. Published by Elsevier B.V.)

Studies have used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between psychopathy and brain connectivity in selected regions of interest as well as networks covering the whole-brain. One of the limitations of these approaches is that brain connectivity is modeled as a constant state through the scan duration. To address this limitation, we apply group independent component analysis (GICA) and dynamic functional network connectivity (dFNC) analysis to uncover whole-brain, time-varying functional network connectivity (FNC) states in a large forensic sample. We then examined relationships between psychopathic traits (PCL-R total scores, Factor 1 and Factor 2 scores) and FNC states obtained from dFNC analysis. FNC over the scan duration was better represented by five states rather than one state previously shown in static FNC analysis. Consistent with prior findings, psychopathy was associated with networks from paralimbic regions (amygdala and insula). In addition, whole-brain FNC identified 15 networks from nine functional domains (subcortical, auditory, sensorimotor, cerebellar, visual, salience, default mode network, executive control and attentional) related to psychopathy traits (Factor 1 and PCL-R scores). Results also showed that individuals with higher Factor 1 scores (affective and interpersonal traits) spend more time in a state with weaker connectivity overall, and changed states less frequently compared to those with lower Factor 1 scores. On the other hand, individuals with higher Factor 2 scores (impulsive and antisocial behaviors) showed more dynamism (changes to and from different states) than those with lower scores., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Studies of individuals with focal brain damage have long been used to expand understanding of the neural basis of psychopathology. However, most previous studies were conducted using small sample sizes and relatively coarse methods for measuring psychopathology or mapping brain-behavior relationships. Here, we examined the factor structure and neural correlates of psychopathology in 232 individuals with focal brain damage, using their responses to the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Factor analysis and voxel-based lesion symptom mapping were used to examine the structure and neural correlates of psychopathology in this sample. Consistent with existing MMPI-2-RF literature, separate internalizing, externalizing, and psychotic symptom dimensions were found. In addition, a somatic dimension likely reflecting neurological symptoms was identified. Damage to the medial temporal lobe, including the hippocampus, was associated with scales related to both internalizing problems and psychoticism. Damage to the medial temporal lobe and orbitofrontal cortex was associated with both a general distrust of others and beliefs that one is being personally targeted by others. These findings provide evidence for the critical role of dysfunction in specific frontal and temporal regions in the development of psychopathology., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'., (© 2018 The Author(s).)

Background: Personality disorders (PD) belong to the most common and most serious mental disorders as regards social dysfunction, inability to work, occurrence of comorbidity and suicidal risk. PDs also crucially influence the incidence, clinical course and treatment response of mental disorders with high suicidal risk, such as depression or substance abuse. One key issue of PD concerns the regulation of emotions., Methods: Both 1 H-/ 31 P-Chemical Shift Imaging (CSI) was applied in a single session to assess neurochemical markers of glutamate function (NAA, Glu) and local energy metabolism (PCr, ATP) in two patient cohorts encompassing 22 cluster B (CB) and 21 cluster C (CC) PD patients, whereby 10 patients of each group were on low-dose antidepressants, and in 60 healthy controls (HC). Non-parametric statistical tests and correlation analyses were performed to assess disease effects on the metabolites and their relation to symptomatology as assessed by SCL-90R self-ratings., Results: Overall comparison including Bonferroni correction revealed significant differences of Glu across all groups in the dorsolateral prefrontal cortex (DLPFC). The following uncorrected results of pairwise tests were obtained: (i) Glu was bilaterally increased in the DLPFC in CB patients, whereas it was - together with NAA - bilaterally decreased in the DLPFC in CC patients and accompanied by increased PCr in the left DLPFC. (ii) NAA and Glu, accompanied by increased PCr, were significantly decreased in the dorsomedial prefrontal cortex (DMPFC) in CC patients. (iii) NAA was decreased in the right anterior cingulate cortex (ACC) in CB patients, and in the left ACC in CC patients with PCr being increased bilaterally. (iv) No associations were observed between metabolites and psychopathology measures., Conclusion: The observations in the DLPFC may reflect a neurobiochemical correlate of disturbed cognitive control function in CB and CC PD. While the alterations in CB patients suggest increased basal activity, the observed patterns in CC patients likely reflect decreased or inhibited activity. The alterations of NAA and Glu levels in the ACC and DMPFC indirectly support the assumption of disturbed neuronal function in regions involved in social cognition and mentalizing abilities in both CB and CC PD. Further studies should include the investigation of metabolites of neuronal inhibition (GABA) and the examination of treatment effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Serotonin has a well-established role in emotional processing and is a key neurotransmitter in impulsive aggression, presumably by facilitating response inhibition and regulating subcortical reactivity to aversive stimuli. In this study 44 men, of whom 19 were violent offenders and 25 were non-offender controls, completed an emotional Go/NoGo task requiring inhibition of prepotent motor responses to emotional facial expressions. We also measured cerebral serotonin 1B receptor (5-HT 1B R) binding with [ 11 C]AZ10419369 positron emission tomography within regions of the frontal cortex. We hypothesized that 5-HT 1B R would be positively associated with false alarms (failures to inhibit nogo responses) in the context of aversive (angry and fearful) facial expressions. Across groups, we found that frontal cortex 5-HT 1B R binding was positively correlated with false alarms when angry faces were go stimuli and neutral faces were nogo stimuli (p = 0.05, corrected alpha = 0.0125), but not with false alarms for non-emotional stimuli (failures to inhibit geometric figures). A posthoc analysis revealed the strongest association in anterior cingulate cortex (p = 0.006). In summary, 5-HT 1B Rs in the anterior cingulate are involved in withholding a prepotent response in the context of angry faces. Our findings suggest that serotonin modulates response inhibition in the context of certain emotional stimuli., (Copyright © 2017. Published by Elsevier Ltd.)

Early diagnosis of anxiety and depression may be facilitated by the use of neurobiological markers. In depression and panic disorder, transcranial sonography (TCS) has revealed decreased echogenicity of the brainstem raphe (BR). The aim of the present study was to detect whether decreased echogenicity of the BR correlates with personality features described in the five-dimension model, especially neuroticism. We examined 100 healthy volunteers using quantitative and qualitative TCS, the five-dimension revised NEO Personality Inventory, Beck´s scales of anxiety and depression, and the Social Re-adjustment Rating Scale (SRRS). Visual BR anechogenicity was found in 11 subjects, BR hypoechogenicity in 29 subjects, and normal BR echogenicity in 60 subjects. The visual assessment correlated with the digital assessment. Comparing the groups with visual BR anechogenicity and BR normoechogenicity, only increased SRRS score and increased agreeableness z-score were significant. Our hypothesis that BR hypoechogenicity reflects an inclination for depression and anxiety characterized by the personality dimension neuroticism was not supported. However, this disposition may be present in a different state, such as stress., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Individual differences in attentional control involve the ability to voluntarily direct, shift, and sustain attention. In studies of the role of attentional control in emotional adjustment, social relationships, and vulnerability to the effects of stress, self-report questionnaires are commonly used to measure this construct. Yet, convincing evidence of the association between self-report scales and actual cognitive performance has not been demonstrated. Across 2 independent samples, we examined associations between self-reported attentional control (Attentional Control Scale; ACS), self-reported emotional adjustment, Five-Factor Model personality traits (NEO Personality Inventory-Revised) and performance measures of attentional control. Study 1 examined behavioral performance on the Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002) and the Modified Switching Task (MST; Suchy & Kosson, 2006) in a large sample (n = 315) of healthy young adults. Study 2 (n = 78) examined behavioral performance on standardized neuropsychological tests of attention, including Conner's Continuous Performance Test-II and subtests from the Wechsler Adult Intelligence Scales, Third Edition (WAIS-III; Psychological Corporation, 1997) and Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001). Results indicated that the ACS was largely unrelated to behavioral performance measures of attentional control but was significantly associated with emotional adjustment, neuroticism, and conscientiousness. These findings suggest that although self-reported attentional control may be a useful construct, researchers using the ACS should exercise caution in interpreting it as a proxy for actual cognitive ability or performance. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Cocaine dependence frequently co-occurs with personality disorders, leading to increased interpersonal problems and greater burden of disease. Personality disorders are characterised by patterns of thinking and feeling that divert from social expectations. However, the comorbidity between cocaine dependence and personality disorders has not been substantiated by measures of brain activation during social decision-making. We applied functional magnetic resonance imaging to compare brain activations evoked by a social decision-making task-the Ultimatum Game-in 24 cocaine dependents with personality disorders (CDPD), 19 cocaine dependents without comorbidities and 19 healthy controls. In the Ultimatum Game participants had to accept or reject bids made by another player to split monetary stakes. Offers varied in fairness (in fair offers the proposer shares ~50 percent of the money; in unfair offers the proposer shares <30 percent of the money), and participants were told that if they accept both players get the money, and if they reject both players lose it. We contrasted brain activations during unfair versus fair offers and accept versus reject choices. During evaluation of unfair offers CDPD displayed lower activation in the insula and the anterior cingulate cortex and higher activation in the lateral orbitofrontal cortex and superior frontal and temporal gyri. Frontal activations negatively correlated with emotion recognition. During rejection of offers CDPD displayed lower activation in the anterior cingulate cortex, striatum and midbrain. Dual diagnosis is linked to hypo-activation of the insula and anterior cingulate cortex and hyper-activation of frontal-temporal regions during social decision-making, which associates with poorer emotion recognition., (© 2015 Society for the Study of Addiction.)

Background: Borderline personality disorder (BPD) and avoidant personality disorder (AvPD) are characterized by hyper-reactivity to negatively-perceived interpersonal cues, yet they differ in degree of affective instability. Recent work has begun to elucidate the neural (structural and functional) and cognitive-behavioral underpinnings of BPD, although some initial studies of brain structure have reached divergent conclusions. AvPD, however, has been almost unexamined in the cognitive neuroscience literature., Methods: In the present study we investigated group differences among 29 BPD patients, 27 AvPD patients, and 29 healthy controls (HC) in structural brain volumes using voxel-based morphometry (VBM) in five anatomically-defined regions of interest: amygdala, hippocampus, medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). We also examined the relationship between individual differences in brain structure and self-reported anxiety and affective instability in each group., Results: We observed reductions in MPFC and ACC volume in BPD relative to HC, with no significant difference among patient groups. No group differences in amygdala volume were found. However, BPD and AvPD patients each showed a positive relationship between right amygdala volume and state-related anxiety. By contrast, in HC there was an inverse relationship between MPFC volume and state and trait-related anxiety as well as between bilateral DLPFC volume and affective instability., Limitations: Current sample sizes did not permit examination of gender effects upon structure-symptom correlations., Conclusions: These results shed light on potentially protective, or compensatory, aspects of brain structure in these populations-namely, relatively reduced amygdala volume or relatively enhanced MPFC and DLPFC volume., (Published by Elsevier B.V.)

Frontotemporal brain sagging syndrome is a dementia associated with hypersomnolence, personality changes, and features of intracranial hypotension on magnetic resonance imaging. The literature is sparse with respect to treatment options; many patients simply worsen. We present a case in which this syndrome responded to lumbar dural reduction surgery. Postoperative magnetic resonance imaging indicated normalization of brain sagging and lumbar intrathecal pressure. Although no evidence of cerebrospinal leak was found, extremely thin dura was noted intraoperatively, suggesting that a thin and incompetent dura could result in this low-pressure syndrome. Clinicians who encounter this syndrome should consider dural reduction surgery as a treatment strategy.

Personality disorders often act as a common denominator for many psychiatric problems, and studies on personality disorders contribute to the etiopathology, diagnosis, and treatment of many mental disorders. In recent years, increasing evidence from various studies has shown distinctive features of personality disorders, and that from genetic and neuroimaging studies has been especially valuable. Genetic studies primarily target the genes encoding neurotransmitters and enzymes in the serotoninergic and dopaminergic systems, and neuroimaging studies mainly focus on the frontal and temporal lobes as well as the limbic-paralimbic system in patients with personality disorders. Although some studies have suffered due to unclear diagnoses of personality disorders and some have included few patients for a given personality disorder, great opportunities remain for investigators to launch new ideas and technologies in the field.

Background: Impulsive physical aggression is a common and problematic feature of many personality disorders. The serotonergic system is known to be involved in the pathophysiology of aggression, and multiple lines of evidence have implicated the serotonin 2A receptor (5-HT(2A)R). We sought to examine the role of the 5-HT(2A)R in impulsive aggression specifically in the orbitofrontal cortex (OFC), given that our own studies and an extensive literature indicate that serotonergic disturbances in the OFC are linked to aggression. We have previously hypothesized that increased 5-HT(2A)R function in the OFC is a state phenomenon that promotes impulsive aggression., Methods: Serotonin 2A receptor availability was measured with positron emission tomography and the selective 5-HT(2A)R antagonist radioligand [(11)C]MDL100907 in two groups of impulsively aggressive personality disordered patients-14 with current physical aggression, and 15 without current physical aggression-and 25 healthy control subjects. Clinical ratings of various symptom dimensions were also obtained., Results: Orbitofrontal 5-HT(2A)R availability was greater in patients with current physical aggression compared with patients without current physical aggression and healthy control subjects; no differences in OFC 5-HT(2A)R availability were observed between patients without current physical aggression and healthy control subjects. No significant differences in 5-HT(2A)R availability were observed in other brain regions examined. Among both groups of impulsively aggressive personality disordered patients combined, OFC 5-HT(2A)R availability was correlated, specifically, with a state measure of impulsive aggression., Conclusions: These findings are consistent with our previously described model in which impulsive aggression is related to dynamic changes in 5-HT(2A)R function in the OFC.

A previous study in proximal myotonic myopathy (PROMM/DM-2) and myotonic dystrophy type 1 (DM-1) using brain positron emission tomography demonstrated a reduced cerebral blood flow in the frontal and temporal regions associated with cognitive impairment. The objective was to investigate further cognitive and behavioural aspects in a new series of patients with DM-1 and PROMM/DM-2. Nineteen patients with genetically determined PROMM/DM-2 and 21 patients with moderately severe DM-1 underwent neuropsychological testing and neuropsychiatric interviews. DM-1 and PROMM/DM-2 patients had significantly lower scores on tests of frontal lobe function compared to controls. Neuropsychiatric interviews demonstrated an avoidant trait personality disorder in both patient groups. Brain single photon emission computed tomography showed frontal and parieto-occipital hypoperfusion. The results suggest that there is a specific cognitive and behavioural profile in PROMM/DM-2 and in DM-1, and that this profile is associated with hypoperfusion in frontal and parieto-occipital regions of the brain.

Objective: Neuroimaging and genetic studies suggest that individual differences in the brain dopaminergic system contribute to the normal variability of human personality (e.g., social detachment and novelty seeking). The authors studied whether presynaptic dopamine function is also associated with personality traits., Method: Presynaptic dopamine synthesis capacity in the brain was measured with positron emission tomography and [(18)F]fluorodopa in 33 healthy adults, and personality traits were assessed with the Karolinska Scales of Personality. Associations were studied by using a linear regression model controlling for the effects of age and gender on both variables., Results: High scores on two of the anxiety-related personality scales, somatic anxiety and muscular tension, and on one aggressivity-related scale, irritability, were significantly associated with low [(18)F]fluorodopa uptake in the caudate. No statistically significant associations were observed between [(18)F]fluorodopa uptake and the detachment scale or scales related to novelty-seeking behavior (impulsiveness and monotony avoidance)., Conclusions: The results suggest a role for the dopaminergic system in the regulation of anxiety in healthy subjects. Together with previous studies, they also indicate differential involvement of various components of the dopaminergic system in normal and pathological personality traits.

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered patients in metabolite and pharmacologic challenge studies. This study used positron emission tomography to explore whether reduced serotonergic function occurs in critical brain regions such as orbital frontal and cingulate cortex that, may play a role in modulating aggression. Six impulsive-aggressive patients and five healthy volunteers were evaluated for changes in regional glucose metabolism after administration of the serotonergic releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers demonstrated increases in orbital frontal and adjacent ventral medial frontal cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive patients showed no significant increases in glucose metabolism after fenfluramine in any region. Compared with volunteers, patients showed significantly blunted metabolic responses in orbital frontal, adjacent ventral medial and cingulate cortex, but not in inferior parietal lobe. These results are consistent with reduced serotonergic modulation of orbital frontal, ventral medial frontal, and cingulate cortex in patients with impulsive-aggressive personality disorders.

The method for measuring serotonin synthesis in human brain uses [11C]alpha-methyl-L-tryptophan as a tracer and positron emission tomography. The alpha-methyl-L-tryptophan is converted to alpha-methylserotonin, which is not a substrate for monoamine oxidase and therefore accumulates in the brain. In a pilot study published recently, rates of serotonin synthesis were found to be higher in men than in women. This was due to the lower plasma free tryptophan in the women under the experimental conditions used, and does not necessarily reflect the situation in all circumstances. Acute tryptophan depletion lowered brain serotonin synthesis by 90% or more. Patients with borderline personality disorder, who exhibit emotional lability and impulsivity, may have lower brain serotonin synthesis rates than healthy controls.

This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = -.56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively.

CNS changes in a case of DRPLA associated with dementia and personality changes were observed by CT, MR and SPECT. Brain CT and MR of the patient revealed progressive cortical atrophy which was recognized in parallel with the clinical course of the progression of dementia and personality changes. SPECT using 123I-iodoamphetamine (IMP) disclosed a diffuse low perfusion of the cerebral cortex, especially in the frontal and temporal lobes. These findings suggest that the dementia and personality changes in this case might be concerned with a dysfunction of the cerebral cortex.