Augmentation of Extinction and Inhibitory Learning in Anxiety and Trauma-Related Disorders.

Although the fear response is an adaptive response to threatening situations, a number of psychiatric disorders feature prominent fear-related symptoms caused, in part, by failures of extinction and inhibitory learning. The translational nature of fear conditioning paradigms has enabled us to develop a nuanced understanding of extinction and inhibitory learning based on the molecular substrates to systems neural circuitry and psychological mechanisms. This knowledge has facilitated the development of novel interventions that may augment extinction and inhibitory learning. These interventions include nonpharmacological techniques, such as behavioral methods to implement during psychotherapy, as well as device-based stimulation techniques that enhance or reduce activity in different regions of the brain. There is also emerging support for a number of psychopharmacological interventions that may augment extinction and inhibitory learning specifically if administered in conjunction with exposure-based psychotherapy. This growing body of research may offer promising novel techniques to address debilitating transdiagnostic fear-related symptoms.

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia.

BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS: In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS: Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma.