Elevated Lipid and Pro-Inflammatory Markers Relate to Future Depression and Anxiety Components: A Cross-Lagged Prospective Network Analysis

Background: Vulnerability theories propose that higher levels of lipid and pro-inflammatory markers precede and relate to future heightened depression and anxiety. Scar models posit the reverse association. However, most studies testing biomarker-psychopathology relations have been cross-sectional, which precludes causal inferences, and did not differentiate biomarker and psychopathology components. We thus used cross-lagged prospective network analysis (CLPN) to investigate this topic. Methods: Community adult women (n = 3,302) completed a self-report (Center for Epidemiologic Studies-Depression scale; CES-D) and provided biomarker samples. CLPN identified true relations (edges) among components (nodes) of psychopathology (depressed mood, anxiety severity, somatic symptoms, interpersonal issues), lipid markers (insulin, glucose, triglycerides), inflammation (C-reactive protein, fibrinogen), low-density lipoprotein-cholesterol (LDL), and high-density lipoprotein-cholesterol (HDL), within and across five time-points. Results: Contemporaneous CLPN revealed true positive edges for somatic symptoms-inflammation, somatic symptoms-lipid markers, and anxiety severity-lipid markers. Temporal networks showed that higher levels of lipid or pro-inflammatory markers were related to greater future depressed mood, somatic symptoms, anxiety severity, and interpersonal issues. Also, lower HDL level was associated with more future somatic symptoms, interpersonal issues, and depressed mood. Further, somatic symptoms and lipid markers had the strongest effect on future nodes in the network. Conclusions: Overall, the results were consistent with vulnerability (vs. scar) models. Possible mechanistic accounts include long-term dysregulated metabolic, endocrine, and immune systems and social disengagement patterns. Cognitive-behavioral and related lifestyle-based therapies that optimize diet, nutrition, and physical activity may effectively target depression and anxiety at the prevention and treatment stages. Other theoretical and clinical implications were discussed.

Longitudinal changes of frailty in 8 years: comparisons between physical frailty and frailty index

Background Few studies have made longitudinal comparisons between frailty phenotype (FP) and frailty index (FI) changes. We aimed to investigate frailty status changes defined by FP and FI concurrently, and to compare the associated factors and incident disability among different combination of FI and FP trajectory groups. Methods Data on respondents aged over 50 who completed the 1999, 2003 and 2007 Taiwan Longitudinal Study on Aging (TLSA) surveys (n = 2807) were excerpted. Changes of FI, FP and major time-dependent variables were constructed by group-based trajectory modeling. Logistic regression was used to investigate the associated factors and relationships with incident disability among different frailty trajectories. Results We identified four FP trajectories – stably robust, worsened frailty, improved frailty, and stably frail and three FI trajectories – stable FI, moderate increase FI and rapid increase FI. Lower self-rated health, mobility impairment, and depressed mood were associated with unfavorable FP and FI changes (all p < 0.001). Regardless of FP trajectory groups, the moderate and rapid increase FI group had significantly more comorbidities than the stable FI group, and more visual, hearing, oral intake impairment, more difficulty in meeting living expenses, and poorer cognitive function in ≥65-year-olds (all p < 0.05). In addition, the worsened frailty, improved frailty, and stably frail groups had ORs for incident disability of 10.5, 3.0, and 13.4, respectively, compared with the stably robust group (all p < 0.01); the moderate and rapid increase FI groups had 8.4-fold and 77.5-fold higher risk than the stable FI group (both p < 0.001). When combining FI and FP trajectories, risk increased with FI trajectory steepness, independent of FP change (all p < 0.01 in rapid increase FI vs stable FI). Conclusions Four FP trajectories (stably robust, worsened frailty, improved frailty, and stably frail) and three FI trajectories (stable FI, moderate increase FI and rapid increase FI) were identified. Lower self-rated health, mobility impairment, and depressed mood were associated with both unfavorable FP and FI trajectories. Nevertheless, even for individuals in stably robust or improved frailty FP groups, moderate or rapid increase in FI, either due to comorbidities, sensory impairment, cognitive deficits, or financial challenges, may still increase the risk of incident disability.

African-American Race Predicts 1-Year Cognitive Decline Among Adults Without Moderate Dementia

Previous literature shows conflicting conclusions about the association between race and cognitive decline, particularly in early impairment. In this study, we aimed to test whether race predicted 1-year change in Montreal Cognitive Assessment (MoCA) score among older adults without moderate-severe dementia. We secondarily explored whether multimorbidity, polypharmacy, depressed mood, antidepressant use, body composition, or frailty changed the association. We analyzed data (n=122) from predominantly African American (AfA, 78.7%) community-dwelling older adults from the south side of Chicago. Participants underwent baseline and 1-year MoCA testing. Age, gender, race, education, monthly income, co-morbidities (Charlson Comorbidity Index), medication use (&lt;5 vs ≥5), depression (PHQ-2), proportion lean mass (DEXA), and the frailty phenotype (range 0-5) were collected at baseline. In a multivariate linear model, we regressed 1-year MoCA score on baseline MoCA score, race, and demographics and then evaluated the impact of each covariate added separately to the model on the race-cognition relationship. The mean MoCA score at baseline was 25.2+/-0.2 (range 18-30) and 41.0% of participants experienced ≥1 point MoCA decline at 1 year. After adjusting for demographics, AfAs experienced a greater 1-year MoCA decline (β= -1.3, p=0.04) compared to other races. The effect size was unchanged after adjusting for multimorbidity and polypharmacy (β= -1.3, p=0.04), attenuated slightly after adjusting for frailty (β= -1.2, p=0.06), depressed mood (β= -1.2, p=0.05), lean mass (β= -1.2, p=0.04), and attenuated notably after adjusting for antidepressant use (β= -1.0, p=0.11). Findings support the need to further explore racial differences in cognitive decline and potentially related anti-depressant underuse.

Within- and across-day patterns of interplay between depressive symptoms and related psychopathological processes: a dynamic network approach during the COVID-19 pandemic

Background In order to understand the intricate patterns of interplay connected to the formation and maintenance of depressive symptomatology, repeated measures investigations focusing on within-person relationships between psychopathological mechanisms and depressive components are required. Methods This large-scale preregistered intensive longitudinal study conducted 68,240 observations of 1706 individuals in the general adult population across a 40-day period during the COVID-19 pandemic to identify the detrimental processes involved in depressive states. Daily responses were modeled using multi-level dynamic network analysis to investigate the temporal associations across days, in addition to contemporaneous relationships between depressive components within a daily window. Results Among the investigated psychopathological mechanisms, helplessness predicted the strongest across-day influence on depressive symptoms, while emotion regulation difficulties displayed more proximal interactions with symptomatology. Helplessness was further involved in the amplification of other theorized psychopathological mechanisms including rumination, the latter of which to a greater extent was susceptible toward being influenced rather than temporally influencing other components of depressive states. Distinctive symptoms of depression behaved differently, with depressed mood and anhedonia most prone to being impacted, while lethargy and worthlessness were more strongly associated with outgoing activity in the network. Conclusions The main mechanism predicting the amplifications of detrimental symptomatology was helplessness. Lethargy and worthlessness revealed greater within-person carry-over effects across days, providing preliminary indications that these symptoms may be more strongly associated with pushing individuals toward prolonged depressive state experiences. The psychopathological processes of rumination, helplessness, and emotion regulation only exhibited interactions with the depressed mood and worthlessness component of depression, being unrelated to lethargy and anhedonia. The findings have implications for the impediment of depressive symptomatology during and beyond the pandemic period. They further outline the gaps in the literature concerning the identification of psychopathological processes intertwined with lethargy and anhedonia on the within-person level.

A Cross-Lagged Prospective Network Analysis of Common Mental Health and Cognitive Functioning Components in Midlife Community Adult Women

Background: The scar theory proposes that heightened depression and anxiety precede and predict worse cognitive functioning outcomes, whereas the vulnerability model posits the opposite pathway. However, most investigations on this topic have been cross-sectional, which precludes causal inferences. Thus, our study used both contemporaneous and temporal cross-lagged panel network analysis to facilitate causal inferences in understanding the relations between psychopathology components and cognitive functioning. Methods: Racially-diverse midlife women (n = 3,302) participated in the Study of Women's Health Across the Nation across two time-points, spanning one year apart. Five psychopathology (anxiety symptoms, depressed mood, somatic symptoms, positive affect, interpersonal problems) and cognitive functioning nodes (working memory (WM), processing speed (PS), visual memory (VSM), auditory memory (ARM)) were assessed. Results: Contemporaneous networks yielded notable inverse between-node relations (edges) for interpersonal problems and reduced VSM and PS, and between depressed mood or anxiety symptoms and VSM, ARM, or PS. Moreover, nodes that had the highest likelihood to bridge psychopathology and cognitive functioning constructs were positive affect, anxiety symptoms, WM, and ARM. Temporal networks produced edges inconsistent with the vulnerability theory. Higher depressed mood and somatic symptoms and lower positive affect were related to reduced future PS, WM, and/or VSM. Likewise, greater interpersonal issues and anxiety symptoms were linked to poorer future ARM and WM. Also, positive affect had the strongest effect on future nodes. Conclusions: These results provide stronger support for the scar theory than the vulnerability theory.

Rostral Anterior Cingulate Activations Inversely Relate To Reward Payoff Maximation & Predict Depressed Mood

Choice selection strategies and decision making are typically investigated using multiple-choice gambling paradigms that require participants to maximize reward payoff. However, research shows that performance in such paradigms suffers from individual biases towards the frequency of gains to choose smaller local gains over larger longer term gain, also referred to as melioration. Here, we developed a simple two-choice reward task, implemented in 186 healthy human adult subjects across the adult lifespan to understand the behavioral, computational, and neural bases of payoff maximization versus melioration. The observed reward choice behavior on this task was best explained by a reinforcement learning model of differential future reward prediction. Simultaneously recorded and source-localized electroencephalography (EEG) showed that diminished theta-band activations in the right rostral anterior cingulate cortex (rACC) correspond to greater reward payoff maximization, specifically during the presentation of cumulative reward information at the end of each task trial. Notably, these activations (greater rACC theta) predicted self-reported depressed mood symptoms, thereby showcasing a reward processing marker of potential clinical utility.