👤 Ana Gavito

The role of chemokines in motor abnormalities (MAs) in first-episode psychosis (FEP) is underexplored. Investigating immune biomarker levels in FEP, their association with MAs, and their differences with individuals without FEP may reveal therapeutic targets. Thirty-eight patients and thirty-four controls were included. Primary outcomes assessed group differences in chemokines related immune whole blood biomarkers, including innate (CCL2, CCL3, and CCL11), compensatory (PPARα, CXCL1, and CB2), natural immune chemotaxis biomarkers (CXCL2 and CXCR4), and growth factors (LPAR2, brain-derived neurotrophic factor [BDNF], and vascular endothelial growth factor [VEGF]). Our secondary aim was to examine their association with the total score of five motor scales: the Neurological Evaluation Scale (NES), Simpson Angus Scale (SAS), catatonia symptom of the Comprehensive Assessment of Symptoms and History (CASH), Barnes Akathisia Rating Scale, and Unified Parkinson's Disease Rating Scale (UPDRS). We found significantly higher levels of protein markers (CCL2, VEGF, and CXCL12) and mRNA expression (CXCR4, PPARα, CB2, and LPAR2) in FEP patients compared to the control group. We only observed positive and significant results for CCL2-UPDRS total and CXCR4-SAS associations in post hoc multivariate analyses (β = 0.401, p = 0.036 and β = 0.58, p = 0.001, respectively). Elevated levels of potential neurotoxic (CCL2) and neuroprotective (PPARα and CB2) biomarkers were seen in FEP patients when compared to controls. Moreover, CCL2 levels seem to be directly associated with Parkinsonism in FEP patients, while CXCR4 may be protective against extrapyramidal symptoms. Further research should clarify immune differences between FEP and non-FEP groups, especially in chemotaxis and endocannabinoid pathways. Show less

Adolescence is a critical developmental window during which exposure to stress and alcohol can induce long-lasting neurobiological alterations. Binge-like alcohol consumption is particularly disruptive to corticostriatal circuits, but the extent to which prior stress history modulates these effects remains poorly understood. Here, we investigated how acute versus repeated restraint stress before intermittent alcohol exposure during adolescence shapes transcriptional changes in the dorsal striatum of male rats. Animals were exposed either to a single (acute) or five-day (repeated) restraint stress at postnatal day (PND) 32-36, followed by four weeks of intermittent intragastric ethanol (3 g/kg) or saline administration. At adult age, striatal mRNA expression of dopaminergic (Drd1, Drd2, Th), glutamatergic (Gls, Gls2, Gria2, Grin2a, Grin2b), endocannabinoid (Cnr1, Cnr2, Napepld, Faah, Dagla, Daglb, Mgll), neurotrophic (Bdnf, Ntrk2), and glial (Gfap, Aif1) genes was quantified. Alcohol exposure upregulated genes associated with glutamate synthesis and receptor signaling, endocannabinoid metabolism, and astrocytic activation. Acute stress amplified alcohol-induced expression of Gls, Gls2, Gria2, Napepld, Faah, Daglb, Ntrk2, and Gfap, while repeated stress blunted these effects and selectively enhanced Drd1, Drd2, Grin2a, and Bdnf expression. Microglial activation (Aif1) was increased by alcohol independently of stress. These results suggest that acute stress sensitizes glutamatergic and endocannabinoid pathways to alcohol, whereas repeated stress engages adaptive mechanisms consistent with the stress inoculation hypothesis. Overall, stress history critically determines the neurobiological outcomes of adolescent alcohol exposure, with implications for resilience and vulnerability to alcohol-induced psychopathology. Show less