Major depressive disorder (MDD) is a heterogeneous with underlying mechanisms that are insufficiently studied. We aimed to identify functional connectivity (FC)-based subtypes of MDD and investigate their biological mechanisms.

Consensus clustering of FC patterns was applied to a population of 829 MDD patients from the REST-Meta-MDD database, with validity assessed across multiple dimensions, including atlas replication, cross-validated classification, and drug-naïve subgroup analysis. Regression models were used to quantify FC alterations in each MDD subgroup compared with 770 healthy controls, and to analyze spatial associations between FC alterations and publicly available gene transcriptomic and neurotransmitter receptor/transporter density databases.

Two stable MDD subtypes emerged: hypoconnectivity (n = 527) and hyperconnectivity (n = 299), which had both shared and distinct regions with remarkable FC alterations (i.e. epicenters) in the default mode network.

There were several common enriched genes (e.g. axon/brain development, synaptic transmission/organization, etc.) related to FC alterations in both subtypes. However, glial cell and neuronal differentiation genes were specifically enriched in the hypoconnectivity and hyperconnectivity subtypes, respectively.

Both subtypes showed spatial associations between FC alterations and serotonin receptor/transporter density. In the hypoconnectivity subtype, FC alterations correlated with GABA and acetylcholine receptor densities, while norepinephrine transporter and glutamate receptor densities were linked to the hyperconnectivity subtype.

Our findings suggested the presence of two neuroimaging subtypes of MDD characterized by hypoconnectivity or hyperconnectivity, demonstrating robust reproducibility. The two subtypes had both shared and distinct genetic mechanisms and neurotransmitter receptor/transporter profiles, suggesting potential clinical implications for this heterogeneous disorder.

To investigate potential contributors to mental fatigue after aneurysmal subarachnoid hemorrhage (aSAH) and angiographically negative subarachnoid hemorrhage (anSAH), with a focus on information processing speed, attentional control, and psychological distress.

This observational study included 101 patients (70 aSAH, 31 anSAH) and 86 controls. Neuropsychological assessments and questionnaires were conducted five months post-SAH. Mental and physical fatigue were assessed with the Dutch Multifactor Fatigue Scale, information processing speed and attentional control with the Trail Making Test and Vienna Test System Reaction Time and Determination Test, and psychological distress with the Hospital Anxiety and Depression Scale.

Patients reported significantly higher mental and physical fatigue than controls (p < .001) and information processing speed and attentional control were significantly lower (p < .05), with no differences between aSAH and anSAH groups. Severe mental fatigue was present in 55.7% of patients with aSAH and 61.3% of patients with anSAH, significantly exceeding the prevalence of severe physical fatigue (p < .05). Higher mental fatigue correlated with worse attentional control in aSAH and with lower information processing speed in anSAH. Both mental and physical fatigue correlated with psychological distress, particularly after anSAH.

The factors related to mental fatigue appear to differ based on the type of SAH, potentially involving problems in information processing speed and attentional control, psychological distress, or both. This study emphasizes the need for individualized rehabilitation strategies addressing both cognitive and psychological factors in managing mental fatigue after SAH.

Negative symptoms in schizophrenia, particularly motivational deficits, pose significant challenges to treatment and recovery. Despite their profound impact on functional outcomes, these symptoms remain poorly understood and inadequately addressed by current interventions.

The CHANSS (Characterising Negative Symptoms in Schizophrenia) study aims to dissect the cognitive mechanisms underlying motivational impairments by focusing on three interconnected domains: executive cognition, motivational cognition and meta-cognition.

This large, international, cross-sectional study recruits a heterogeneous sample of patients across illness stages – from first-episode psychosis to treatment-resistant schizophrenia – and uses a comprehensive cognitive battery, clinical scales, self-report measures and computerised cognitive tasks. Four novel tasks assess key processes in motivated behaviour: option generation, reward-based decision-making, risk sensitivity and performance self-evaluation. By incorporating control for secondary influences like depression, psychosis, sedation and illness chronicity, the study seeks to identify distinct cognitive and behavioural subtypes within motivational dysfunction.

CHANSS tests the hypothesis that specific patient profiles exhibit predominant impairments in one or more cognitive domains, which may differentially affect goal-directed behaviour. The study’s design allows exploration of hierarchical relationships between cognitive processes, such as how neurocognitive deficits may cascade to impair motivation and self-evaluation.

Ultimately, CHANSS aims to advance mechanistic understanding of motivational deficits in schizophrenia and pave the way for personalised, targeted interventions. Its findings may inform future clinical trials and contribute to a shift away from one-size-fits-all approaches towards more effective, stratified treatment strategies in schizophrenia.

Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability.

Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals.

SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences.

SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.

Few studies examine the relationship between physical activity, multiple physical fitness domains (cardiorespiratory fitness, strength, speed), and cognition. Our objective was to investigate the association between physical activity and executive function in middle-aged and older adults and examine whether modifiable physical fitness components explain the relationship between physical activity and cognition.

Self-reported moderate-to-vigorous physical activity and objective measures of cardiorespiratory fitness (2-minute walk test), strength (grip strength), speed (4-meter walk test), and executive function were collected from 623 adults within the Human Connectome Project–Aging (ages 36 – 100 years; mean = 59.2 years; 57.8% female). Relative importance metrics, multiple regression, and conditional process analysis were used to examine relationships of age, physical activity, and physical fitness with executive function.

Greater physical fitness was related to better executive function performance (β = 0.28, p < .001). Physical activity was not associated with executive function (β = −0.04, p = .16). There was an indirect relationship between physical activity and executive function through physical fitness (ab = 0.02, 95% CI: 0.004 – 0.04). This association was explained primarily by the indirect association of cardiorespiratory fitness with physical activity and executive function. The indirect association of cardiorespiratory fitness with physical activity and executive function was significant in older study participants (mean (59 years) and + 1 SD (74 years)), but not younger (−1 SD (44 years)), although between-group comparisons were not significant.

These data highlight potential differential associations with cognition when considering physical activity and physical fitness, and the importance of considering multiple domains of physical fitness in relation to physical activity and cognitive performance.

This systematic review and meta-analysis aimed to review existing measures of subjective cognition during menopause and to estimate the correlation between subjective and objective cognition in perimenopausal and postmenopausal women.

Eligible studies reported scores for at least one subjective and objective measure of cognition for perimenopausal or postmenopausal women. EMBASE, Medline, and PsycINFO were searched for eligible studies on November 22nd 2024. The risk of bias in individual studies was evaluated using a modified QUADAS-2 form. The results of the review were summarized in narrative form. Studies that reported correlations between subjective and objective cognition were synthesized using a multilevel meta-analysis.

The sample included 5629 participants over 24 studies, including 295 perimenopausal women, 5086 postmenopausal women, and 248 women across mixed peri- and post-menopausal samples. Twelve measures of subjective cognition were used across studies. Six studies were included in the meta-analysis. A small significant correlation was observed between subjective cognition and objective measures of learning efficiency (r = .12; CI = .02 to .23). Correlations across other cognitive domains were non-significant.

Our findings suggest subjective cognition may be associated with performance on measures of learning efficiency, offering a starting point for further research on menopausal brain fog. The present findings highlight the need for a reliable measure of subjective cognitive symptoms associated with menopause. Additionally, a better characterization of the neuropsychological profile of menopausal brain fog is needed to progress research in this field and ultimately improve clinical support for women experiencing these symptoms.

Healthy sleep contributes to better cognitive functioning in children. This study sought to investigate the role of pre-injury sleep disturbance as a predictor or moderator of cognitive functioning across 6 months post-injury in children with mild traumatic brain injury (mTBI) or orthopedic injury (OI).

Participants were 143 children with mTBI and 74 with OI, aged 8 – 16 years, prospectively recruited from the Emergency Departments of two children’s hospitals in Ohio, USA. Parents rated their children’s pre-injury sleep retrospectively using the Sleep Disorders Inventory for Students. Children completed the National Institutes of Health (NIH) Toolbox Cognition Battery at 10 days and 3 and 6 months post-injury.

Group differences in both overall performance and reaction time on the Flanker Inhibitory Control and Attention Test varied significantly as a function of the level of pre-injury sleep disturbance as well as time since injury. At the 10 day visit, among children with worse pre-injury sleep, mTBI was associated with slower reaction times relative to OI. Among children with worse pre-injury sleep, those with mTBI improved over time while those with OI did not. Main effects of pre-injury sleep and time since injury were found for several other NIH Toolbox subtests, with poorer performance associated with worse pre-injury sleep and early vs. later timepoints.

These results suggest that pre-existing sleep disturbances and mTBI are jointly associated with poorer executive functioning post-injury. Interventions to improve sleep might help mitigate the effects of mTBI on children’s cognitive functioning.

Research indicates that demographic (e.g., age, education) and sociocultural (e.g., acculturation) factors can impact neuropsychological test performance among ethnoculturally diverse adults. Some studies suggest that greater acculturation to the United States (U.S.) is associated with better neurocognitive functioning, though no meta-analysis to date has examined this relationship. This review provides a comprehensive synthesis of the literature and determines the magnitude of the relationship between acculturation and neuropsychological test performance.

A literature search explored all published articles through January 1, 2024, using three databases (i.e., PubMED/MEDLINE, PsycInfo, PsycNET). Data to calculate study effect sizes (i.e., Fisher’s z) were extracted from in-text results, tables, and figures.

Findings (k = 18 included in quantitative analyses) revealed a small to medium (r = 0.29, partial r = 0.20, p < .01), statistically significant relationship between higher U.S. acculturation and better neuropsychological test performance. Moderation analyses indicated that language of testing emerged as a significant moderator, testing in English yielded larger effect sizes compared to testing in other languages (B = 0.29, p < .05).

Neuropsychological test performance is significantly associated with U.S. acculturation, and results suggest that the magnitude may vary depending on study methodologies and samples (e.g., ethnocultural group, U.S. born vs. immigrant) examined. The current review also provides recommendations for incorporating acculturation assessment into clinical practice and highlights the need to examine the clinical utility of acculturation tools in conjunction with neuropsychological tests to assist in clinical decision-making with ethnoculturally diverse populations.

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, but worries about cognitive side effects remain. This retrospective study evaluated cognitive outcomes and the antidepressant efficacy of ECT in a real-life sample of patients with treatment-resistant uni- or bipolar depression.

We included 90 depressed inpatients aged 49 ± 13.8 (SD) years who underwent 10 ± 2.1 (SD) unilateral or bitemporal ECT treatments and completed an extensive pre- and post-treatment psychological test battery. The Hamilton Depression Rating Scale (HAMD) and the Mini-Mental State Examination (MMSE) were evaluated as main outcomes pre-/post-ECT treatment.

There was no significant change in MMSE scores between pre-/post-treatment assessments (β = 0.10, 95% confidence interval [CI] [−0.44, 0.25], p = 0.58), indicating no negative effect on global cognition. A minority of patients (N = 3) experienced a reduction of ≥5 points in the MMSE. Most cognitive tests showed no difference; however, some domains revealed statistically significant improvements (visual learning and motoric reaction time), whereas one domain showed a significant decline (verbal learning). Higher age and higher stimulus doses predicted worse outcomes in some cognitive domains. While ECT significantly reduced depressive symptoms measured by HAMD (β = −5.51, 95% CI [−7.08, −3.94], p < 0.001), depressive symptoms were not associated with cognitive outcomes.

No major cognitive changes were observed. While test results indicated deterioration in verbal learning and improvement in visual learning and motoric reaction time, effect sizes were small, and other cognitive tests showed no significant changes. The main limitation is the absence of retrograde memory assessment.