[Validation of an Icelandic version of the Geriatric Depression Scale (GDS).].

OBJECTIVE: Health-related quality of life (HRQL) is increasingly used to estimate needs for medical treatment, to evaluate its outcome and quality of care. The aim of this study was to compare the HRQL of several diagnostic groups before and after treatment with the HL-test (HL = IQL, Icelandic Quality of Life test) and to study its validity for measuring changes in quality of life. MATERIAL AND METHODS: Patients on waiting lists for coronary catheterization, orthopedic or urologic operations, patients in psychiatric out-patient treatment and patients entering treatment for alcohol dependence were asked to fill in the HL-test, a total of 1195 patients. Three months after treatment they were retested. The results of tests were standarized with population norms available to make them directly comparable with those of the general population. RESULTS: The response rate was 75% in each round. The HRQL of all patients was reduced in all aspects compared to that of the general population, that of the heart and urology patients less so than that of the orthopedic and psychiatric patients. Each group had a specific profile, especially marked for the orthopedic and psychiatric patients. Following treatment the HRQL or some aspects of it improved in all groups, especially for those which it had been most impaired. CONCLUSIONS: Studies of HRQL provide information useful for planning and delivery of health services. The HL-test is an instrument with good validity and reliability which is easy to use for such studies.

Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with panic disorder.

We searched for mutations in the CCK gene in panic disorder with single-strand conformational polymorphism (SSCP) analysis of the three exons and promotor region of the gene. We found a C-->T transition at position -36 (CCK(-36C-->T)) in a GC box, a binding site for transcription factor Sp1, in the promotor region. The allele frequency was 0.168 (95% CI, 0.116-0.221) in 98 persons with panic disorder and 0.083 (95% CI, 0.059-0.107) in 247 geographically matched, unscreened controls. A transmission disequilibrium test based on panic disorder as the affected phenotype was nonsignificant (chi2 = 0.93), but when panic disorder or attacks were considered as affected, statistically significant transmission disequilibrium was detected (chi2 = 4.00, P < 0.05). Linkage analysis was uninformative. In exploratory analyses to search for clinical correlations, the "T" allele was found in 59% of 22 persons with panic attacks but not panic disorder, compared with 31% of those who met the criteria for panic disorder. An association between the CCK polymorphism and panic disorder cannot be considered established due to the inconsistencies in the results noted above, but if the provisional association can be replicated, the findings are consistent with CCK(-36C-->T) being a disease-susceptibility allele that alone is neither necessary nor sufficient to cause panic disorder but that increases vulnerability by acting epistatically.

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.

Psychopharmacoepidemiology in Iceland: effects of regulations and new medications.

The sale of psychotropic medications in Iceland has waxed and waned during the past 20 years with approximately 5 years between peak and bottom quantities sold. Apparently, it has decreased following restrictions imposed by the public health authorities and increased again following the introduction of new drug. In order to study this further, all prescriptions for psychotropic medications to non-hospitalized inhabitants of the capital city (Reykjavík) and dispensed by pharmacists there during 1 month in 1984, 1989 and 1993 were analysed in order to estimate the 1-month prevalence of psychopharmacological use. The results support the hypothesis partly as prescriptions for tranquillizers decreased in 1989 as well as the amount of tranquillizers and hypnotics prescribed following new restrictions, whereas the prevalence odds ratio of obtaining prescriptions for hypnotics remained unchanged. The proportion of patients receiving excessive amounts of tranquillizers and/or hypnotics decreased. The prevalence of excessive use of these drugs (i.e. > 90 DDD/month) was 0.5% in 1993. In 1993 the prevalence of the use of antidepressants as well as the amount prescribed had increased substantially following the introduction of the new selective serotonin reuptake inhibitor medications. Thus, the prevalence of patients obtaining any psychotropic medication remained unchanged from 1984 to 1993.

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.

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.

No evidence of linkage between schizophrenia and D3 dopamine receptor gene locus in Icelandic pedigrees.

The D3 dopamine receptor gene is an important candidate gene for schizophrenia, since--because of its almost exclusive expression in the limbic system--it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. Pairwise linkage analyses were carried out between the D3 dopamine receptor gene locus (DRD3) and schizophrenia (including major depression among its pleiotropic manifestations). On the basis of these analyses, which assumed a penetrance of 0.71 and a dominant mode of inheritance, we were able to exclude the DRD3 locus with a lod score of -2.50 in four Icelandic pedigrees. The area of exclusion (lod score < -2.00) extended 1.2 centimorgans. We conclude that the genetic predisposition to schizophrenia in these pedigrees is not due to a mutation in the DRD3 locus. However, these results cannot exclude the possibility that a defect in other genes regulating the expression of the D3 dopamine receptor gene could be involved in the pathogenesis of schizophrenia or that linkage analyses in other families or population-based association studies might show a positive result.