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Frontiers in Aging Neuroscience 2024Sleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to...
BACKGROUND
Sleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to characterize, for the first time, the associations between sleep characteristics and subsequent cognitive performance in a sample of aging American Indians.
METHODS
We performed analyses on data collected in two ancillary studies from the Strong Heart Study, which occurred approximately 10 years apart with an overlapping sample of 160 American Indians (mean age at follow-up 73.1, standard deviation 5.6; 69.3% female and 80% with high school completion). Sleep measures were derived by polysomnography and self-reported questionnaires, including sleep timing and duration, sleep latency, sleep stages, indices of sleep-disordered breathing, and self-report assessments of poor sleep and daytime sleepiness. Cognitive assessment included measures of general cognition, processing speed, episodic verbal learning, short and long-delay recall, recognition, and phonemic fluency. We performed correlation analyses between sleep and cognitive measures. For correlated variables, we conducted separate linear regressions. We analyzed the degree to which cognitive impairment, defined as more than 1.5 standard deviations below the average Modified Mini Mental State Test score, is predicted by sleep characteristics. All regression analyses were adjusted for age, sex, years of education, body mass index, study site, depressive symptoms score, difference in age from baseline to follow-up, alcohol use, and presence of allele.
RESULTS
We found that objective sleep characteristics measured by polysomnography, but not subjective sleep characteristics, were associated with cognitive performance approximately 10 years later. Longer sleep latency was associated with worse phonemic fluency ( = -0.069, = 0.019) and increased likelihood of being classified in the cognitive impairment group later in life (odds ratio 1.037, = 0.004). Longer duration with oxygen saturation < 90% was associated with better immediate verbal memory, and higher oxygen saturation with worse total learning, short and long-delay recall, and processing speed.
CONCLUSION
In a sample of American Indians, sleep characteristics in midlife were correlated with cognitive performance a decade later. Sleep disorders may be modifiable risk factors for cognitive impairment and dementia later in life, and suitable candidates for interventions aimed at preventing neurodegenerative disease development and progression.
PubMed: 38903901
DOI: 10.3389/fnagi.2024.1346807 -
ACS Chemical Neuroscience Jul 2024Chronic hypoxic exposure triggers the onset and progression of cognitive dysfunction; however, the mechanisms underlying chronic hypoxia-induced neuroinflammation and...
Chronic hypoxic exposure triggers the onset and progression of cognitive dysfunction; however, the mechanisms underlying chronic hypoxia-induced neuroinflammation and its contribution to cognitive dysfunction remain poorly understood. Although inflammation and hypoxia are interdependent, numerous recent studies have linked the development of various human diseases to hypoxia-induced inflammation. In this study, we focused on the NLRP3 inflammasome with novel analogues of cytokine release inhibitory drug 3 (CRID3), a class of small molecule inhibitors for the NLRP3 inflammasome, to investigate their potential contribution to alleviating chronic hypoxia-induced neuroinflammation using the zebrafish model. The designed CRID3 analogues - were prepared from 2-methyl furan-3-carboxylate, following a four-step reaction sequence and fully characterized by NMR and mass spectral analysis. The administration of CRID3 analogues - led to a notable reduction in neuroinflammation and an increase in glial proliferation markers in both sexes. In addition, we investigated the potential effects of CRID3 analogues - through various behavioral tasks to assess their role in ameliorating post-hypoxic behavioral deficits and cognitive impairment. Notably, the study revealed that post-chronic hypoxia, male zebrafish exhibited significantly higher levels of inflammatory marker expression than females. Furthermore, we observed that the neurogenic response to treatment with CRID3 derivative varied depending on the sex, with females showing a sex-specific differential increase in neurogenesis compared to males. This work emphasizes the significance of considering sex differences into account in developing therapeutic strategies for neurological disorders, as shown by the sex-specific molecular and behavioral changes in zebrafish cognitive impairment and neuroinflammation.
Topics: Animals; Zebrafish; Anti-Inflammatory Agents; Memory Disorders; Hypoxia; Disease Models, Animal; Male; Female; Neuroinflammatory Diseases; Inflammation; Cognitive Dysfunction
PubMed: 38902941
DOI: 10.1021/acschemneuro.4c00154 -
BMC Psychiatry Jun 2024Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that...
BACKGROUND
Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed to assess the role of interleukin-2 (IL-2) and interleukin-10 (IL-10) in the pathophysiology and development of GAD.
METHODS
This study recruited 50 GAD patients diagnosed according to the DSM-5 criteria and 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all study subjects. The socio-demographic and clinical characteristics of the study population were determined using pre-structured questionnaires or interviews, and cytokine serum levels were estimated using commercially available ELISA kits.
RESULTS
We observed reduced serum IL-10 levels in GAD patients compared to HCs (33.69 ± 1.37 pg/ml vs. 44.12 ± 3.16 pg/ml). Also, we observed a significant negative correlation between altered IL-10 levels and GAD-7 scores (r=-0.315, p = 0.039). Moreover, IL-10 serum measurement exhibited good predictive value in receiver operating characteristics (ROC) analysis with an area under the curve (AUC) value of 0.793 (p < 0.001) with 80.65% sensitivity and 62.79% specificity at a cutoff value of 33.93 pg/ml. Conversely, we noticed elevated serum IL-2 levels in GAD patients than in HCs (14.81 ± 2.88 pg/ml vs. 8.08 ± 1.1 pg/ml); however, it failed to maintain any significant association with GAD-7 scores, implying that IL-2 might not be involved in GAD pathogenesis. The lower AUC value (0.640; p > 0.05) exhibited by IL-2 serum measurement in ROC analysis further supported that IL-2 might not be associated with GAD.
CONCLUSION
This study provides new insights into the complex interplay between anti-inflammatory cytokines and GAD pathogenesis. Based on the present findings, we can assume that IL-10 but not IL-2 may be associated with the pathophysiology and development of GAD. However, further research with a larger population size and longitudinal design is required to confirm the potential diagnostic efficacy of IL-10.
Topics: Humans; Interleukin-2; Interleukin-10; Female; Case-Control Studies; Anxiety Disorders; Male; Adult; Middle Aged; Biomarkers; ROC Curve
PubMed: 38902708
DOI: 10.1186/s12888-024-05911-z -
Archives of Sexual Behavior Jul 2024Forensic inpatients reside for long periods in restricted environments, which do not support the presence of sexual experiences or the expression of existing needs....
Forensic inpatients reside for long periods in restricted environments, which do not support the presence of sexual experiences or the expression of existing needs. However, sexuality and sexual health are important aspects in the overall recovery from mental illness. Given the lack of national policies, management decisions are bestowed upon individual institutions and staff members. This research aims to describe the current sexual policies in 32 forensic psychiatric wards in Flanders (the Dutch-speaking part of Belgium), varying from low to high security, and explore the perspective of forensic inpatients regarding such policies. The research questions were answered using a survey that questioned the different forensic units. Only 56% of the wards had a sexual policy at the hospital level. Results showed no significant differences in the applicable sexual policies between the security levels, but individual differences and inconsistencies exist in the rules and agreements applied among different wards. Subsequently, 15 semi-structured in-depth interviews with inpatients were conducted using a phenomenological approach. Most of the respondents were dissatisfied with their sexuality and experienced various barriers in meeting their sexual wants and needs. The results have an added value for clinical practice and lead to recommendations in the development of an integrated sexual policy.
Topics: Humans; Pilot Projects; Female; Male; Adult; Forensic Psychiatry; Belgium; Middle Aged; Sexual Behavior; Inpatients; Surveys and Questionnaires; Mental Disorders; Sexual Health
PubMed: 38902489
DOI: 10.1007/s10508-024-02873-x -
Digestive Diseases and Sciences Jun 2024Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional...
BACKGROUND
Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA.
METHODS
Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data.
RESULTS
The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs.
CONCLUSION
This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.
PubMed: 38902460
DOI: 10.1007/s10620-024-08478-7 -
BMJ Case Reports Jun 2024This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also...
This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted.
Topics: Humans; Male; Hypogonadism; Kallmann Syndrome; Seminal Vesicles; Kidney; Ejaculatory Ducts; Adult; Penis
PubMed: 38901851
DOI: 10.1136/bcr-2023-259363 -
Behavioral and Brain Functions : BBF Jun 2024Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication,...
BACKGROUND
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model.
METHODS
Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala.
RESULTS
C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin's beneficial effects on myelin gene expression.
LIMITATIONS
Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin's effects need further examination to understand its' potential as an ASD therapeutic.
CONCLUSIONS
Our work demonstrates the C58/J mouse model's utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.
Topics: Animals; Male; Microglia; Mice; Amygdala; Female; Oligodendroglia; Autism Spectrum Disorder; Mice, Inbred C57BL; Social Behavior; Gene Expression Profiling; Phenotype; Sex Characteristics; Transcriptome; Disease Models, Animal; Oxytocin
PubMed: 38898502
DOI: 10.1186/s12993-024-00240-3 -
Psychoneuroendocrinology Jun 2024Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, resulting from deficits in insulin secretion, insulin action, or both....
Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, resulting from deficits in insulin secretion, insulin action, or both. Whilst the role of insulin in the peripheral nervous system has been ascertained in countless studies, its role in the central nervous system (CNS) is emerging only recently. Brain insulin has been lately associated with brain disorders like Alzheimer's disease, obsessive compulsive disorder, and attention deficit hyperactivity disorder. Thus, understanding the role of insulin as a common risk factor for mental and somatic comorbidities may disclose novel preventative and therapeutic approaches. We evaluated general metabolism (glucose tolerance, insulin sensitivity, energy expenditure, lipid metabolism, and polydipsia) and cognitive capabilities (attention, cognitive flexibility, and memory), in adolescent, young adult, and adult male and female TALLYHO/JngJ mice (TH, previously reported to constitute a valid experimental model of T2DM due to impaired insulin signaling). Adult TH mice have also been studied for alterations in gut microbiota diversity and composition. While TH mice exhibited profound deficits in cognitive flexibility and altered glucose metabolism, we observed that these alterations emerged either much earlier (males) or independent of (females) a comprehensive constellation of symptoms, isomorphic to an overt T2DM-like phenotype (insulin resistance, polydipsia, higher energy expenditure, and altered lipid metabolism). We also observed significant sex-dependent alterations in gut microbiota alpha diversity and taxonomy in adult TH mice. Deficits in insulin signaling may represent a common risk factor for both T2DM and CNS-related deficits, which may stem from (partly) independent mechanisms.
PubMed: 38896988
DOI: 10.1016/j.psyneuen.2024.107102 -
Journal of Developmental and Behavioral... Jun 2024To determine whether the prevalence of psychosocial risk in children and adolescents changed from before to during the COVID-19 pandemic and whether these changes...
OBJECTIVE
To determine whether the prevalence of psychosocial risk in children and adolescents changed from before to during the COVID-19 pandemic and whether these changes differed by age group, sex, and season, based on a standardized psychosocial measure completed as a routine part of primary care.
METHODS
Children and adolescents aged 5.5 to 17.9 years were screened with a parent report Pediatric Symptom Checklist-17 (PSC-17P) between November 2017 and June 2022. Changes in the prevalence of psychosocial risk (global, internalizing, externalizing, and attention scales) from before to during the pandemic were compared by age group, sex, and season.
RESULTS
In a sample of 459,767 health supervision visits, the prevalence of PSC-17P global, internalizing, and attention risk worsened significantly from before to during the pandemic, especially among female adolescents (ages 12.0-17.9). For a pediatrician seeing a hypothetical sample of 1000 adolescent girls, the expected number at risk would have increased from 103 to 131 on the global scale (26.6% increase), from 189 to 231 on the internalizing subscale (22.0% increase), and from 60 to 82 on the attention subscale (35.7% increase). Seasonality had a large effect, with significantly lower PSC-17P risk in the summer every year.
CONCLUSION
Data from a large, national sample of pediatric visits suggested that global, internalizing, and attention concerns increased slightly overall from before to during the COVID-19 pandemic, with different patterns by age group and sex. Adolescent girls showed substantially increased global, internalizing, and attention problems. These increases support the need for further research and additional individual and system-level interventions.
PubMed: 38896783
DOI: 10.1097/DBP.0000000000001273 -
Autism Research : Official Journal of... Jun 2024Younger siblings (SIBS) of children with autism exhibit a wide range of clinical and subclinical symptoms including social, cognitive, language, and adaptive functioning...
Younger siblings (SIBS) of children with autism exhibit a wide range of clinical and subclinical symptoms including social, cognitive, language, and adaptive functioning delays. Identifying factors linked with this phenotypic heterogeneity is essential for improving understanding of the underlying biology of the heterogenous outcomes and for early identification of the most vulnerable SIBS. Prevalence of neurodevelopmental (NDD) and neuropsychiatric disorders (NPD) is significantly elevated in families of children with autism. It remains unknown, however, if the family history associates with the developmental outcomes among the SIBS. We quantified history of the NDDs and NPDs commonly reported in families of children with autism using a parent interview and assessed autism symptoms, verbal, nonverbal, and adaptive skills in a sample of 229 SIBS. Multiple regression analyses were used to examine links between family history and phenotypic outcomes, whereas controlling for birth year, age, sex, demographics, and parental education. Results suggest that family history of schizophrenia, depression, anxiety, bipolar disorder, and intellectual disability associate robustly with dimensional measures of social affect, verbal and nonverbal IQ, and adaptive functioning in the SIBS. Considering family history of these disorders may improve efforts to predict long-term outcomes in younger siblings of children with autism and inform about familial factors contributing to high phenotypic heterogenetity in this cohort.
PubMed: 38896553
DOI: 10.1002/aur.3175