Attention to Threats and Combat-Related Posttraumatic Stress Symptoms Prospective Associations and Moderation by the Serotonin Transporter Gene Combat-Related Posttraumatic Stress

Wald I, Degnan KA, Gorodetsky E, et al. — Mon, 01 Apr 2013 00:00:00 GMT

Importance

Combat places soldiers at risk for posttraumatic stress disorder (PTSD). The excessive rates of PTSD and other adjustment disorders in soldiers returning home make it imperative to identify risk and resilience factors that could be targeted by novel therapeutic treatments.

Objective

To investigate the interplay among attention to threat, combat exposure, and other risk factors for PTSD symptoms in soldiers deployed to combat.

Design and Setting

Longitudinal prospective study of Israeli Defense Force infantry soldiers carried out in 2008 through 2010. Repeated measurements during a 1-year period included baseline and predeployment data collected in training camps and deployment data collected in the combat theater.

Participants

Infantry soldiers (1085 men; mean age, 18.8 years).

Main Outcome Measures

Postcombat PTSD symptoms.

Results

Soldiers developed threat vigilance during combat deployment, particularly when they were exposed to high-intensity combat, as indicated by faster response times to targets appearing at the location of threat relative to neutral stimuli (P < .001). Threat-related attention bias also interacted with combat exposure to predict risk for PTSD (P < .05). Bias toward threat at recruitment (P < .001) and bias away from threat just before deployment (P < .05) predicted postcombat PTSD symptoms. Moreover, these threat-related attention associations with PTSD were moderated by genetic and environmental factors, including serotonin transporter (5-HTTLPR) genotype.

Conclusions and Relevance

Combat exposure interacts with threat-related attention to place soldiers at risk for PTSD, and interactions with other risk factors account for considerable variance in PTSD vulnerability. Understanding these associations informs research on novel attention bias modification techniques and prevention of PTSD.

FKBP5 and Attention Bias for Threat Associations With Hippocampal Function and Shape FKBP5 and Attention Bias for Threat

Fani N, Gutman D, Tone EB, et al. — Mon, 01 Apr 2013 00:00:00 GMT

Importance

The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamic-pituitary-adrenal axis functioning and has been associated with many stress-related psychiatric disorders. The study of intermediate phenotypes, such as emotion-processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates risk for psychiatric disorders.

Objective

To examine whether allelic variations for a putatively functional single-nucleotide polymorphism associated with FKBP5 gene regulation (rs1360780) would relate differentially to attention bias for threat. this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphologic substrates of differential hippocampal response were also measured.

Design

Cross-sectional study conducted from 2010 to 2012 examining associations between genotype, behavioral response, and neural response (using functional magnetic resonance imaging [fMRI]) on the dot probe; voxel-based morphometry and global and local shape analyses were used to measure structural differences in hippocampi between genotype groups.

Setting

Participants were recruited from primary care clinics of a publicly funded hospital in Atlanta, Georgia.

Participants

An African American cohort of adults (N = 103) was separated into 2 groups by genotype: one genotype group included carriers of the rs1360780 T allele, which has been associated with increased risk for posttraumatic stress disorder and affective disorders; the other group did not carry this allele. Behavioral data included both sexes (N = 103); the MRI cohort (n = 36) included only women.

Main Outcome Measures

Behavioral and fMRI (blood oxygen level–dependent) response, voxel-based morphometry, and shape analyses.

Results

Carriers of the rs1360780 T allele showed an attention bias toward threat compared with individuals without this allele (F_1,90 = 5.19, P = .02). Carriers of this allele demonstrated corresponding increases in hippocampal activation and differences in morphology; global and local shape analyses revealed alterations in hippocampal shape for TT/TC compared with CC genotype groups.

Conclusion

Genetic variants of FKBP5 may be associated with risk for stress-related psychiatric disorders via differential effects on hippocampal structure and function, resulting in altered attention response to perceived threat.

JAMA Psychiatry: Neurogenetics Topic Collection

Attention to Threats and Combat-Related Posttraumatic Stress Symptoms Prospective Associations and Moderation by the Serotonin Transporter Gene Combat-Related Posttraumatic Stress

FKBP5 and Attention Bias for Threat Associations With Hippocampal Function and Shape FKBP5 and Attention Bias for Threat