Twin Designs and Causal Inference PDF

Twin designs and causal inference Reading 12 November 2023 21:06 Source Notes Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression Introduction (Kendler & Gardner, 2010) Causal Pathways to Psychiatric Illness ○ Elucidating causal pathways to psychiatric...

Twin designs and causal inference Reading 12 November 2023 21:06 Source Notes Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression Introduction (Kendler & Gardner, 2010) Causal Pathways to Psychiatric Illness ○ Elucidating causal pathways to psychiatric illness is a critical research goal. ○ Randomized controlled trials are not feasible for many psychiatric disorders due to ethical or practical reasons. ○ Two approaches remain to evaluate causal processes: natural experiments and statistical methods. Dependent Stressful Life Events (dSLEs) and Prior Depressive Episodes (PDEs) as Risk Factors for Major Depression (MD) ○ dSLEs and PDEs are associated with increased risk for MD. ○ The causal nature of these associations is unclear. ○ The critical question is whether the association between these risk factors and MD is causal or noncausal. Counterfactual/Interventionist theories of causation ○ If the association between risk factors and MD is causal, reducing risk factor exposure will reduce rates of disease. ○ If the association is noncausal, altering risk factor exposure will not affect illness rates. Shared covariates ○ Many factors predispose to both dSLEs and MD, including neuroticism, PDEs, and genetic risk for MD. ○ The association between dSLEs and MD might result from these shared covariates. Recurring MD ○ Numerous risk factors for MD—including genes and childhood adversities—have long-lasting effects. ○ The tendency for MD to recur could arise without one depressive episode having a causal effect on the next. Study Design and Methods ○ This study used a natural experiment (twins) and a specialized statistical method (propensity analysis) to address the questi on of causality. ○ The co-twin control method examined outcomes in twin pairs discordant for risk factor exposure. ○ Propensity analysis simulated a case-control study in a cohort assessed for the risk factor, outcome, and covariates predicting risk factor exposure. Co-twin control method ○ The co-twin control method examines outcomes in twin pairs discordant for risk factor exposure. ○ Twin pairs raised together are matched for their rearing environment and their genes. Propensity analysis ○ Propensity analysis simulates a case-control study. ○ For each case (an individual exposed to the risk factor), an unexposed control is selected matched on the probability of bein g a case. Samples ○ These 2 methods were applied separately in male -male and female-female twin samples for the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Methods Dependent Stressful Life Events (dSLEs) ○ Participants were assessed for the occurrence of 11 classes of personal and 4 classes of network events. ○ Interrater reliability for the occurrence and dating of SLE categories was 0.93 and 0.82, respectively. ○ Dependence of SLEs was conceptualized as the probability that a respondent’s own behavior contributed to the SLE. ○ A dSLE was defined as probably or clearly dependent. Diagnoses of Major Depression (MD) ○ Diagnoses of MD in the past year were made according to DSM -IV criteria. ○ For each reported episode, the respondents described its duration and date of onset and offset. ○ Of the MD episodes examined in the dSLE and PDE analyses, 36.4% and 40.4%, respectively, denied prior episodes (i.e., were po tentially first onsets). Relationship between dSLEs and MD ○ The relationship between dSLEs and risk for depressive episode onset in the month of the dSLE and 2 subsequent months was exp lored. ○ 18 covariates were chosen as predictors of dSLE exposure. ○ The covariates included birth year, parental warmth, childhood sexual abuse, parental loss, neuroticism, introversion, self -esteem, early-onset anxiety disorder, conduct disorder, lifetime traumas, social support, lifetime diagnosis of alcohol abuse or dependence, lifetime diagnosis of nicotine dependence, lifetime diagnosis of illicit drug abuse or dependence, history of divorce, history of MD more than 1 year before the FF3 or MM1 interview, marital quality, and difficulties. Relationship between PDE and MD ○ The relationship between PDE and risk for a subsequent depressive episode was evaluated. ○ MD episodes reported at the MM1 and FF1 interviews were used as risk factors, and those reported at the MM2 and FF2 interview s were used as the outcomes. ○ 10 covariates were selected as potential predictors of PDE. ○ The covariates included birth year, years of education, childhood sexual abuse, neuroticism, history of MD before the past ye ar, introversion, self-esteem, social support, difficulties, and parental warmth. Statistical Analysis ○ Co-twin control analyses were conducted to obtain twin pairs discordant for the risk factor exposure. ○ Logistic regression was used to calculate odds ratios (ORs). ○ Propensity score analyses were conducted to compare propensity matching to the co -twin control approach. ○ A nearest neighbour or a greedy matching algorithm was used to create matched pairs discordant for exposure. ○ A multiple imputation approach was used to include individuals with missing values for some variables. Results dSLEs as a Causal Risk Factor for an MD Episode Male-Male Pairs ○ Exposure to a dSLE in the year before the MM1 interview was strongly associated with an onset of MD within 3 months (OR, 4.55 ; 90% CI, 3.49-5.90; P