Psychological Medicine[JOURNAL]
Sun
200 papers
Bidirectional associations between irritable bowel syndrome and psychological distress: a longitudinal population-based study.
Yu YJ, Huang YC, Weng TH … +5 more , Huang HY, Lai FC, Lin TC, Yu PC, Chien WC
Psychol Med · 2026 Feb · PMID 41667938 · Full text
BACKGROUND: Irritable bowel syndrome (IBS) commonly co-occurs with psychological distress, including depression and anxiety, but the temporal and bidirectional nature of this relationship remains unclear. Dysregulation o...
BACKGROUND: Irritable bowel syndrome (IBS) commonly co-occurs with psychological distress, including depression and anxiety, but the temporal and bidirectional nature of this relationship remains unclear. Dysregulation of the gut-brain-microbiota axis has been proposed as a shared mechanism. METHODS: We conducted two retrospective, population-based cohort studies using Taiwan's National Health Insurance Research Database (2000-2015). Cohort 1 assessed the risk of incident IBS among patients with newly diagnosed depression or anxiety, while Cohort 2 evaluated the risk of subsequent depression or anxiety among patients with newly diagnosed IBS. Propensity score matching, multivariable Cox regression, and Fine-Gray competing risk models were applied. RESULTS: IBS was associated with increased risks of depression (adjusted hazard ratio [aHR] = 1.55) and anxiety (aHR = 1.68). Conversely, depression and anxiety were associated with higher risks of developing IBS (aHR = 1.45 and 1.51, respectively). Associations were stronger among females and younger adults aged 18-39 years. Sleep disorders (SDs) showed the strongest modifying effect in both directions (sub-distribution HR ≈ 1.60). Results were consistent across sensitivity analyses. CONCLUSIONS: This nationwide longitudinal study demonstrates a robust bidirectional association between IBS and psychological distress, supporting integrated screening and multidisciplinary care approaches targeting gut-brain interactions.
The risk for major depression and bipolar disorder in the offspring of informative parental mating types: a Swedish population-based study.
Kendler K, Sundquist J, Sundquist K … +1 more , Abrahamsson L
Psychol Med · 2026 Feb · PMID 41667937 · Full text
BACKGROUND: Seeking to clarify the parent-offspring transmission of Major Depression (MD) and type I Bipolar Disorder (BD), we examined offspring MD and BD risk in five informative parental pairs: Unaffected x MD, Unaffe...
BACKGROUND: Seeking to clarify the parent-offspring transmission of Major Depression (MD) and type I Bipolar Disorder (BD), we examined offspring MD and BD risk in five informative parental pairs: Unaffected x MD, Unaffected x BD, MDxMD, MDxBD and BDxBD. METHODS: We identified 289,637 individuals born in Sweden 1970-1990, followed through 2018, from parents with MD and/or BD identified from Swedish medical registers. We quantified the MD→MD, BD→BD, MD→BD and BD→MD parent-offspring transmission and explored effects of parental illness on MD→BD conversions. RESULTS: The risk for MD was modestly and similarly increased in offspring of Unaffected x MD (HR=1.64) and Unaffected x BD parents (HR=1.53), higher in MDxMD and MDxBD pairings (HRs=2.39 and 2.47) and slightly lower in BDxBD matings (HR=2.29). By contrast, risk for BD was much higher in Unaffected x BD versus Unaffected x MD matings (HRs = 5.59 vs. 1.70), further elevated modestly in MDxBD matings (HR=6.26) and very high in BDxBD matings (HR=13.61). The rate of offspring MD→BD conversions was substantially increased by parental BD but not parental MD. Offspring BD was equally predicted by paternal and maternal affective illness while offspring MD was more strongly predicted by maternal than paternal affective illness. CONCLUSIONS: Examining risk for MD and BD in offspring of different parental mating types of MD and BD is an informative strategy for further clarifying the cross-generational transmission of these two partially related and partially distinct mood disorders.
Replicated evidence for an accelerated rate of whole-body aging in schizophrenia.
Whitman ET, Passiatore R, Knodt AR … +17 more , Pergola G, Antonucci LA, Bertolino A, Blasi G, D'Ambrosio E, Elliott ML, Kikidis GC, Lella A, Lupo A, Raio A, Rampino A, Sambuco N, Selvaggi P, Weinberger DR, Moffitt TE, Caspi A, Hariri AR
Psychol Med · 2026 Feb · PMID 41656957 · Full text
BACKGROUND: People with schizophrenia develop more chronic diseases at a younger age and die younger than people in the general population. It has been hypothesized that this excess morbidity and mortality could be parti...
BACKGROUND: People with schizophrenia develop more chronic diseases at a younger age and die younger than people in the general population. It has been hypothesized that this excess morbidity and mortality could be partially due to accelerated aging in schizophrenia. If true, this would motivate the development of 'gero-protective' interventions to reduce chronic disease burden in schizophrenia. However, it has been difficult to test this hypothesis, in part, due to the limited ability to measure aging in samples of people with schizophrenia. METHODS: We utilized a novel neuroimaging biomarker of the longitudinal pace of aging, DunedinPACNI, to test for accelerated whole-body aging in schizophrenia across four neuroimaging datasets (total = 2,096, 48% female) accessed through the Lieber Institute for Brain Development, the University of Bari Aldo Moro, and the North American Prodrome Longitudinal Study - 3. RESULTS: We found consistent evidence of faster DunedinPACNI in schizophrenia compared with controls. In contrast, youth at clinical-high risk for psychosis did not have faster DunedinPACNI compared to controls. Unaffected siblings of patients also did not have faster DunedinPACNI than controls. Faster DunedinPACNI in schizophrenia was not explained by tobacco smoking or antipsychotic medication use. CONCLUSIONS: The results support the hypothesis that schizophrenia is accompanied by accelerated aging. Results were inconsistent with some of the most obvious explanations for accelerated aging in schizophrenia (familial risk, smoking, and iatrogenic medication effects). Research should aim to uncover why people who have schizophrenia age rapidly, as well as the utility of early disease-risk monitoring and anti-aging interventions in schizophrenia.
Co-occurrence of psychotic disorders and borderline personality disorder: a systematic review and meta-analysis.
Jourdan J, Estric C, O'Donoghue B … +2 more , Chanen A, Schandrin A
Psychol Med · 2026 Feb · PMID 41656953 · Full text
BACKGROUND: The co-occurrence of psychotic disorders and borderline personality disorder (BPD) complicates clinical management, with overlapping symptoms exacerbating morbidity and impairing therapeutic outcomes. This sy...
BACKGROUND: The co-occurrence of psychotic disorders and borderline personality disorder (BPD) complicates clinical management, with overlapping symptoms exacerbating morbidity and impairing therapeutic outcomes. This systematic review and meta-analysis aimed to estimate the prevalence of psychotic disorders and BPD co-occurrence, including with first-episode psychosis (FEP) and to describe associated sociodemographic and clinical characteristics. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four databases were systematically searched from inception to June 2025. Eighteen studies met the inclusion criteria. Data extraction and quality appraisal (Effective Public Health Practice Project tool) were conducted independently by two reviewers. Random-effects meta-analyses estimated pooled prevalence rates. RESULTS: The pooled prevalence of BPD in people with psychotic disorders was 22.7% (95% CI: 14.2–34.3%), while 14.3% (95% CI: 5.5–32.1%) of individuals with BPD had a comorbid psychotic disorder. In FEP samples, 40.0% (95% CI: 21.9–61.3%) met the criteria for BPD. People with both conditions, often young women, showed greater emotional dysregulation, suicidality, psychotic symptoms, and social dysfunction. Trauma, dissociation and substance use emerged as frequent vulnerability factors. However, most studies were cross-sectional, with small samples and high heterogeneity ( > 80%), limiting generalizability. CONCLUSION: This co-occurrence constitutes a distinct clinical subgroup with complex needs. Categorical diagnostic approaches may fail to capture the dimensional nature of overlapping affective and psychotic symptoms. Integrative and personalized care pathways, especially in early intervention settings, are warranted. This review was registered in PROSPERO (CRD42024577525).
Antidepressant effect of transcranial pulse stimulation (TPS) targeting neuropsychiatric disorders: a retrospective analysis.
Mitterwallner M, Radjenovic S, Grigoryeva D … +9 more , Bender L, Gaal M, Osou S, Zettl AA, Plischek N, Lachmair P, Herzhauser K, Matt E, Beisteiner R
Psychol Med · 2026 Feb · PMID 41646033 · Full text
BACKGROUND: Depression is a common comorbidity in neuropsychiatric disorders, affecting a significant proportion of patients with neurodegenerative diseases. Traditional antidepressants show limited efficacy, particularl...
BACKGROUND: Depression is a common comorbidity in neuropsychiatric disorders, affecting a significant proportion of patients with neurodegenerative diseases. Traditional antidepressants show limited efficacy, particularly in cases involving comorbid depressive symptoms, highlighting the need for alternative treatments. METHODS: Here we provide the first data on possible benefits of add-on therapy with transcranial pulse stimulation (TPS). Based on the largest patient sample in the emerging field of focused ultrasound (FUS) neuromodulation to date, a retrospective analysis was conducted on 88 patients with various neuropsychiatric diagnoses to evaluate the impact of TPS on depressive symptoms, measured by the Beck Depression Inventory (BDI-II). RESULTS: The study revealed significant improvements in BDI-II scores posttreatment ( = 88), with the most substantial effects observed in more severely impacted patients: individuals with minimal to severe depression (BDI-II ≥9; = 32) experienced an average reduction of 5.22 points (29.46%), while those with mild to severe depression (BDI-II ≥14; = 15) showed an even greater mean improvement of 10.40 points (40.51%). These results surpassed established thresholds for clinical relevance and substantially exceeded placebo effect sizes observed in relevant brain stimulation studies. Moreover, depression score improvement was independent of diagnostic group (dementia, movement disorders, or other), improvement of the primary diagnosis, antidepressant medication, and baseline cognitive status, highlighting the potential of TPS as an effective therapeutic add-on intervention for patients receiving state-of-the-art treatments. CONCLUSIONS: The study's findings indicate that TPS enhances depression outcomes in neuropsychiatric patients, particularly in those with more severe depressive symptoms.
Impulsivity-related predictors of adolescent substance use initiation.
Gilman J, Potter K, Kaur J … +7 more , Lee P, Schuster R, Bjork J, Weigard A, Evins AE, Roffman J, Tervo-Clemmens B
Psychol Med · 2026 Feb · PMID 41646030 · Full text
BACKGROUND: Neurodevelopmental models regard impulsivity as a central risk factor for adolescent substance use. However, the practical utility of impulsivity in predicting substance use is complicated by variability amon...
BACKGROUND: Neurodevelopmental models regard impulsivity as a central risk factor for adolescent substance use. However, the practical utility of impulsivity in predicting substance use is complicated by variability among measures that encompass multiple methods and theoretical domains. Prior research has been constrained by cross-sectional designs, small sample sizes, and/or the use of a narrow subset of impulsivity measures. METHOD: Leveraging the ABCD dataset ( = 11,868), we identified and replicated correlations among impulsivity measures and assessed their prospective longitudinal and concurrent predictive utility regarding adolescent substance use outcomes before 15 years old. We then used simulation to inform how associations between impulsivity and substance use vary across sampling strategies (population vs. high-risk cohorts) and sample sizes. FINDINGS: Correlations between questionnaire and behavioral measures of impulsivity were small, and questionnaires significantly outperformed behavioral measures in predicting substance use initiation, largely due to the contribution of the CBCL externalizing scale. Predictions of substance use based on impulsivity were statistically detectable but small according to clinical standards (AUCs 0.6-0.76), exhibiting sensitivity to sample size and base rate of substance use, and thus, poor absolute predictive performance. Large samples ( > 1,000) were needed to achieve adequate power for impulsivity measures to predict substance use initiation. CONCLUSION: These results support a significant but small contribution of impulsivity in predicting the onset of early adolescent substance use, indicating that these factors alone are insufficient for clinically deployable prediction. In community samples, large sample sizes are needed for reproducible impulsivity prediction of adolescent substance use.
Mindfulness and psychotic-like experiences in nonclinical populations: a systematic review and two meta-analyses.
Mysko K, Gear EQ, Ellett L
Psychol Med · 2026 Feb · PMID 41634965 · Full text
This systematic review and meta-analyses provide the first synthesis of the literature on trait mindfulness and psychotic-like experiences (PLEs). Theoretical models suggest a protective function of mindfulness and it is...
This systematic review and meta-analyses provide the first synthesis of the literature on trait mindfulness and psychotic-like experiences (PLEs). Theoretical models suggest a protective function of mindfulness and it is important to understand any potential role of mindfulness in the prevention and treatment of PLEs. We examined the following: (1) What is the relationship between trait mindfulness and PLEs in nonclinical populations?; and (2) What is the effect of mindfulness-based interventions (MBIs) on PLEs in nonclinical populations? Five databases were searched, and effect sizes were extracted for each study. Seventeen papers were included in the review. Eleven papers explored the relationship between mindfulness and PLEs, and the meta-regression found a small negative association between PLEs and mindfulness ( = 8; pooled correlation = -0.25; 95% confidence interval [CI]: -0.37, -0.13, < .001). Eight studies investigated the effect of MBIs on PLEs and the summary effect was not significant in the meta-analysis ( = 5; pooled standard mean difference = .09; 95% CI: -0.61, 0.79, = 0.80). Overall, the findings suggest that higher levels of mindfulness are associated with reduced PLEs, with no evidence for the effectiveness of MBIs in reducing PLEs. Findings should be interpreted cautiously given the small number of studies and high heterogeneity in the meta-analyses. Future studies are needed to determine whether MBIs might prevent the transition to psychosis or an at-risk mental state and might usefully measure a broader range of clinically relevant outcomes.
Placebo and Nocebo Phenomena in Schizophrenia Spectrum Disorders: A Narrative Review on Current Knowledge and Potential Future Directions - CORRIGENDUM.
Pujji SD, Colloca L, Waltz JA
Psychol Med · 2026 Feb · PMID 41623108 · Full text
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Cognitive reserve and effects of air pollution mixture on cognitive function in dementia-free adults.
Ko J, Noh Y, Koh SB … +5 more , Lee SK, Kim SY, Tran-Thi HN, Cho J, Kim C
Psychol Med · 2026 Feb · PMID 41622871 · Full text
BACKGROUND: Extensive evidence links air pollution exposure to cognitive decline; however, it remains unclear whether cognitive reserve and brain reserve modify this association. We examined the moderating roles of cogni...
BACKGROUND: Extensive evidence links air pollution exposure to cognitive decline; however, it remains unclear whether cognitive reserve and brain reserve modify this association. We examined the moderating roles of cognitive reserve contributors and brain reserve in the association between air pollution and cognitive function in dementia-free adults. METHODS: Cross-sectional data were obtained from 650 participants who underwent 3T brain magnetic resonance imaging and completed the Montreal Cognitive Assessment (MoCA). Cognitive reserve contributors were assessed based on education, occupation, and social engagement. Brain reserve was quantified using the ventricle-to-brain ratio derived from brain scans. Five-year average concentrations of particulate matter with diameters ≤10 and ≤2.5 μm and nitrogen dioxide were estimated based on residential addresses. Partial least squares structural equation modeling was applied to construct latent variables representing the air pollution mixture and composite cognitive reserve (contributors). Analyses examined whether cognitive reserve contributors and brain reserve modified associations of air pollution with MoCA scores and suspected mild cognitive impairment. RESULTS: In individuals with an average level of cognitive reserve, a 1-standard deviation increase in air pollution mixture was associated with a 0.24-point decrease in MoCA scores (95% confidence interval [CI]: -0.31 to -0.16). This association was attenuated in individuals with higher cognitive reserve ( = -0.12; 95% CI: -0.25 to 0.02) and intensified in those with lower cognitive reserve ( = -0.36; 95% CI: -0.37 to -0.35). The moderating effect of brain reserve was not significant. CONCLUSIONS: Higher cognitive reserve may mitigate the effects of air pollution on cognitive function.
Education shares distinct genetic influences with substance use and disorder.
Davis CN, Khan Y, Piserchia Z … +2 more , Gray JC, Kranzler HR
Psychol Med · 2026 Feb · PMID 41622852 · Full text
BACKGROUND: Educational attainment (EA), which comprises cognitive (CogEA) and noncognitive (NonCogEA) components, is positively genetically correlated with alcohol and cannabis use but negatively correlated with alcohol...
BACKGROUND: Educational attainment (EA), which comprises cognitive (CogEA) and noncognitive (NonCogEA) components, is positively genetically correlated with alcohol and cannabis use but negatively correlated with alcohol and cannabis use disorders (AUD and CUD). These paradoxical associations suggest that shared genetic influences with EA may differ by level of substance involvement. METHODS: To test this, we examined the shared genetic architecture of EA, CogEA, and NonCogEA with alcohol consumption (AC), AUD, lifetime cannabis use (CanUse), and CUD. We used bivariate causal mixture models, local genetic correlation analyses, and conditional/conjunctional false discovery rate analyses to identify global, regional, and variant-level overlap for EA and substance-related trait pairs. RESULTS: EA shared 57.57% of causal variants with AC and 62.42% with AUD, while sharing 48.07% of causal variants with CanUse and 84.18% with CUD. Among shared variants for AC, 48.12% had concordant effects with CogEA and 52.86% with NonCogEA. For AUD, 38.40% and 41.02% of causal variants had concordant effects with CogEA and NonCogEA, respectively. CanUse had higher concordance with CogEA (71.42%) and NonCogEA (65.56%) than CUD (37.97% and 42.23%, respectively). Functional enrichment in brain tissues varied across substance use and EA pairs. CONCLUSIONS: EA is associated with greater alcohol and cannabis use and lower risk for AUD and CUD, a pattern that reflects both concordant and discordant variant effects. CogEA and NonCogEA show partially distinct patterns, particularly for cannabis-related traits, highlighting the importance of disaggregating EA to clarify the genetic architecture underlying its paradoxical associations with substance-related traits.
A stage-specific cascade of neural dysfunction emotional conflict processing in major depressive disorder.
Li D, Li D, Liu R … +6 more , Zang Z, Liu K, Feng Y, Zhou J, Yang Z, Wang G
Psychol Med · 2026 Feb · PMID 41622849 · Full text
BACKGROUND: Persistent affective disturbance is a core, disabling feature of major depressive disorder (MDD), thought to stem from a dysfunctional interaction between emotional bias and cognitive control. However, the un...
BACKGROUND: Persistent affective disturbance is a core, disabling feature of major depressive disorder (MDD), thought to stem from a dysfunctional interaction between emotional bias and cognitive control. However, the underlying neural dynamics are debated, with studies reporting both hyper- and hypoactivation. This study utilized high-temporal-resolution electroencephalogram (EEG) to resolve this discrepancy by examining distinct stages of emotional information processing. METHODS: We recruited 175 medication-free patients with MDD (Hamilton Depression Rating Scale-17 ≥ 14) and 101 healthy controls (HCs) who completed an emotional Stroop task while an EEG was recorded. We analyzed event-related potentials reflecting conflict monitoring (N250), inhibition (N450), and resolution (LSP) using a 2 (group) × 2 (valence) × 2 (congruency) analysis of variance. RESULTS: Results revealed a stage-specific neural cascade. Compared to HCs, the MDD group showed: (1) hypoactivation during initial conflict monitoring (attenuated N250 amplitude); (2) compensatory hyperactivation during conflict inhibition (a significant N450 interaction revealed generalized conflict activity in MDD, unlike the context-specific response in HCs); and (3) subsequent hypoactivation during conflict resolution (reduced LSP amplitude for negative stimuli). Crucially, altered N450 correlated with depression severity, and the entire neural cascade predicted behavioral performance. CONCLUSIONS: The apparent contradiction in the literature reflects a multistage process. MDD is characterized by an inefficient neural cascade: an initial deficit in conflict monitoring is followed by compensatory overactivation during inhibition, which ultimately proves insufficient, leading to impaired late-stage resolution. This temporally specific model advances our understanding of the pathophysiology of depression and identifies potential stage-specific targets for intervention.
The role of altered decision dynamics and dorsolateral prefrontal cortex to amygdala causal circuitry in the aberrant efficacy of emotion suppression in subthreshold depression.
Niu L, Toulopoulou T, Song X … +9 more , Li Q, Dai H, Chen K, Zhang J, Chen X, Chen Z, Wang X, Zhang D, Zhang R
Psychol Med · 2026 Jan · PMID 41612649 · Full text
BACKGROUND: Individuals with subthreshold depression (StD), a potentially preclinical stage of major depression, may habitually employ maladaptive expression suppression strategies in emotion regulation. However, the eff...
BACKGROUND: Individuals with subthreshold depression (StD), a potentially preclinical stage of major depression, may habitually employ maladaptive expression suppression strategies in emotion regulation. However, the effect of emotional suppression (EES) and underlying neural mechanisms remain unclear. METHODS: Data came from two samples (Sample 1: 55 StD, 60 healthy controls (HC); Sample 2: 23 StD, 20 HC). Both samples completed expression suppression tasks. Using drift diffusion modeling, we decomposed performance on the emotional assessment process into separate processing components, particularly the speed of information update (drift rate), to examine how depression and emotional suppression affect decision-making. To further reveal the potential mechanism, we conducted fMRI scanning in Sample 2 and characterized latent neurocircuit driving emotion suppression and drift rate using dynamic causal modeling (DCM). RESULTS: The EES negatively correlated with drift rate. StD showed reduced efficacy of EES and faster drift rates of negative preference. Greater activation was observed in the dorsolateral prefrontal cortex (dlPFC) and amygdala in StD during suppression. DCM analysis revealed that inefficient EES might be explained by the stronger connection from the right dlPFC to the right amygdala, while the faster drift rate might be attributed to a stronger connection from the left amygdala to the right dlPFC. CONCLUSIONS: Our study uncovered novel latent behavioral and neurocircuit mechanisms of early risk for depression. Ineffective emotional suppression in StD is associated with faster accumulation of negative evidence. The underlying neural mechanism may involve aberrant regulation between the dlPFC and amygdala in negative contexts.
Genome-wide investigation highlights global and local pleiotropy linking neurodevelopmental disorders to acquired hearing problems.
Zhang Q, Cabrera-Mendoza B, Chen Q … +4 more , Davtian D, Qiu D, He J, Polimanti R
Psychol Med · 2026 Jan · PMID 41593863 · Full text
BACKGROUND: Neurodevelopmental disorders have been associated with hearing problems (HP) later in life, but there is limited information regarding their shared biology. METHODS: We leveraged large-scale genome-wide datas...
BACKGROUND: Neurodevelopmental disorders have been associated with hearing problems (HP) later in life, but there is limited information regarding their shared biology. METHODS: We leveraged large-scale genome-wide datasets to estimate genetic correlation (global and local), polygenic overlap, and locus-specific pleiotropy among HP, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Tourette syndrome (TS). Then, we investigated shared molecular functions, biological processes, and cellular components, and performed a drug-repurposing analysis to identify compounds that may target the pathogenic processes linking neurodevelopmental disorders to HP. RESULTS: We observed high genetic correlation of HP with ASD (rg = 0.22) and TS (rg = 0.22). With respect to HP-ADHD polygenic overlap, 34% of the causal variants were shared between these conditions, with only 74% of them showing concordant effect directions. We also identified nine chromosomal regions with evidence of ADHD-HP local genetic correlations with pleiotropic effects on other outcomes, such as smoking initiation, brain-imaging phenotypes, and bilirubin levels. With respect to HP-ASD, we observed an inverse local genetic correlation within chromosomal region. Pleiotropy among HP, ASD, and ADHD was also identified in two variants (rs325485 and rs2207286) included within 95% credible sets related to neuropsychiatric conditions, altered hearing function, and other traits such as risk taking and insomnia. Drug-repurposing analyses identified anisomycin for HP-ASD shared biological mechanisms and five compounds related to HP-ADHD pleiotropy. CONCLUSIONS: Our findings provide evidence that the comorbidity between neurodevelopmental disorders and HP is at least partially due to shared pathogenic processes acting through intrinsic and extrinsic factors.
Efficacy of cognitive behavioral therapy in treating repetitive negative thinking, rumination, and worry - a transdiagnostic meta-analysis - CORRIGENDUM.
Stenzel KL, Keller J, Kirchner L … +2 more , Rief W, Berg M
Psychol Med · 2026 Jan · PMID 41592808 · Full text
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Emotional and cognitive effects of menopause and hormone replacement therapy.
Zuhlsdorff K, Langley C, Bethlehem R … +3 more , Warrier V, Romero Garcia R, Sahakian BJ
Psychol Med · 2026 Jan · PMID 41587742 · Full text
BACKGROUND: Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms....
BACKGROUND: Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This study aims to investigate the impact of menopause and HRT on mental health, cognitive function, and brain structure. METHODS: We analyzed data from nearly 125,000 participants in the UK Biobank to assess associations between menopause, HRT use, and outcomes related to mental health, cognition, and brain morphology. Specifically, we focused on gray matter volumes in the medial temporal lobe (MTL) and anterior cingulate cortex (ACC). RESULTS: Menopause was associated with increased levels of anxiety, depression, and sleep difficulties. Women using HRT reported greater mental health challenges than post-menopausal women not using HRT. Post-hoc analyses revealed that women prescribed HRT had higher levels of pre-existing mental health symptoms. In terms of brain structure, MTL and ACC volumes were smaller in post-menopausal women compared to pre-menopausal women, with the lowest volumes observed in the HRT group. CONCLUSIONS: Our findings suggest that menopause is linked to adverse mental health outcomes and reductions in gray matter volume in key brain regions. The use of HRT does not appear to mitigate these effects and may be associated with more pronounced mental health challenges, potentially due to underlying baseline differences. These results have important implications for understanding the neurobiological effects of HRT and highlighting the unmet need for addressing mental health problems during menopause.
The causal interplay between depression and alcohol use from adolescence to young adulthood: a Mendelian randomization study.
Wang X, Xiang S, Kang J … +28 more , Zhai R, Zheng C, Banaschewski T, Bokde ALW, Brühl R, Desrivières S, Flor H, Garavan H, Gowland P, Grigis A, Heinz A, Martinot JL, Martinot MP, Artiges E, Nees F, Orfanos DP, Paus T, Poustka L, Smolka MN, Hohmann S, Holz N, Vaidya N, Walter H, Whelan R, Schumann G, IMAGEN Consortium, Jia T, Feng J
Psychol Med · 2026 Jan · PMID 41587741 · Full text
BACKGROUND: Depression is often comorbid with alcohol use problems, and sex differences may further complicate this interplay. METHODS: We conducted a longitudinal study using a large European adolescent cohort assessed...
BACKGROUND: Depression is often comorbid with alcohol use problems, and sex differences may further complicate this interplay. METHODS: We conducted a longitudinal study using a large European adolescent cohort assessed at ages 14 (baseline, BL), 16 (follow-up 1, FU1), 19 (follow-up 2, FU2), and 23 (follow-up 3, FU3). Depression and alcohol use were measured using standardized behavioral scales. Cross-lagged analysis, improved Mendelian randomization (MR) analysis, and mediation analysis were conducted to infer the causal interplay. RESULTS: 2110 adolescents were included at baseline (49% male). Depression and alcohol consumption demonstrated a significant positive correlation ( = 0.094, = 1.58E-05, 95% CI = [0.052, 0.137]), which gradually diminished over time and eventually became significantly negative. Depression and alcohol use problems remained strongly correlated across three timepoints ( > 0.074, < 6.76E-03). Cross-lagged analysis suggested that depression predicted future alcohol use problems: = 0.058, = 0.021, 95% CI = [0.009, 0.108]; = 0.142, = 8.34E-07, 95% CI = [0.113, 0.263]. MR analyses confirmed this causal interplay ( = 0.043, longitudinal < 0.001). Interestingly, MR analyses also indicated that alcohol consumption might alleviate depression ( = -0.022, longitudinal = 0.043), particularly in females at FU3, of which the anxiety status and the personality trait neuroticism largely mediated the effect. These findings were validated in an independent matched sample (N = 562) from Human Connectome Project. CONCLUSIONS: Depression may predict future alcohol use problems, whereas moderate alcohol consumption might alleviate depressive symptoms, especially in females.
Network dynamics of depression, anxiety, sleep disturbances, and suicidal symptoms in Chinese adolescents: a longitudinal cross-sectional and cross-lagged panel network analysis.
Sun B, Zhang J, Ma Y … +1 more , He H
Psychol Med · 2026 Jan · PMID 41572826 · Full text
BACKGROUND: Depression in adolescents involves complex interactions among depression, anxiety, sleep disturbances, and suicidal symptoms. Network theory offers insights into dynamic symptom relationships during recovery....
BACKGROUND: Depression in adolescents involves complex interactions among depression, anxiety, sleep disturbances, and suicidal symptoms. Network theory offers insights into dynamic symptom relationships during recovery. METHODS: Of 797 adolescents initially enrolled, 649 with complete baseline data were included in the network analyses; 458 and 277 participants were retained at the 1-month and 3-month follow-ups, respectively. Cross-sectional Gaussian Graphical Models and Cross-Lagged Panel Network (CLPN) analyses examined relationships among nine symptom domains: depression, somatic/subjective anxiety, sleep quantity/quality, daytime insomnia, passive/active sleepiness, and suicidal ideation/tendency. Network centrality and bootstrap validation assessed parameter stability. RESULTS: Cross-sectional networks showed structural invariance across timepoints (p>0.05). Subjective anxiety demonstrated highest centrality at T0-T1, while somatic symptoms dominated at T2. Depression maintained high closeness centrality throughout. Although betweenness centrality also suggested a central role for depression, its lower stability (CS < 0.5) necessitates a more cautious interpretation of this specific metric. CLPN revealed more predictive relationships during T0→T1 (76.5% significant edges) than T1→T2 (24.7%). Active sleepiness strongly predicted subsequent somatic anxiety (B=0.683) and depression (B=0.647). Suicide ideation-tendency showed stable bidirectional connections. Network stability was excellent (CS>0.5) except betweenness centrality. CONCLUSIONS: Central symptoms evolved during recovery, with subjective anxiety initially dominant but somatic symptoms becoming central over time. The early post-treatment period showed heightened symptom network activity, with sleep disturbances identified as robust predictors of subsequent affective deterioration. Findings support dynamic, network-informed interventions targeting evolving symptom centrality and predictive pathways, particularly addressing sleep-related symptoms and suicide risk during critical recovery phases.
Using large biobanks for psychiatric genomic research: Consistency of clinical and genetic aspects of recorded depression across US states in the All of Us Research Program.
Keyes KM, Gimbrone C, Rutherford C … +6 more , Zhang Y, Choi K, Smith L, Greenland P, Smoller JW, Argos M
Psychol Med · 2026 Jan · PMID 41572452 · Full text
BACKGROUND: Large biobanks offer unprecedented data for psychiatric genomic research, but concerns exist about representativeness and generalizability. This study examined depression prevalence and polygenic risk score (...
BACKGROUND: Large biobanks offer unprecedented data for psychiatric genomic research, but concerns exist about representativeness and generalizability. This study examined depression prevalence and polygenic risk score (PRS) associations in the data to assess potential impacts of nonrepresentative sampling. METHODS: Depression prevalence and correlates were analyzed in two subsamples: those with self-reported personal medical history (PMH) data (N = 185,232 overall; N = 114,739 with genetic data) and those with electronic health record (EHR) data (N = 287,015 overall; N = 206,175 with genetic data). PRS weights were estimated across ancestry groups. Associations of PRS with depression were examined by state and ancestry. RESULTS: Depression prevalence varied across states in both PMH (16.7-35.9%) and EHR (0.2-45.8%) data. Concordance between PMH and EHR diagnoses was low (kappa: 0.29, 95% CI: 0.30-0.30). Overall, one standard deviation increase in depression PRS was associated with lifetime depression based on PMH (odds ratio [OR] = 1.05, 95% confidence interval [CI]: 1.04-1.07) and EHR (OR = 1.05, 95% CI: 1.04-1.07). Results were generally consistent by ancestry, with the strongest signal for European ancestry (PMH: OR = 1.10, 95% CI: 1.08-1.12; EHR: OR = 1.07, 95% CI: 1.05-1.10). Associations between PRS and lifetime depression were largely consistent and significant associations varied minimally (ORs = 1.06-1.45) by state of residence in both subsamples. CONCLUSIONS: Recorded depression prevalence by state in demonstrates a wide range, likely reflecting recruitment differences, EHR data completeness, and true geographic variation; yet PRS associations remained relatively stable. As studies like expand, accounting for sample composition and measurement approaches will be crucial for generating actionable findings.
Plasma phosphorylated tau 217 and neurofilament light chain on the association between depressive symptoms and cognitive decline: The Shanghai Aging Study.
Xia W, Xu C, Xiao Z … +4 more , Zhou X, Zhao Q, Ding D, Deng W
Psychol Med · 2026 Jan · PMID 41556110 · Full text
BACKGROUND: Depressive symptoms are closely associated with cognitive decline and risk of incident dementia, and plasma biomarkers may play a significant role in this relationship. We aimed to investigate the influence o...
BACKGROUND: Depressive symptoms are closely associated with cognitive decline and risk of incident dementia, and plasma biomarkers may play a significant role in this relationship. We aimed to investigate the influence of plasma biomarkers and explore the underlying mechanisms. METHODS: This study included 1,658 dementia-free community residents recruited in 2009-2011 from the Shanghai Aging Study. At baseline, we assayed plasma phosphorylated tau 217 (p-tau217) and neurofilament light chain (NfL), and assessed depressive symptoms using the Center for Epidemiologic Studies Depression scale. Cox regression models were performed to estimate the risks of incident dementia and Alzheimer's disease (AD) during the 5-year follow-up. Parallel and serial mediation models were applied to investigate whether plasma p-tau217 and NfL mediated the relationship between depressive symptoms and cognitive decline. RESULTS: Older adults with depressive symptoms had higher risks of dementia and AD, especially among those with higher concentrations of baseline plasma p-tau217/NfL. Sex-specific analysis revealed that depressive symptoms combined with high plasma NfL increased AD risk in men (hazard ratio, HR [95% confidence interval, CI] = 5.89 [2.01, 17.27], = 0.001), whereas women with depressive symptoms and high plasma p-tau217 showed higher AD risk (HR [95%CI] = 6.07 [2.82, 13.09], < 0.001). Parallel mediation analysis revealed that plasma p-tau217/NfL mediated the relationship between depressive symptoms and cognitive decline, respectively. Additionally, serial mediation analysis found p-tau217 precedes NfL within the mediating pathway ( = 0.403, bootstrap 95% CI: 0.347, 0.452). CONCLUSIONS: Plasma p-tau217 and NfL could individually or jointly mediate the relationship between depressive symptoms and cognitive decline.
Autonomous conversational agents for loneliness, social isolation, depression, and anxiety in older people without cognitive impairment: Systematic review and meta-analysis.
Satake Y, Costello H, Naran N … +3 more , Ishimaru D, Ikeda M, Howard R
Psychol Med · 2026 Jan · PMID 41556104 · Full text
Loneliness is a major psychological challenge in older adulthood, contributing to increased risks of depression, anxiety, and mortality. Conversational agents - technologies that interact with users via natural language...
Loneliness is a major psychological challenge in older adulthood, contributing to increased risks of depression, anxiety, and mortality. Conversational agents - technologies that interact with users via natural language - have emerged as potential tools to support psychological well-being in later life. This systematic review and meta-analysis evaluated the effects of autonomous conversational agents, including robotic and nonrobotic systems, on loneliness, as well as social isolation, depression, and anxiety in older people without cognitive impairment. Seventeen studies with pre-post intervention data were included. Nine used physically embodied robots and eight employed nonrobotic agents, such as personal voice assistants, chatbots, or screen-based embodied agents. Due to the limited number of high-quality comparison studies, all meta-analyses were based on within-group pre-post comparisons. Meta-analytic results showed mild to moderate improvements in loneliness (standardized mean changes using change score [SMCC] = 0.350, 95% confidence interval [CI]: 0.180-0.520) and depression (SMCC = 0.464, 95% CI: 0.327-0.602), with no study reporting symptom worsening. No study included validated measures of social isolation, and only one assessed anxiety. These findings indicate that conversational agents may offer scalable support for older adults' mental health, with potential especially for reducing loneliness and depression. Nonetheless, methodological limitations, including lack of blinded outcome assessment, inconsistent reporting, and heterogeneous intervention designs, underscore the need for more rigorous research. Advances in large language models may further enhance the responsiveness and relevance of these technologies for supporting psychological well-being in aging populations.
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