Stanley I. Shyn

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Background Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Methods Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. Results We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11–1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. Conclusions We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.

Genetic effects influencing risk for major depressive disorder in China and Europe

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Peer Mentoring Process for Psychiatry Curriculum Revision: Lessons Learned from the “Mod Squad”

Effective faculty development is crucial for the success of medical residency programs. Traditional approaches to faculty development have focused on developing the knowledge and teaching skills of the individual participant. The established formats are centralized programs, seminars, workshops, and retreats, which are often conducted away from the workplace context in which faculty actually teach. These formats have demonstrated value, as described in a 2012 review of faculty development programs [1]. As more has been discovered about how people learn in the workplace, however, prominent scholars in faculty development have called for an expanded model that supports the social and community aspects of workplace learning, beyond an exclusive focus on individual competence. Ideally, faculty development enables faculty members to enter into a new intellectual and social community of like-minded individuals who share a passion for teaching [2]. To support the larger social enterprise of teaching and learning, some scholars have encouraged use of alternative formats for faculty development, such as conducting activities at the workplace within the practice communities. This progression from formal, individual programs to informal, group programs has been described as “work-based learning” and “communities of practice,” or groups of people with shared interests and a common knowledge domain who learn together through ongoing collaboration [3]. Steinert [3] argues that it is in the everyday workplace, where teachers conduct their clinical and teaching activities—and where they interact with faculty, colleagues, and students—that learning most often takes place. By working together in a clinical or classroom setting and discovering opportunities for learning, teachers acquire knowledge and develop novel educational approaches. Further, faculty development initiatives should use faculty members’ social networks to improve adoption of educational innovations [4]. In response to this trend, the University of Washington Department of Psychiatry and Behavioral Sciences developed a workplace-situated, hands-on faculty development program for its practice community of both junior and senior clinicianeducator faculty to accomplish these goals: (1) create a venue for participants to find community through peer relationships and support for teaching activities, (2) develop participants’ instructional competence in curriculum development, (3) enhance participants’ leadership skills and content expertise, and (4) renew the curriculum for six modules in the resident didactic series. Herein, we describe the process of curriculum revision using a workplace-based community of practice, learning activities utilized by the group, and challenges with examples.