Schizophrenia is a serious cognitive disorder characterized by disruptions in neurotransmission, a process requiring the coordination of multiple kinase-mediated signaling events. Evidence suggests that the observed deficits in schizophrenia may be due to imbalances in kinase activity that propagate through an intracellular signaling network. Specifically, 3′-5′-cyclic adenosine monophosphate (cAMP)-associated signaling pathways are coupled to the activation of neurotransmitter receptors and modulate cellular functions through the activation of protein kinase A (PKA), an enzyme whose function is altered in the frontal cortex in schizophrenia. In this study, we measured the activity of PKA in human postmortem anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) tissue from schizophrenia and age- and sex-matched control subjects. No significant differences in PKA activity were observed in male and female individuals in either brain region; however, correlation analyses indicated that PKA activity in the ACC may be influenced by tissue pH in all subjects and by age and tissue pH in females. Our data provide novel insights into the function of PKA in the ACC and DLPFC in schizophrenia.

Schizophrenia is a neuropsychiatric illness characterized by altered neurotransmission, in which adenosine, a modulator of glutamate and dopamine, plays a critical role that is relatively unexplored in the human brain. In the present study, postmortem human brain tissue from the anterior cingulate cortex (ACC) of individuals with schizophrenia (n = 20) and sex- and age-matched control subjects without psychiatric illness (n = 20) was obtained from the Bronx–Mount Sinai NIH Brain and Tissue Repository. Enriched populations of ACC pyramidal neurons were isolated using laser microdissection (LMD). The mRNA expression levels of six key adenosine pathway components—adenosine kinase (ADK), equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), ectonucleoside triphosphate diphosphohydrolases 1 and 3 (ENTPD1 and ENTPD3), and ecto-5′-nucleotidase (NT5E)—were quantified using real-time PCR (qPCR) in neurons from these individuals. No significant mRNA expression differences were observed between the schizophrenia and control groups (p > 0.05). However, a significant sex difference was found in ADK mRNA expression, with higher levels in male compared with female subjects (Mann–Whitney U = 86; p < 0.05), a finding significantly driven by disease (t₍₁₇₎ = 3.289; p < 0.05). Correlation analyses also demonstrated significant associations (n = 12) between the expression of several adenosine pathway components (p < 0.05). In our dementia severity analysis, ENTPD1 mRNA expression was significantly higher in males in the “mild” clinical dementia rating (CDR) bin compared with males in the “none” CDR bin (F_{(2, 13)} = 5.212; p < 0.05). Lastly, antipsychotic analysis revealed no significant impact on the expression of adenosine pathway components between medicated and non-medicated schizophrenia subjects (p > 0.05). The observed sex-specific variations and inter-component correlations highlight the value of investigating sex differences in disease and contribute to the molecular basis of schizophrenia’s pathology.

The COVID-19 pandemic has significantly impacted the mental health of college students in the United States (U.S.). Here, we review studies that explored the effect of the COVID-19 pandemic on mental health measures and coping strategies of university students. Previously published studies conducted in this population, using tools like the PHQ-9, GAD-7, and PSS-10 questionnaires demonstrated a notable increase in the prevalence of depression, anxiety, stress and suicidal ideation. Female and advanced college students were particularly vulnerable, consistently showing higher scores for anxiety and stress. Females also displayed greater depression severity scores compared to their male counterparts; however, some advanced students displayed lower scores compared to the first-year undergraduate students. There was an overall decrease in suicidal ideation among college students during the pandemic; however, some schools were found to have an increase in the level of suicidal ideation. The shared negative effects of COVID-19 among college students encompassed health, academic, and lifestyle domains. Coping strategies varied, with "support from friends and family" being predominant. In addition, an overall underutilization of mental health resources was reported. Non-pharmacological therapies, particularly lifestyle modifications such as regular exercise, demonstrated efficacy in alleviating symptoms; however, challenges such as underuse and patient compliance were prevalent. These findings highlight the necessity of promoting mental health resources, addressing gender and academic level-specific vulnerabilities, and implementing accessible non-pharmacological interventions to mitigate the mental health impact of pandemics on U.S. college students.