Search PubMed⌕ Search

Biomedical subjects

R D Strous

Publications and source records attributed to R D Strous.

14 recordsLinked to original sources
PubMed2001

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes.

Dopamine is a major neurotransmitter in the central nervous system, and its receptors are associated with a number of neuropathological disorders such as Parkinson's disease and schizophrenia. Although the precise pathophysiology of schizophrenia remains unknown, the dopaminergic hypothesis of the illness assumes that the illness results from excessive activity at dopamine synapses in the brain. Because, at present, the diagnosis of schizophrenia relies on descriptive behavioral and symptomatic information, a peripheral measurable marker may enable a simpler, more rapid, and more accurate diagnosis and monitoring. In recent years, human peripheral blood lymphocytes have been found to express several dopamine receptors (D(3), D(4), and D(5)) by using molecular biology techniques and binding assays. It has been suggested that these dopamine receptors found on lymphocytes may reflect receptors found in the brain. Here we demonstrate a correlation between the D(3) dopamine receptor on lymphocytes and schizophrenia and show a significant elevation of at least 2-fold in the mRNA level of the D(3), but not of the D(4), dopamine receptor in schizophrenic patients. This increase is not affected by different antipsychotic drug treatments (typical or atypical). Moreover, nonmedicated patients exhibit the same pattern, indicating that this change is not a result of medical treatment. We propose the D(3) receptor mRNA on blood lymphocytes as a marker for identification and followup of schizophrenia.

Adult↗
PubMed2001

Analysis of neurosteroid levels in attention deficit hyperactivity disorder.

Neurosteroids are important neuroactive substrates with demonstrated involvement in several neurophysiological and disease processes. Attention deficit hyperactivity disorder (ADHD) has been associated with dysregulation of the catecholaminergic and serotonergic systems, however its relationship to irregularities or changes in neurosteroid levels remains unknown. We examined the relationship between blood levels of dehydroepiandrosterone (DHEA), its principal precursor pregnenolone and its principal metabolite dehydroepiandrosterone sulphate (DHEAS) in 29 young male subjects aged 7-15 years with DSM-IV criteria of ADHD. Subjects were evaluated by a specially designed scale, following which patients were divided into two groups according to severity of symptomatology. Results indicated significant inverse correlations between clinical symptomatology and levels of DHEA and pregnenolone in the total group. These inverse correlations were particularly evident in the less severe group of subjects. Levels of DHEA and DHEAS were inversely correlated with the hyperactivity subscale. Furthermore, using median blood levels as a cut-off indicator, higher blood levels of DHEA and DHEAS were associated with fewer ADHD symptoms, in particular hyperactivity symptomatology. Our findings suggest a possible protective effect of various neurosteroids on the expression of ADHD symptomatology.

Adolescent↗
PubMed2001

Olanzapine-induced leukopenia with human leukocyte antigen profiling.

Olanzapine is an atypical antipsychotic medication frequently used in the management of psychotic states. While it has proved to be safe compared to clozapine with regard to haematotoxicity, because it has only been available for a few years, full documentation of its haematological side-effects remains incomplete. We report a case of olanzapine-induced leukopenia with associated neutropenia. Since clozapine-induced haematotoxicity has been associated with characteristic human leukocyte antigen (HLA) groups, HLA typing was determined in this patient. Following failure with typical antipsychotic medication, the patient received 10 mg/day of olanzapine. Three weeks later, he developed fever and a significant decrease in leukocyte count. Olanzapine was immediately discontinued. HLA typing was determined. The white cell count returned to normal and the fever, most probably secondary to the low white cell count, subsided with antibiotic treatment. HLA typing results were: A1 24, B7, B35, DRB1*15, DRB1*11, DRB3*01-03, DRB5*01-02. Olanzapine may induce serious leukopenia and neutropenia. HLA typing in this single patient demonstrated a distinct haplotype compared to that previously observed in clozapine-induced haematoxicity.

Clozapine↗
PubMed2000

Effects of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey.

Substance use disorders, particularly those involving alcohol, marijuana, and cocaine, are highly prevalent among patients with schizophrenia and contribute markedly to its overall morbidity. Unfortunately, standard (typical) antipsychotic medications do not seem to reduce substance use in patients with schizophrenia and may even increase it. Recently, however, a few anecdotal case reports and two previous small "N" surveys have found that clozapine, an atypical antipsychotic medication, seems to decrease substance use in patients treated with this drug for their psychoses. The authors report data from a retrospective survey of substance use in 58 patients treated with clozapine who had a history of comorbid schizophrenia (or schizoaffective disorder) and substance use disorder. Of these 58 patients, 43 were being treated with clozapine at the time of the survey; the remaining 15 patients had discontinued clozapine before the survey. The survey involved chart review and clinician interview to assess change in substance use and global clinical symptoms while receiving treatment with clozapine. More than 85% of the patients who were active substance users at the time of initiation of treatment with clozapine decreased their substance use over the course of clozapine administration. For patients who continued treatment with clozapine up to the present, the decrease in substance use was strongly correlated with a decrease in global clinical symptoms. Data from this retrospective survey further support the previous observations that clozapine reduces substance use among patients with schizophrenic disorders. Moreover, the data suggest the need for prospective controlled studies of the effects of clozapine on substance use in this population.

Adult↗
PubMed1997

Analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association with aggressive and antisocial behavior.

We have recently characterized a functional polymorphism in the catechol-O-methyltransferase (COMT) gene that is responsible for substantial variability in COMT enzymatic activity found in humans. A common low-activity variant of the enzyme contains a methionine residue at amino acid 158 of membrane-bound COMT whereas the common high activity variant has a valine at this site. Considering the role of COMT in dopamine metabolism and the involvement of dopaminergic pathways in the pathogenesis of schizophrenia and violence, we screened 37 patients with schizophrenia to determine whether or not a behavioral association with the COMT polymorphism exists. Patients were assessed for dangerousness on the basis of a history of violent and threatening behavior, crime, cocaine and alcohol abuse, and other antisocial behaviors. We found that schizophrenic patients who were homozygous for the low activity allele were judged by their psychiatrists to be at higher risk for aggressive and dangerous behavior than those who were homozygous for the high activity allele (Kruskal-Wallis statistic = 10.43; P = 0.003).

Adult↗
PubMed1997

Impaired precision, but normal retention, of auditory sensory ("echoic") memory information in schizophrenia.

Working memory is the type of memory that allows one to hold information in mind while working on a task or problem. The present study investigated attention-independent auditory sensory ("echoic") memory in 18 schizophrenic participants and 17 controls. Schizophrenic participants showed impaired delayed tone matching performance in comparison with controls. However, when groups were matched for performance at 1 s by varying the difficulty of the task across groups, schizophrenic participants showed normal retention of information as reflected in normal tone matching performance. These findings demonstrate that schizophrenic may be in the sensitivity of the system rather than the duration for which memory traces were retained.

Adult↗
PubMed1995

Auditory sensory ("echoic") memory dysfunction in schizophrenia.

OBJECTIVE: Studies of working memory dysfunction in schizophrenia have focused largely on prefrontal components. This study investigated the integrity of auditory sensory ("echoic") memory, a component that shows little dependence on prefrontal functioning. METHOD: Echoic memory was investigated in 20 schizophrenic subjects and 20 age- and IQ-matched normal comparison subjects with the use of nondelayed and delayed tone matching. RESULTS: Schizophrenic subjects were markedly impaired in their ability to match two tones after an extremely brief delay between them (300 msec) but were unimpaired when there was no delay between tones. CONCLUSIONS: Working memory dysfunction in schizophrenia affects brain regions outside the prefrontal cortex as well as within.

Acoustic Stimulation↗
PubMedDate not supplied

Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine?

Alcohol and other drugs of abuse are commonly used by persons with schizophrenia and contribute to the overall morbidity of the disorder. Standard, or typical, antipsychotic drugs do not limit such substance use and may even render it more likely. However, preliminary data from our group and others suggest that the atypical antipsychotic clozapine may decrease substance use in this population. While recognizing the likelihood that substance use decreases negative symptoms (as well as extrapyramidal symptoms) in persons with schizophrenia, we hypothesize that the biological basis of substance use relates to a "reward-deficiency syndrome" secondary to dysfunctional dopamine-mediated mesocorticolimbic neurons in these individuals. We further suggest that clozapine's beneficial effect in patients with comorbid schizophrenia and substance use disorders may relate to its presumed ability to ameliorate the deficits in both the mesocortical and mesolimbic dopaminergic neuronal projections through its various actions on dopaminergic, serotonergic, and particularly noradrenergic neurons.

Animals↗