Auditory Cortex is Important in the Extinction of Two Different Tone-Based Conditioned Fear Memories in Rats

Extensive fear extinction research is guided by the view that there are structures in the brain that develop inhibitory control over the expression of conditioned fear memories. While the medial prefrontal cortex has recently captured attention as the locus of plasticity essential for extinction of conditioned fear, the auditory cortex is another plausible cortical area involved in extinction learning since it is considered a sufficient conditioned stimulus (CS) pathway in tone fear conditioning. We examined the role of auditory cortex in extinction of auditory-based fear memories with a standard tone-on conditioning, wherein a tone CS predicted a footshock unconditioned stimulus (US), or a novel tone-off conditioning, in which the tone was continually present and the offset of the tone was the CS predicting the US. Rats with bilateral auditory cortex lesions were trained in either paradigm and subsequently trained in extinction to the CS. Auditory cortex lesions had no effect on acquisition but impaired extinction to both CSs. These findings indicate that the auditory cortex contributes to extinction of wide-ranging auditory fear memories, as evidenced by deficits in both tone-on CS and tone-off CS extinction training

Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4+ Counts > 500 cells/mm3: Findings from the Strategic Timing of AntiRetroviral Treatment (START) Trial.

BACKGROUND Low CD4+ recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4+ counts > 500 cells/mm. SETTING United States, Africa, Asia, Europe & Israel, Australia, Latin America. METHODS Among immediate-ART participants in the Strategic Timing of AntiRetroviral Therapy trial, low CD4+ recovery was defined as a CD4+ increase < 50 cells/mm from baseline after 8 months despite viral load ≤ 200 copies/mL. Risk factors for low recovery were investigated with logistic regression. RESULTS 39.7% of participants had low CD4+ recovery. Male gender (OR 1.53, p = 0.007), lower screening CD4+ (OR 1.09 per 100 fewer cells/mm, p = 0.004), higher baseline CD8+ (OR 1.05 per 100 more cells/mm, p < 0.001), and lower HIV RNA (OR 1.93 per log10 decrease, p < 0.001) were associated with low CD4+ recovery. D-dimer had a quadratic association with low CD4+ recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, odds of low recovery were elevated across levels of screening CD4+ count, but at higher levels, odds of low CD4+ recovery were greater among those with lower versus higher screening CD4+. CONCLUSION Low CD4+ recovery is frequent among participants starting ART at high CD4+ counts. Risk factors include male gender, lower screening CD4+ cell counts, higher CD8+ cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4+ recovery on clinical outcomes

The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects: Results in ~25,000 subjects

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status