Showing papers by "Herbert M. Lachman published in 1997"
TL;DR: It is found that schizophrenic patients who are 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 homozygously for the high activity allele.
Abstract: 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 = 1043; P = 0003)
223 citations
TL;DR: Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse, as compared with control research volunteers reporting insignificant lifetime use of addictive substances.
Abstract: Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates to contribute to genetic components of interindividual differences in vulnerability to substance abuse. COMT plays a prominent role in dopaminergic circuits important for drug reward, and COMT alleles encode enzymes whose activities vary from three- to four-fold. We compared COMT allele frequencies in control research volunteers reporting insignificant lifetime use of addictive substances with those in volunteers reporting substantial polysubstance use. Homozygosity for the high-activity COMT allele was found in 18% of controls, 31% of volunteers with high lifetime substance use, and 39% meeting DSMIII-R substance abuse criteria [odds ratio (relative risks) 2.0 (control vs. use; 95% confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P < 0.008)]. Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse.
186 citations
TL;DR: Results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22, as well as suggestive evidence for linkage in both the UCSD/UBC family set and in the combined families.
Abstract: Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characterized by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities, that results from a microdeletion of chromosome 22q11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American population (University of California, San Diego/University of British Columbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A maximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod scores of 1.68 and 1.28 were obtained at this marker under dominant and recessive models, respectively. Four additional markers were subsequently typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sibpair analyses were similarly positive in the UCSD/UBC families (P = 0.017), and in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22.
104 citations
82 citations
TL;DR: No significant association was detected with the codon 158 COMT polymorphism, which suggests that the catechol-O-methyltransferase polymorphism is not a susceptibility gene in BPD.
Abstract: Abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders. Consequently, alterations in genes that are involved in catecholamine metabolism could be potential candidates for bipolar affective disorder (BPD) vulnerability. One such candidate is catechol-O-methyltransferase (COMT). A functional polymorphism has recently been characterized that is responsible for substantial variability in COMT enzymatic activity. A relatively low activity allele is associated with a methionine residue at amino acid 158 of membrane bound COMT whereas a high activity variant has a valine at this site. We have now screened 63 unrelated patients with BPD for this functional polymorphism. However, no significant association was detected. This suggests that the codon 158 COMT polymorphism is not a susceptibility gene in BPD.
48 citations