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ItemG-protein beta 3 subunit genetic variation moderates five-year depressive symptom trajectories of primary care attendeesBousman, CA ; Potiriadis, M ; Everall, IP ; Gunn, JM (ELSEVIER SCIENCE BV, 2014-08-20)BACKGROUND: Genetic variation in the G-protein β3 subunit (GNB3) has previously been associated with gene splicing that has been further linked to increased signal transduction and major depressive disorder. However, the effect of GNB3 genetic variation on depressive symptom trajectories is currently unknown. The aim of the present study is to examine whether genetic variation in GNB3 moderates depressive symptom trajectories among 301 primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study. METHODS: Depressive symptoms were assessed using three measures: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria were measured at baseline, 24, 36, 48, and 60 months post-baseline, whereas, PHQ-9 and CESD measurements were taken at baseline, 12, 24, 36, 48, and 60 months post-baseline. Two haplotype-tagging single nucleotide polymorphisms [rs5443 (C825T) and rs5440] spanning the GNB3 gene including ~1Kb upstream and downstream of the gene boundaries were genotyped. RESULTS: Five-year PHQ-9 and CESD depressive symptom trajectories were moderated by rs5440. Carriers of the rs5440 GG genotype had more favourable depressive symptom trajectories compared to AG or AA genotype carriers. The rs5443 polymorphism did not moderate depressive symptom trajectories, regardless of the measure used. LIMITATIONS: Generalizability to depressed populations outside of the primary care setting may be limited. CONCLUSIONS: These results provide novel evidence suggesting genetic variation in the 5-prime region of GNB3 moderates depressive symptom trajectories among primary care attendees.
ItemNo Preview AvailableSelf-Rated Health and Long-Term Prognosis of DepressionAmbresin, G ; Chondros, P ; Dowrick, C ; Herrman, H ; Gunn, JM (ANNALS FAMILY MEDICINE, 2014-01-01)PURPOSE: Indicators of prognosis should be considered to fully inform clinical decision making in the treatment of depression. This study examines whether self-rated health predicts long-term depression outcomes in primary care. METHODS: Our analysis was based on the first 5 years of a prospective 10-year cohort study underway since January 2005 conducted in 30 randomly selected Australian primary care practices. Participants were 789 adult patients with a history of depressive symptoms. Main outcome measures include risks, risk differences, and risk ratios of major depressive syndrome (MDS) on the Patient Health Questionnaire. RESULTS: Retention rates during the 5 years were 660 (84%), 586 (74%), 560 (71%), 533 (68%), and 517 (66%). At baseline, MDS was present in 27% (95% CI, 23%-30%). Cross-sectional analysis of baseline data showed participants reporting poor or fair self-rated health had greater odds of chronic illness, MDS, and lower socioeconomic status than those reporting good to excellent self-rated health. For participants rating their health as poor to fair compared with those rating it good to excellent, risk ratios of MDS were 2.10 (95% CI, 1.60-2.76), 2.38 (95% CI, 1.77-3.20), 2.22 (95% CI, 1.70-2.89), 1.73 (95% CI, 1.30-2.28), and 2.15 (95% CI, 1.59-2.90) at 1, 2, 3, 4, and 5 years, after accounting for missing data using multiple imputation. After adjusting for age, sex, multimorbidity, and depression status and severity, self-rated health remained a predictor of MDS up to 5 years. CONCLUSIONS: Self-rated health offers family physicians an efficient and simple way to identify patients at risk of poor long-term depression outcomes and to inform therapeutic decision making.