Background Human anxiety disorders are complex diseases with largely unknown etiology.
October 2, 2017
Background Human anxiety disorders are complex diseases with largely unknown etiology. dehydratase) in interpersonal phobia, = .009 with (dynein light chain 2) in generalized FK866 supplier anxiety disorder, and = .004 with (prosaposin) in panic disorder. Conclusions Our findings suggest that variants in these genes might predispose to specific human stress disorders. These results illustrate the potential power of cross-species methods in identification of candidate genes for psychiatric disorders. (15,16). Briefly, the 12-month prevalence of DSM-IV mental disorders was estimated from a representative sample (= 6005) of the Finnish general adult ( 30 years of age) population with the Composite International Diagnostic Interview (CIDI). Finland represents a well-characterized genetic isolate (17), with approximately 2% of individuals with foreign descent. No ethnic groups were excluded during recruitment to obtain a representative epidemiological cohort, but the interview was conducted in Finnish, excluding all non-fluent foreigners. A computer-aided version of the mental health interview (M-CIDI) was administered by trained non-psychiatric healthcare professionals and designed to determine the 12-month prevalence of a set of clinically and epidemiologically relevant mental disorders. These included major depressive disorder, dysthymia, generalized anxiety disorder, panic disorder with or without agoraphobia, agoraphobia, interpersonal phobia, and alcohol abuse and dependence. The total quantity of reliably performed mental health interviews was 6005, amounting to 75% of the original sample. Compared with CIDI participants, the dropouts (= 981) experienced somewhat higher scores in the Beck Depressive disorder Inventory (BDI), indicating depressive symptoms, and General Health Questionnaire-12 (GHQ-12), indicating psychic distress. They also experienced slightly older age, lower education, and were more frequently single. Although this might bias the final results toward underestimation of prevalence of mental disorders in the general population, we believe that the most common stress disorders are well-represented in our cohort. Due to the structure of the interview, we were not able to reliably diagnose obsessive-compulsive disorder and post-traumatic stress disorder and chose to focus on a subset of the most clinically relevant stress disorders in the Finnish populace. From this cohort, we in the beginning selected all individuals with a DSM-IV anxiety disorder diagnosis for analysis (core diagnostic group). In addition, we broadened our definition of anxiety disorder subjects to include individuals with sub-threshold diagnoses as defined by the CIDI (extended diagnostic group). For each case, we selected two control subjects who lacked diagnosed stress or major mental disorders and were matched according to gender, age ( 1 year), and hospital catchment area. The DNA was not available from 34 subjects (15 cases and 19 control subjects), and therefore, the final analyzed study sample consisted of 321 cases and 653 control subjects (Table 1). Forty-one core subjects were diagnosed with more than one anxiety disorder (5 with three disorders, and 36 with two disorders). The most frequent combination of diagnoses was panic disorder comorbidity with interpersonal phobia (18 subjects). Table 1 Demographic Characteristics of the Health 2000 Anxiety Disorder Study Sample Single Nucleotide Polymorphism Selection The association study was carried out in two stages. In stage I, we examined the known human homologues FK866 supplier of 13 stress candidate genes recognized in the mouse (14) with a set of 139 carefully selected single nucleotide polymorphisms (SNPs; Table 2). In stage II, we followed FK866 supplier up on positive findings by genotyping 69 additional markers from genes Rabbit polyclonal to PGM1 showing evidence for association after stage I. The 208 markers selected for genotyping represented three different variance groups: non-synonymous SNPs, haplotype-tagging SNPs, and putative polymorphic microRNA (miRNA) binding sites. Table 2 Investigated Candidate Genes.