Cognitive impairment in major depressive disorder (MDD) may be driven by neuro-inflammatory processes involving pro-inflammatory cytokines.

This study aimed to examine the relationship between serum tumour necrosis factor-alpha (TNF-α) levels and cognitive performance across different domains in individuals with MDD.

Sixty patients with MDD and 60 healthy controls were recruited. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum TNF-α levels were measured via flow cytometry.

After adjusting for covariates, RBANS total and subscale scores were significantly lower in MDD patients compared with controls (P < 0.001), while log10-transformed TNF-α levels were significantly higher in the MDD group (P = 0.006). In MDD patients, log10TNF-α levels were inversely correlated with immediate memory scores after adjusting for confounding factors (r = −0.35, P = 0.009); however, this relationship was not observed in healthy controls (r = −0.02, P = 0.90). Stepwise multivariate regression analysis further confirmed the negative association of log10TNF-α with immediate memory scores in MDD patients (β = −14.58, t = −4.14, P < 0.001), but not in healthy controls (β = −0.02, t = −0.14, P = 0.89).

These findings suggest that elevated serum TNF-α may contribute to the pathophysiology of MDD and is specifically associated with deficits in immediate memory.

Prior research indicates that both structural and functional networks are compromised in older adults experiencing depressive symptoms. However, the potential impact of abnormal interactions between brain structure and function remains unclear. This study investigates alterations in structural–functional connectivity coupling (SFC) among older adults with depressive symptoms, and explores how these changes differ depending on the presence of physiological comorbidities.

We used multimodal neuroimaging data (dMRI/rs-fMRI) from 415 older adults with depressive symptoms and 415 age-matched normal controls. Subgroups were established within the depressive group based on the presence of hypertension, hyperlipidemia, diabetes, cerebrovascular disease, and sleep disorders. We examined group and subgroup differences in SFC and tracked its alterations in relation to symptom progression.

Older adults with depressive symptoms showed significantly increased SFC in the ventral attention network compared with normal controls. Moreover, changes in SFC within the subcortical network, especially in the left amygdala, were closely linked to symptom progression. Subgroup analyses further revealed heterogeneity in SFC changes, with certain physiological health factors, such as metabolic diseases and sleep disorders, contributing to distinct neural mechanisms underlying depressive symptoms in this population.

This study identifies alterations in SFC related to depressive symptoms in older adults, primarily within the ventral attention and subcortical networks. Subgroup analyses highlight the heterogeneous SFC changes associated with metabolic diseases and sleep disorders. These findings highlight SFC may serve as potential markers for more personalized interventions, ultimately improving the clinical management of depression in older adults.

Little is known regarding the shared genetic architecture underlying the phenotypic associations between depression and preterm birth (PTB). We aim to investigate the genetic overlap and causality of depression with PTB.

Leveraging summary statistics from the largest genome-wide association studies for broad depression (Ntotal = 807,533), major depression (Ntotal = 173,005), bipolar disorder (Ntotal = 414,466), and PTB (Ntotal = 226,330), we conducted a large-scale genome-wide cross-trait analysis to assess global and local genetic correlations, identify pleiotropic loci, and infer potential causal relationships

Positive genetic correlations were observed between PTB and broad depression (rg = 0.242), major depression (rg = 0.236), and bipolar disorder (rg = 0.133) using the linkage disequilibrium score regression, which were further verified by the genetic covariance analyzer. Local genetic correlation was identified at chromosome 11q22.3 (harbors NCAM1-TTC12-ANKK1-DRD2) for PTB with depression. Cross-trait meta-analysis identified two loci shared between PTB and broad depression, two loci shared with major depression, and five loci shared with bipolar disorder, among which three were novel (rs7813444, rs3132948 and rs9273363). Mendelian randomization demonstrated a significantly increased risk of PTB for genetic liability to broad depression (odds ratio [OR]=1.30; 95% confidence interval [CI]: 1.11-1.52) and major depression (OR=1.27; 95%CI: 1.08-1.49), and the estimates remained significant across the sensitivity analyses.

Our findings demonstrate an intrinsic link underlying depression and PTB and shed novel light on the biological mechanisms, highlighting an important role of early screening and effective intervention of depression in PTB prevention, and may provide novel treatment strategies for both diseases.

Insomnia disorder, characterized by chronic sleep disruption, often co-occurs with maladaptive emotional memory processing. However, much remains unknown regarding the evolution of emotional memories and their neural representations over time among individuals with insomnia disorder.

We examined the electroencephalographic (EEG) activities during emotional memory encoding, post-encoding sleep, and multiple retrieval phases – including immediate post-encoding, post-sleep, and a 7-day delayed retrieval – among 34 participants with insomnia disorder and 35 healthy control participants.

Healthy controls exhibited adaptive dissipation of emotional memory: memory declined over time, accompanied by reduced subjective feelings toward negative memories. In contrast, participants with insomnia exhibited impaired dissipation: they retained both the emotional content and affective tone of the memories, with diminished time-dependent declines in memory and affect. Beyond behavioral performance, only participants with insomnia maintained stable neural representations of emotion over time, a pattern absent in healthy controls. Additionally, during the post-encoding sleep, slow-wave sleep (SWS), and rapid eye movement (REM) sleep durations predicted the adaptive dissipation of emotional memory over time, but only among healthy participants.

These findings highlight abnormalities in emotional memory processing among individuals with insomnia disorder and underscore the important function of SWS and REM sleep in facilitating adaptive emotional memory processing.

Social determinants of health (SDHs) exert a significant influence on various health outcomes and disparities. This study aimed to explore the associations between combined SDHs and mortality, as well as adverse health outcomes among adults with depression.

The research included 48,897 participants with depression from the UK Biobank and 7,771 from the US National Health and Nutrition Examination Survey (NHANES). By calculating combined SDH scores based on 14 SDHs in the UK Biobank and 9 in the US NHANES, participants were categorized into favourable, medium and unfavourable SDH groups through tertiles. Cox regression models were used to evaluate the impact of combined SDHs on mortality (all-cause, cardiovascular disease [CVD] and cancer) in both cohorts, as well as incidences of CVD, cancer and dementia in the UK Biobank.

In the fully adjusted models, compared to the favourable SDH group, the hazard ratios for all-cause mortality were 1.81 (95% CI: 1.60–2.04) in the unfavourable SDH group in the UK Biobank cohort; 1.61 (95% CI: 1.31–1.98) in the medium SDH group and 2.19 (95% CI: 1.78–2.68) in the unfavourable SDH group in the US NHANES cohort. Moreover, higher levels of unfavourable SDHs were associated with increased mortality risk from CVD and cancer. Regarding disease incidence, they were significantly linked to higher incidences of CVD and dementia but not cancer in the UK Biobank.

Combined unfavourable SDHs were associated with elevated risks of mortality and adverse health outcomes among adults with depression, which suggested that assessing the combined impact of SDHs could serve as a key strategy in preventing and managing depression, ultimately helping to reduce the burden of disease.

The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.

To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.

We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.

Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.

Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.