Journal of neurology and psychology最新文献

Background: Depression is a debilitating and difficult-to-treat condition in people with HIV (PWH) despite viral suppression on antiretroviral therapy (ART). Depression is associated with activation of the PKR-like ER kinase (PERK) pathway, which regulates protein synthesis in response to metabolic stress. We evaluated common PERK haplotypes that influence PERK expression in relation to depressed mood in PWH.

Methods: PWH from 6 research centers were enrolled in the study. Genotyping was conducted using targeted sequencing with TaqMan. The major PERK haplotypes A, B, and D were identified. Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II). Covariates including genetically-defined ancestry, demographics, HIV disease/treatment parameters and antidepressant treatments were assessed. Data were analyzed using multivariable regression models.

Results: A total of 287 PWH with a mean (SD) age of 57.1±7.8 years were enrolled. Although the largest ethnic group was non-Hispanic white (n=129, 45.3%), African-American (n=124, 43.5%) and Hispanic (n=30, 10.5%) made up over half the sample. 20.3% were female and 96.5% were virally suppressed. Mean BDI-II was 9.6±9.5, and 28.9% scored above the cutoff for mild depression (BDI-II>13). PERK haplotype frequencies were AA57.8%, AB25.8%, AD 10.1%, and BB4.88%. PERK haplotypes were differentially represented according to genetic ancestry (p=6.84e-6). BDI-II scores were significantly higher in participants with the AB haplotype (F=4.45, p=0.0007).This finding was robust to consideration of potential confounds.

Conclusion: PERK haplotypes were associated with depressed mood in PWH.Consequently, pharmacological targeting of PERK-related pathways might amelioratedepression in PWH.

Background: Astrocytes become activated with certain infections, and this might alter the brain to trigger or worsen depressed mood. Indeed, astrocytes are chronically activated in people with HIV infection (PWH), who are much more frequently depressed than people without HIV (PWoH). A particularly disabling component of depression in PWH is apathy, a loss of interest, motivation, emotion, and goal-directed behavior. We tested the hypothesis that depression and apathy in PWH would be associated with higher levels of a biomarker of astrocyte activation, glial fibrillary acidic protein (GFAP), in cerebrospinal fluid (CSF).

Methods: We evaluated PWH in a prospective observational study using the Beck Depression Inventory-II (BDI-II) and additional standardized assessments, including lumbar puncture. We measured GFAP in CSF with a customized direct sandwich ELISA method. Data were analyzed using ANOVA and multivariable regression.

Results: Participants were 212 PWH, mean (SD) age 40.9±9.14 years, median (IQR) nadir and current CD4 199 (57, 326) and 411 (259, 579), 65.1% on ART, 67.3% virally suppressed. Higher CSF GFAP correlated with worse total BDI-II total scores (Pearson correlation r=0.158, p-value=0.0211), and with worse apathy scores (r=0.205, p=0.0027). The correlation between apathy/depression and GFAP was not in fluenced by other factors such as age or HIV suppression status.

Conclusions: Astrocyte activation, reflected in higher levels of CSF GFAP, was associated with worse depression and apathy in PWH. Interventions to reduce astrocyte activation -- for example, using a peptide-1 receptor (GLP-1R) agonist -- might be studied to evaluate their impact on disabling depression in PWH.

Concussion in athletes can contribute to early neuropsychological changes that may be indicative of future neurodegenerative disease. One of the hallmark findings of chronic traumatic encephalopathy is anxiety and impulsive behavior that often develops early in the course of the disease. The behavioral dysfunction can be grouped into a broader category referred to as cognitive disruption. The current gold standard for diagnosing chronic neurodegeneration is post-mortem evaluation of tauopathy to identify neurofibrillary tau tangles in neurons. Few studies, however, have looked at clinical correlations between acute injury and chronic neurodegeneration in terms of behavior. This lack of focus towards translational study has limited advancements towards treatment. In this pilot investigation, the acute cognitive and emotional (anger, impulsivity, and anxiety) affects of concussion in a cohort of collegiate athletes (n = 30) are examined and compared to findings in the post-mortem pathologic features of chronic traumatic encephalopathy. Specifically, the role of the seroternergic system with alpha synuclein and tauopathy staining and the potential for early clinically relevant behavioral and pharmaceutical interventions was investigated. The purpose was to determine if athletes began demonstrating cognitive disruption present in post-mortem evaluation during the acute phase of injury. The acute data was collected via questionnaires within ten days of the athletes' concussion diagnosis. Results demonstrated that 11 of 30 athletes (36%) scored in a diagnosable range of anxiety post-concussion, and athletes scored above the norm in state-anger (M = 22.9, SD = 9.99), indicating severe emotional disturbance. A limitation is that due to the long time frame from acute injury to the development of neurodegeneration individual athletes cannot be tracked in longevity thus limiting the findings to the realm of correlation. The findings from this pilot study warrant further investigation into the neuropsychological aspects for how to manage concussion and prevent degenerative disease.

Sphingolipids are enriched in the Central Nervous System (CNS) and display multiple biological functions. They participate in tissue development, cell recognition and adhesion, and act as receptors for toxins. During myelination, a variety of interactive molecules such as myelin basic protein, myelin associated glycoprotein, phospholipids, cholesterol, sphingolipids, etc., participate in a complex fashion. Precise roles of some sphingolipids in myelination still remain unexplored. Our investigation delineated participation of several sphingolipids in myelination during rat brain development as well as in human brain demyelination during pathogenesis of Multiple Sclerosis (MS). These sphingolipids included Ceramide (Cer)/dihydroceramide (dhCer), Sphingosine (Sph)/dihydrosphingosine (dhSph), and glucosyl/galactosylceramide (glc/galCer) as we detected these by column chromatography, high performance thin-layer chromatography, gas chromatography-mass spectrometry, and high-performance liquid chromatography. Cer/dhCer level rises during rat brain development starting at Embryonic stage (E) until postnatal day (P21), then gradually falls until the maturity (P30 and onwards), and remains steady maintaining a constant ratio (4-4.5:1) throughout the brain development. GlcCer is the initial Monoglycosylceramide (MGC) that appears at early Postnatal stage (P8) and then GalCer appears at P10 with an increasing trend until P21 and its concentration remains unaltered. Sph and dhSph profiles show a similar trend with an initial peak at P10 and then a comparatively smaller peak at P21 maintaining a ratio of (2-2.5:1) of Sph:dhSph. The profiles of all these sphingolipids, specifically at P21, clearly indicate their importance during rat brain development but somewhat unspecified roles in myelination. While Cer has been reported to involve in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, Sph being a potent inhibitor of protein kinase C has recently been implicated in CNS demyelination due to MS. Inflammatory cytokines stimulate Sph elevation in MS brains and lead to demyelination due to oligodendrocyte death as we examined by using human oligodendroglioma culture. In conclusions, sphingolipids are essential for brain development but they have deleterious effects in demyelinating diseases such as MS.

The Institute of Medicine (2015) has proposed a new clinical case definition for what had been known as chronic fatigue syndrome (CFS). This new criteria involved the following domains: substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities; post-exertional malaise; unrefreshing sleep; and at least one of the two following symptoms: cognitive impairment or orthostatic intolerance. In addition, in August of 2015, the CFS Advisory Committee, which makes recommendations to the Secretary of US Department of Health and Human Services, proposed that the Canadian 2003 criteria should serve as the research case for CFS. Up to now, there have not been any published investigations comparing these clinical and research criteria. Using patient samples collected in the United States, Great Britain, and Norway, the current study compared and contrasted patients who met the clinical and research criteria. Overall findings indicated that those meeting the research criteria in comparison to those meeting the clinical criteria were significantly more impaired on a wide variety of symptoms and functional areas. The implications of these findings are discussed.