Biomedical subjects

L J Siever

Publications and source records attributed to L J Siever.

At least 37 records · Page 2Linked to original sources

PubMed1999

Genetic antecedents of dopamine dysfunction in schizophrenia.

BACKGROUND: Relatives of schizophrenic probands frequently manifest attenuated features of this illness including the negative symptoms and the milder positive psychotic symptoms. These two symptom dimensions are hypothesized to be associated with decreased and increased brain dopamine (DA) functions, respectively, raising the possibility that DA abnormalities may be present in the relatives of schizophrenic probands. METHODS: Plasma homovanillic acid (HVA), the major DA metabolite and an indicator of brain DA activity, was measured in nonpsychotic, physically healthy first-degree relatives (n = 55) of schizophrenic probands and in normal subjects (n = 20) without a family history of schizophrenia. RESULTS: Plasma HVA inversely correlated with negative symptoms and positively correlated with attenuated positive symptoms. Also, relatives had decreased plasma HVA compared to normal subjects, consistent with the fact that these relatives are characterized by negative symptoms. These findings were not related to major peripheral factors that could affect plasma HVA suggesting that the findings may reflect changes in brain DA activity. CONCLUSIONS: Negative symptoms indicating a genetic diathesis to schizophrenia in relatives may have a biologic basis in reduced DA activity and the DA dysfunction of schizophrenia may have genetic antecedents. This opens an important new avenue for further study of DA in this illness.

Adult↗

PubMed1999

Serum cholesterol and impulsivity in personality disorders.

Decreased serum cholesterol has been associated with impulsive aggressive behaviors. This study was designed to explore the relationship between serum cholesterol levels and measures of impulsive aggression in personality disordered patients. Forty-two personality disordered patients (14 borderline personality disorder, 28 other personality disorders) were included. Fasting serum cholesterol was measured by standard enzymatic assay. An ANOVA was performed with factors of gender and diagnosis, looking at two-way interactions between the factors and serum cholesterol. Patients with borderline personality disorder were found to have significantly lower serum cholesterol than non-borderline personality disorders. A significant interaction effect was also seen between gender and diagnosis with the male patients having lower cholesterol levels. This study suggests there may be a relationship between borderline personality disorder and low serum cholesterol.

Adult↗

PubMed1999

Relationship between depression and borderline personality disorder.

The frequent occurrence of depressive symptoms in patients with borderline personality disorder has generated considerable interest in the nature of the relationship between borderline personality disorder and the depressive disorders. Data from the perspectives of phenomenology, biology, family history, course of illness, comorbidity patterns, and treatment response have been brought to bear on the question. Reviews based on research available by 1985 and 1991, respectively, arrived at differing conclusions: (1) that both disorders shared common but non-specific sources, and (2) that the two disorders were unrelated but co-occurred because of the high prevalence of each. Since the time of these reviews, additional evidence has become available from a wider range of biological investigations, better controlled comorbidity studies, studies of the relationship of psychosocial stressors to the course of each disorder and neuroimaging studies. In reviewing the more recent findings, we propose the less parsimonious hypothesis that the disorders co-occur, both because they share some common biological features and because the psychosocial sequella of each can contribute to the development of the other.

Borderline Personality Disorder↗

PubMed1999

d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography.

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered patients in metabolite and pharmacologic challenge studies. This study used positron emission tomography to explore whether reduced serotonergic function occurs in critical brain regions such as orbital frontal and cingulate cortex that, may play a role in modulating aggression. Six impulsive-aggressive patients and five healthy volunteers were evaluated for changes in regional glucose metabolism after administration of the serotonergic releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers demonstrated increases in orbital frontal and adjacent ventral medial frontal cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive patients showed no significant increases in glucose metabolism after fenfluramine in any region. Compared with volunteers, patients showed significantly blunted metabolic responses in orbital frontal, adjacent ventral medial and cingulate cortex, but not in inferior parietal lobe. These results are consistent with reduced serotonergic modulation of orbital frontal, ventral medial frontal, and cingulate cortex in patients with impulsive-aggressive personality disorders.

Adult↗

PubMed1999

Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.

OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.

Adult↗

PubMed1998

Plasma norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations and severity of depression in combat posttraumatic stress disorder and major depressive disorder.

BACKGROUND: Catecholamines are thought to play a significant role in the pathophysiology of posttraumatic stress disorder (PTSD), but findings in PTSD have been discrepant. METHODS: To obtain more information about catecholamine activity in PTSD, we sampled plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations over a 24-hour period in men with PTSD (n = 15) and major depressive disorder (MDD) (n = 12), and nonpsychiatric comparison subjects (n = 13), under unstimulated conditions. Chronobiological analyses were performed to determine possible changes in the circadian and ultradian release of these hormones. RESULTS: Significant group differences were present for mean plasma NE levels (p = .03), but not MHPG. NE levels were significantly associated with severity of depression in the PTSD group (p = .002). Therefore, PTSD subjects were further subdivided into those with and without a comorbid secondary depression. Increased NE levels were only present in PTSD subjects who did not have a secondary depression. This study also found no significant group differences on any of the chronobiological parameters. CONCLUSIONS: The results clarify that increased NE levels in PTSD may be confined to the subgroup of subjects who do not have comorbid depression, and as such, may help resolve some of the discrepancies in the literature regarding basal catecholamine activity.

Activity Cycles↗

PubMed1998

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.

Adult↗

PubMed1998

Lateral ventricular enlargement in schizophrenic probands and their siblings with schizophrenia-related disorders.

BACKGROUND: To investigate possible genetic determinants of ventricular enlargement in schizophrenia, we compared lateral ventricle/brain ratios (VBRs) in schizophrenic patients with their own siblings, some with and some without other schizophrenia-related disorders [e.g., schizotypal personality disorder (SPD)], as well as with a group of unrelated normal controls. METHODS: VBRs, measured by computed tomography, were compared in both groupwise and within-sibship analyses, the latter method providing a measure of control over familial/genetic factors related to VBR, but unrelated to schizophrenia. RESULTS: The VBRs were significantly different across the groups, but the only significant pairwise group comparison was between the schizophrenia and no-SRD family member groups. In the within-sibship analyses, however, the VBRs of those with SPD and schizophrenia were similar, and both groups had significantly larger VBRs than their own siblings without SRD. In addition, siblings with a negative family history for SRD had larger VBRs than family history positive siblings. CONCLUSIONS: The results suggest that specific schizophrenia-related genetic factors may help determine ventricular enlargement in familial schizophrenia. The larger VBRs in family history negative siblings might be attributable to genetic factors not specifically associated with schizophrenia, but which nevertheless increase its susceptibility.

Adult↗

PubMed1998

Verbal learning and memory in schizotypal personality disorder.

The investigation of cognitive deficits in patients with schizotypal personality disorder (SPD) is important both to establish commonalities between SPD and schizophrenia and to clarify the significance of these cognitive deficits for schizophrenic disorders. The purpose of this study was to examine verbal learning and memory with the California Verbal Learning Test (CVLT) in a group of patients with SPD (n=24) and a group of patients with personality disorders other than SPD (OPD; n=25). The results indicated that SPD patients learned significantly fewer words with practice on the CVLT than OPD patients (F=4.32, df=1,47, p < 0.05), and their rate of learning was reduced relative to normative standards. These findings suggest that SPD patients have a deficit in verbal learning that is similar to, although not as severe as, the impairments seen in schizophrenia.

Adult↗

PubMed1998

Serotonin transporter protein gene polymorphism and personality measures in African American and European American subjects.

OBJECTIVE: The SLC6A4 locus encodes the serotonin transporter, which in turn mediates the synaptic inactivation of the neurotransmitter serotonin. A polymorphism located in the 5' promoter region of the gene is associated with altered transcriptional activity of SLC6A4; an earlier study reported an association of the polymorphism with anxiety- and depression-related traits, including harm avoidance and neuroticism. The authors attempted to replicate this finding. METHOD: They assessed genotype at the SLC6A4 promoter polymorphism, and an additional polymorphism in intron 2, in 322 American subjects of European and African ancestry, some with diagnoses of a personality disorder or substance dependence and some normal comparison subjects. Harm avoidance was measured by the Tridimensional Personality Questionnaire in all subjects, and neuroticism was measured by the NEO Five-Factor Inventory in 185 subjects. Allele frequencies in the groups were compared, and hierarchical multiple regression was used to examine the correlation of demographic features, psychiatric diagnostic group, and genotype with harm avoidance and neuroticism scores. RESULTS: Although the demographic factors and psychiatric diagnoses had effects on harm avoidance and neuroticism scores, there was no main effect of genotype on these personality measures. In the context of these overall negative findings, interactions were observed between sex and promoter system genotype and between race and promoter system genotype which suggest that the present findings are not wholly inconsistent with those of the earlier study. CONCLUSIONS: The authors were unable to replicate the association finding. The specific phenotypic composition of the groups studied with respect to other behaviors could have influenced ability to detect association of SLC6A4 polymorphisms with personality measures; population stratification for this locus is also of potential importance.

Adult↗

PubMed1998

Genome scan of schizophrenia.

OBJECTIVE: The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHOD: A genomewide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals--126 of them with schizophrenia-related psychoses--from 43 pedigrees. Nonparametric linkage analysis was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirically derived p values reached nominal levels of significance at eight marker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002). CONCLUSIONS: The results do not support the hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychiatric disorders) has limited power to detect genes of small effect or those that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely to contain schizophrenia susceptibility genes.

Chromosome Mapping↗

PubMed1998

Relationship between posttraumatic stress disorder characteristics of Holocaust survivors and their adult offspring.

OBJECTIVE: There is controversy regarding the long-lasting effects of the Holocaust on the adult children of Holocaust survivors. In the present study the authors examined the relationship between posttraumatic stress disorder (PTSD) characteristics of Holocaust survivors and their adult children to determine whether differences in symptom severity or diagnostic status of parents would be associated with similar characteristics in their adult children. METHOD: Holocaust survivors (N = 22) and their offspring (N = 22) were interviewed with several instruments to assess lifetime trauma history, effect of trauma on one's life, level of intrusive and avoidance symptoms in response to reminders of the Holocaust, current and lifetime PTSD, and current and lifetime axis I psychiatric disorder other than PTSD. RESULTS: There were significant relationships between parents and children regarding the effect of trauma on one's life and level of intrusive, but not avoidance, symptoms in response to reminders of the Holocaust. Offspring with traumatic events were more likely to develop PTSD if their parents had PTSD. CONCLUSIONS: Symptoms in offspring may be related to presence and severity of symptoms in the parent. Furthermore, PTSD in the parent may be a risk factor for PTSD in offspring.

Adult↗

PubMed1997

Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness.

Three central indices of serotonin (5-HT) system activity in human subjects were examined to: (a) estimate intercorrelations among 5-HT indices and (b) compare correlations of these indices with a measure of assaultiveness (Buss-Durkee 'Assault') in personality-disordered individuals. Cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentration and prolactin responses to m-chlorophenylpiperazine (m-CPP) m-CPP (PRL[m-CPP]) and fenfluramine (PRL[FEN]), served as indices of pre-, post- and 'net'-synaptic central 5-HT activity, respectively. PRL[D,L-FEN] responses were inversely related to CSF 5-HIAA concentration and positively correlated with PRL[m-CPP] responses. Both PRL[D,L-FEN] and PRL[m-CPP] response data correlated equally, and inversely, with BD Buss-Durkee Assault when the same subjects were examined. Basal CSF 5-HIAA concentration did not correlate with Buss-Durkee 'Assault'. PRL responses to challenge probes which involve activation of 5-HT post-synaptic receptors may correlate better than a basal measure of pre-synaptic 5-HT function with a tendency to assaultive behavior in non-criminally aggressive personality-disordered individuals.

Adult↗

PubMed1997

Regional cerebral blood flow during the Wisconsin Card Sort Test in schizotypal personality disorder.

Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography in 10 patients with schizotypal personality disorder (SPD) and nine age- and sex-matched normal volunteers. Subjects performed both the Wisconsin Card Sort Test (WCST) and a control task, the Symbol Matching Test (SMT). Four-way analyses of variance were performed to assess relative rCBF of the prefrontal cortex and of the medial temporal region. Normal volunteers showed more marked activation in the precentral gyrus, while SPD patients showed greater activation in the middle frontal gyrus. Relative flow in the left prefrontal cortex was correlated with better WCST performance in normal volunteers. SPD patients, however, showed no such correlations in the left prefrontal cortex, but demonstrated correlations of good and bad performance with CBF in the right middle and inferior frontal gyrus, respectively. Thus, at least some SPD patients demonstrate abnormal patterns of prefrontal activation, perhaps as a compensation for dysfunction in other regions.

Adult↗

PubMed1997

Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging.

Magnetic resonance imaging (MRI) was performed in 12 patients with schizotypal personality disorder (SPD), 11 patients with chronic schizophrenia, and 23 age- and sex-matched normal volunteers. MRI slices were acquired in the axial plane at 1.2-mm intervals, and the ventricles were traced on every other slice. The lateral ventricular system was divided into the anterior horn, temporal horn, and dorsal lateral ventricle. Schizophrenic patients had larger left anterior and temporal horns than the normal volunteers. Size of the left anterior and temporal horn in SPD patients was intermediate between those of normal volunteers and schizophrenic patients and differed significantly from schizophrenic patients. The left-minus-right difference was larger in schizophrenic patients than in normal volunteers or SPD patients. Thus, in their structural brain characteristics, as well as in their clinical symptomatology, SPD patients evidence, in attenuated form, abnormalities resembling those found in full-fledged schizophrenia. The findings suggest that decreased left hemispheric volume, in frontal and temporal regions, may characterize both psychotic and non-psychotic disorders of the schizophrenia spectrum.

Adult↗

PubMed1997

Attentional and eye tracking deficits correlate with negative symptoms in schizophrenia.

Thirty patients with a DSM-III-R diagnosis of schizophrenia were assessed for severity of schizophrenic symptoms using the Brief Psychiatric Rating Scale (BPRS) and were tested on a Continuous Performance Test (CPT) and a smooth pursuit eye tracking task. Negative symptoms were significantly correlated with eye tracking impairment (r = 0.43, p < 0.01) and CPT deficits (r = 0.67, p < 0.001), but performance on neither task was correlated with positive symptoms. CPT performance and eye tracking performance were modestly correlated with each other (r = 0.39, p < 0.01) and CPT performance was found to be a stronger predictor of negative symptoms than eye tracking performance. These data indicate that neurocognitive markers of vulnerability to schizophrenia are associated with negative rather than positive symptoms.

Adult↗

PubMed1997

Validity of the family history method for identifying schizophrenia-related disorders.

We examined the family history method's validity for identifying schizophrenia related disorders (SRD) by comparing family history and family study derived diagnoses. First degree relatives (n = 284) of 48 psychiatrically disordered probands, predominantly with schizophrenia, were diagnosed using the Family History RDC (FH-RDC) which include three psychotic schizophrenia related disorders (P-SRD): schizophrenia, chronic SAD and chronic unspecified functional psychosis (CUFP). Supplementary criteria for schizophrenia related personality disorders (SRP), derived to identify schizotypal and paranoid personality disorders (PD), were also assessed. About two thirds of these relatives (n = 196; 69.0%) were independently diagnosed by RDC and DSM-III-R on both axis I and axis II in a family study. The specificity was 1.0 (178/178) and the sensitivity of the family history derived diagnosis for P-SRD was 0.72 (13/18). Sensitivity for P-SRD was improved, however, by inclusion of SRP which captured three of the five false negative relatives. The sensitivity of SRP for schizotypal or paranoid PD was 0.39 (15/38) and the specificity was 0.92 (127/138). The FH-RDC have moderately good sensitivity and excellent specificity for the psychotic schizophrenia related disorders. While family history criteria for SRP are not a good proxy for schizotypal or paranoid PD, they can enhance the family history method's sensitivity for SRD.

Adult↗

PubMed1997

Age-related changes in the association between serotonergic function and aggression in boys with ADHD.

The results of several studies have indicated an inverse relationship between central serotonergic (5-HT) mechanisms and aggression in animals and adults, but studies in children have yielded conflicting results. This study assessed 5-HT function, using a fenfluramine (FEN) challenge procedure, in an attempt to replicate a previously reported enhancement of the prolactin (PRL) response to FEN in aggressive relative to nonaggressive ADHD boys. The study failed to replicate the previous finding. Samples from both studies were then examined to reconcile the discrepant findings. The samples differed significantly in age. The entire group (n = 50) was then divided into older and younger subgroups and reanalyzed using a two-way (age-group x aggression) analysis of covariance (ANCOVA) controlling for plasma medication level. The ANCOVA generated a significant age-group x aggression interaction. Young aggressive boys had a significantly greater PRL response to FEN than young nonaggressive boys, but no such difference existed in the older age-group. These findings raise the possibility of different developmental trajectories in 5-HT function between aggressive and nonaggressive boys.

Aggression↗