Effects of the serotonin transporter polymorphism and history of major depression on overgeneral autobiographical memory

Abstract

Overgeneral autobiographical memory (OGM) is a key memory deficit in major depressive disorder (MDD). Much research has examined cognitive mechanisms underlying OGM, but little work has investigated potential neurobiological influences. There is preliminary evidence that a genetic serotonergic vulnerability coupled with depressive symptoms may be associated with other memory impairments, and experimental research suggests a role for serotonin in OGM. We investigated whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was associated with OGM in interaction with a lifetime history of MDD in 370 young adults in a longitudinal study of risk for emotional disorders. There was a significant interaction between 5-HTTLPR genotype and lifetime history of MDD in predicting OGM. Among S allele homozygotes, MDD history was associated with greater OGM, whereas no significant relationship between MDD history and OGM emerged among L carriers. Furthermore, there was evidence that a greater number of S alleles were associated with greater memory specificity in individuals without a history of MDD. Implications for understanding cognitive and biological risk for depression are discussed.

Keywords:

• Overgeneral autobiographical memory
• Autobiographical memory specificity
• 5-HTTLPR
• Depression
• Genetic association

We also gratefully acknowledge the assistance of the many students who helped with data collection.

We would like to thank the National Institute of Mental Health [grant number R01 MH065652 to Drs. Mineka and Zinbarg, R01 MH065651 to Dr. Craske, and F31 MH088014 to Dr. Sumner] and the Institute for Policy Research, Northwestern University, Faculty Fellowship (to Dr. Adam) for supporting our research.

We also gratefully acknowledge the assistance of the many students who helped with data collection.

We would like to thank the National Institute of Mental Health [grant number R01 MH065652 to Drs. Mineka and Zinbarg, R01 MH065651 to Dr. Craske, and F31 MH088014 to Dr. Sumner] and the Institute for Policy Research, Northwestern University, Faculty Fellowship (to Dr. Adam) for supporting our research.

Notes

¹ OGM has been associated with trauma-related psychopathology (see Williams et al., 2007 for a review), and thus we chose to exclude the small number of individuals who met criteria for posttraumatic stress disorder and acute stress disorder from these analyses. We also excluded those with a history of bipolar disorder, major depression due to a general medical condition, substance-induced mood disorder and dysthymia in order to have a relatively homogenous sample of those with a history of unipolar major depression.

² Reliability of categorical SCID diagnoses was assessed with both Cohen's kappa and adjusted kappa due to uneven prevalence of counts in the categories being compared (specifically, low base rates of cases with disorders relative to cases with no disorders). This imbalance has been found to attenuate Cohen's kappa. An adjusted kappa adjusts cell frequencies to evenly distribute the prevalence of cases across categories.

³ When we excluded the three participants who were in a current major depressive episode at the time of the AMT, the 5-HTTLPR Genotype × History of MDD interaction remained statistically significant with at least as large a standardised effect size, F change(1, 361) = 4.49, p = .04, b = −0.07, SE(b) = 0.03, β = −0.20, t = −2.12, p = .04. Thus, this interaction did not seem to be due to current MDD status at the AMT.