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Biomedical subjects

R R Crowe

Publications and source records attributed to R R Crowe.

At least 55 records · Page 3Linked to original sources

A linkage study of chromosome 11q in schizophrenia.

The long arm of chromosome 11 is of interest in schizophrenia research because of three independent reports of balanced 11q translocations cosegregating with schizophrenia and other major psychiatric illness in pedigrees. In addition, a number of candidate genes for psychosis are located in the translocated regions. These include the dopamine D2 receptor, porphobilinogen deaminase, which has shown an allelic association with schizophrenia, and neural cell adhesion molecule, a cell surface glycoprotein involved in neuronal cell-cell recognition during brain development. To search for a schizophrenia locus on chromosome 11q, we conducted linkage analyses in 12 multiplex pedigrees. Sixteen DNA markers, including the above three candidate genes, were used to screen the entire long arm of chromosome 11. None of these markers were supportive of linkage to schizophrenia regardless of whether the affected phenotype was defined narrowly or broadly, whether high or low penetrance was assumed. Both dominant and recessive models tested more than 130 centimorgans of chromosome 11q, and therefore, the reported translocation regions. The results provide no evidence for a susceptibility locus for schizophrenia on chromosome 11q in these pedigrees.

Chromosome Mapping↗

Excluding linkage between panic disorder and the gamma-aminobutyric acid beta 1 receptor locus in five Icelandic pedigrees.

The GABAA receptor subunits are candidate genes for panic disorder because the receptor is the site of action for the anxiolytic effects of the benzodiazepines. We tested for linkage between a tetranucleotide repeat polymorphism at the GABAA beta 1 locus, located on chromosome 4p13-p12, and panic disorder defined by DSM-III-R criteria in 5 Icelandic pedigrees. Both a narrow affection status (definite panic disorder and agoraphobia) and a broad one (including probable cases of these disorders) were tested. With the narrow definition, at a recombination fraction of 0.00, the lod scores in the 5 pedigrees ranged from -3.240 to +0.063, the total score across all 5 pedigrees being -8.299. With the broad definition at the same recombination fraction, the individual lod scores ranged from -2.614 to -0.489, with the total being -8.089. Thus, linkage between panic disorder/agoraphobia and the GABAA beta 1 locus in these pedigrees is exceedingly unlikely.

Adult↗

Alpha 2 adrenergic receptor subtypes in depression: a candidate gene study.

Alpha 2 adrenergic receptors play an important role in regulating the neuronal release of norepinephrine through presynaptic feedback inhibition in the locus ceruleus. Therefore, alpha 2 adrenergic autoreceptors may underlie some aspects of the pathogenesis and symptomatic expression of depressive illness. We studied two brain-expressed alpha 2 adrenergic receptor genes as genetic markers in linkage analyses in 17 multiplex pedigrees of unipolar depression. Neither of the genes was supportive of linkage to depression. Lod scores of less than -2 were found in both familial pure depressive disease pedigrees and in depression spectrum disease pedigrees. Therefore, we conclude that depression in our pedigrees is not related to mutations in the two alpha 2 adrenergic receptor genes tested.

Adult↗

Alcoholism and the D2 receptor gene.

The allelic association of the human dopamine D2 receptor gene and alcoholism was evaluated in 20 male alcoholics and 20 controls (sex, race, and geographic place of birth matched). This study further examines the issue of alcoholism severity and A1 allele frequency. No difference in A1 allele frequency was observed between these two groups. Similarly, no relationship between alcoholism severity and A1 frequency within the alcoholics was demonstrated.

Adult↗

Adrenergic receptor genes as candidate genes for panic disorder: a linkage study.

OBJECTIVE: Several lines of investigation suggest that the noradrenergic neurotransmitter system may be involved in the pathogenesis of panic disorder. Since a mutation in a gene coding for one of the adrenergic receptors could account for both the familial nature and autonomic dysfunction of panic disorder, the authors performed analyses of the linkage between panic disorder and five adrenergic receptor loci. METHOD: The subjects were 14 multiplex pedigrees with DSM-III panic disorder or agoraphobia with panic attacks. The loci tested were the alpha 1/beta 2 pair on chromosome 5q32-q34, the alpha 2/beta 1 pair on chromosome 10q24-q26, and a second alpha 2 locus on chromosome 4. Flanking loci were included in the analysis on chromosomes 5 and 10 to increase the informativeness of the adrenergic receptor loci. RESULTS: Lod scores less than -2.0 were found at all five receptor loci. CONCLUSIONS: These findings provide strong evidence against the possibility that genetic mutation at any of these loci is responsible for panic disorder in these pedigrees.

Adolescent↗

Lack of linkage to chromosome 5q11-q13 markers in six schizophrenia pedigrees.

We examined linkage between schizophrenia and five genetic markers on chromosome 5 in six pedigrees. Analyses were run considering the affected phenotype to be schizophrenia, schizophrenia plus a spectrum of related disorders, and these disorders plus any axis I diagnosis. None of the analyses were suggestive of linkage at any of the markers, either considering the pedigrees individually or in the aggregate. In our pedigrees, multipoint linkage analyses excluded much of the region that had supported linkage in an earlier study. These findings are consistent with other attempts to replicate the chromosome 5 linkage finding.

Chromosome Mapping↗

Close linkage of esterase-D to unipolar depression and alcoholism is ruled out in eight pedigrees.

Unipolar depression and alcoholism were tested for genetic linkage to esterase-D at 13q14.1. Tight linkage to esterase-D was ruled out for three phenotypes using three models of penetrance: (1) unipolar depression and alcoholism taken together as affected, (2) unipolar depression alone as affected with alcoholism considered unaffected and (3) alcoholism alone as affected with unipolar depression considered unaffected. This study does not support an earlier finding of possible linkage between the esterase-D locus at 13q14.1 and alcoholism.

Adolescent↗

Close linkage between panic disorder and alpha-haptoglobin excluded in 10 families.

We previously reported a lod score of 2.3 suggesting linkage between panic disorder and the alpha-haptoglobin locus on chromosome 16q22 in 26 pedigrees. In the present study we tested for linkage between alpha-haptoglobin and panic disorder in 10 new pedigrees and excluded a gene for panic disorder from 6 centimorgans (recombination fraction, 0.06) surrounding the alpha-haptoglobin locus. The data were analyzed under a variety of assumptions about the transmission of panic disorder, and linkage was excluded by all genetic models but one. When lod scores from the present set of 10 pedigrees were pooled with those from the first 26, no evidence of genetic heterogeneity was found, and the maximum lod score was 0.67 at a recombination fraction of 0.17. Taken as a whole, the present findings do not support the presence of a disease gene for panic disorder closely linked to the alpha-haptoglobin locus on chromosome 16q22.

Adult↗

Linkage of c-Harvey-ras-1 and INS DNA markers to unipolar depression and alcoholism is ruled out in 18 families.

Eighteen families informative for c-Harvey-ras-1 and INS DNA markers were tested for linkage to unipolar depression and alcoholism. No evidence of linkage was found between these DNA markers and the disorders observed in the families. This study fails to replicate the Old Order Amish Study and suggests that a significant degree of genetic heterogeneity may be present among psychiatric disorders.

Adolescent↗

The Iowa multiplex family study of schizophrenia: linkage analyses on chromosome 5.

We analysed six multiplex pedigrees of schizophrenia for linkage to two DNA probes mapping to the chromosome 5q11-q13 region where linkage to a gene for schizophrenia was recently reported. Analyses were conducted using three penetrance models and considering the affected state to be schizophrenia, the schizophrenia spectrum, and all psychiatric diagnoses. All analyses gave consistently negative lod scores. Although the region was not formally excluded, no evidence for linkage was found.

Chromosomes, Human, Pair 5↗

Panic disorder: genetic considerations.

Panic disorder is a common illness that can have serious consequences, including increased long-term mortality. Family and twin studies suggest that it is a genetic disorder and transmission patterns within families are compatible with a hypothesis of a disease gene predisposing to the condition. Recently, it has become possible to locate disease genes causing familial disorders through linkage analysis. A preliminary linkage analysis of panic disorder at the University of Iowa found suggestive but inconclusive evidence of linkage to the alpha-haptoglobin locus on chromosome 16q22. Future strategies for identifying disease genes in anxiety disorders are described.

Anxiety Disorders↗

The application of genetic methods to the study of disease associations in psychiatry.

The problem of multiple diagnoses in the same patient is a very real one in psychiatry. Theoretical causes of disease associations are reviewed and illustrated with examples from a variety of psychiatric conditions. These include Huntington's disease and depression, mitroprolapse and panic attacks, anxiety disorder and depression, and others.

Agoraphobia↗

Reliability of the telephone interview in diagnosing anxiety disorders.

The reliability of psychiatric diagnosis using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version in personal and telephone interviews with 39 subjects was assessed using a 12- to 19-month test-retest design. Interrater reliability was high (kappa, .69 to .84) for the diagnosis of panic disorder, agoraphobia with panic attacks, probable panic disorder, major depression, and alcohol abuse. We conclude that it is possible to reliably make these lifetime diagnoses in a family study using the telephone interview.

Agoraphobia↗

Delusional disorder: jealous and nonjealous types.

We studied the records of 101 patients with delusional disorder admitted to the Psychiatric Hospital between 1920 and 1980 and divided the sample into those with jealous (43) and those with nonjealous (58) delusions. Patients and relatives were located by telephone and follow-up information was collected. Compared with the nonjealous patients, the jealous ones were more likely to have had a single delusion, and to have experienced a more benign course as indicated by a lower rate of hospitalization and outpatient treatment. The original delusion tended to remain and the illness did not develop into another form of delusional disorder or other psychiatric illness.

Adult↗