Academic journal article Cognitive, Affective and Behavioral Neuroscience

5-HTTLPR, HTR1A, and HTR2A Cumulative Genetic Score Interacts with Mood Reactivity to Predict Mood-Congruent Gaze Bias

Academic journal article Cognitive, Affective and Behavioral Neuroscience

5-HTTLPR, HTR1A, and HTR2A Cumulative Genetic Score Interacts with Mood Reactivity to Predict Mood-Congruent Gaze Bias

Article excerpt

Published online: 19 March 2014

(Q> Psychononric Society, Inc. 2014

Abstract Genetic variation within the serotonin system has been associated with biased attention for affective stimuli and, less consistently, with vulnerability for major depressive dis- order. In particular, 5-HTTLPR, HTR1A (rs6295), and HTR2A (rs6311) polymorphisms have been linked with biased cogni- tion. The present study developed a serotonergic cumulative genetic score (CGS) that quantified the number of risk alleles associated with these candidate polymorphisms to yield a single CGS. The CGS was then used to model genetic influ- ence on the relationship between reactivity to a negative mood induction and negatively biased cognition. A passive-viewing eye-tracking task was administered to 170 healthy volunteers to assess sustained attention for positive, dysphoric, neutral, and threatening scenes. Participants were then induced into a sad mood and readministered the passive-viewing task. Change in gaze bias, as a function of reactivity to mood induction, was the primary measure of cognitive vulnerability. Results suggest that, although none of the individual genes interacted with mood reactivity to predict change in gaze bias, individuals with higher serotonin CGS were significantly more likely to look toward dysphoric images and away from positive images as mood reactivity increased. These findings suggest that a CGS approach may better capture genetic influences on cognitive vulnerability and reaffirm the need to examine multilocus approaches in genomic research.

Keywords Serotonin * Sad mood induction * Mood reactivity Attention bias Cumulative genetic risk Cognitive vulnerability


Maladaptive cognitive processes are a common characteristic of affective psychopathologies, including major depressive disorder (MDD; Beck, 1967, 1987). The failure to properly allocate cognitive resources has been linked to dysregulated experience of emotion and has been identified as a putative risk factor for the onset and maintenance of mood disorders (Gotlib & Joormann, 2010; Gross, 2001). Specifically, atten- tion biased toward mood-congruent stimuli has been consis- tently observed in depressed individuals, relative to healthy controls (Koster, De Raedt, Goeleven, Franck, & Crombez, 2005). Sustained attention for negative, mood-congruent stim- uli is believed to contribute to depression by increasing the emotional impact of negative information in the environment and, thereby, exacerbating the effects of stressful life events (Beck, 1967; Clark, Beck, & Alford, 1999). Furthermore, attention biased toward mood-congruent stimuli is thought to detract from more adaptive cognitive mechanisms, such as cognitive reappraisal and the integration of contextual information (Beck, 2008; Clark et al., 1999).

Increased attentional bias has been observed following negative environmental experiences (Bar-Haim et al., 2010; Disner et al., 2013) and is believed to be an intermediary endophenotype linking life stress to mental illness (Beevers & Carver, 2003; De Raedt & Koster, 2010). In a laboratory environment, negative environmental factors can be manipu- lated in a controlled fashion by inducing a sad mood state in research participants. Sad mood inductions increase negative affect and serve as a laboratory analog for an individual's reactivity to external stressors that create sad mood (Blaney, 1986; Segal, Gemar, & Williams, 1999).

Importantly, individuals who are more reactive to environ- mental stressors and display stronger cognitive biases follow- ing mood provocation, often referred to as cognitive reactivity, are considered particularly vulnerable to the onset or recur- rence of affective disorders such as MDD (De Raedt & Koster, 2010; Pine et al., 2005; Scher, Ingram, & Segal, 2005; Segal et al., 2006). Understanding the factors that influence cogni- tive reactivity to sad moods is critical for a better understand- ing of the etiology of cognitive vulnerability to depression. …

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