Objective

Although 25% of people with bipolar disorder (BD) are over age 60, there is a dearth of research on older age bipolar disorder (OABD). This report describes an initial effort to create an integrated OABD database using the U.S. National Institute of Mental Health Data Archive (NDA). Goals were to: 1) combine data from three BD studies in the United States that included overlapping data elements; 2) investigate research questions related to aims of the original studies; and 3) take an important first step toward combining existing datasets relevant to aging and BD.

Methods

Data were prepared and uploaded to the NDA, with a focus on data elements common to all studies. As appropriate, data were harmonized to select or collapse categories suitable for cross-walk analysis. Associations between age, BD symptoms, functioning, medication load, medication adherence, and medical comorbidities were assessed. The total sample comprised 451 individuals, mean age 57.7 (standard deviation: 13.1) years.

Results

Medical comorbidity was not significantly associated with either age or functioning and there did not appear to be an association between medication load, comorbidity, age, and adherence. Men and African-Americans were significantly more likely to have poor adherence. Both BD mania and depression symptoms were associated with functioning, but this differed across studies.

Conclusion

Despite limitations including heterogeneity in study design and samples and cross-sectional methodology, integrated datasets represent an opportunity to better understand how aging may impact the presentation and evolution of chronic mental health disorders across the lifespan.

Schizophrenia is characterized by physical (mainly metabolic and cardiovascular) comorbidity and shortened lifespan. High sensitivity C-reactive protein (hs-CRP), an inflammatory marker of hepatic origin linked to metabolic and cardiovascular diseases and mortality in the general population, has been reported to be elevated in people with schizophrenia. However, the relationship of hs-CRP to psychiatric and medical risk factors, after controlling for potentially confounding variables such as smoking, is not well established in schizophrenia. We assessed hs-CRP levels along with various demographic, psychiatric, and metabolic measures in 88 clinically stable outpatients with schizophrenia or schizoaffective disorder and 71 age epoch-matched comparison subjects with no history of a major psychiatric illness. hs-CRP levels were significantly higher in individuals with schizophrenia than in comparison subjects. Higher hs-CRP levels in the schizophrenia group were associated with female gender, more severe negative symptoms, greater medical comorbidity, and worse metabolic risk factors including BMI, fasting glucose, and hemoglobin A1c levels. hs-CRP was not related to age, race, education, smoking status, antipsychotic dosage, or cognitive impairment. Longitudinal studies are needed to investigate the relationship between hs-CRP and long-term health outcomes including metabolic syndrome, cardiovascular disease, and mortality in schizophrenia.

Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo₂-lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.

Background

Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age.

Methods

We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years.

Results

Overall, LTL was inversely associated with age (t(249) = -6.2, p < 0.001), and a gender effect on the rate of LTL decrease with age was found (t(249) = 2.20, p = 0.029), with men declining more rapidly than women. No significant overall effect of diagnosis on the rate of decline was detected. However, at the average sample age (48 years), there was a significant gender effect in both schizophrenia and HC groups (t(249) = 2.48, p = 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) = 2.43, p = 0.016) - at the average sample age, women with schizophrenia had shorter LTL than HC women.

Discussion

Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women.

Intestinal microbiome and gut-brain axis have been receiving increasing attention for their role in the regulation of brain/behavior and possible biological basis of psychiatric disorders. Several recent clinical studies have linked the microbiome with neuropsychiatric conditions, although the literature on schizophrenia is quite limited. This study investigated gut microbiome composition in 50 individuals, including 25 persons with chronic schizophrenia and 25 demographically-matched non-psychiatric comparison subjects (NCs). Stool samples were collected and assayed using 16S rRNA sequencing of the V4 region. Examination of unweighted UniFrac and Bray-Curtis dissimilarity revealed significant community-level separation in microbiome composition between the two subject groups. At the phylum level, Proteobacteria were found to be relatively decreased in schizophrenia subjects compared to NCs. At the genus level, Anaerococcus was relatively increased in schizophrenia while Haemophilus, Sutterella, and Clostridium were decreased. Within individuals with schizophrenia, abundance of Ruminococcaceae was correlated with lower severity of negative symptoms; Bacteroides was associated with worse depressive symptoms; and Coprococcus was related to greater risk for developing coronary heart disease. Our findings provide evidence of altered gut microbial composition in persons with chronic schizophrenia and suggest a need for larger and longitudinal studies of microbiome in schizophrenia.

AbstractSubjective cognitive decline (SCD), or internal feelings of reduced mental capacity, is of increasing interest in the scientific, clinical, and lay community. Much of the extant literature is focused on SCD as a risk factor for Alzheimer’s disease in older adults, while less attention has been paid to non-cognitive health correlates of SCD across adulthood. Consequently, we investigated physical and mental health correlates of SCD in younger, middle-aged, and older adults. We recruited 3,407 U.S. residents through Amazon’s Mechanical Turk, an online labor market. Participants completed a 90-item self-report survey questionnaire assessing sociodemographic characteristics, physical health, sleep, depression, anxiety, loneliness, wisdom, self-efficacy, and happiness. Overall, 493/1930 (25.5%) of younger adults (18-49) and 278/1032 (26.9%) of older adults (50 or older) endorsed the SCD item. Multivariate analysis of variance and follow-upt-tests revealed worse physical and mental health characteristics in people endorsing SCD compared to those who did not, with effect sizes primarily in the medium to large range. Additionally, age did not moderate relationships between SCD and physical and mental health. Results suggest that SCD is associated with a diverse set of negative health characteristics such as poor sleep and high body mass index, and lower levels of positive factors including happiness and wisdom. Effect sizes of psychological correlates of SCD were as large as (or larger than) those of physical correlates, indicating that mental health and affective symptoms may be critical to consider when evaluating SCD. Overall, findings from this large, national U.S. sample suggest the presence of relationships between SCD and multiple psychological and perceived health factors; our results also show that SCD may be highly prevalent in both younger and older adults, suggesting that it be assessed across the adult lifespan.

Objective

Loneliness is a prevalent and serious public health problem due to its effects on health, well-being, and longevity. Understanding correlates of loneliness is critical for guiding efforts toward the development of evidence-based strategies for prevention and intervention. Considering that patterns of association between age and loneliness vary, the present study sought to examine age-related differences in risk and protective factors for loneliness.

Methods

Correlates of loneliness were examined through a large web-based survey of 2,843 participants (aged 20-69 years) from across the United States from April 10, 2019, through May 10, 2019. Participants completed the 4-item UCLA Loneliness Scale, San Diego Wisdom Scale (with the following subscales measuring components of wisdom: Prosocial Behaviors, Emotional Regulation, Self-Reflection, Acceptance of Divergent Values, Decisiveness, and Social Advising), and other scales measuring psychosocial variables. Multivariate regression analyses were conducted to identify the best model of loneliness and examine potential age-related differences.

Results

Age demonstrated a nonlinear quadratic relationship with loneliness (Wald statistic = 5.48, P = .019); levels were highest in the 20s and lowest in the 60s with another peak in the mid-40s. Across all decades, loneliness was associated with not having a spouse or partner (P < .001), sleep disturbance (P < .02), lower prosocial behaviors (P < .001), and smaller social network (P < .001). Lower social self-efficacy (P < .001) and higher anxiety (P < .005) were associated with worse loneliness in all age decades, except the 60s. Loneliness was uniquely associated with decisiveness in the 50s (P = .012) and with education (P = .046) and memory complaints (P = .013) in the 60s.

Conclusions

Our findings identify several potentially modifiable targets related to loneliness, including several aspects of wisdom and social self-efficacy. Differential predictors at different decades suggest a need for a personalized and nuanced prioritizing of prevention and intervention targets.

We investigated subjective cognitive complaints (SCCs), as well as physical and mental health factors, in adults and older adults. U.S. residents (N = 2,962) were recruited via the Amazon Mechanical Turk platform and completed a 90-item survey. Overall, 493/1930 (25.5%) of younger adults and 278/1032 (26.9%) of older adults endorsed SCCs. Analyses revealed worse physical and mental health characteristics in the SCC+ compared to the SCC- group, with primarily medium (Cohen's d = 0.50) to large (0.80) effect sizes. Age did not moderate relationships between SCCs and physical/mental health. Results suggest that SCCs are associated with a diverse set of negative health characteristics such as poor sleep and high body mass index, and lower levels of positive factors, including happiness and wisdom. Effect sizes of psychological correlates were at least as large as those of physical correlates, indicating that mental health is critical to consider when evaluating SCCs.

Objective

Wisdom has gained increasing interest among researchers as a personality trait relevant to well-being and mental health. We previously reported development of a new 24-item San Diego Wisdom Scale (SD-WISE), with good to excellent psychometric properties, comprised of six subscales: pro-social behaviors, emotional regulation, self-reflection (insight), tolerance for divergent values (acceptance of uncertainty), decisiveness, and social advising. There is controversy about whether spirituality is a marker of wisdom. The present cross-sectional study sought to address that question by developing a new SD-WISE subscale of spirituality and examining its associations with various relevant measures.

Methods

Data were collected from a national-level sample of 1,786 community-dwelling adults age 20-82 years, as part of an Amazon M-Turk cohort. Participants completed the 24-item SD-WISE along with several subscales of a commonly used Brief Multidimensional Measure of Religiousness/Spirituality, along with validated scales for well-being, resilience, happiness, depression, anxiety, loneliness, and social network.

Results

Using latent variable models, we developed a Spirituality subscale, which demonstrated acceptable psychometric properties including a unidimensional factor structure and good reliability. Spirituality correlated positively with age and was higher in women than in men. The expanded 28-item, 7-subscale SD-WISE total score (called the Jeste-Thomas Wisdom Index or JTWI) demonstrated acceptable psychometric properties. The Spirituality subscale was positively correlated with good mental health and well-being, and negatively correlated with poor mental health. However, compared to other components of wisdom, the Spirituality factor showed weaker (i.e., small-to-medium vs. medium-to-large) association with the SD-WISE higher-order Wisdom factor (JTWI).

Conclusion

Similar to other components as well as overall wisdom, spirituality is significantly associated with better mental health and well-being, and may add to the predictive utility of the total wisdom score. Spirituality is, however, a weaker contributor to overall wisdom than components like pro-social behaviors and emotional regulation. Longitudinal studies of larger and more diverse samples are needed to explore mediation effects of these constructs on well-being and health.

This paper aims to compare mental and physical health, cognitive functioning, and selected biomarkers of aging reflecting metabolic pathology and inflammation, in outpatients with schizophrenia from two residential settings: residential care facilities (RCFs) and living with someone in a house/apartment. This cross-sectional study examined community-dwelling adults with schizophrenia either in RCFs (N = 100) or in a house/apartment with someone (N = 76), recruited for two NIH-funded studies in San Diego. Assessments included measures of mental/physical health, cognitive function, and metabolic (glycosylated hemoglobin, cholesterol) and inflammatory (C-Reactive Protein, Tumor Necrosis Factor-alpha, Interleukin-6) biomarkers of aging. General logistic models were used to analyze factors associated with residential status. RCF residents had several indicators of worse prognosis (never being married, higher daily antipsychotic dosages, increased comorbidities and higher Framingham risk for coronary heart disease) than individuals living with someone. However, RCF residents had better mental well-being and lower BMI, as well as comparable biomarkers of aging as those living with someone. While the cross-sectional nature of the study does not allow us to infer causality, it is possible that the supportive environment of RCFs may have a positive impact on mental and physical health of persons with schizophrenia. Longitudinal follow-up studies are needed to test this hypothesis.