Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.

The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.

Reexperiencing and anxious arousal symptoms in relation to volumes of thalamus nuclei in posttraumatic stress spectrum adults.

INTRODUCTION: Trauma reexperiencing is dominated by recollection of sensory-perceptual elements of the trauma, pointing to involvement of the sensory thalamus. This study examined posttraumatic stress symptoms in relation to volumes of thalamic nuclei that were grouped based on their predominant functions. We hypothesized that reexperiencing, controlling for other symptom dimensions, would correlate with volumes of thalamic nuclei involved in primary and higher-order sensory processing. METHODS: Seventy-two trauma-exposed adults were interviewed with the Clinician Administered PTSD Scale for DSM-IV and underwent 3T magnetic resonance imaging. Scores were derived for reexperiencing, anxious arousal, dysphoric arousal, emotional numbing, and avoidance symptoms. These were entered as simultaneous predictors in five separate regression analyses, with age, sex, and total thalamus volume as covariates, predicting volumesf of five thalamus nuclear groupings corrected for intracranial volume: Specific sensory, associative-sensory, associative-cognitive, intralaminar, and motor groupings. RESULTS: Reexperiencing symptoms were significantly positively correlated with volumes of the motor thalamic grouping, which included the ventral anterior, ventral lateral, and ventromedial nuclei. Anxious arousal was significantly negatively correlated with volumes of all five thalamic groupings. CONCLUSIONS: Reexperiencing symptoms were correlated with volumes of the motor thalamus, while anxious arousal symptoms were related to all thalamic subregion volumes. Thalamic nuclei involved in motor functions, including oculomotor control and motor planning, may be implicated in posttraumatic reexperiencing symptoms.

The antidepressant impact of minocycline in rodents: A systematic review and meta-analysis.

Evidence from recent animal studies suggest that minocycline, a broad-spectrum antibiotic capable of regulating immune processes, may possess antidepressant properties. These studies, however, have yet to be comprehensively reviewed. Accordingly, this systematic review and meta-analysis summarizes the extant literature examining the effect of minocycline on depressive-like behavior in rodent models. PubMed, PsycINFO, and Web of Science databases were systematically searched for articles that met prespecified inclusion and exclusion criteria, and standardized mean differences (SMDs) were calculated for each continuous measure of depressive-like behavior. The overall effect of minocycline on depressive-like behavior was estimated using robust variance estimation meta-analysis. Separate subgroup analyses were conducted on diseased vs healthy animal models, different rodent species, and immobility-based vs anhedonia-based measures of depressive-like behavior. A total of 22 preclinical studies (816 animals) were included. Overall, minocycline reduced depressive-like behavior in rodents (SMD = -1.07, 95% CI -1.41--0.74, p < 0.001). Subgroup analyses revealed that minocycline reduced depressive-like behavior in diseased, but not healthy, animal models. Finally, minocycline was found to reduce both immobility-based and anhedonia-based outcomes. These findings suggest that minocycline may be an effective treatment of core depressive symptoms, and that further investigation of minocycline treatment for clinically relevant depression in humans is warranted.