General Practice - Research Publications

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    The Brain-Derived neurotrophic Factor Val66Met Polymorphism Moderates the effects of childhood abuse on severity of Depressive symptoms in a Time-Dependent Manner
    Webb, C ; Gunn, JM ; Potiriadis, M ; Everall, IP ; Bousman, CA (FRONTIERS MEDIA SA, 2016-08-29)
    Cross-sectional studies have demonstrated that the brain-derived neurotrophic factor (BDNF) Val66Met single-nucleotide polymorphism moderates the association between exposure to negative life events and depression outcomes. Yet, it is currently unclear whether this moderating effect is applicable to positive life events and if the moderating effect is stable over time. To address these gaps in the literature, we examined clinical and BDNF genotypic data from a 5-year prospective cohort of 310 primary care attendees. Primary care attendees were selected based on existence of depressive symptoms at screening. Depressive symptoms were assessed at baseline and annually for 5 years post-baseline using the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9). Linear mixed models assessed differences in depressive symptom severity over the 5-year follow-up period by BDNF Val66Met and history of life events, both negative and positive. Analysis identified a novel three-way interaction between the BDNF Val66Met polymorphism, history of severe childhood abuse, and time. Post hoc analysis stratified by time showed a two-way interaction between Val66Met and severe childhood abuse at baseline that was not detectable at any other time point. An interaction between Val66Met and positive life events was not detected. Our longitudinal results suggest that the BDNF Val66Met polymorphism moderates the depressive symptom severity experienced by those with a history of severe childhood abuse but does so in a time-dependent manner. Our results further support the notion that gene-environment-depression interactions are dynamic and highlight the importance of longitudinal assessment of these interactions. Given these novel longitudinal findings; replication is required.
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    Serotonin transporter polymorphism (5HTTLPR), severe childhood abuse and depressive symptom trajectories in adulthood
    Nguyen, TB ; Gunn, JM ; Potiriadis, M ; Everall, IP ; Bousman, CA (ROYAL COLL PSYCHIATRISTS, 2015-06-01)
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    G-protein beta 3 subunit genetic variation moderates five-year depressive symptom trajectories of primary care attendees
    Bousman, 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.