Volume reduction and shape abnormality of the hippocampus have been associated with mood disorders. However, the hippocampus is not a uniform structure and consists of several subfields, such as the cornu ammonis (CA) subfields CA1–4, the dentate gyrus (DG) including a granule cell layer (GCL) and a molecular layer (ML) that continuously crosses adjacent subiculum and CA fields. It is known that cellular and molecular mechanisms associated with mood disorders may be localized to specific hippocampal subfields. Thus, it is necessary to investigate the link between the in vivo hippocampal subfield volumes and specific mood disorders, such as bipolar disorder (BD) and major depressive disorder (MDD). In the present study, we used a state-of-the-art hippocampal segmentation approach, and we found that patients with BD had reduced volumes of hippocampal subfields, specifically in the left CA4, GCL, ML, and both sides of the hippocampal tail, compared to healthy subjects and patients with MDD. The volume reduction was especially severe in patients with bipolar I disorder (BD-I). We also demonstrated that hippocampal subfield volume reduction was associated with the progression of the illness. For patients with BD-I, the volumes of the right CA1, ML and Sub decreased as the illness duration increased, and the volumes of both sides of the CA2/3, CA4, and hippocampal tail had negative correlations with the number of manic episodes. These results indicated that among the mood disorders the hippocampal subfields were more affected in BD-I compared to BD-II and MDD, and manic episodes had focused progressive effect on the CA2/3 and CA4 and hippocampal tail.

Background: We report contemporary trends in nationwide incidence of intracerebral hemorrhage (ICH) across demographic and regional strata over a 15-year period. Methods: Utilizing the Nationwide Inpatient Sample (2004–2018) and US Census Bureau data, we calculated ICH incidence rates for age, race/ethnicity, sex, and hospital region sub-cohorts across 5 consecutive 3-year periods (2004–2006 to 2016–2018). We fit Poisson and log binomial regression models to evaluate demographic and regional differences in ICH incidence and trends in prevalence of hypertension and past/current anticoagulant use among hospitalized ICH patients. Results: Overall, the annual incidence rate (95% CI) of ICH per 100 000 was 23.15 (23.10–23.20). The 3-year incidence of ICH (per 100 000) increased from 62.79 in 2004 to 2006 to 78.86 in 2016 to 2018 (adjusted incidence rate ratio, CI: 1.11 [1.02–1.20]), coinciding with increased 3-year prevalence of hypertension and anticoagulant use among hospitalized ICH patients (adjusted risk ratio, CI: hypertension—1.16 [1.15–1.17]; anticoagulant use—2.30 [2.14–2.47]). We found a significant age-time interaction, whereby ICH incidence increased significantly faster among those aged 18 to 44 years (adjusted incidence rate ratio, CI: 1.10 [1.05–1.14]) and 45 to 64 years (adjusted incidence rate ratio, CI: 1.08 [1.03–1.13]), relative to those aged ≥75 years. Conclusions: Rising ICH incidence among young and middle-aged Americans warrants ICH prevention strategies targeting these economically productive age groups.

Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, resulting in changes consistent with an allostatic load model of neurocognitive impairment.The present study measured potential markers of allostatic load in individuals with comorbid cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white matter (WM), telomere length, and impulsivity/attentional bias were obtained. WM (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by the telomere to single copy gene (T/S) ratio. Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and FA were associated with years of cocaine use (R2 = 0.56 and 0.51, both p < .005) but not years of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, exploratory regression using an elastic-net model determined that more years of cocaine use, older age, larger HDDM drift rate differences and shorter telomere length were all predictive of WM as measured by RD (model R2 = 0.79). Collectively, the results provide modest support linking CUD/AUD to putative markers of allostatic load.

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Background Sex differences in post-stroke cognitive decline have not been systematically evaluated in a nationally representative cohort. We use a quasi-experimental design to investigate sex differences in rate of post-stroke cognitive decline. Methods Utilizing the event study design, we use the Health and Retirement Study (HRS) data (1996–2016) to evaluate the differences (percentage points [95% Confidence interval]) in the rate of change in cognitive function, measured using the modified version of the Telephone Interview for Cognitive Status (TICS-m) score, before and after incident stroke, and among patients with and without incident stroke. We estimated this event study model for the overall study population and separately fit the same model for male and female participants. Results Of 25,872 HRS participants included in our study, 14,459 (55.9%) were females with an overall mean age (SD) of 61.2 (9.3) years. Overall, 2,911 (11.3%) participants reported experiencing incident stroke. Participants with incident stroke (vs. no stroke) had lower baseline TICS-m score (15.6 vs. 16.1). Among participants with incident stroke, the mean pre-stroke TICS-m score was higher than the mean post-stroke TICS-m score (14.9 vs. 12.7). Event study revealed a significant short-term acceleration of cognitive decline for the overall population (4.2 [1.7–6.6] percentage points, p value = 0.001) and among female participants (5.0 [1.7–8.3] percentage points, p value = 0.003). We, however, found no evidence of long-term acceleration of cognitive decline after stroke. Moreover, among males, incident stroke was not associated with significant changes in rate of post-stroke cognitive decline. Conclusion Females, in contrast to males, experience post-stroke cognitive deficits, particularly during early post-stroke period. Identifying the sex-specific stroke characteristics contributing to differences in post stroke cognitive decline may inform future strategies for reducing the burden of post-stroke cognitive impairment and dementia.

Background Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD. Methods Euthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer. Results Compared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = −0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048). Conclusion Our results support the involvement of inflammatory pathways in structural brain changes in BD.

Background: We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAb) against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), an emerging public health problem. Methods and Findings: In a retrospective cohort study, we identified patients with clinically significant PASC using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an 8-hospital tertiary healthcare system in the greater Houston metropolitan (primary analyses). Analyses were then replicated across a global research network database. We included all adults (>= 18) who survived beyond 28-days of their index infection. PASC was defined as experiencing constitutional (palpitations, malaise / fatigue, headache) or systemic (sleep disorder, shortness of breath, mood / anxiety disorders, cough, and cognitive impairment) symptoms beyond 28-day post-infection period. Instances of PASC were excluded if the symptoms were present pre-COVID or if they resolved within four weeks of initial infection. We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Primary analyses included 53,239 subjects (54.9% female), of whom 5,929, 11.1% (CI: 10.9 - 11.4), experienced PASC. Both, vaccinated breakthrough cases (vs. unvaccinated) and mAb treated patients (vs. untreated) had lower likelihoods for developing PASC, aOR (CI): 0.58 (0.52, 0.66), and 0.77 (0.69, 0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared to mAb treatment. Replication analysis found almost identical frequency of PASC (11.2%) and similar protective effects against PASC for the COVID-19 vaccine: aOR (CI) 0.25 (0.21 - 0.30) and mAb treatment: 0.62 (0.59 - 0.66). Discussion: Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, at present, vaccination is the most effective tool to potentially prevent long-term clinical and socio-economic consequences of COVID-19.

Experiencing stressful events throughout one's life, particularly childhood trauma, increases the likelihood of being diagnosed with Major Depressive Disorder (MDD). Raised levels of cortisol, and markers of inflammation such as Interleukin (IL-6) and C-reactive protein (CRP), have been linked to both early life stress and MDD. We aimed to explore the biological stress signatures of early stress and MDD on hippocampal sub regional volumes using 7 Tesla MRI imaging. A cohort of 71 MDD patients was compared against 46 age and sex-matched healthy volunteers. MDD subjects had higher averages of IL-6 and CRP levels. These differences were significant for IL-6 levels and trended for CRP. There were no significant group differences in any of the hippocampal subfields or global hippocampal volumes; further, there were no hippocampal subfield differences between MDD subjects with high levels of our biological stress measures and MDDs with normal levels.