Post-traumatic stress influences the brain even in the absence of symptoms: A systematic, quantitative meta-analysis of neuroimaging studies

Background/Aims: Functional connectivity studies based on region of interest approach suggest altered functional connectivity of the default mode network (DMN), executive control network (ECN), and salience network (SN). The aim of this study is to determine whether intranetwork and internetwork brain connectivity are altered in both post-traumatic stress disorder (PTSD) patients and traumatized subjects without PTSD using a data-driven approach. Methods: Resting-state functional MRI data were acquired for 27 patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC). Functional connectivity within the DMN, ECN, and SN as well as functional and effective connectivity between these resting-state networks were examined with independent component analysis (ICA), and then compared between groups by conducting analysis of variance. Results: Within the DMN, the TEC group showed decreased and increased functional connectivity in the superior frontal gyrus compared with the PTSD group and the HC group, respectively. The TEC group showed increased angular functional connectivity within the DMN and decreased functional connectivity in the superior temporal gyrus/posterior insula within the SN relative to the HC group. Compared with the TEC group, the PTSD group showed increased functional connectivity in the middle frontal gyrus and supplementary motor area within the ECN as well as in the inferior frontal gyrus/anterior insula within the SN. The PTSD group showed decreased functional connectivity in the supplementary motor area within the SN relative to both control groups. Moreover, the PTSD showed increased excitatory influence from the ECN to DMN compared with both control groups, while the TEC group showed increased inhibitory influence from the DMN to ECN compared with the HC group. Intranetwork functional connectivity within the DMN and SN is altered in traumatized subjects irrespective of PTSD diagnosis. PTSD patients also showed altered intranetwork functional connectivity within the ECN. Conclusions: Distinct changes of effective connectivity between the DMN and ECN in the PTSD group and TEC group may reflect different compensatory mechanisms for rebalance of resting-state networks in the two groups.

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Impulsivity and sensation seeking have been linked to hazardous drinking, increased sexual risk behaviors, and lower treatment adherence among persons living with HIV (PLH). The dopamine active transporter1 (DAT1 or SLC6A3) gene has been linked to impulsivity and sensation seeking in several populations but has not been investigated among populations of PLH. This study used data from 201 PLH who report a recent history of heavy episodic drinking. Results indicate that DAT1*10R vs DAT1*9R genotype was related to higher propensity for risk taking (standardized difference score (d) = 0.30 [95% CI: 0.02;0.59]), more hazardous drinking (d = 0.35 [0.05;0.64]), and more condomless sex (rate ratio (RR)= 2.35[1.94; 2.85]), but were counter-intuitively associated with fewer sexual partners (RR = 0.65[0.43;0.91]) and possibly better treatment adherence (d = 0.32 [−0.01;0.65]). Results are consistent with the suggested associations between DAT1 and risk-taking behavior. The counter-intuitive finding for partner selection and treatment adherence may be evidence of additional factors that place PLH at risk for engaging in hazardous drinking as well as relationship difficulties and problems with treatment adherence (e.g., depressive symptoms, avoidant coping, trauma history). Caution is required when using a single gene variant as a marker of complex behaviors and these findings need to be replicated using larger samples and additional variants.