Search PubMed⌕ Search

Biomedical subjects

R R Crowe

Publications and source records attributed to R R Crowe.

At least 37 records · Page 2Linked to original sources
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

Chromosome 5 workshop.

In schizophrenia, evidence consistent with linkage in the 5q23.3-q31.1 region emerged from three independent samples. In addition, a moderately retarded woman with schizophrenia with an interstitial deletion overlapping this region was reported at the workshop. A second region of interest for schizophrenia is the 5p14.1-p13.1 region, where lod scores as high as 4.37 were found in one pedigree. Chromosome 5p15 gave a non-parametric linkage (NPL) score of 2.18 (p < 0.02) in one study. Several genome scans have not found evidence of excess allele sharing in these regions, although in most cases the genome scans did not include the markers that had resulted in provisional evidence of linkage. A large pedigree of bipolar illness has shown provisional evidence of linkage at, or near, the dopamine transporter locus at 5p15.3; the maximum lod score obtained was 2.72 at D5S417. In other regions, a genome scan of bipolar disorder gave NPL scores of 2.98 at D5S812 and 3.76 at D5S423. The third disorder of interest is attention deficit hyperactivity disorder (ADHD) because two studies have reported an association with the 480 bp allele at the dopamine transporter locus. A poster presented at the Congress reported a failure to replicate the association in a sample with considerable power to detect the effect size previously reported.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Genome scan of schizophrenia.

OBJECTIVE: The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHOD: A genomewide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals--126 of them with schizophrenia-related psychoses--from 43 pedigrees. Nonparametric linkage analysis was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirically derived p values reached nominal levels of significance at eight marker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002). CONCLUSIONS: The results do not support the hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychiatric disorders) has limited power to detect genes of small effect or those that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely to contain schizophrenia susceptibility genes.

Chromosome Mapping↗
PubMed1997

Increased levels of a mitochondrial DNA deletion in the brain of patients with bipolar disorder.

Mutations in mitochondrial DNA (mtDNA) have been implicated in the pathophysiology of affective disorders. To examine possible pathophysiological significance of mtDNA deletions in bipolar disorder, the concentration of the 4977-base-pair deletion in mtDNA in the autopsied brains of 7 patients with bipolar disorder, 9 suicide victims, and 9 controls was examined using a quantitative polymerase chain reaction method. The ratio of deleted to wild-type mtDNA in cerebral cortex was significantly higher in patients with bipolar disorder [0.23 +/- 0.18 (mean +/- SD)%] compared with that in age-matched controls (0.06 +/- 0.07%, p < 0.05). This result supports a hypothesis that mtDNA deletions may play a role in the pathophysiology of bipolar disorder.

Adult↗
PubMed1997

Quantitative analysis of leukocyte mitochondrial DNA deletion in affective disorders.

Mutations in mitochondrial DNA (mtDNA) are implicated in the pathophysiology of affective disorders. To determine whether the 4977-base-pair deletion in mtDNA is more frequent in affective disorders, we quantitated the concentration of this deletion in leukocyte mtDNA in 34 probands with affective disorders (20 bipolar and 14 unipolar) and 20 controls. We found no significant difference in the quantitative ratio of deletion to wild-type mtDNA between patients and controls. One patient with unipolar depression and 1 of 2 patients previously reported as having a large quantity of the deleted mtDNA did have a markedly high ratio; however, the deletion did not segregate with the disease in these two families. These results do not support a hypothesis that the 4977-base-pair deletion plays an important role in the pathophysiology of affective disorders.

Adult↗
PubMed1997

A linkage study of schizophrenia to markers within Xp11 near the MAOB gene.

A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular genetic studies produced weak evidence for linkage of schizophrenia to the proximal short arm of the X-chromosome, while some other regions were not ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a maternal pattern of inheritance (Study I), and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheritance at a theta of 0.20) for locus DXS7, with scores below 0.50 for other markers in this region (MAOB, DXS228, and ARAF1). Significant allele sharing among affected sibling pairs was present at DXS7. In the second study, positive lod scores were observed at MAOB (highest of 2.16 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for recessive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-chromosome have been investigated without evidence for linkage being found, a locus predisposing to schizophrenia in the proximal short arm of the X-chromosome is not excluded.

Chromosome Mapping↗
PubMed1997

Candidate gene study of eight GABAA receptor subunits in panic disorder.

OBJECTIVE: gamma-Aminobutyric acid type A (GABAA) receptor subunit genes are candidate genes for panic disorder. Benzodiazepine agonists acting at this receptor can suppress panic attacks, and both inverse agonists and antagonists can precipitate them. The human GABAA receptor subtypes are composed of various combinations of 13 subunits, each encoded by a unique gene. The authors tested eight of these subunits in a candidate gene linkage study of panic disorder. METHOD: In 21 U.S. and five Icelandic multiplex pedigrees of panic disorder, 104 individuals had DSM-III-R panic disorder (the narrowly defined affected phenotype) and 134 had either this diagnosis or subsyndromal panic disorder characterized by panic attacks that failed to meet either the criterion of attack frequency or the number of criterion symptoms necessary for a definite diagnosis (the broadly defined affected phenotype). The authors conducted lod score linkage analyses with both phenotypes using both a dominant and a recessive model of inheritance for the following loci: GABRA1-GABRA5 (alpha 1-alpha 5), GABRB1 (beta 1), GABRB3 (beta 3), and GABRG2 (gamma 2). RESULTS: The results failed to support the hypothesis that any of these genes cause panic disorder in a majority of the pedigrees. CONCLUSIONS: Within the limitations of the candidate gene linkage method, panic disorder does not appear to be caused by mutation in any of the eight GABAA receptor genes tested.

Adult↗
PubMed1997

The life-time rates of three major mood disorders and four major anxiety disorders in alcoholics and controls.

AIMS: While psychiatric symptoms are common in the general population and even more prevalent in alcoholics, their clinical implications are not clear. The goal of this study was to establish the life-time rates of several independent and concurrent mood and anxiety disorders in alcoholics, controls and their relatives. DESIGN: Structured interviews were administered to alcoholics entering treatment, their relatives, and controls. SETTING: The study was carried out in six different centers in the United States as part of the Collaborative Study on the Genetics of Alcoholism (COGA). PARTICIPANTS: Data were gathered from 2713 alcohol dependent subjects (probands and their alcoholic relatives) and 919 controls. MEASUREMENTS: The timeline-based Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview was administered face to face by trained, closely supervised interviewers. The life-time rates for concurrent and independent disorders were determined for three DSM-III-R major mood and four major anxiety disorders. FINDINGS: Some form of independent mood disorder was seen during the life-time in slightly fewer alcoholics than controls (14.0% and 17.1%), but alcoholics did show higher rates of independent bipolar disorder (2.3% vs. 1.0%). The life-time rate for independent anxiety disorders was significantly higher in alcoholics than controls (9.4% vs. 3.7%), with most of the differential related to panic disorder (4.2% vs. 1.0%) and social phobia (3.2% vs. 1.4%), but no significant group differences for agoraphobia or obsessive-compulsive disorder. In general, these findings regarding mood and anxiety disorders were reflected in close relatives. CONCLUSIONS: The large majority of alcohol-dependent men and women in this sample did not have any of the independent mood or anxiety disorders evaluated here. However, there was evidence of enhanced risks among alcoholics for independent bipolar, panic and social phobic disorders. Studies which do not distinguish carefully between independent and concurrent mood and anxiety disorders in alcoholics are likely to report much higher rates of co-morbid psychiatric disorders than those that distinguish between the two types of syndromes.

Adult↗
PubMed1996

Missense mutation of the cholecystokinin B receptor gene: lack of association with panic disorder.

Cholecystokinin tetrapeptide (CCK4) is known to induce panic attacks in patients with panic disorder at a lower dose than in normal controls. Therefore, the cholecystokinin B (CCKB) receptor gene is a candidate gene for panic disorder. We searched for mutations in the CCKB gene in 22 probands of panic disorder pedigrees, using single-strand conformation polymorphism (SSCP) analysis. Two polymorphisms were detected. A polymorphism in an intron (2491 C-->A) between exons 4 and 5 was observed in 10 of 22 probands. A missense mutation in the extracellular loop of exon 2 (1550 G-->A, Val125-->Ile) was found in only one proband. This mutation was also examined in additional 34 unrelated patients with panic disorder and 112 controls. The prevalence rate of this mutation was 8.8% in patients with panic disorder (3/34) and 4.4% in controls (5/112). The mutation did not segregate with panic disorder in two families where this could be tested. These results suggest no pathophysiological significance of this mutation in panic disorder.

Adult↗
PubMed1995

Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders.

The principal brain synaptic vesicular monoamine transporter (VMAT2) is responsible for the reuptake of serotonin, dopamine, norepinephrine, epinephrine, and histamine from the cytoplasm into synaptic vesicles, thus contributing to determination of the size of releasable neurotransmitter vesicular pools. Potential involvement of VMAT2 gene variants in the etiology of schizophrenia and related disorders was tested using polymorphic VMAT2 gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia, schizophreniform, schizoaffective, and schizotypal disorders and mood incongruent psychotic depression. Assuming genetic homogeneity, complete (theta = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models. Allelic variants at the VMAT2 locus do not appear to provide major genetic contributions to the etiology of schizophrenia spectrum disorders in these pedigrees.

Genetic Linkage↗
PubMed1995

Exclusion of close linkage of the dopamine transporter gene with schizophrenia spectrum disorders.

OBJECTIVE: Involvement of genetic factors in the pathogenesis of schizophrenia spectrum disorders has been indicated in twin, adoption, and familial aggregation studies; the pivotal role played by the dopamine transporter in dopaminergic neurotransmission makes it a candidate gene for these disorders. Detection of close linkage between a dopamine transporter marker and schizophrenia spectrum disorders would strongly support the existence of causal relationships between genetic mutations at the dopamine transporter locus and the disease phenotype. METHOD: The authors assessed the linkage between this gene and schizophrenia spectrum disorders by using polymorphic dopamine transporter gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia as well as schizophreniform, schizoaffective, and schizotypal disorders and mood-incongruent psychotic depression. RESULTS: Complete (theta = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models. CONCLUSIONS: These results indicate that allelic variants at the dopamine transporter locus do not provide major genetic contributions to the etiology of schizophrenia and related disorders in these pedigrees.

Alleles↗
PubMed1995

The prevalence of major anxiety disorders in relatives of alcohol dependent men and women.

OBJECTIVE: The relationship between alcohol dependence and lifelong major anxiety disorders is complex. The literature indicates a close association between anxiety symptoms and drinking behavior. However, it is difficult to determine whether the anxiety conditions are lifelong disorders or if they represent temporary organic conditions related to alcohol intoxication and withdrawal. One approach to understanding more about the relationships between alcohol dependence and major anxiety disorders is to observe the rate of anxiety-related diagnoses in close relatives of alcoholics. This approach evaluates whether alcoholism and major anxiety disorders might share a common genetic basis. METHOD: The data presented here describe the rates of four major anxiety disorders in 591 interviewed first-degree relatives of alcohol dependent men and women. The data were gathered through face-to-face structured standardized interviews. RESULTS: The analyses reveal that after focusing on DSM-III-R anxiety disorders, controlling for the potential presence of temporary organic conditions in the subject and considering the impact of assortative mating in their parents, the life-time risk for panic disorder in close biological family members of alcoholics is 3.4%; for agoraphobia, 1.4%; for social phobia, 2.3%; and for obsessive-compulsive disease, 1.4%. CONCLUSIONS: These data do not indicate an exceptionally high rate of anxiety disorders among close relatives of alcoholics. While other mechanisms might contribute to relationship between alcoholism and major anxiety disorders, the results do not support evidence of a common genotype for the two disorders.

Adolescent↗
PubMed1994

Magnetic resonance imaging in familial versus sporadic cases of schizophrenia.

Magnetic resonance imaging findings were compared in 22 familial and 29 sporadic cases with DSM-III-R diagnoses of schizophrenia, schizoaffective, or schizophreniform disorders. Volumetric measurements were used to assess the size of brain structures, including the cranium, cerebrum, lateral ventricles, temporal horns, third ventricle, lenticular nuclei, amygdaloid-hippocampal complex, and cerebellum, as well as the asymmetry of the lateral ventricles. Increased volume of the lenticular nuclei and greater ventricular asymmetry (the left ventricle being larger) were found in familial cases compared with sporadic cases and normal control subjects. It is possible that increased lenticular nuclei volume and greater lateral ventricular asymmetry reflect the role of genetic factors in schizophrenia.

Adolescent↗
PubMed1994

Validity of the familial and sporadic subtypes of schizophrenia.

OBJECTIVE: A common means of subtyping schizophrenia is to use family history. Familial schizophrenia is defined by a family history of psychotic disorders, and sporadic schizophrenia is defined by the absence of such a history. Some writers have proposed that familial cases are mostly genetic, while the causes of sporadic schizophrenia are primarily environmental. The object of this report is to consider the theoretical and empirical support for the validity of this classification. METHOD: A review of studies examining the familial-sporadic distinction in schizophrenia was based on papers located through a MEDLINE search and published bibliographies. Because of the great variation in the methodological rigor of the studies, the authors rated them on a scale assessing 10 methodological features. Studies achieving at least 50% of the maximum possible score were selected for review. RESULTS: Only 29 of 69 studies located met the selection criteria, and even among the studies selected, important methodological shortcomings were noted. Despite an impressive number of comparisons between groups of subjects with familial and sporadic schizophrenia, few differences were found. In addition, few differences were replicated and supported by studies using designs other than the familial-sporadic distinction. CONCLUSIONS: The scarcity of studies with adequate methodology precludes any definitive judgment about the validity of the familial-sporadic distinction in schizophrenia. The delineation of predominantly genetic and predominantly environmental subtypes of schizophrenia will likely require large sample sizes, valid methods for the diagnosis of relatives, and stringent definitions of familiarity and sporadicity. Moreover, research strategies other than the familial-sporadic distinction may be better suited to identify such subtypes.

Adult↗
PubMed1993

Candidate genes in psychiatry: an epidemiological perspective.

Interest in candidate genes in psychiatry has been revived by the success of that approach in Alzheimer's disease as well as by discouragement over the results to date of searches for linkage. If mutations in candidate genes could be detected directly many of the complexities of searching for them indirectly through linkage could be avoided. As attractive as this approach may sound, mutation searches with candidate genes will introduce a new set of difficulties: the large number and low a priori probability of potential candidate genes virtually guarantees that most positive findings will be false positives. Consequently, if candidate genes are to be systematically studied, procedures need to be established for minimizing and efficiently disconfirming false positive results.

False Positive Reactions↗
PubMed1993

Pseudoautosomal locus for schizophrenia excluded in 12 pedigrees.

A pseudoautosomal locus for schizophrenia has been proposed based on observations of an excess of same-sex affected sibling pairs over opposite-sex pairs when the transmitting parent is the father. Such a pattern of partial concordance by sex related to paternal transmission would be difficult to explain by any biologic mechanism other than pseudoautosomal transmission of schizophrenia. To test the pseudoautosomal hypothesis, 37 sibling pairs concordant for the schizophrenia spectrum were identified from 24 nuclear pedigrees. No significant difference in concordance for sex was found between sibships of paternal and maternal transmission of schizophrenia. Next, a linkage analysis was performed in 12 informative pedigrees, examining seven marker loci spanning the pseudoautosomal region. Both strict schizophrenia and a broader schizophrenia spectrum were analyzed as the affected phenotype, and both autosomal dominant and autosomal recessive models were tested. None of the markers supported linkage to either schizophrenia or the schizophrenia spectrum. Lod scores of less than -4 were obtained across the entire pseudoautosomal region by means of multipoint linkage analyses in the autosomal dominant model. In the autosomal recessive model, the respective lod scores were less than -2. We conclude that there is no evidence of a pseudoautosomal locus for schizophrenia in our pedigrees in any of the genetic models we tested.

Chromosome Mapping↗