A study of autism using X chromosome DNA probes.
Explore the source record for details and available documents.
Autistic Disorder↗
Biomedical subjects
R R Crowe
Publications and source records attributed to R R Crowe.
Chromosomal localization of the human diazepam binding inhibitor gene.
We have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the gamma-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes.
Animals↗
A linkage study of panic disorder.
We tested for linkage between panic disorder and a battery of 29 genetic markers in 26 families. Linkage between panic disorder and 18 of the marker loci could be excluded at a recombination fraction of 0.00, nine at a recombination fraction of 0.05, and four at a recombination fraction of 0.10. The 18 loci are distributed over ten chromosomes. One locus was suggestive of linkage. The maximum lod score for alpha-haptoglobin was 2.27 at a recombination fraction of 0.0, representing odds in favor of linkage of 186.1. alpha-Haptoglobin has been mapped to chromosome 16q22. The results demonstrate that linkage studies of psychiatric disorders can yield informative results by identifying tentative linkages that merit further investigation and by excluding regions of the genome from future linkage searches.
Adult↗
A family study of generalized anxiety disorder.
The frequency of generalized anxiety disorder was higher among first-degree relatives of probands with generalized anxiety (N = 20) than among the relatives of control subjects (N = 20), but it was not higher among relatives of probands with panic disorder (N = 40) or agoraphobia (N = 40). Also, the frequency of panic disorder was higher among relatives of probands with panic disorder than among control relatives but was not higher among relatives of generalized anxiety probands. Relatives of probands with generalized anxiety who had the same disorder had a mild, stress-related illness. The results confirm the separation between generalized anxiety disorder and panic disorder but challenge the distinction between generalized anxiety and adjustment disorders.
Adjustment Disorders↗
Relationship between panic disorder and agoraphobia. A family study.
A family study of patients with agoraphobia (n = 40), panic disorder (n = 40), and nonanxious controls (n = 20) showed that the morbidity risk for panic disorder was increased among the relatives of agoraphobics (8.3%) and the relatives of patients with panic disorder (17.3%). The morbidity risk for agoraphobia was also increased among the relatives of agoraphobics (11.6%) but not the relatives of panic disorder patients (1.9%). Male relatives of agoraphobics were shown to be at higher risk for alcohol disorders (30.8%). No greater risk for primary affective disorders was found among the relatives of agoraphobic or panic disorder patients or among the relatives of probands with secondary depression compared with relatives of probands without secondary depression. Probands and relatives with agoraphobia reported an earlier onset of illness, more persistent and disabling symptoms, more frequent complications, and a less favorable outcome than probands and relatives with panic disorder. The findings suggest that agoraphobia is a more severe variant of panic disorder. They also lend support to the separation between anxiety disorders and affective disorders.
Adult↗
Seizures following the withdrawal of alprazolam.
Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose for 10 weeks. A review of available case reports suggests that seizures, like other withdrawal phenomena, are more apt to occur with short-acting benzodiazepines. To prevent their occurrence these drugs should be discontinued gradually and consideration given to substituting long-acting drugs during the withdrawal period. Physicians should remain alert to the fact that seizures may occur as early as 24 hours after the abrupt withdrawal of short-acting benzodiazepines.
Adult↗
A withdrawal syndrome after abrupt discontinuation of alprazolam.
A patient who received therapeutic doses of alprazolam for 8 weeks experienced a withdrawal syndrome beginning 18 hours after its abrupt discontinuation. Short-acting and minimally sedating benzodiazepines may have increased potential for withdrawal reactions.
Adult↗
The genetics of panic disorder and agoraphobia.
Panic disorder, comprising also agoraphobia for the purpose of this review, has a prevalence of 1.2-8.4 per cent, affecting females twice as frequently as males, and has a mean age of onset of 25. It is one of the more familial diseases in Psychiatry in that 2/3 of cases have relatives affected with the same condition, and the risk to first degree relatives is approximately 3-4 times the rate of the general population. Although some family studies have suggested an overlap in the transmission of panic disorders and depression, and a common diathesis hypothesis has been proposed, depression is more common in the families of depressives, as in panic disorder in the families of probands with panic disorder. Twin studies of anxiety disorders, although limited in number, report a 30-40 per cent concordance among MZ twins, against 0-4 per cent among DZ twins, which supports a genetic predisposition. The mode of transmission is uncertain. Studies which have used the 'ancestral pairs' method (which examines the incidence of the condition in maternal versus paternal forebears, on the assumption that single locus transmission is favored by unilateral clustering, and polygenic theories are favored by a more even spread) have favored single locus transmission, although such unilateral clustering can still be accommodated within a multifactorial-polygenic hypothesis. Potential biological markers for the condition are reviewed. The observation that lactate infusion can precipitate panic attacks in predisposed individuals is well established. The association with mitral valve prolapse suggests that perhaps 38 per cent of patients presenting with symptoms of panic disorders have mitral valve prolapse on echocardiography. The possibility of an endogenous anxiety-producing agent that binds to the benzodiazepine receptor is discussed.
Adolescent↗
Mitral valve prolapse and panic disorder.
Recently, there has been considerable interest in the association between panic attacks and mitral valve prolapse. This article reviews the syndrome of mitral valve prolapse, the data on its association with panic attacks, and possible reasons for such an association. Clinical implications are also discussed.
Adult↗
Current concepts. Electroconvulsive therapy--a current perspective.
Explore the source record for details and available documents.
Depression↗
Diazepam and propranolol in panic disorder and agoraphobia.
The response to diazepam and propranolol hydrochloride was compared in 21 patients who (with one exception) met DSM-III criteria for panic disorder and agoraphobia. Each drug was administered for two weeks in double-blind fashion according to a crossover design. The response to diazepam was significantly superior on all measures. By observer rating, 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol. Panic attacks and phobic symptoms responded to diazepam, but not to propranolol. The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders.
Adult↗
Affective disorder not linked to HLA in a large bipolar kindred.
Recent studies have suggested genetic linkage between the major histocompatibility complex and affective disorder. We tested this hypothesis in a large pedigree of bipolar affective disorder in which 22 of 37 relatives were interviewed and HLA typing was carried out on 20. The findings provided no evidence for linkage between affective disorder and HLA antigens. Our findings are discussed along with those of other linkage studies bearing on this question.
Adolescent↗
A comparison of panic disorder and generalized anxiety disorder.
Subjects from a family study who had panic disorder and generalized anxiety disorder were compared on the pattern of their symptoms, age and type of onset, personality characteristics, course of illness, and outcome. Subjects with generalized anxiety disorder were shown to have fewer autonomic symptoms and an earlier, more gradual onset. Their illness was also observed to have a more chronic course and a more favorable outcome, although these differences were not statistically significant. The validity of generalized anxiety disorder and panic disorder as discrete diagnostic entities is supported.
Adult↗
Psychiatric disorders among relatives of surgical controls.
The risks of various psychiatric illnesses among the first-degree relatives of 160 surgical control patients were estimated. Morbidity risks were calculated separately for males and females because of previous findings showing significant sex differences for certain diagnoses. The findings, based on ICD-9 criteria, demonstrate a significantly higher risk of depression, neurosis, and organic brain syndrome in females than in males. The risk of alcoholism was significantly higher in males.
Adult↗
Bipolar illness. The sex-polarity effect in affectively ill family members.
We examined the sex ratios of unipolar and bipolar affective disorder in 14 studies of bipolar illness. The data are highly consistent in demonstrating that (1) females are more frequently affected than males; (2) among affected females, the ratio of unipolar depression to bipolar illness is about 2:1; whereas (3) among affected males, the ratio of bipolar to unipolar illness is approximately 1:1. This curious discrepancy between the sexes may hold a clue to understanding familial transmission as well as heterogenicity in bipolar illness.
Bipolar Disorder↗
Family study of agoraphobia. Report of a pilot study.
A family study of agoraphobia (n = 20), panic disorder (n = 20), and nonanxious controls (n = 20) showed the morbidity risk for all anxiety disorders to be 32% among first-degree relatives of agoraphobics, 33% among relatives of patients with panic disorder and 15% among relatives of controls. Relatives of agoraphobics were also shown to be at higher risk for alcohol disorders. Female relatives were found to be at greater risk for anxiety disorders, reflecting their increased susceptibility to these illnesses, and male relatives were at greater risk for alcohol disorders. The increased risk for anxiety disorders in the relatives of agoraphobics was not specific for agoraphobia but included panic disorder and other phobias as well. The findings indicate that agoraphobia is a familial disorder and that family data may help to determine whether agoraphobia is separate from other anxiety and phobic disorders.
Adult↗
A family study of panic disorder.
In a family study of panic disorder, we collected data on 278 first-degree relatives of 41 probands with panic disorder and 262 relatives of 41 control probands. The morbidity risk for panic disorder was 17.3% in the first group, and an additional 7.4% were categorized as having probable panic disorder. Both rates were significantly higher than the respective rates in the control relatives, 1.8% and 0.4%. The risk of panic disorder in female subjects was twice that in male subjects. The rate of generalized anxiety disorder was the same in both groups of families. No other psychiatric disorders were increased in the families of patients with panic disorder. In a preliminary genetic analysis, we tested the single major locus and the multifactorial polygenic transmission models. Neither model was excluded by the data. We conclude that panic disorder is a familial disease that affects women twice as frequently as men and is not associated with an increased familial risk of other psychiatric conditions. Its method of transmission remains uncertain.
Adult↗