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We investigated the relationship between cerebrospinal fluid (CSF) and plasma biomarkers of inflammation, neurodegeneration, and neurocognitive performance in people with HIV (PWH), using longitudinal samples from two previously published cohorts: ACTG A5090 (virally suppressed on antiretroviral therapy, ART) and A736 (ART-naïve or failing). We analyzed paired CSF and plasma samples, as well as 7-domain standardized neurocognitive test scores, at baseline and 24 weeks. Biomarkers included markers of inflammation (e.g., TNF-α, IL-6, IP-10) and neurodegeneration (e.g., NFL, p-Tau217, Aβ42), which were quantified via high-sensitivity immunoassays. Associations with cognition were tested using regression, mediation, and interaction models. Cross-sectional analyses revealed nominal associations between inflammatory markers and cognitive performance, with plasma IL-6 and IP-10 at baseline, and CSF TNFα at week 24 showing the strongest correlations (p < 0.05, uncorrected); however, none survived correction for multiple comparisons. Conversely, higher CSF Aβ42 and plasma BDNF were positively associated with memory and executive function. Longitudinally, biomarker changes did not significantly predict change in global cognition (ΔNPZ-8); the strongest trend (p-Tau217, ρ = -0.12, p = 0.38) was not statistically significant, and multivariate models failed to identify robust predictors (R These results suggest a potential role of CSF TNFα in mediating the neurocognitive effects of HIV and highlight compartment-specific inflammatory dynamics. Plasma TNFα, GFAP, and NFL may serve as peripheral indicators of CNS pathology, though with only moderate concordance. Astrocyte-tau interactions require cautious interpretation pending replication in larger cohorts. Show less

We aim to verify clinical (depressive symptoms, rates of psychiatric admissions, and suicide attempts) and neurobiological (Brain-Derived Neurotrophic Factor - BDNF) changes in outpatients with depression undergoing evidence-based psychotherapies (EBP) over a 6-month follow-up. Longitudinal, naturalistic, prospective study, with 47 outpatients undergoing EBP, and 48 healthy controls (HC) for the BDNF levels comparisons. Data were collected at baseline and 6-month follow-up. Statistical analysis was performed using a paired t-test and a multiple linear regression model. BDI scores did not differ between baseline and 6-month follow-up (p = 0.253), and the rates of hospitalizations and suicide attempts at 6-month follow-up were 4.2% (2 cases reported). All patients were using psychotropics. BDNF levels at baseline and after 6-month follow-up did not vary significantly in the patient group (p = 0.314). There was no difference between patients' BDNF levels at baseline and HC BDNF levels (p = 0.211) and between patients' BDNF levels at 6-month follow-up and HC BDNF levels (p = 0.772). Using a mood stabilizer increased the BDNF levels. BDNF levels remained stable. Adding psychotherapy to medication may be associated with low rates of suicide attempts and psychiatric admissions in our sample. Our findings reinforce the importance of combined treatment in preventing adverse outcomes in naturalistic settings. Evidence supports the clinical effectiveness and economic efficiency of psychotherapy for patients with mental disorders, suggesting that outpatient psychotherapy can benefit healthcare systems and patients. Our findings corroborate the literature and reinforce the importance of psychotherapy associated with pharmacotherapy (combined treatment) to prevent outcomes such as further hospitalizations and suicide attempts, even in individuals with a history of severe psychiatric conditions. Research on how psychotherapy works, in terms of psychological mechanisms and its underlying effects on biological processes, is crucial. Scientific evidence makes it possible to include psychotherapies in public health policies worldwide, benefiting individuals suffering from mental disorders. Evidence from naturalistic designs is scarce in the literature. Show less

Brain-derived neurotrophic factor (BDNF) has been suggested to support dopaminergic neuron's endurance and dopamine release. Its Val66Met polymorphism might modify Parkinson's disease (PD) evolution, although evidence in Asian populations remains limited. This study aimed to explore how the BDNF rs6265 genotypes are associated with the clinical characteristics and longitudinal progression patterns of PD patients in a Korean population. A total of 247 patients were enrolled and followed for a mean duration of 50.9 ± 23.9 months. Baseline and/or periodic assessments captured motor severity, non-motor burden, cognition, orthostatic stress, cardiac denervation, and presynaptic dopamine transporter availability. The repeated measures were manipulated to infer any genotypic differences in the trajectories of each clinical domain. Genotype frequencies were 31.2% (77/247) for Val/Val and 68.8% (170/247) for Met-allele carriers. Baseline clinical characteristics and presynaptic dopamine transporter availability were comparable between genotypes; however, Val homozygotes showed more preserved myocardial innervation and poorer non-frontal cognitive performance. Longitudinal analyses demonstrated genotype-specific increases in motor and cognitive severity. Compared to Met-allele carriers, the homozygous Val group exhibited accelerated motor progression and more rapid decline in frontal domain after three years of follow-up. The differences in myocardial denervation at diagnosis, cognitive profiles, and motor progression might suggest a potential modulatory role of BDNF polymorphism in PD progression in the Korean population. Show less