Cognitive phenotypes in patients with drug-resistant temporal lobe epilepsy: Relationships with cortisol and affectivity.

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) is a neurological disorder characterized by cognitive deficits. This study examined whether patients with TLE and different cognitive phenotypes differ in cortisol levels and affectivity while controlling for demographic and clinical variables. Methods: In this cross-sectional study, 79 adults with TLE underwent neuropsychological evaluation in which memory, language, attention/processing speed, executive function, and affectivity were assessed. Six saliva samples were collected in the afternoon to examine the ability of the hypothalamic-pituitary-adrenal (HPA) axis to descend according to the circadian rhythm (C1 to C6). The cortisol area under the curve concerning ground (AUCg) was computed to examine global cortisol secretion. RESULTS: Three cognitive phenotypes were identified: memory impairment, generalized impairment, and no impairment. The memory-impairment phenotype showed higher cortisol levels at C4, C5, and C6 than the other groups (p = 0.03, η2 = 0.06), higher cortisol AUCg than the generalized-impairment phenotype (p = 0.004, η2 = 0.14), and a significant reduction in positive affectivity after the evaluation (p = 0.026, η2 = 0.11). Higher cortisol AUCg and reductions in positive affectivity were significant predictors of the memory-impairment phenotype (p < 0.001; Cox and Snell R2 = 0.47). CONCLUSIONS: Patients with memory impairment had a slower decline in cortisol levels in the afternoon, which could be interpreted as an inability of the HPA axis to inhibit itself. Thus, chronic stress may influence hippocampus-dependent cognitive function more than other cognitive functions in patients with TLE.

Neurocognitive and clinical profile of male patients with substance use disorder in early remission phase with and without comorbid depression.

Substance Use Disorder (SUD) represents one of the most frequent conditions worldwide which commonly coexists with major depressive disorder (MDD). This comorbidity (SUD + MDD) is one of the most prevalent with patients showing certain social and clinical characteristics that could lead to a worsening of their cognitive performance. However, despite these particularities, only a few studies have addressed the possible differences in cognitive performance between patients with SUD + MDD compared with those with SUD-only patients. Therefore, the aim of this study is to examine the clinical and cognitive profile of patients with SUD + MDD vs. SUD-only who are in early remission phase. For this purpose, 271 male patients underwent a clinical and neuropsychological assessment (SUD + MDD group: N = 101; SUD-only group: N = 170). Results indicated that SUD + MDD patients showed worse cognitive performance than SUD in visuospatial reasoning, verbal memory and learning, recognition, and processing speed even after a 3-month period of abstinence. Furthermore, these patients exhibited more self-reported prefrontal symptoms, as well as worse social and clinical conditions. This study indicates that the neurocognitive and clinical profile of patients with SUD + MDD could represent a risk since their characteristics have been associated with poorer recovery and prognosis. Our results could be helpful in clinical practice highlighting the need for cognitive remediation strategies in these populations, providing information that would allow the implementation of more appropriate treatments and preventive strategies.

ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet in male mice.

Glucocorticoids modulate glucose homeostasis, acting on metabolically active tissues such as liver, skeletal muscle, and adipose tissue. Intracellular regulation of glucocorticoid action in adipose tissue impacts metabolic responses to obesity. ATP-binding cassette family C member 1 (ABCC1) is a transmembrane glucocorticoid transporter known to limit the accumulation of exogenously administered corticosterone in adipose tissue. However, the role of ABCC1 in the regulation of endogenous glucocorticoid action and its impact on fuel metabolism has not been studied. Here, we investigate the impact of Abcc1 deficiency on glucocorticoid action and high-fat-diet (HFD)-induced obesity. In lean male mice, deficiency of Abcc1 increased endogenous corticosterone levels in skeletal muscle and adipose tissue but did not impact insulin sensitivity. In contrast, Abcc1-deficient male mice on HFD displayed impaired glucose and insulin tolerance, and fasting hyperinsulinaemia, without alterations in tissue corticosterone levels. Proteomics and bulk RNA sequencing revealed that Abcc1 deficiency amplified the transcriptional response to an obesogenic diet in adipose tissue but not in skeletal muscle. Moreover, Abcc1 deficiency impairs key signalling pathways related to glucose metabolism in both skeletal muscle and adipose tissue, in particular those related to OXPHOS machinery and Glut4. Together, our results highlight a role for ABCC1 in regulating glucose homeostasis, demonstrating diet-dependent effects that are not associated with altered tissue glucocorticoid concentrations.