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T Reich

Publications and source records attributed to T Reich.

At least 55 records · Page 3Linked to original sources
PubMed1998

Genome-wide search for genes affecting the risk for alcohol dependence.

Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3-8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50-60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations.

Adolescent↗
PubMed1998

Familial transmission of substance dependence: alcohol, marijuana, cocaine, and habitual smoking: a report from the Collaborative Study on the Genetics of Alcoholism.

BACKGROUND: Alcoholism and substance dependence frequently co-occur. Accordingly, we evaluated the familial transmission of alcohol, marijuana, and cocaine dependence and habitual smoking in the Collaborative Study on the Genetics of Alcoholism. METHODS: Subjects (n=1212) who met criteria for both DSM-III-R alcohol dependence and Feighner definite alcoholism and their siblings (n=2755) were recruited for study. A comparison sample was also recruited (probands, n=217; siblings, n=254). Subjects were interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism. The familial aggregation of drug dependence and habitual smoking in siblings of alcohol-dependent and non-alcohol-dependent probands was measured by means of the Cox proportional hazards model. RESULTS: Rates of alcohol, marijuana, and cocaine dependence and habitual smoking were increased in siblings of alcohol-dependent probands compared with siblings of controls. For siblings of alcohol-dependent probands, 49.3% to 50.1% of brothers and 22.4% to 25.0% of sisters were alcohol dependent (lifetime diagnosis), but this elevated risk was not further increased by comorbid substance dependence in probands. Siblings of marijuana-dependent probands had an elevated risk of developing marijuana dependence (relative risk [RR], 1.78) and siblings of cocaine-dependent probands had an elevated risk of developing cocaine dependence (RR, 1.71). There was a similar finding for habitual smoking (RR, 1.77 in siblings of habitual-smoking probands). CONCLUSIONS: Alcohol, marijuana, and cocaine dependence and habitual smoking are all familial, and there is evidence of both common and specific addictive factors transmitted in families. This specificity suggests independent causative factors in the development of each type of substance dependence.

Adolescent↗
PubMed1998

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage.

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

Alcoholism↗
PubMed1998

The unified biosocial model of personality in schizophrenia families and controls.

This report describes the application of a unified biosocial model of personality developed by C.R. Cloninger to a sample of families identified through a proband with schizophrenia and a sample of controls. Families of schizophrenic patients were ascertained in USA and Austria. We could detect differences between females and males in their response to positive reinforcement (Reward Dependence) and differences between young and old people with respect to the response to new and/or exciting situations (Novelty Seeking). In general, results obtained for individuals from schizophrenia families and controls were similar. These results are not substantially influenced by psychiatric disorders in individuals. Psychiatric diagnosis may have an influence on the third dimension of Cloninger's model, designated Harm Avoidance. Analysis showed that patients with a diagnosis of schizophrenia or from the schizophrenia spectrum try harder to avoid punishment or aversive stimuli than family members with another psychiatric disorder or without a psychiatric diagnosis as well as controls. The results are promising and further research is needed to evaluate the structure of the proposed personality model in families and the relationship of personality to psychiatric status.

Adult↗
PubMed1998

A family-based analysis of the association of the dopamine D2 receptor (DRD2) with alcoholism.

The possible association of the DRD2 locus, and in particular the Taql-A1 allele, with alcoholism remains controversial, in part because of differences in allele frequencies among populations. To avoid problems associated with differences in allele frequencies in different populations, we tested whether the DRD2 locus is associated with alcohol dependence in a large family-based sample. Neither the transmission/disequilibrium test nor the Affected Family-Based Controls test provide any evidence of linkage or association between the DRD2 locus and alcohol dependence.

Alcoholism↗
PubMed1998

A family-based analysis of whether the functional promoter alleles of the serotonin transporter gene HTT affect the risk for alcohol dependence.

A population association between a regulatory variation in the promoter of the serotonin transporter gene (HTT) and severe alcohol dependence was recently reported. We analyzed this potential association in a large number of systematically ascertained families in the United States; these families had at least three first-degree relatives who were alcohol-dependent. Analyses focused on individuals defined as alcohol-dependent by criteria from ICD-10 and on subsets of these individuals reporting withdrawal-related symptoms. Application of the transmission disequilibrium test did not provide support for either linkage or association between this functional polymorphism and alcohol dependence; there was no significant bias in the transmission of either allele to the alcohol-dependent offspring. We also report that African Americans differ from Caucasians in allele frequencies for this polymorphism.

Adult↗
PubMed1998

Amplitude of visual P3 event-related potential as a phenotypic marker for a predisposition to alcoholism: preliminary results from the COGA Project. Collaborative Study on the Genetics of Alcoholism.

Recent data collected at six identical electrophysiological laboratories from the large national multisite Collaborative Study on the Genetics of Alcoholism provide evidence for considering the P3 amplitude of the event-related potential as a phenotypic marker for the risk of alcoholism. The distribution of P3 amplitude to target stimuli at the Pz electrode in individuals 16 years of age and over from 163 randomly ascertained control families (n = 687) was compared with those from 219 densely affected alcoholic families (n = 1276) in which three directly interviewed first-degree relatives met both DSM-III-R and Feighner criteria at the definite level for alcohol dependence (stage II). The control sample did not exclude individuals with psychiatric illness or alcoholism to obtain incidence rates of psychiatric disorders similar to those of the general population. P3 amplitude data from control families was converted to Z-scores, and a P3 amplitude beyond 2 SD's below the mean was considered an "abnormal trait." When age- and sex-matched distributions of P3 amplitude were compared, members of densely affected stage II families were more likely to manifest low P3 amplitudes (2 SD below the mean) than members of control families, comparing affected and unaffected offspring, and all individuals; all comparisons of these distributions between groups were significant (p < 0.00001). P3 amplitude means were also significantly lower in stage II family members, compared with control family members for all comparisons, namely probands, affected and unaffected individuals (p < 0.0001), and offspring (p < 0.01). Furthermore, affected individuals from stage II families, but not control families, had significantly lower P3 amplitudes than unaffected individuals (p < 0.001). Affected males from stage II families had significantly lower P3 amplitudes than affected females (p < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a biological phenotypic marker that has genetic underpinnings.

Adolescent↗
PubMed1998

Women with bipolar disorder: findings from the NIMH Genetics Initiative sample.

Bipolar I (BPI) mood disorder is a severe recurrent mental Illness with a population prevalence of 1 percent. Evidence is strong for genetic risk factors in onset. However, unlike unipolar mood disorders, in which women outnumber men by 2 to 1, for BPI disorder, the male:female ratio is equal. Perhaps for this reason, relatively little research has examined gender-related risks in BPI course. This article presents data from 186 BPI women and 141 BPI men ascertained as part of the NIMH Genetics Initiative, a multisite collaborative molecular genetic study. Subjects were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). DIGS items included a medical history, and for women, questions concerning psychiatric disorders in relation to childbearing, the menstrual cycle, and menopause. Almost half of BPI women who had been pregnant reported having experienced severe emotional disturbances in relation to childbearing, with close to one-third reporting episode onset during pregnancy. Two-thirds of BPI women reported frequent premenstrual mood disturbances and almost 20 percent of postmenopausal BPI women reported severe emotional disturbances during the menopausal transition. More BPI women than men reported thyroid disorder and migraine headaches. Findings are discussed in relation to gender differences in population and other clinical samples, and in terms of their implications for the development of new treatments and preventive interventions.

Adult↗
PubMed1998

Linkage of an alcoholism-related severity phenotype to chromosome 16.

There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.

Adult↗
PubMed1997

Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 1, 6, 8, 10, and 12.

A report on an initial genome screen on 540 individuals in 97 families was collected as part of the NIMH Genetics Initiative on Bipolar Disorder. Families were ascertained to be informative for genetic linkage and underwent a common ascertainment and assessment protocol at four clinical sites. The sample was genotyped for 65 highly polymorphic markers from chromosomes 1, 6, 8, 10, and 12. The average intermarker interval was 16 cM. Genotypic data was analyzed using affected sib pair, multipoint affected sib pair, and pedigree analysis methods. Multipoint methods gave lod scores of approximately two on chromosomes 1, 6, and 10. The peak lod score on chromosome 6 occurred at the end of the q-arm, at some distance from the 6p24-22 area previously implicated for schizophrenia. We are currently genotyping additional markers to reduce the intermarker interval around the signals. The interpretation of results from a genome screen of a complex disorder and the problem of achieving a balance between detecting false positive results and the ability to detect genes of modest effect are discussed.

Bipolar Disorder↗
PubMed1997

Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 3, 5, 15, 16, 17, and 22.

As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16,17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (theta) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage.

Alleles↗
PubMed1997

Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X.

We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder-recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk lambda(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring lambda(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with lambda(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the markers in Xp22 would have lambda(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have lambda(i) > 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies.

Bipolar Disorder↗
PubMed1997

Subgenual prefrontal cortex abnormalities in mood disorders.

Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the prefrontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

Adult↗
PubMed1997

A meta-analysis of chromosome 18 linkage data for bipolar illness.

We find a meta-data set (715 families, up to 1,124 sib pairs) for bipolar illness to have a strong signal in a 10 cM region around D18S40, and excess paternal sharing on the q arm near marker D18S64. We describe a method for meta-analysis of microsatellite marker data using affected sib-pair (ASP) methodology. Inherent difficulties in such analysis include heterogeneity of allele frequencies and protocol design, measurement errors in genotyping, and map construction. Using identity-by-descent (IBD) allele sharing as the dependent variable, a logistic regression to test for heterogeneity finds only mild heterogeneity, and a limited parent-of-origin effect.

Alleles↗
PubMed1997

Age-of-onset or age-cohort changes in the lifetime occurrence of depression?

In a re-investigation of the NIMH Psychobiology of Depression data, we have studied the question of shifts towards earlier onset together with the question of steadily increasing lifetime risk of major depression in successive birth-cohorts. Using a contingency-table approach, it turned out that inhomogeneities with respect to successive birth-cohorts exclusively showed up in the neighborhood of principally unobservable combinations of the variables under investigation. Standard approaches to testing independence in cross-classified data, such as the quasi-independence model, yielded highly significant results. Through the definition of a log-linear model with weights which replaces the 'discrete' truncation of the quasi-independence approach by a 'smoothed' truncation, it was possible to fully explain the observed age-of-onset shifts, thus supporting the hypothesis that age-of-onset and birth-cohort are independent. With respect to the question of generational changes in the lifetime risk of depression this independence implied that such changes should occur at equal rates across all ages of onset. The analysis yielded significantly larger cohort sizes for the two youngest birth-cohorts, a fact which might be interpreted as an indication of increasing environmental impacts on the genetically predisposed vulnerability during recent years. However, our cross-sectional survey data were, by design, not an optimal basis for a reliable assessment of changes in the lifetime risk of depression, because the risk estimate derived from affected-only survey data corresponds to the probability that a depressive belongs to a certain birth-cohort and is only loosely related to the lifetime risk of this cohort (which is the probability that a person belonging to a certain birth-cohort develops depression). We therefore conclude, firstly, that method effects are likely to explain a major portion of secular trends thus far reported in the literature, and, secondly, that there appears to be no clear necessity to include changing environmental effects into quantitative genetic modelling.

Adolescent↗
PubMed1997

A linkage map of chromosome 6 based on 2 large kindreds segregating bipolar affective disorder.

Twenty-eight markers, both simple sequence repeats (SSRs) and restriction fragment length polymorphisms (RFLPs), were genotyped on members of 2 large pedigrees (OOA, BIP167) segregating bipolar affective disorder. Using the multipoint program "build" of CRIMAP and odds of placement 1000:1, a unique sex-averaged map was generated that spans 227 cM and includes 26 markers. The two other markers were placed on the map with a lower likelihood. The female recombination map is larger than the male recombination map by about 80%. Linkage analysis between the polymorphisms and the disease in the OOA screening pedigree did not result in any significantly positive lod scores nor did a non-parametric, identity-by-descent, method generate any significant p-values. BIP167 was analyzed for allele sharing at the simple sequence repeat loci and significant associations were not found. At present we conclude, that the pedigrees under study do not have a major predisposition gene for bipolar affective disorder on chromosome 6 under the diagnostic and transmission models analyzed by the 2 different methods.

Bipolar Disorder↗