Papers by Michael Dobrusin
World Journal of Biological Psychiatry, 2008
Consanguinity may contribute to the incidence of schizophrenia in offspring despite the usually a... more Consanguinity may contribute to the incidence of schizophrenia in offspring despite the usually accepted polygenic model of schizophrenia inheritance. Bedouin Arab families in southern Israel have a high rate of cousin marriages as do families throughout most Arab societies. We studied consanguinity in the parents of schizophrenic patients admitted in a defined catchment area of southern Israel, compared to a control group of parents of all infants born to Bedouin mothers in this catchment area. There was a small but significant increase in the rate of cousin marriages among the parents of schizophrenia patients compared to parents of infant controls. These results are consistent with claims that inbreeding can contribute to the incidence of schizophrenia even as a polygenic illness. However, the absence of a better matched control group limits confidence in the results.
Psychiatric Genetics, 2006
An analysis of 80 British parent-offspring trios by Wei and Hemmings in 2000 revealed thre1e out ... more An analysis of 80 British parent-offspring trios by Wei and Hemmings in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be strongly associated with schizophrenia. In our present study, we have examined NOTCH4 markers in large samples of German and Palestinian-Arab origin. Our study population comprised a German case-control sample (n=512 schizophrenia patients and n=232 controls) and two independent parent-offspring trio samples of German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a total of ten single nucleotide polymorphisms within the NOTCH4 locus and the adjacent loci, spanning a region of approximately 100 kb. Neither single marker nor haplotype analyses showed association with schizophrenia. In addition, analyses of the German case-control and trio samples revealed no significant association between NOTCH4 polymorphisms and early-onset schizophrenia. Our results suggest that NOTCH4 is unlikely to play a major role in the genetic predisposition to schizophrenia in the German or the Palestinian-Arab population.
Neuropsychologia, 2007
Patients with schizophrenia show attention deficit characterized by a larger validity effect (fas... more Patients with schizophrenia show attention deficit characterized by a larger validity effect (fast responses to cued than uncued stimuli) in the right visual field than in the left visual field. In addition, schizophrenia patients do not show inhibition of return (IOR-a mechanism that enables efficient visual search), unless attention is summoned back to the center after the peripheral cue. The present study examined the short-term effect of neuroleptic medications on these two components of visual spatial attention in schizophrenia patients. In order to do this we tested schizophrenia patients that were treated with long-acting neuroleptic medication. These patients were treated once a month, which allowed us to test them with either low or high levels of medication. Here we show that neuroleptic medications reverse the attentional hemispheric asymmetry. In the group with a high level of medication fast RTs to cued trials were found in the right visual field, while in the group with a low level of medication the opposite pattern was found -fast RTs to cued trials were found in the left visual field. In addition, level of medication did not influence IORregardless of the level of medication, IOR was observed only when attention was summoned back to the center, unlike control group. These finding suggest an imbalance in dopaminergic activity, possibly in subcortical structures such as the basal ganglia. This study also shows a dissociation between the two components of visual orienting of attention and suggests that facilitation and inhibition are independent processes.
Human Psychopharmacology: Clinical and Experimental, 1999
Biological Psychiatry, 1998
Background: Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity o... more Background: Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme is also found in the cerebrospinal fluid (CSF), where it may prove useful as a marker of dysfunctional PI signal transduction. Methods: IMPase activity was measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic patients. In addition, and to gain an insight into the factors that influence the levels of CSF IMPase, enzyme activity was measured in subgroups of schizophrenic patients treated for 3-7 days with lithium or 7 days with inositol. Results: CSF IMPase activity was significantly increased by 88% in depressed and by 172% in schizophrenic patients relative to control subjects. Lithium produced a marked increase in CSF IMPase activity in the group as a whole, and this group effect could be more specifically attributed to 3 of the 8 individuals in whom enzyme activity increased by over 300%. On the other hand, inositol had no effect on CSF IMPase activity. Conclusions: In the absence of a clear relationship between CSF IMPase activity and neuronal PI signaling pathways it is not possible to correlate these changes with altered neuronal function. Nevertheless, increased CSF IMPase activity in depression and schizophrenia may be a marker of the pathophysiological processes underlying these disorders. Moreover, the large lithium-induced increase in IMPase activity seen in a subgroup of schizophrenic subjects suggests a differential regulation of CSF enzyme activity in these patients.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2006
American Journal of Medical Genetics, 2003
COMT is a ubiquitous enzyme crucial to catechol metabolism. The molecular basis of COMT thermolab... more COMT is a ubiquitous enzyme crucial to catechol metabolism. The molecular basis of COMT thermolability, that leads to three to fourfold differences in enzyme activity, is due to a substitution of valine with methionine in the Val158/108Met polymorphism. Of special interest is the role of this gene in major psychoses especially since a microdeletion (22q11) containing the COMT gene (velo-cardio-facial syndrome) also carries with it several types of behavioral disorders, including an increased prevalence of schizophrenia. Almost 20 genetic studies have examined the role of COMT in schizophrenia with ambiguous results. Towards clarifying the role of this polymorphism in conferring risk for psychosis, we examined a large group of culturally and ethnically akin Palestinian Arab schizophrenic triads (N ¼ 276) using both a case-control and family-based study. In 194 informative triads with at least one heterozygote parent, no preferential transmission of either COMT allele was observed in this sample (TDT statistic chi-square ¼ 0.14 NS; 131 COMT valine alleles were transmitted and 125 alleles not transmitted). However, using a case-control design a significant increase (Likelihood ratio ¼ 3.935, P ¼ 0.047) in the valine allele was observed in the group of schizophrenic patients (N ¼ 276) compared to an ethnically matched control group (N ¼ 77). The association was stronger in female patients (P ¼ 0.012) similar to other studies showing that some COMT behavioral effects are gender sensitive. In summary, by case-control design but not by a familybased study, there is a weak effect in female patients of the high activity COMT allele in conferring risk for schizophrenia.
American Journal of Medical Genetics, 2001
The 5HT2C receptor has a high affinity for clozapine, a nontypical neuroleptic, and has therefore... more The 5HT2C receptor has a high affinity for clozapine, a nontypical neuroleptic, and has therefore been postulated to play a role in mediating negative symptoms and neuroleptic response in schizophrenia. In the current study, the Cys23Ser 5HT2C serotonin receptor polymorphism was examined for linkage to schizophrenia by genotyping 207 nuclear families consisting of both parents and schizophrenic child and using the transmission disequilibrium test to examine possible preferential transmission of these alleles from 68 heterozygous mothers to their ill child. No evidence was obtained for preferential transmission of the Cys23Ser 5HT2C alleles in schizophrenia in either of the two main ethnic groups examined (German and Palestinian Arab) or in the combined cohort (TDT chi-square = 0.00, NS).
American Journal of Medical Genetics, 2001
American Journal of Medical Genetics, 2000
Several recent meta-analyses appear to show a weak but significant effect of both forms of the gl... more Several recent meta-analyses appear to show a weak but significant effect of both forms of the gly/ser DRD3 polymorphism in conferring risk for schizophrenia. Since most studies have employed the artifact-prone case-control design, we thought it worthwhile to examine the role of this polymorphism using a robust family-based strategy in an ethnic group not previously systematically studied in psychiatric genetics, Palestinian Arabs. We failed to obtain any evidence in 129 Palestinian triads, using the haplotype relative risk (allele frequency: Pearson chi-square = 0.009, P > 0.1, df = 1, n = 258 alleles) or transmission disequilibrium test design (chi-square = 0.38, P > 0.1, n = 86 families) for association/linkage (or increased homozygosity) of the DRD3 Bal I polymorphism to schizophrenia in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:778-780, 2000.
Neuropsychology, 2001
This research examined 2 components of visual orienting in medicated schizophrenia patients: the ... more This research examined 2 components of visual orienting in medicated schizophrenia patients: the validity effect and the inhibition of return (IOR). In the 1st experiment, patients showed the expected asymmetry in orienting attention, that is, larger validity effect in the right visual field than in the left. However, this asymmetry was due to a deficit in facilitatory processes rather than a disengagement deficit. In addition, patients showed a deficit in IOR. In the 2nd experiment, a 2nd central cue for summoning attention, explicitly, back to the center was used. In this experiment, normal IOR in schizophrenia patients was found. Because it was shown that schizophrenia patients do not have a disengagement deficit, IOR possibly could not be observed because of the increased facilitation in that location. It was proposed that the abnormality in visual attention in schizophrenia is due to a deficit in inhibitory processes.
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Papers by Michael Dobrusin