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Biomedical subjects

Vivian Mitropoulou

Publications and source records attributed to Vivian Mitropoulou.

At least 19 recordsLinked to original sources

Dispositional impulsivity in normal and abnormal samples.

Impulsive behaviors, which can include aggression, substance use and suicide, are common and core features of the DSM Axis II Cluster B personality disorders. The construct of dispositional impulsivity is multidimensional and a number of self-report measures have been created to represent features of this trait (e.g., novelty seeking, behavioral disinhibition, nonplanning). Because these questionnaires are rarely administered together in the same sample, little is known about how they are related to one another. The current study was conducted to examine the structure of dimensional impulsive personality traits in a large normative sample (n=351). Analyses revealed that dispositional impulsivity was represented by three moderately correlated latent factors labeled thrill seeking, nonplanning and disinhibited behavior. Confirmatory factor analyses were also used to examine the extent to which the internal structure of these impulsive personality traits was similar in a sample defined as abnormal (i.e., DSM-III-R Cluster B PD diagnoses; n=70). Results revealed that the structure of these traits was consistent across the two samples in a model that constrained factor loadings and structural covariances (NFI=0.89; CFI=95; RMSEA=0.04). In addition, correlational relationships between the impulsivity factor scores and behavioral and sociodemographic factors (e.g., socioeconomic status, substance use) were consistent across the two samples. These results help to establish a common framework for understanding the multidimensional nature of impulsivity. Results from these analyses also lend support to a large body of work that demonstrates that normal and abnormal personality features are related.

Aggression↗

Blunted hormone responses to Ipsapirone are associated with trait impulsivity in personality disorder patients.

Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders.

Adult↗

Catechol-O-methyltransferase Val158Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups.

OBJECTIVE: A single-nucleotide polymorphism of the gene coding for catechol-O-methyltransferase (COMT Val(158)Met) is associated with prefrontal-dependent task performance in schizophrenia. We evaluated the relationship of the COMT genotype with diagnostic status and cognitive performance in schizotypal personality disorder. METHODS: Unmedicated outpatients with schizotypal personality disorder (SPD; n = 67) and non-schizotypal personality disorder (NSPD; n = 154) by DSM-III-R, and normal control (NC; n = 60) participants were genotyped at the COMT Val(158)Met locus. Of these, 98 Caucasians (23 SPD, 52 NSPD and 23 NC) performed a brief neurocognitive battery: Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Visuospatial Working Memory (DOT) and Visual Delayed Recall (Wechsler Memory Scale Visual Reproduction, WMS-VR). RESULTS: Allele distribution was not significantly different in the full sample (by chi(2)) for the SPD group compared with either the NC or combined NC/NSPD groups. In analyses of variance of Caucasian individuals, the SPD group performance met or approached significantly worse performance than NC, NSPD or both groups, on the PASAT, CVLT and WMS-VR. In regression analyses of cognitive performance, the COMT genotype was significantly associated with performance on WCST and PASAT, independent of diagnosis, with the Val/Val genotype associated with the worse performance. CONCLUSIONS: (1) Allelic variation in COMT activity is unrelated to the diagnosis of SPD in this sample. (2) Individuals with SPD exhibit multiple deficits in prefrontal and temporal lobe-dependent tasks. (3) The COMT genotype is related to performance on prefrontal cortex-dependent tasks and may contribute to the deficit in prefrontal-dependent memory processes in SPD as it does in schizophrenia.

Adult↗

Reduced anterior and posterior cingulate gray matter in borderline personality disorder.

BACKGROUND: Structural abnormalities in prefrontal and cingulate gyrus regions-important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in right anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. METHODS: MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. RESULTS: Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD had isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. CONCLUSIONS: The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders.

Adult↗

Neuropsychological performance in schizotypal personality disorder: importance of working memory.

BACKGROUND: Cognitive deficits consistently have been reported in schizophrenia patients and in patients with schizotypal personality disorder. For this study, the authors wanted to identify which of the domains of cognitive impairment represent "core" deficits of schizophrenia, comparing subjects with schizotypal personality disorder to two comparison groups: healthy volunteers and patients with personality disorders unrelated to schizophrenia. METHOD: Three groups completed a neuropsychological battery: patients with DSM-III-R schizotypal personality disorder (N=82); patients with DSM-III-R personality disorders unrelated to schizophrenia (i.e., a personality disorder other than schizotypal, schizoid, or paranoid [N=44]); and healthy volunteers (N=63). The battery included the California Verbal Learning Test, Trailmaking Test parts A and B, the Dot test of working memory, the Stroop Color and Word Test, the Paced Auditory Serial Addition Test, the WMS visual reproduction test, and the WAIS-R vocabulary and block design. RESULTS: Normative standards for performance that controlled for age, gender, and education were created from the scores of the healthy volunteers. Overall, schizotypal personality disorder patients performed significantly worse than the healthy volunteers and those with personality disorders unrelated to schizophrenia. Specifically, patients with schizotypal personality disorder demonstrated impaired performance on the Paced Auditory Serial Addition Test, WMS visual reproduction test, Dot test, and California Verbal Learning Test. In addition, in a regression analysis, performance on the Paced Auditory Serial Addition Test demonstrated the largest effect size. Indeed, it accounted for unique variance above and beyond all other cognitive measures, since controlling for Paced Auditory Serial Addition Test performance abolished group differences across all other measures. CONCLUSIONS: Patients with schizotypal personality disorder demonstrated moderate cognitive impairment compared with healthy volunteers (significant for seven out of 11 measures). These differences reached statistical significance for tasks of working memory, episodic memory, and delayed recall. Working memory performance accounted for the group differences. This study supports the view that working memory represents a core deficit of schizophrenia spectrum disorders.

Adult↗

Efficacy of open-label venlafaxine in subjects with major depressive disorder: associations with neuroendocrine response to serotonergic and noradrenergic probes.

An open-label pilot study explored the relationship between severity of depressive symptoms and venlafaxine dose required for clinical efficacy in outpatients with major depressive disorder (MDD). The utility of the neuroendocrine response to serotonergic (ipsapirone) and noradrenergic (clonidine) probes as predictors of venlafaxine dosage required for effective treatment was also explored. Nineteen medically healthy medication-free outpatients over 18 years of age who met criteria for MDD were studied. Participants received either a 20-mg dose of ipsapirone orally, a 0.002-mg/kg intravenous dose of clonidine, or placebo. Following a 1-week single-blind placebo lead-in, all subjects were treated with immediate release venlafaxine. Low-dose responders were defined as those subjects experiencing a >50% decrease in depression score on 37.5 mg, b.i.d., and high-dose responders were defined as those subjects experiencing similar improvement on venlafaxine doses of 75 mg, b.i.d., or higher. Subjects responding to low-dose treatment had a lower mean baseline Hamilton depression score than subjects requiring high-dose treatment. Neuroendocrine and temperature responses to clonidine or ipsapirone challenges were not significantly different in the high- vs. low-dose responders. Evaluation of models of "serotonergic-responsive" and norepinephrine-responsive" depression requires larger numbers of patients.

Administration, Oral↗

Effects of acute metabolic stress on the dopaminergic and pituitary-adrenal axis activity in patients with schizotypal personality disorder.

BACKGROUND: Stress has been associated with the onset of schizophrenia and exacerbation of psychotic symptoms. Patients with schizotypal personality disorder (SPD), the prototypic schizophrenia spectrum disorder, do not develop the frank psychosis of schizophrenia and appear clinically to be less reactive to stress than schizophrenic patients. Schizophrenic patients demonstrate increased dopaminergic (DA) and hypothalamic-pituitary-adrenal-axis (HPA) activation following 2-deoxyglucose (2-DG), an acute metabolic (glycopyruvic) stressor, compared to healthy volunteers (HV). We hypothesized that SPD patients would demonstrate comparable or lower DA and HPA responses after 2-DG to HV. METHODS: Fifteen SPD patients and 13 HV were administered 2-DG (40 mg/kg, i.v.) in a double-blind, placebo-controlled, randomized protocol. The area under the curve (AUC) was determined for plasma HVA, ACTH and cortisol (utilizing baseline and post infusion indices). RESULTS: 2-DG induced significant increases in ACTH, cortisol and HVA concentrations in both groups and cortisol elevations were significantly lower in patients with SPD than in HV. CONCLUSIONS: Patients with SPD have a blunted cortisol and a normal dopaminergic response to 2-DG. These results are consistent with the hypothesis that SPD patients are better buffered against DA and HPA overactivation in response to stress.

Acute Disease↗

Striatal amphetamine-induced dopamine release in patients with schizotypal personality disorder studied with single photon emission computed tomography and [123I]iodobenzamide.

BACKGROUND: Previous imaging studies demonstrated that schizophrenia is associated with increased amphetamine-induced dopamine (DA) release in the striatum, most pronounced during episodes of illness exacerbation. Schizotypal personality disorder (SPD) is a schizophrenia spectrum disorder, genetically related to schizophrenia. The goal of this study was to investigate striatal DA function in patients with SPD. METHODS: In our study, 13 SPD patients and 13 matched healthy control subjects underwent single photon emission computed tomography (SPECT) scan during bolus plus constant infusion of the D2/3 radiotracer [123I]iodobenzamide (IBZM). Striatal specific to nonspecific equilibrium partition coefficient (V(3)") was measured at baseline and following amphetamine administration (.3 mg/kg). RESULTS: No significant differences were observed in baseline V(3)" between groups. Amphetamine induced a larger decrease in [123I]IBZM V(3)" in SPD patients (-12 +/- 5%) compared with control subjects (-7 +/- 5%, p =.03). CONCLUSIONS: The reduction in [123I]IBZM V(3)" induced by amphetamine in SPD was similar to that observed in remitted schizophrenia patients (-10 +/- 9%, n = 17), but significantly lower than that observed during illness exacerbation (-24 +/- 13%, n = 17). This suggests that DA dysregulation in schizophrenia spectrum disorders might have a trait component, present in remitted patients with schizophrenia and in SPD, and a state component, associated with psychotic exacerbations but not SPD.

Adult↗

Context-processing deficits in schizotypal personality disorder.

Research suggests that schizotypal personality disorder (SPD) is a part of the spectrum of schizophrenia-related illnesses. This article hypothesizes that a deficit in the representation and maintenance of context is a core cognitive disturbance in schizophrenia and that SPD individuals should demonstrate context-processing deficits. To test this hypothesis, the authors administered 3 versions of their AX-CPT task, designed to assess context processing, to 35 healthy controls and 26 individuals with DSM-IV SPD. They also administered working memory and selective attention tasks. SPD individuals displayed context representation deficits similar to those found in schizophrenia but did not show the same additional deficits in context maintenance. Context processing was strongly associated with working memory and selective attention performance in the SPD individuals.

Adult↗

Neurobiologic function and temperament in subjects with personality disorders.

BACKGROUND: Personality traits have been hypothesized to involve specific neurotransmitter systems. In order to test this model, the relationship between the responses to serotonergic and noradrenergic probes, central cerebrospinal fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional Personality Questionnaire (TPQ) were evaluated in a cohort of personality disorder subjects. METHODS: A total of 142 patients meeting at least one personality disorder (meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria) participated in these studies. The prolactin response to fenfluramine (a measure of serotonin function) was obtained for 110 subjects; growth hormone response to clonidine (a measure of noradrenergic function) was obtained for 77 subjects, while homovanillic acid (HVA) at baseline, an index of dopaminergic function, was available for 103 subjects. Measures of central neurotransmitter function (dopaminergic, serotonergic, and noradrenergic: HVA, 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylglycol, respectively) were available for 36 subjects. Separate regression analyses utilizing each of the hypothesized associations, where the TPQ total scores were used as the dependent measures and the biologic indices were the independent measures were conducted. Exploratory correlational analyses between these biologic measures and the four dimensions of the TPQ (and its subscales) were also conducted. (Correlations are reported if they would remain significant at P<.01 level after Bonferroni correction for multiple comparisons across the six neuroendocrine measures). RESULTS: In the regression analyses, there was a trend association between CSF and plasma HVA in predicting novelty-seeking (P<.07). No other significant associations were found in the other three measures. Regarding the individual correlational analyses, the persistence scale of the TPQ was significantly positively correlated with the growth hormone response to clonidine (r=.30, P<.008). The sentimentality subscale (reward dependence) was positively correlated with CSF 5-hydroxyindolacetic acid (r=0.45, P<.001), while the attachment subscale (also reward dependence) was correlated with CSF 3-methoxy-4-hydroxyphenylglycol (r=0.49, P<.002). CONCLUSION: Limited support was provided for a relationship between monoamines, particularly dopamine and novelty-seeking as well as norepinephrine and reward dependence but other hypothesized relationships were not supported by these measures.

Brain↗

Abuse and neglect in childhood: relationship to personality disorder diagnoses.

BACKGROUND: Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples. METHODS: This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for ~2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution. RESULTS: Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men. CONCLUSION: These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder.

Adult↗

The role of childhood trauma in differences in affective instability in those with personality disorders.

BACKGROUND: This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174). METHODS: Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure. RESULTS: A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21-.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores. CONCLUSION: This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder.

Adolescent↗

Reduced processing resource availability in schizotypal personality disorder: evidence from a dual-task CPT study.

Performance on a dual-task information processing task was investigated in 23 schizotypal personality disorder patients (SPD), 29 patients with other noncluster A personality disorders (OPD) and 8 non-psychiatric healthy controls (NC). All participants were assessed using a computer-based visual continuous performance test (CPT) and an auditory CPT individually, and administered again simultaneously in a dual-task condition. The SPD group showed a greater increase in the number of errors of omission than the OPD group or normal controls on the CPT tasks in the dual-task conditions. Performance operating characteristics indicated that the SPD patients did not allocate their attention in a manner different from the healthy controls, suggesting that poorer performance was due to resource limitations in the dual task condition and not strategic failures. These results are similar to previous studies of patients with schizophrenia, where performance deficits on information processing tests have been shown to be related to resource limitations more than failures in effective allocation of attention.

Acoustic Stimulation↗

The relationship of borderline personality disorder to posttraumatic stress disorder and traumatic events.

OBJECTIVE: The authors examined the relationship of borderline personality disorder to posttraumatic stress disorder (PTSD) with respect to the role of trauma and its timing. METHOD: The Trauma History Questionnaire and the PTSD module of the Structured Clinical Interview for DSM-III-R were administered to 180 male and female outpatients with a diagnosis of one or more DSM-III-R personality disorders. Path analysis was used to evaluate the relationship between borderline personality disorder and PTSD. RESULTS: High rates of early and lifetime trauma were found for the subject group as a whole. Compared to subjects without borderline personality disorder, subjects with borderline personality disorder had significantly higher rates of childhood/adolescent physical abuse (52.8% versus 34.3%) and were twice as likely to develop PTSD. In the path analysis of the relationship between borderline personality disorder and PTSD, none of the different types of paths (direct path, indirect paths through adulthood traumas, paths sharing the antecedent of childhood abuse) was significant. The associations with both trauma and PTSD were not unique to borderline personality disorder; paranoid personality disorder subjects had an even higher rate of comorbid PTSD than subjects without paranoid personality disorder, as well as elevated rates of physical abuse and assault in childhood/adolescence and adulthood. CONCLUSIONS: The associations of personality disorder with early trauma and PTSD were evident, but modest, in borderline personality disorder and were not unique to this type of personality disorder. The results do not appear substantial or distinct enough to support singling out borderline personality disorder from the other personality disorders as a trauma-spectrum disorder or variant of PTSD.

Adolescent↗

Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression.

OBJECTIVE: Previous studies using the 1.0-mg dexamethasone suppression test (DST) in subjects with personality disorders have produced mixed results. However, these studies focused on major depression and did not consider the possible effects of the comorbidity of posttraumatic stress disorder (PTSD). PTSD has been shown to be associated with increased cortisol suppression. To investigate the effect of PTSD, the authors conducted a 0.5-mg DST, which is more sensitive than the 1.0-mg DST for detection of increased cortisol suppression, in a group of subjects with personality disorders. METHOD: Subjects with personality disorders (N=52) ingested 0.5 mg of dexamethasone. Pre- and postfasting blood samples were drawn for measurement of cortisol levels. A three-way analysis of covariance was used to test for the main effects of major depression, PTSD, and gender on percent cortisol suppression, with plasma dexamethasone concentration as a covariate. Secondary analyses assessed for main and interaction effects of age at which trauma(s) occurred and a diagnosis of borderline personality disorder. RESULTS: Neither major depression nor gender had a significant effect on percent cortisol suppression. Subjects with PTSD had significantly higher percent cortisol suppression than subjects with major depression. Age at which trauma(s) occurred and a borderline personality disorder diagnosis had no significant main or interaction effects on cortisol suppression. CONCLUSIONS: A high level of cortisol suppression was associated with PTSD in subjects with personality disorder. This finding is similar to published findings for PTSD subjects without personality disorders. Major depression, gender, age when trauma(s) occurred, and a diagnosis of borderline personality disorder did not have significant main or interaction effects on cortisol suppression.

Adult↗

Risperidone in the treatment of schizotypal personality disorder.

OBJECTIVE: Schizotypal personality disorder (SPD) has many phenomenological, genetic, physiologic, and neuroanatomical commonalities with schizophrenia. Patients with the disorder often suffer from marked social and occupational impairment, yet they have been difficult to treat with medications because of their unusual sensitivity to side effects. This study was designed to determine whether low-dose risperidone treatment is acceptable to SPD patients and can reduce characteristic schizotypal symptoms. In addition, if SPD patients respond to an antipsychotic medication, this will provide support for the notion of a commonality in treatment response between SPD and schizophrenia. METHOD: Twenty-five patients with DSM-IV-defined SPD were entered into a 9-week randomized, double-blind, placebo-controlled study of low-dose risperidone (starting dose of 0.25 mg/day, titrated upward to 2 mg/day) in the treatment of SPD. Patients were rated with the Positive and Negative Syndrome Scale (PANSS), the Schizotypal Personality Disorder Questionnaire, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from 1995 to 2001. RESULTS: The subjects had a low incidence of depression and of comorbid borderline personality disorder. Patients receiving active medication had significantly (p <.05) lower scores on the PANSS negative and general symptom scales by week 3 and on the PANSS positive symptom scale by week 7 compared with patients receiving placebo. Side effects were generally well tolerated, and there was no group difference in dropout rate for side effects. CONCLUSION: Low-dose risperidone appears to be effective in reducing symptom severity in SPD and is generally well tolerated.

Adolescent↗

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity.

BACKGROUND: Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). METHODS: We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. RESULTS: Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p <.006). CONCLUSIONS: Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Adult↗

Cognitive and brain function in schizotypal personality disorder.

Schizotypal personality disorder, a diagnosis defined partially in terms of a genetic relatedness to schizophrenia, has begun to receive extensive investigative study. While the exact etiologic relationship between schizotypal personality disorder and schizophrenia remains to be determined, three models have been considered: (1) the two may be distinct disorders, (2) they may be essentially identical disorders but expressed with different degrees of severity, or (3) they may be related disorders with a partially overlapping etiology that might account for the many similarities yet the lack of psychosis or severe deficits in schizotypal individuals. Some of the recent research in the structural and functional neuroanatomy, neurochemistry, cognitive function, and pharmacology of schizotypal personality disorder is reviewed with citation of the most recent findings from our laboratory and others. Both schizotypal and schizophrenic subjects appear to show abnormalities in temporal lobe volume, but schizotypal subjects do not appear to show the volumetric decreases in frontal cortex that schizophrenic patients evidence. Abnormalities in thalamic nuclei parallel these findings-the pulvinar, which projects to temporal association and sensory cortices, is reduced in both disorders, but the mediodorsal nucleus, which projects extensively to the frontal cortex, is reduced in schizophrenic patients but not in schizotypal patients. Functional imaging studies suggest that there may be abnormalities in frontal activation in both disorders, but that schizotypal individuals can recruit alternative regions to accomplish tasks requiring frontal lobe activation that may help compensate. Imaging studies of the subcortex including FDG/PET imaging of metabolic activity during a verbal learning task, SPECT imaging studies which measure binding of IBZM and its displacement following amphetamine administration, and plasma HVA determinations following 2-deoxyglucose administration all suggest the possibility of relatively reduced dopaminergic subcortical activity in schizotypal individuals compared to schizophrenic patients. Cognitive function is also impaired in the areas of working memory, verbal learning, and attention in schizotypal patients, as in schizophrenic patients, and they may be particularly susceptible to cognitive tasks with high context dependence, as in schizophrenia. Preliminary trials of catecholaminergic agents suggest that these agents may be able to improve these impaired cognitive functions.

Benzamides↗