L.J. Siever

Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study.

To assess the relationship between two phenotypes in an extremely well-characterized population of personality disorder patients-impulsive aggression and prolactin response to fenfluramine-and tryptophan hydroxylase (TPH) genotype, TPH genotype (at an intronic polymorphic site) and prolactin response to fenfluramine were assessed in 40 Caucasian patients with personality disorder. Impulsive aggression was assessed by using the Buss-Durkee Hostility Inventory (BDHI). Twenty-one male patients with the LL genotype had higher BDHI scores than men with the UL or the UU genotype. No relationship between genotype and prolactin response to fenfluramine was found. It was concluded that impulsive-aggressive behavior in male personality disorder patients may be associated with the TPH genotype.

Effects of Amphetamine on Visuospatial Working Memory Performance in Schizophrenia Spectrum Personality Disorder

Our objective was to determine if amphetamine improves visuospatial working memory, which is impaired in the schizophrenia spectrum and may be modulated by dopamine in prefrontal cortex. To this end, oral amphetamine (30 mg) was administered to 12 patients with schizophrenia spectrum personality disorders and 13 patients with other, nonschizophrenia-related personality disorders. Visuospatial working memory was assessed using the Dot test; a test in which subjects are asked to memorize and reproduce the position of a dot on a sheet of paper. Patients with schizophrenia spectrum personality disorders performed significantly worse than the comparison group in the placebo condition and showed significantly greater improvement after amphetamine, as compared to a nonschizophrenia-related personality disorder comparison group. Patients with greatest impairment at baseline improved most. Amphetamine tended to improve negative symptoms; whereas, positive symptoms remained unchanged. Amphetamine may improve visuospatial working memory in schizophrenia spectrum patients.

Physostigmine and cognition in schizotypal personality disorder

There is evidence that reduced cholinergic activity may play a role in the pathophysiology of cognitive impairment in the schizophrenia spectrum. We tested the effects of physostigmine, an anticholinesterase inhibitor, on visuospatial working memory as evaluated by the Dot test, and on verbal learning and recall as measured by a serial learning task in patients with schizotypal personality disorder. Physostigmine tended to improve the Dot test, but not serial verbal learning performance in these patients.

Memory impairment in schizophrenic patients with tardive dyskinesia.

Memory functioning was contrasted in 40 schizophrenic patients with and without tardive dyskinesia (TD). Visual and verbal memory tests were used to investigate specific types of impairments. The presence of TD was ascertained using the Abnormal Involuntary Movement Scale (AIMS). TD patients scored significantly lower than non-TD patients on two measures of visual learning, though no differences were found for verbal learning or immediate recall. These results are consistent with previous reports that schizophrenic patients with TD demonstrate impaired cognitive functioning. They also raise the possibility that the neurochemical and structural changes underlying TD may produce specific deficits in memory for visual materials. In addition, a significant relationship was found between total score on the Brief Psychiatric Rating Scale (BPRS) and performance on all of the test measures included in the cognitive test battery. This demonstrates the importance of attending to the overall level of schizophrenic symptomatology when evaluating results from experimental learning tasks.

Alpha2-adrenergic receptor function in patients with unipolar and bipolar affective disorders

Alpha 2-adrenergic receptor function was measured in platelets from unipolar (UP) depressed, bipolar (BP) depressed, and bipolar euthymic patients and normal control subjects. Only the platelets from UP depressed patients were different from control in having an increased number of alpha 2-receptors, a decreased percent norepinephrine inhibition of prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production, and a decrease in PGE1 stimulation of cAMP production. Platelets from BP patients, depressed or euthymic, were not significantly different from control subjects. These preliminary data suggest that alpha 2-adrenergic receptor function and PGE1 stimulation of cAMP production are diminished in UP patients.

Central Serotoninergic Stimulation by Fenfluramine Challenge Does Not Affect Plasma Thyrotropin-Stimulating Hormone Levels in Man

Thyrotropin-stimulating hormone (TSH) and prolactin (PRL) responses to an acute oral challenge of fenfluramine (60 mg), a central serotoninergic (5-hydroxytryptamine) releasing/uptake inhibiting agent, were examined in 8 healthy males in order to assess the role of central serotoninergic stimulation in the release of TSH. Plasma PRL, but not TSH, was significantly elevated by fenfluramine. These data suggest that central serotoninergic activity does not play an important role in the physiologic release of plasma TSH in man. Further, thyrotropin-releasing hormone is unlikely to be the PRL-releasing factor involved in the fenfluramine-induced stimulation of PRL.

Tricyclic response in obsessive compulsive disorder.

Therapeutic responses to the tricyclic antidepressant clomipramine have been demonstrated in five double blind studies of patients with obsessive compulsive disorder. Biological alterations in patients with obsessive compulsive disorder resemble those of depressed patients for the dexamethasone suppression test, for some measures of sleep physiology, and in similar neuroendocrine responses to clonidine. Clomipramines antiobsessional effect does not require high baseline depression ratings or biological abnormalities similar to those seen in depressives. Preliminary results suggest that in contrast to depressives, patients with obsessive compulsive disorder may respond to clomipramine but not to the tricyclic antidepressant desipramine.

Vocational functioning in schizotypal and paranoid personality disorders.

Impaired vocational functioning is a hallmark of schizophrenia, but limited research has evaluated the relationships between work and schizophrenia-spectrum personality disorders, including schizotypal (SPD) and paranoid personality disorder (PPD). This study compared employment history and job characteristics of 174 individuals drawn from the community or clinic, based on four personality disorder groups: SPD Only, PPD Only, SPD+PPD, and No SPD or PPD. Symptoms and cognitive functioning were also assessed. Both PPD and/or SPD were associated with lower rates of current employment, and a history of having worked at less cognitively complex jobs than people without these disorders. Participants with PPD were less likely to have a history of competitive work for one year, whereas those with SPD tended to have worked at jobs involving lower levels of social contact, compared with those without these disorders. When the effects of symptoms and cognitive functioning were statistically controlled, PPD remained a significant predictor of work history, and SPD remained a significant predictor of social contact on the job. The findings suggest that impaired vocational functioning is an important characteristic of SPD and PPD.

Gender differences in the clinical characteristics and psychiatric comorbidity in patients with antisocial personality disorder

Gender is an important variable in the study of mental health because of the actual and perceived differences between men and women. Relatively little is known how males and females differ in their manifestations of antisocial personality disorder (ASPD). Demographic and clinical features of 323 participants with ASPD were assessed and recorded. Women had fewer episodes of antisocial behavior involving or not involving police, higher scores on the Childhood Trauma Questionnaire (CTQ) and on Emotional Abuse and Sexual Abuse subscales of the CTQ compared to men. CTQ scores positively correlated with the number of episodes of antisocial behavior involving police in men but not in women. The percentage of patients with comorbid borderline and histrionic personality disorders was higher and the percentage of participants with cocaine use disorder was lower among women compared to men. Comorbid alcohol use disorder was frequent in both groups, while a higher percentage of women had comorbid mood disorders compared to men. Logistic regression analysis demonstrates that CTQ scores, histrionic personality disorder, and antisocial behavior involving the police drive the difference between the groups. Our findings indicate that treatment of individuals with ASPD should focus on the management of comorbid psychiatric disorders.

The stability of plasma growth hormone and MHPG responses to repeated clonidine challenge in normal males

Clonidine is a centrally acting alpha 2-adrenergic agonist used in many psychiatric studies to assess adrenergic functioning. The short- and long-term stability of plasma growth hormone (GH) and plasma 3-methoxy-4-hydroxy phenylglycol (MHPG) responses to clonidine (2 micrograms/kg IV) over a 60-min period were assessed in subsets of 13 male normal controls on 2 consecutive days (Study A; n = 11) and on 2 days separated by several months (Study B; n = 11). In Study A, no significant differences between consecutive days were found in either baseline plasma GH or MHPG or their responses to clonidine. The 60 minute plasma GH responses between consecutive days were highly correlated (r = 0.75, n = II, p < .001), while the 60 min plasma MHPG responses were not. In Study B, no significant differences in baseline plasma GH or MHPG, or their responses to clonidine challenge, were found between the 2 test days. However, neither the plasma GH responses nor the plasma MHPG responses to clonidine at 60 min correlated significantly between the 2 study days separated by several months. Both in Study-A and in Study B, 8 of 11 subjects had a stable GH response to clonidine across both study days when defined dichotomously (blunted < 4 ng/ml; otherwise, not blunted). These results suggest that the plasma GH response and plasma MHPG response to clonidine are unaffected by repeat clonidine challenge separated by 24 h, and that the plasma GH response to clonidine may be more stable over time than the plasma MHPG response to clonidine.