Search

Background Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology. Methods Using positron emission tomography with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology (n = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, hippocampus) differed as a function of CU status. Results Past-year CU (n = 22) was associated with 18.62%–19.12% higher mGlu5 availability in frontal and 14.24%–16.55% higher mGlu5 in limbic ROIs relative to participants with no recent CU. Similarly, past-month or monthly CU (n  =  16) was associated with higher mGlu5 availability in frontal (18.05%–20.62%) and limbic (15.53%–16.83%) ROIs. mGlu5 availability in the orbitofrontal cortex and amygdala was negatively associated with depressive symptoms in the past-year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs and with perceptions of worthlessness and past failures (r 's = −.47 to.66, P 's = .006–.033) in the ventromedial prefrontal cortex. Participants with CU reported lower mean depressive symptoms (P 's = .006–.037) relative to those without CU. Conclusions These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population. [ABSTRACT FROM AUTHOR]

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [11C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls. The PTSD group exhibited a significantly lower magnitude LPS-induced increase in TSPO availability in an a priori prefrontal-limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte-macrophage colony-stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self-reported sickness symptoms did not differ between groups; these findings highlight group differences in central-peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia-mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease. [ABSTRACT FROM AUTHOR]

Objectives This study examines the main and moderating effects of childhood abuse or neglect severity, income, and family social support on the presence of postpartum depressive symptoms (PDS). Methods Participants included 183 postpartum mothers who endorsed a history of childhood maltreatment (CM) and enrolled in a longitudinal study of mother and child outcomes. Participants completed questionnaires to assess CM severity, associated societal and maternal characteristics, and depressive symptom severity. Results The results confirm previously identified links between CM severity and PDS. Further, hierarchical linear regression analyses indicate the interaction of household income and interpersonal support from the family attenuates the relationship between CM severity and PDS. The final model accounted for 29% of the variance of PDS scores, a large effect size. Conclusions This study is the first to demonstrate interrelationships between income and social support on resilience to postpartum psychopathology in childhood trauma-surviving women. Social support appeared to protect against PDS for all mothers in this study while income only conferred a protective effect when accompanied by family support. For clinicians, this implies the need to focus on improving family and other relationships, especially for at-risk mothers., Author(s): Maria Muzik [sup.1] [sup.2] , Rujuta Umarji [sup.3] , Minden B. Sexton [sup.1] [sup.4] , Margaret T. Davis [sup.1] [sup.4] [sup.5] Author Affiliations: (1) grid.214458.eDepartment of Psychiatry, University of [...]

The metabotropic glutamate receptor 5 (mGluR5) is a promising treatment target for psychiatric disorders due to its modulatory effects on glutamate transmission. Using [11C]ABP688, we previously showed that the rapidly acting antidepressant ketamine decreases mGluR5 availability. The mGluR5 radioligand [18F]FPEB offers key advantages over [11C]ABP688; however, its suitability for drug challenge studies is unknown. We evaluated whether [18F]FPEB can be used to capture ketamine-induced effects on mGluR5. Seven healthy subjects participated in three [18F]FPEB scans: a baseline, a same-day post-ketamine, and a 24-h post-ketamine scan. The outcome measure was V T/ f P, obtained using a two-tissue compartment model and a metabolite-corrected arterial input function. Dissociative symptoms, heart rate and blood pressure increased following ketamine infusion. [18F]FPEB V T/ f P decreased by 9% across the cortex after ketamine infusion, with minimal difference between baseline and 24-h scans. Compared to our previous work using [11C]ABP688, the magnitude of the ketamine-induced change in mGluR5 was smaller using [18F]FPEB; however, effect sizes were similar for the same-day post-ketamine vs. baseline scan (Cohen's d = 0.75 for [18F]FPEB and 0.88 for [11C]ABP688). [18F]FPEB is therefore able to capture some of the effects of ketamine on mGluR5, but [11C]ABP688 appears to be more suitable in drug challenge paradigms designed to probe glutamate transmission. [ABSTRACT FROM AUTHOR]

Despite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. [11C]PBR28 Positron Emission Tomography brain imaging of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals with PTSD and 26 healthy individuals—with or without trauma exposure. Prefrontal-limbic TSPO availability in the PTSD group was negatively associated with PTSD symptom severity and was significantly lower than in controls. Higher C-reactive protein levels were also associated with lower prefrontal-limbic TSPO availability and PTSD severity. An independent postmortem study found no differential gene expression in 22 PTSD vs. 22 controls, but showed lower relative expression of TSPO and microglia-associated genes TNFRSF14 and TSPOAP1 in a female PTSD subgroup. These findings suggest that peripheral immune activation in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses positing neuroimmune activation as central to stress-related pathophysiology. Neuroinflammation has been proposed to accompany the peripheral inflammation observed in PTSD. Here, authors find lower in vivo and postmortem levels of neuroimmune marker TSPO (translocator protein) in PTSD, in association with greater PTSD severity and higher plasma CRP. [ABSTRACT FROM AUTHOR]