What's a GWAS? What can it teach me about bipolar disorder?

The paper we discuss is H Tyagi et al. (2019) A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects. Biological Psychiatry 85:726-734.

You can find a copy of the Yale Brown Obsessive Compulsive Scale (Y-BOCS), complete with detailed instructions for administering the scale, here.

A bit more information on the set-shifting/cognitive flexibility task used in the study can be found here.

The paper we discuss is  K Humphreys, JC Blodgett, and TH Wagner. Estimating the Efficacy of Alcoholics Anonymous Without Self-Selection Bias: An Instrumental Variables Re-Analysis of Randomized Clinical Trials. Alcoholism: Clinical and Experimental Research. 2014; 38(11): 2688-2694.

The primary outcomes from Project MATCH, which looked at the efficacy of different psychotherapeutic interventions for alcohol use disorder, can be found here.

Helpful reference on instrumental variables analysis: ML Maciejewski and MA Brookhart. Using Instrumental Variables to Address Bias from Unobserved Confounders. JAMA 2019; 321(21): 2124-2125.

Another example of using instrumental variable analysis to address an important question in psychiatry (this time, related to ECT and hospital re-admission): AT LoSasso. Use of Instrumental Variables Methods in Examining Psychiatric Readmissions. JAMA Psychiatry 2017; 74(8): 805-806.

The article we discuss is MA Raskind et al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. New England Journal of Medicine 2018; 378(6):507-517

For an  example of an earlier study that DID find benefit of prazosin for PTSD, check out Raskind, MA et al. A Trial of Prazosin for Combat Trauma PTSD with Nightmares in Active-Duty Soldiers Returned from Iraq and Afghanistan. Am J Psychiatry 2013; 170: 1003-1010.

Recent meta-analyses of the efficacy of prazosin for PTSD can be found here and here. 

A brief review on the ethical principles of equipoise in research.

The paper we talk about: ED-SAFE Primary Outcomes .

The authors discuss their approach to the study in the ED-SAFE Design Paper.

Straight-forward reviews of cluster randomized trials and the step-wedge design.

The paper we discuss is Psychiatric Genomics Consortium. Genome-Wide Association Study Identifies 30 Loci Associated with Bipolar Disorder. Nature Genetics 2019; 51:793-803.

Here's an incredibly helpful review on understanding genome wide association studies (GWAS): TA Pearson and TA Manolio. How to Interpret a Genome-Wide Association Study. JAMA 2008; 299(11):1335-1344.

Find out more about the Psychiatric Genomics Consortium. 

The paper we discuss is TD Girard et al. Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med 2018; 379(26):2506-2516. This paper is part of the ABPN MOC program. The podcast authors are not associated with the MOC program and have no knowledge of the questions about the article included in the MOC program.

The JAMA Guide to Statistics and Methods has an easy-to-read, 1.5 page overview of the odds ratio.

The paper we discuss is BA Clementz et al. Identification of Psychosis Biotypes Using Brain-Based Biomarkers. Am J Psychiatry  2016; 173(4): 373-384.

Here's the paper Dr Toups mentions about depression, biotypes, and treatment response:  AT Drysdale et al. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine 2017; 23: 28-28.

The  discussion about psychiatric nosology has led to some heated discussions and received a bit of attention in the popular press.  The New Yorker's take is here.

We are not the only the psychiatry podcast that has discussed these questions. There's also an excellent discussion on the first episode of the podcast Ten to the Fifteenth, which is produced by the National Neuroscience Curriculum Initiative.

The paper we discuss in this episode is V Popova et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined with a Newly Initiated Oral Antidepressant in Treatment Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry  2019; 176(6): 428-438.

For a deeper understanding of the factors that contribute to placebo response, check out  BR Rutherford and SP Roose. A Model of Placebo Response in Antidepressant Clinical Trials. Am J  Psychiatry  2013; 170:723-733.

Lots of data about the placebo response in antidepressant clinical trials:

BT Walsh et al. Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing. JAMA 2002; 287(14):1840-1847.

W Rief et al . Meta-analysis of the Placebo Response in Antidepressant Trials. Journal of Affective Disorders 2009; 118:1-8.

TA Furukawa et al. Placebo Response Rates in Antidepressant Trials: A Systematic Review of Published and Unpublished Double-Blind Randomised Controlled Studies. Lancet Psychiatry 2016; 3:1059-1066. 

The paper we discuss is M Linehan et al. Dialectical Behavior Therapy for High Suicide Risk in Individuals with Borderline Personality Disorder:  A Randomized Clinical Trial and Component Analysis. JAMA Psychiatry 2015; 72(5):475-482. 

We LOVE the JAMA Guide to Statistics and Medicine for quick, clinically relevant overviews of important issues in clinical trials design and analysis. Here's there article on non-inferiority designs. 

Suicidal Behavior During Lithium and Valproate Treatment

Use the link above to get to the paper we discuss in this episode or use the following citation to find it. 

Song, J et al. Suicidal Behavior During Lithium and Valproate Treatment: A Within-Individual 8-Year Prospective Study of 50,000 Patients with Bipolar Disorder. Am J Psychiatry 2017; 174:795-802.