Schizophrenia susceptibility and chromosome 6p24-22.
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Chromosomes, Human, Pair 6↗
Biomedical subjects
L J Siever
Publications and source records attributed to L J Siever.
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. However, these veterans showed a circumscribed cognitive deficit, manifested by the presence of substantial retroactive interference and revealed by a significant decrement in retention following exposure to an intervening word list. CONCLUSIONS: The data suggest that patients with PTSD may have fairly specific deficits in the monitoring and regulation of memory information.
Adult↗
Circadian regulation of basal cortisol levels in posttraumatic stress disorder.
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Activity Cycles↗
Reduced prolactin response to fenfluramine challenge in personality disorder patients is not due to deficiency of pituitary lactotrophs.
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Adult↗
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. Clozapine treatment completely blocked mCPP-induced ACTH and prolactin release suggesting that clozapine blocks serotonin receptors that mediate these hormone responses.
Adrenocorticotropic Hormone↗
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. Axis II diagnosis were made according to DSM-III criteria after a structured interview of the proband, using the Structured Interview for Diagnosing Personality Disorders, given by two raters and a similar interview with a knowledgeable informant by another rater. RESULTS: Reduced prolactin responses to the 5-HT releasing/uptake inhibiting agent fenfluramine was associated with an elevated morbid risk of impulsive personality disorder traits in the first-degree relatives of patients with a primary DSM-III diagnosis of a personality disorder. Quantitative scores on assessments of impulsive aggression in the probands were not correlated with an increased morbid risk for impulsive personality disorder traits. A trend in the same direction was noted for affective personality disorder traits and alcoholism. CONCLUSIONS: These results suggest that a central 5-HT system abnormality in probands is associated with an increased risk of impulsive aggression in their first-degree relatives, and that assessment of central 5-HT system function in probands may be a more sensitive parameter for identification of this familial trait than the presence of impulsive aggressive behaviors in the proband.
Aggression↗
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. Each of these tests contributed unique variance to the discrimination between groups. The groups did not differ significantly on the number of perseverative errors on the Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Revised block design or vocabulary, or Trailmaking, part A. Eight relatives who met DSM-III-R criteria for schizotypal personality disorder were more impaired than the remaining 46 relatives on letter fluency, but otherwise their performance was similar to that of nonschizotypal relatives. These data suggest that close relatives of schizophrenic patients may have subtle neuropsychological impairments that are not necessarily associated with clinical symptoms of schizophrenia spectrum disorders.
Adult↗
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.
Adrenergic alpha-Agonists↗
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.
Attention↗
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. RESULTS: The aggressive group had a significantly greater prolactin response to the fenfluramine challenge than the nonaggressive subgroup. The groups did not differ on peripheral measures of neurotransmitter function. CONCLUSIONS: These data suggest that aggressive and nonaggressive children with attention deficit hyperactivity disorder differ in central 5-HT functioning.
Aggression↗
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. Smooth pursuit eye tracking of sinusoidal and constant velocity targets was recorded by an infrared eye tracking system. Two raters evaluated pursuit gain and large and small saccades in the direction of the target and in the direction opposite to that of the target (quantitative ratings) and constant velocity (qualitative rating). RESULTS: Patients with schizotypal personality disorder and patients with other personality disorders and two or more schizotypal traits, but not those with fewer than two schizotypal traits, had significantly poorer qualitative ratings of tracking than the normal comparison subjects. Neither gain nor any of the saccadic measures significantly differed between groups. The number of large saccades in the direction of the target was the only quantitative variable that predicted low qualitative ratings. Qualitatively poor tracking was associated with the deficit-like, but not the psychotic-like, symptoms of schizotypal personality disorder. CONCLUSIONS: Patients with schizotypal personality disorder demonstrate qualitatively poorer tracking than comparison groups, and the impaired tracking is associated with deficit-like symptoms.
Adult↗
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 < 0.03). Only acutely depressed patients had a greater decrease in plasma cortisol in response to clonidine than to placebo (t = 2.5, p < 0.02). Statistically controlling for both diurnal variation and baseline cortisol, acute, but not remitted, depressed patients had a greater decrease in plasma cortisol in response to clonidine than did the controls (analysis of covariance: F[1,35] = 4.26, p < 0.05). These results support a state-dependent noradrenergic-HPA axis regulatory disturbance in depressed patients, suggesting that clonidine inhibits the elevated plasma cortisol in acute depression but not the normal concentrations observed in remitted depression or healthy controls.
Adult↗
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. Comparison of those patients with blunted TSH responses (< 7.0 microU/ml) versus those without blunted response (< or = 7.0 microU/ml) also did not reveal a significant difference. In addition, the TSH response to TRH did not correlate with dimensional assessments of state or trait depression, anxiety, or with past history of suicide attempt or alcohol abuse. These data suggest that TRH stimulation testing has limited utility in the evaluation of major depression or other relevant affective states/traits in personality-disordered patients. Affective symptoms in personality-disordered patients do not seem to be associated with dysregulation of the hypothalamic-pituitary-thyroid axis.
Adult↗
Norepinephrine responses to postural and isometric stressors in acute and remitted depression.
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Adult↗
CSF homovanillic acid in schizotypal personality disorder.
CSF concentrations of homovanillic acid (HVA) were measured in 10 patients with schizotypal personality disorder and 14 patients with other personality disorders. The patients with schizotypal personality disorder had higher CSF HVA concentrations than the patients with other personality disorders. Furthermore, the psychotic-like schizotypal symptoms correlated positively with the CSF HVA concentrations. These results suggest a central dopaminergic dysfunction associated with the psychotic-like symptoms of schizotypal personality disorder.
Adult↗
Schizophrenia-related and affective personality disorder traits in relatives of probands with schizophrenia and personality disorders.
OBJECTIVE: The possible heterogeneity of the schizophrenia-related personality disorder traits associated with DSM-III criteria for schizotypal personality disorder was investigated using the family history method. A familial relationship to schizophrenia was hypothesized for schizophrenia-related personality disorder traits without coexisting affective personality disorder traits, pure schizophrenia-related personality disorder traits. Alternatively, a familial relationship with borderline personality disorder was hypothesized for schizophrenia-related personality disorder traits with comorbid affective personality disorder traits. METHOD: Criteria for schizophrenia-related and affective personality disorder traits were used to assess the 588 nonpsychotic first-degree relatives of 55 chronic schizophrenic probands and 67 probands with personality disorders. The probands with one or more DSM-III personality disorders were categorized as having schizotypal personality disorder without borderline personality disorder (pure schizotypal personality disorder), borderline personality disorder without schizotypal personality disorder (pure borderline personality disorder), both disorders, or neither. RESULTS: The morbid risk of all cases of schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder than in relatives of probands with neither schizotypal nor borderline personality disorder; however, it differed only slightly from that observed in the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. In contrast, the risk of pure schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder, while the risk of coexisting schizophrenia-related and affective personality disorder traits was lower in both of these groups than among the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. CONCLUSIONS: These results offer preliminary indications that schizotypal personality disorder features present without comorbid affective personality disorder traits may more specifically characterize the personality characteristics familially related to schizophrenia. Furthermore, they indicate that schizotypal personality disorder features as currently defined are found in relatives of patients other than those with schizophrenia or schizotypal personality disorder.
Adult↗
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. Algorithms for 10 DSM-III-R axis II disorders were developed to produce diagnoses at two levels of severity; these were validated against multiple indicators of distress and functional impairment. RESULTS: The overall prevalence of personality disorders peaked at age 12 in boys and at age 13 in girls and declined thereafter. Obsessive-compulsive personality disorder was the most prevalent moderate axis II disorder, narcissistic personality disorder the most prevalent severe disorder, and schizotypal personality disorder the least prevalent axis II disorder, based on both moderate and severe diagnostic thresholds. All moderate axis II disorders were associated with significantly greater odds for at least five of 12 diagnostic validators. Longitudinal follow-up revealed that although most axis II disorders did not persist over a 2-year period, subjects with disorders identified earlier remained at elevated risk for receiving a diagnosis again at follow-up. CONCLUSIONS: These findings suggest that a substantial minority of adolescents who are not in treatment qualify for DSM-III-R personality disorder diagnoses and that these diagnoses are associated with increased risk of psychological distress and functional impairment.
Adolescent↗
The boundaries of schizophrenia.
Evidence from a variety of domains including the phenomenologic, genetic, psychological, neuropsychological, psychophysiologic, neurochemical, imaging, outcome, and treatment response suggests that schizotypal personality disorder is related closely to chronic schizophrenia and that this disorder may be part of a continuum of schizophrenia-related disorders. Questions remain as to how the boundaries of schizophrenia should be defined. The commonalities across the schizophrenia spectrum as well as the differences between disorders on the spectrum need to be clarified further. A multidimensional approach to the pathogenesis of the schizophrenia-related disorders offers a beginning opportunity for such a clarification. The study of patients with schizotypal personality disorder suggest that a dimension of deficit-like or "negative" symptoms of asociality and interpersonal impairment may be associated with neuropsychological and psychophysiologic correlates of altered cortical, particularly frontal, function and raise the possibility in structural changes as reflected in increased ventricular size in frontal and third ventricle areas. On the other hand, the psychotic-like or "positive" symptoms seem to be more related to increases in dopaminergic activity that may be partially responsive to neuroleptic treatment. It is conceivable that these two dimensions may represent partially distinct but potentially interactive pathophysiologic processes that may converge and interact to result in chronic schizophrenia. In this way, the study of the boundaries of schizophrenia and the milder schizophrenia-related personality disorders may provide important clues as to the genetic and pathophysiology of chronic schizophrenia itself, as well as to illuminate a set of disorders that are clinically underrecognized but probably more prevalent than more severe forms of schizophrenia.
Attention↗