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Biomedical subjects

L J Siever

Publications and source records attributed to L J Siever.

At least 19 recordsLinked to original sources
PubMed2001

Suicide, impulsive aggression, and HTR1B genotype.

BACKGROUND: Suicidality and impulsive aggression are partially heritable, and postmortem brain studies suggest that abnormalities in serotonin 1B may be associated with suicide. Studies of serotonin 1B "knockout" mice show an increase in aggressive behavior relative to wild-type mice. METHODS: We assessed the relationship between genotype at the HTR1B locus and both suicide history and impulsive aggression in personality disorders. RESULTS: The "G" allele of a polymorphic gene at the HTR1B locus was associated with a history of suicide attempts in white patients with personality disorders [chi(2)(1) = 9.3, p =.01, n = 90]. No relationship was found between HTR1B genotype and self-reported impulsive aggression. CONCLUSIONS: This preliminary finding suggests that allelic variability at the HTR1B locus may be associated with the susceptibility to suicide attempts in patients with personality disorders.

Adult↗
PubMed2001

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia.

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

Relationship between central serotonergic function and aggression in prepubertal boys: effect of age and attention-deficit/hyperactivity disorder.

Data indicate that diminished central serotonergic (5-HT) function is related to aggression in adults, but discrepant findings in children suggest that age or the presence of attention-deficit/hyperactivity disorder (ADHD) may influence this relationship. This study examined whether age or ADHD affects the association between 5-HT and aggression in 7-11-year old clinically-referred boys. Forty-six boys were divided into non-aggressive ADHD, aggressive ADHD, and aggressive non-ADHD groups based on responses to interviews and ratings of behavior. Central 5-HT function was assessed by measuring the prolactin response to a 1-mg/kg oral dose of D,L-fenfluramine. There was no significant difference in the prolactin response across the three groups of boys. Furthermore, when examined dimensionally, prolactin response was largely unrelated to ratings of aggression, even after controlling for ADHD. Finally, age was not associated with prolactin response, and had no effect on the relationship between prolactin response and aggression. This study provides further evidence that there is no clear relationship between central 5-HT function and aggression in disruptive boys. Moreover, these data do not confirm the hypothesis that age or the presence of ADHD influence the relationship between 5-HT and childhood aggression.

Age Factors↗
PubMed2001

Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder.

BACKGROUND: The importance of neuronal interactions in development, the cortical dependence of many thalamic nuclei, and the phenomenon of transsynaptic degeneration suggest possible abnormalities in thalamic nuclei with connections to other brain regions implicated in schizophrenia. Because frontal and temporal lobe volumes are diminished in schizophrenia, volume loss could characterize their primary thalamic relay nuclei (mediodorsal nucleus [MDN] and pulvinar). METHODS: Tracers delineated the thalamus, MDN, and pulvinar on contiguous 1.2-mm magnetic resonance images in 12 schizophrenic patients, 12 with schizotypal personality disorder (SPD), and 12 normal control subjects. The MDN and pulvinar were rendered visible by means of a Sobel intensity-gradient filter. RESULTS: Pixel overlap for delineation of all structures by independent tracers was at least 80%; intraclass correlations were r = 0.78 for MDN and r = 0.83 for pulvinar. Pulvinar volume was smaller in schizophrenic (1.22 +/- 0.24 cm(3)) and SPD (1.20 +/- 0.23 cm(3)) patients than controls (1.37 +/- 0.25 cm(3)). Differences for MDN were not statistically significant; however, when expressed as percentage of total brain volume, pulvinar and MDN together were reduced in SPD (0.14%) and schizophrenic (0.15%) patients vs controls (0.16%). Reductions were more prominent in the left hemisphere, with MDN reduced only in the schizophrenic group, and pulvinar in both patient groups. Total thalamic volume did not differ among the 3 groups. CONCLUSIONS: Measurement of MDN and pulvinar in magnetic resonance images is feasible and reproducible. Schizophrenic and SPD patients have volume reduction in the pulvinar, but only schizophrenic patients show reduction relative to brain volume in MDN.

Adult↗
PubMed2001

Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia.

BACKGROUND: Schizotypal personality disorder (SPD) shares social deficits and cognitive impairment with schizophrenia, but is not typically characterized by frank psychosis. Because striatal size and functional activity have both been shown to be associated with psychotic symptoms, we carried out the first study of SPD to assess the caudate and putamen for comparison with findings in schizophrenia. METHODS: Patients with SPD (n = 16), schizophrenic patients (n = 42), and age- and sex-matched normal control subjects (n = 47) were assessed with magnetic resonance imaging. All of the patients with SPD and subsamples of the schizophrenic patients (n = 27) and control subjects (n = 32) were also assessed with positron emission tomography using fluorodeoxyglucose F-18. RESULTS: The relative size of the putamen in controls was significantly larger than in patients with SPD and significantly smaller than in schizophrenic patients, while the relative size of the caudate was similar in all 3 groups. Compared with control values, relative glucose metabolic rate in the ventral putamen was significantly elevated in patients with SPD and reduced in schizophrenic patients. When subsamples of schizophrenic patients (n = 10) and patients with SPD (n = 10) both of whom never received medication were compared, this pattern was more marked, with the highest value for the putamen being found in patients with SPD for the ventral slice and the lowest value for the right dorsal putamen. CONCLUSIONS: Patients with SPD showed reduced volume and elevated relative glucose metabolic rate of the putamen compared with both schizophrenic patients and controls. These alterations in volume and activity may be related to the sparing of patients with SPD from frank psychosis.

Adult↗
PubMed2001

Variability and severity of depression and anxiety in post traumatic stress disorder and major depressive disorder.

In order to better characterize the similarities in and differences between the nature of the affective disturbance associated with Posttraumatic Stress Disorder (PTSD) and with Major Depressive Disorder (MDD), self-reported mood and anxiety ratings were examined in PTSD subjects, MDD subjects, and subjects without a psychiatric disorder while they were undergoing a chronobiologic study. Based on serial ratings on visual analogue scales over a 24 hr period, PTSD subjects showed comparable levels of depression as the MDD group, as measured by the mean and maximum levels of mood; however, they had greater mood variability, as measured by the range and coefficients of variation of the mood ratings. The MDD but not the PTSD group had significantly lower mood variability than the non-psychiatric group, as measured by the coefficients of variation. The PTSD group reported higher levels of anxiety than the non-psychiatric or MDD group but showed no differences in any measure of variability of anxiety. These findings suggest there are phenomenologic differences in the affective symptoms experienced by patients with PTSD and with MDD and that mood variability may distinguish between them.

Adult↗
PubMed2001

Are the interpersonal and identity disturbances in the borderline personality disorder criteria linked to the traits of affective instability and impulsivity?

This study examines the degree to which two putative biologically influenced personality traits, affective instability and impulsive aggression, are associated with some of the interpersonal and intrapsychic disturbances of borderline personality disorder (BPD) and with choice of defense mechanism. In a sample of 152 personality disorder patients, affective instability and impulsive aggression were measured. Defense mechanisms were assessed in 140 of these patients using the Defensive Style Questionnaire (DSQ). The correlations between the traits of affective instability and impulsive aggression and the eight DSM-III-R criteria for borderline personality disorder and 20 DSQ defenses were examined. Affective instability was significantly correlated with the DSM-III-R criteria of identity disturbance, chronic emptiness or boredom, inappropriate anger, suicidality, and the affective instability criteria. It also was associated with the defenses of splitting, projection, acting out, passive aggression, undoing, and autistic fantasy. Impulsive aggression was related to unstable interpersonal relationships, inappropriate anger and impulsiveness and with the defense of acting out. It was negatively correlated with the defenses of suppression and reaction formation. A number of the interpersonal and experiential disturbances and defense mechanisms that are features of BPD are associated with the traits of affective instability and impulsive aggression among patients with personality disorders.

Adult↗
PubMed2001

A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder.

BACKGROUND: Borderline personality disorder is characterized by affective instability, impulsivity, and aggression and is associated with considerable morbidity and mortality. Since anticonvulsant agents may be helpful in such symptomatology, we compared divalproex sodium with placebo in patients with borderline personality disorder. METHOD: A 10-week, parallel, double-blind design was conducted. Sixteen outpatients meeting Structured Clinical Interview for DSM-IV Axis II Personality Disorders criteria for borderline personality disorder were randomly assigned to receive placebo (N = 4) or divalproex sodium (N = 12). Change was assessed in global symptom severity (Clinical Global Impressions-Improvement Scale [CGI-I]) and functioning (Global Assessment Scale [GAS]) as well as in specific core symptoms (depression, aggression, irritability, and suicidality). RESULTS: There was significant improvement from baseline in both global measures (CGI-I and GAS) following divalproex sodium treatment. A high dropout rate precluded finding significant differences between the treatment groups in the intent-to-treat analyses, although all results were in the predicted direction. CONCLUSION: Treatment with divalproex sodium may be more effective than placebo for global symptomatology, level of functioning, aggression, and depression. Controlled trials with larger sample sizes are warranted to confirm these preliminary results.

Adolescent↗
PubMed2000

Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder.

The size and shape of the corpus callosum were assessed on sagittal section magnetic resonance images in 27 patients with schizophrenia, 13 patients with schizotypal personality disorder (SPD), and 30 healthy volunteers. High-resolution 1.2mm axial SPGR images were acquired and resectioned so that the sagittal plane passed through the anterior and posterior commissures and was parallel to the interhemispheric fissure. The corpus callosum and the whole brain were traced on midsagittal section slices of each brain, and the callosum was divided into 30 anteroposterior sectors. Pixel-by-pixel chi-square and thin-plate spline analyses were used to assess between-group shape differences. Size of the corpus callosum was smaller anteriorly in the genu of the corpus callosum and posteriorly in the splenium in schizophrenic patients than in normal controls. The genu of the corpus callosum was larger in SPD patients than in schizophrenic patients or normal controls. The posterior corpus callosum was largest in normal controls, smaller in SPD patients, and smallest in schizophrenic patients. Shape analysis was consistent with these size comparisons, and suggested a downward bowing of the corpus callosum in schizophrenic and SPD patients. SPD patients also had a region of the callosum just posterior to the genu that was narrower than in the other two groups. The decreases in corpus callosal size in schizophrenia varied directly with length of illness, perhaps indicative of a progressive process. The patient-control differences in callosal size and shape are consistent with a hypothesis of decreased connectivity between the left and the right hemispheres in schizophrenia and SPD.

Adult↗
PubMed2000

Visuospatial working memory in schizotypal personality disorder patients.

BACKGROUND: Cognitive processing deficits have been identified as an abnormality that schizotypal personality disorder (SPD) individuals share with schizophrenic patients. It has been hypothesized that impaired working memory may be a critical component of several of the more complex cognitive deficits found in schizophrenia spectrum patients. METHOD: 18 DSM-III-R SPD patients, and 17 normal comparison subjects were compared on a pen and paper visuospatial working memory task. Moreover, we identified a second psychiatric comparison group comprised of nine patients with other, non-odd cluster personality disorder diagnoses who met no more than one of the SPD criteria and were also tested on the same task. Each person was given 14 immediate recall trials and 10 trials using a 10 s delay. RESULTS: SPD patients performed significantly worse than normal control subjects on the working memory task. SPD patients also performed significantly worse compared to the non-schizophrenia-related personality disorder psychiatric comparison group. CONCLUSIONS: Like schizophrenic patients, SPD patients demonstrate working memory impairment compared to normal controls. This impairment may be specific to the schizophrenia-related personality disorders.

Adult↗
PubMed2000

New perspectives on schizotypal personality disorder.

Schizotypal personality disorder is the prototype of the schizophrenia-related personality disorders and has been demonstrated to have phenomenologic, biologic, treatment, and outcome characteristics similar to those of schizophrenic patients. These studies suggest that patients with schizotypal personality disorder, like schizophrenic patients, show cognitive impairment, but the impairment is more focal and involves primarily working memory, verbal learning, and sustained attention rather than generalized intellectual deficits. Schizotypal patients, like schizophrenic patients show reductions in temporal lobe volume, but seem to be spared the frontal volume reductions found in some studies of schizophrenic patients and in our laboratory. Better frontal "buffering" may prevent the more severe cognitive and social deterioration associated with schizophrenia. Furthermore, schizotypal patients appear to show less susceptibility to psychotic symptoms, in part perhaps because of better buffered subcortical dopaminergic activity as suggested by recent data from a SPECT/amphetamine paradigm, glucose metabolic study, and structural studies of basal ganglia. These findings are discussed in terms of a model of schizotypal personality disorder where schizotypal patients have better capacity for compensatory buffering in lateral and subcortical brain regions, protecting them from the more severe symptoms of chronic schizophrenia.

Amphetamines↗
PubMed2000

Neurotransmitter dysfunction in patients with borderline personality disorder.

Neurotransmitter system dysfunction may contribute to the borderline personality disorder traits of impulsive aggression and affective instability. This article reviews evidence from neurochemical assays, receptor-density studies, neuroendocrine-challenge paradigms, functional neuroimaging studies, and candidate-gene research, which converge to identify particular neurotransmitter systems that seem to be dysregulated in patients with borderline personality disorder.

Acetylcholine↗
PubMed2000

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.

Adult↗
PubMed2000

Schizotypal symptoms in the relatives of schizophrenia patients: an empirical analysis of the factor structure.

This study examined the nature of schizotypal symptoms in the relatives of schizophrenia patients and investigated phenomenological differences in symptomatology manifested by a familial sample and a clinical sample of personality disorder patients. Confirmatory factor analyses were used to test models of DSM-III-R schizotypal symptoms in the first degree relatives (n = 172) of schizophrenia patients. A multisample analysis was conducted to determine whether the same model adequately described the schizotypal symptoms rated in the relatives of schizophrenia patients and in clinically selected personality disorder patients. The results indicated that a three-factor model consisting of cognitive/perceptual, interpersonal, and disorganization factors yielded the best fit to the data from the relatives of schizophrenia patients, but that this model did not adequately describe both the relatives of schizophrenia patients and personality disorder patients. These findings indicate that the structure of schizotypal symptoms in the relatives of schizophrenia patients is similar to the three-factor model of schizophrenia symptoms often reported, but not the same as the structure of schizotypal symptoms in clinically selected personality disorder patients.

Adolescent↗
PubMed1999

Serotonin and the prediction of response time to fluoxetine in patients with mild depression.

Serotonin (5-HT) dysregulation has been associated with major depressive disorder (MDD); a blunted prolactin (PRL) response to D,L-fenfluramine (FEN) has been associated with MDD. Pharmacologic manipulation of the serotonin system with a selective serotonin reuptake inhibitor (SSRI) is effective in the treatment of depression. However, the relationship between pre-treatment 5-HT activity and response to SSRIs is not well understood. This study investigated the relationship between 5-HT dysregulation and response to fluoxetine (FLU). Twenty patients with MDD entered a double-blind placebo-controlled trial of fluoxetine preceded by D,L-fenfluramine stimulation. Patients were assigned randomly to either FLU, 20 mg QD, or placebo (PLA) for an 11-week trial. No relationship was found between the PRL response to FEN and response to FLU. Among the seven responding to FLU, there was a significant negative correlation between PRL response and the time until sustained response to FLU (r = -0.93, P < 0.001, n = 7). Although preliminary, this study suggests that low baseline serotonin activity may be associated with a slower response to FLU in depression.

Adult↗