Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree.

We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia--schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.

The factor structure of schizotypal symptoms in a clinical population.

There is some support for the hypothesis that the factor structure of schizophrenia symptoms is similar to the factor structure of schizotypal symptoms in nonschizophrenia populations. However, no studies to date have examined schizotypal symptoms in patients with personality disorders. In this study, confirmatory factor analyses were conducted to test the relative fit of several models of the factorial structure of schizotypal symptoms in patients diagnosed with personality disorders.

Event-related potentials in schizotypal personality disorder.

This study examined whether abnormalities in event-related potentials (ERPs), reported in schizophrenia, extend to patients with schizotypal personality disorder (SPD). Auditory ERPs in an oddball paradigm were obtained in 19 SPD patients, 17 schizophrenic patients, and 20 normal control subjects (NCs). Schizophrenic patients had lower P300 amplitude than NCs; the P300 amplitude of SPD patients was intermediate, showing a linear trend but not a significant group difference.

Cognitive function and biological correlates of cognitive performance in schizotypal personality disorder.

There is evidence that some schizophrenic patients have deficits on tests of cognitive function, particularly tests of executive function, including the Wisconsin Card Sorting Test (WCST) and the Trail-making Test, Part B. This study was conducted to determine the generalizability of these findings across the schizophrenia spectrum to schizotypal personality disorder (SPD). Forty DSM-III SPD patients, 56 nonschizophrenia-related other personality disorder (OPD) patients, and 32 normal volunteers from two medical centers performed tests of executive function such as the WCST, Trail-making Part B, Stroop Word-Color Test, and Verbal Fluency, as well as tests of more general intellectual functioning such as the Wechsler Intelligence Scale-Revised Vocabulary and Block Design subtests, and Trail-making Part A.

Lateral ventricular enlargement in schizotypal personality disorder.

Although an increase in the ratio of ventricular space to brain (ventricle-brain ratio), VBR) on computed tomography (CT) has been among the most robust findings in chronic schizophrenia, VBR has not been investigated in a large, well-characterized clinical population of patients with schizotypal personality disorder (SPD), a clinical entity with a phenomenologic, gentle biological, and treatment response relationship to chronic schizophrenia. Accordingly, CT scans were obtained in 36 male SPD patients, 23 males with other personality disorders, 133 male schizophrenic patients, and 42 male normal volunteers. The mean body of the lateral VBR was significantly greater in the SPD patients than in the patients with other personality disorders.

Diurnal neuroendocrine and autonomic function in acute and remitted depressed male patients.

This study evaluated diurnal data gathered hourly (1000 to 1800 hours) in males during acute depression and during remission of depression and in age-range/gender-matched normal controls. Mean, peak, variability, and time-course of the noradrenergic metabolite, plasma 3-methoxy, 4-hydroxyphenylglycol [MHPG]), plasma cortisol, and autonomic (mean arterial blood pressure [MAP] and heart rate) variables were examined. Compared to controls, acutely depressed, but not remitted depressed, patients had 1) an earlier plasma MHPG peak, 2) a greater intragroup variability of plasma MHPG, 3) a higher plasma cortisol concentration, 4) a lower MAP, and 5) tended to increase MAP more slowly than did the normal controls.

Smooth pursuit performance in patients with affective disorders or schizophrenia and normal controls: analysis with specific oculomotor measures, RMS error and qualitative ratings.

Smooth pursuit performance in schizophrenia and affective disorders has generally been found to be abnormal using a variety of measures. The purpose of this study was to assess patients with these disorders and normal controls in order to compare the different measures across diagnoses. Smooth pursuit was assessed using quantitative specific measures (gain, catch-up saccade rate and amplitude, square-wave jerk rate, number of anticipatory saccades and total time scored), as well as two global measures: root mean-square error (RMS) and qualitative rating.

Learning and memory in combat veterans with posttraumatic stress disorder.

Objective: The authors investigated a broad range of memory functions for stimuli unrelated to trauma to determine whether symptoms such as intrusive memories might reflect an underlying cognitive deficit unrelated to the psychological content of the traumatic memory in patients with posttraumatic stress disorder (PTSD).

Method: The authors measured the intellectual functioning of 20 male combat veterans with PTSD and 12 normal comparison subjects using the WAIS and evaluated them for performance on memory using the California Verbal Learning Test.

Results: Veterans with PTSD showed normal abilities in the functions of initial attention, immediate memory, cumulative learning, and active interference from previous learning.

Eye movement impairment and schizotypal psychopathology.

Objective: Eye movement dysfunction in relation to a smooth pursuit task has been documented in schizophrenic patients and in patients with the related personality disorder, schizotypal personality disorder. To investigate which quantitative measures are associated with the eye movement dysfunction and whether the dysfunction is more related to the psychotic-like or the deficit-like symptoms of schizotypal personality disorder, ratings of eye movements in several groups of subjects were compared.

Method: The study groups consisted of 26 patients with schizotypal personality disorder, 42 patients with other personality disorders (22 who also had two or more schizotypal personality traits and 20 who had fewer than two), and 37 normal comparison subjects.

Performance of nonpsychotic relatives of schizophrenic patients on cognitive tests.

We tested 54 nonpsychotic first degree relatives of 23 schizophrenic probands and 18 control subjects matched for age and education on several neuropsychological tests. The tests were selected to assess overall intellectual ability or because previous work indicated that they are particularly sensitive measures of cognitive dysfunction in schizophrenic patients. The relatives of schizophrenic patients performed significantly worse than the control subjects on tests of verbal fluency and on Trailmaking, part B.

Clozapine treatment and its effect on neuroendocrine responses induced by the serotonin agonist, m-chlorophenylpiperazine.

The effects of clozapine treatment on neuroendocrine responses induced by the serotonin agonist, m-chlorophenylpiperazine (mCPP) were examined. mCPP and placebo were administered after a 2-week drug-free period and again after 5 weeks of clozapine treatment in nine schizophrenic inpatients. Adrenocorticotropic hormone (ACTH), prolactin, and mCPP levels were measured.

Familial correlates of reduced central serotonergic system function in patients with personality disorders.

Background: To test the hypothesis that evidence of reduced central serotonergic (5-HT) system function in probands with personality disorders is associated with an elevated morbid risk of psychopathological conditions putatively associated with 5-HT dysfunction in first-degree relatives of these probands.

Methods: Data were collected during a study of the 5-HT correlates of behavior in male patients with DSM-III personality disorders conducted at a Veterans Affairs medical center. Probands in this study were selected from those patients who had undergone both a fenfluramine hydrochloride challenge and a family history assessment.

Serotonergic function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder.

Objective: This study was designed to assess central serotonergic (5-HT) function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder.

Method: Prolactin response to a challenge dose of the 5-HT agonist d,l-fenfluramine was assessed in 25 7-11-year-old boys with attention deficit hyperactivity disorder who were divided into aggressive and nonaggressive subgroups. In addition, the subgroups were compared on plasma catecholamine metabolites and platelet 5-HT.

Effects of ipsapirone in healthy subjects: a dose-response study.

A dose-response study of ipsapirone (IPS), a 5HT1a partial agonist, was conducted in healthy male subjects. IPS was administered in doses of 5, 10 and 20 mg PO in a placebo-controlled, double-blind design to 15 subjects on 4 test days separated by at least 3 days. Oral temperature, ACTH, cortisol, prolactin, blood pressure, pulse rate and behavioral variables were assessed every 30 min for 3 h after administration of tablets (at 10:00 A.

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.

Biologic factors in schizotypal personal disorders.

New studies of the boundaries of schizophrenia suggest that schizotypal personality disorder is biologically and genetically related to schizophrenia with alterations in brain structure/function related to deficit-like symptoms and increased dopaminergic function to psychotic-like symptoms.

The cortisol response to clonidine in acute and remitted depressed men.

To assess the relationship between the hypothalamo-pituitary-adrenal (HPA) axis and the noradrenergic system in patients with major depression, 26 normal controls, 32 acutely depressed patients, and 21 patients with remitted depression, all men, were administered intravenous clonidine (2 micrograms/kg) or placebo. Acute, but not remitted, depressed patients had a greater plasma cortisol baseline than did normal controls (t = 2.0, p < 0.

Serotonin function and treatment response to clozapine in schizophrenic patients.

Objective: Clozapine is the only compound proven to be effective in the 20% of schizophrenic patients refractory to treatment with conventional neuroleptics. Although its mechanism of action has not been elucidated, clozapine appears, in contrast to most conventional neuroleptics, to be a potent serotonin (5-HT) antagonist. This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it.

The TRH-stimulation test in DSM-III personality disorder.

The authors examined thyrotropin-releasing hormone (TRH) stimulation testing in the neuroendocrine evaluation of DSM-III major depressive disorder in 26 consecutive medication-free, medically healthy patients meeting a primary DSM-III diagnosis of axis II personality disorder. Thyroid-stimulating hormone (TSH) responses to TRH challenge were not significantly different between patients with or without major depression at time of study, or between patients with or without a life history of major affective disorder. Further, TSH responses to TRH among 11 healthy male nonpsychiatric controls were not significantly different from those in patients with personality disorders.

Prevalence and stability of the DSM-III-R personality disorders in a community-based survey of adolescents.

Objective: The purpose of this study was to estimate the prevalence, concurrent validity, and stability of DSM-III-R personality disorders in a large community-based sample of adolescents.

Method: A randomly selected community sample of 733 youths ranging in age from 9 to 19 years was followed over a 2-year period. The protocol consisted of structured interviews with the adolescents and their mothers and self-report questionnaires.