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Neurobiologic Function and Temperament in Subjects With Personality Disorders
- Vivian Mitropoulou, Robert L. Trestman, Antonia S. New, Janine D. Flory, Jeremy M. Silverman, Larry J. Siever
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- Journal:
- CNS Spectrums / Volume 8 / Issue 10 / October 2003
- Published online by Cambridge University Press:
- 07 November 2014, pp. 725-730
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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.
The Role of Childhood Trauma in Differences in Affective Instability in Those With Personality Disorders
- Marianne Goodman, Daniel S. Weiss, Harold Koenigsberg, Vladimir Kotlyarevsky, Antonia S. New, Vivian Mitropoulou, Jeremy M. Silverman, Karen O'Flynn, Larry J. Siever
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- Journal:
- CNS Spectrums / Volume 8 / Issue 10 / October 2003
- Published online by Cambridge University Press:
- 07 November 2014, pp. 763-770
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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.
Abuse and Neglect in Childhood: Relationship to Personality Disorder Diagnoses
- Linda M. Bierer, Rachel Yehuda, James Schmeidler, Vivian Mitropoulou, Antonia S. New, Jeremy M. Silverman, Larry J. Siever
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- Journal:
- CNS Spectrums / Volume 8 / Issue 10 / October 2003
- Published online by Cambridge University Press:
- 07 November 2014, pp. 737-754
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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.
Functional MRI of visuospatial working memory in schizotypal personality disorder: a region-of-interest analysis
- HAROLD W. KOENIGSBERG, MONTE S. BUCHSBAUM, BRADLEY R. BUCHSBAUM, JASON S. SCHNEIDERMAN, CHEUK Y. TANG, ANTONIA NEW, MARIANNE GOODMAN, LARRY J. SIEVER
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- Journal:
- Psychological Medicine / Volume 35 / Issue 7 / July 2005
- Published online by Cambridge University Press:
- 08 March 2005, pp. 1019-1030
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Background. Functional MRI studies have begun to identify neural networks implicated in visuospatial working memory in healthy volunteers and patients with schizophrenia. The study of schizotypal personality disorder (SPD) provides regional analysis in unmedicated patients in the schizophrenia spectrum.
Method. Unmedicated patients with SPD by DSM-IV criteria and normal controls were assessed with fMRI while performing a visuospatial working-memory task. It required the subjects to retain the location of three dots located on the circumference of an imaginary circle and then respond to a query display in which one dot was presented and the subject required to press a button to indicate whether the probe dot location was previously displayed. Subject groups did not differ significantly in spatial memory scores. The exact Talairach and Tournoux coordinates of brain areas previously reported to show activation with spatial memory tasks were assessed.
Results. The majority of these locations showed BOLD response activation significantly less in patients during the memory retention period, including the left ventral prefrontal cortex, superior frontal gyrus, intraparietal cortex and posterior inferior gyrus. Regions in the right middle prefrontal and prestriate cortex showed greater activation at a trend level for patients with SPD than for normal controls. In addition, we replicated the findings of increased activation with the task in healthy volunteers in the premotor areas, ventral prefrontal cortex and parietal cortex.
Conclusions. SPD patients show decreased activation compared to healthy volunteers in key frontal regions and we also provided a partial replication of findings reported in healthy subjects.