Psychological Medicine[JOURNAL]
Sun
200 papers
Network diffusion modeling predicts spatiotemporal gray matter alterations in internet gaming disorder.
Cui S, Wang M, Xu X … +6 more , Wei M, Luo X, Li X, Huang Z, Huang O, Dong GH
Psychol Med · 2026 May · PMID 42130282 · Full text
BACKGROUND: Recent research indicates that neuropathological alterations may propagate via brain networks, as illustrated by network diffusion models (NDMs). The application of NDM to internet gaming disorder (IGD) has y...
BACKGROUND: Recent research indicates that neuropathological alterations may propagate via brain networks, as illustrated by network diffusion models (NDMs). The application of NDM to internet gaming disorder (IGD) has yet to be evaluated. This study was set to identify possible epicenters of neuroanatomical alterations using NDM in IGD. METHODS: Structural magnetic resonance imaging (MRI) data were obtained from 288 IGD participants and 165 matched recreational game users. Gray matter volume (GMV) was computed through CAT12 and segmented according to the Brainnetome Atlas. NMD was utilized to simulate the propagation of pathology. We initiated diffusion from each location to pinpoint probable epicenters of GMV alterations in IGD and correlated eigenmodes of the Laplacian matrix with observed atrophy and expansion patterns. RESULTS: Abnormal brain regions with altered GMV were observed in IGD. Specifically, IGD demonstrated a great loss in GMV in the caudal cuneus gyrus, precentral and postcentral gyrus, as well as the cingulate cortex while simultaneously exhibiting an increase in the amygdala. The pallidus and putamen showed positive correlations with gaming craving. Both the right cingulate gyrus and the left amygdala were identified by the model as significant epicenters of disease dissemination. CONCLUSIONS: The results suggest that gray matter morphological abnormalities can predict temporal sequencing of pathology progression in IGD. Subcortical gray matter volume increases in reward-processing-related regions were positively correlated with gaming craving severity in IGD, consistent with altered reward processing and motivational drive in addiction models.
The longitudinal trajectories of mental health outcomes in healthcare workers in England during the COVID-19 pandemic.
Penfold C, Almeida-Meza P, Redaniel T … +15 more , Scott LJ, Moran P, Raine R, Bhundia R, Greenberg N, Wessely S, Croak B, Morriss R, Madan I, Aitken P, Rafferty AM, Dorrington S, Murphy D, Stevelink SAM, Lamb D
Psychol Med · 2026 May · PMID 42130277 · Full text
BACKGROUND: The COVID-19 pandemic raised concerns about the mental health of an already burdened healthcare workforce. This study examined mental health trajectories among healthcare workers (HCWs) across the pandemic an...
BACKGROUND: The COVID-19 pandemic raised concerns about the mental health of an already burdened healthcare workforce. This study examined mental health trajectories among healthcare workers (HCWs) across the pandemic and identified personal and employment factors associated with different symptom patterns. METHODS: Longitudinal data were drawn from the NHS CHECK cohort, including clinical and non-clinical staff from 18 NHS Trusts in England (April 2020-April 2023). Growth curve and growth mixture models identified latent classes of HCWs characterized by distinct trajectories of probable common mental disorders. Secondary outcomes included anxiety, depression, alcohol misuse, and post-traumatic stress symptoms. Logistic regression examined associations between baseline personal and employment characteristics and class membership. RESULTS: The analytical sample included 22,764 participants. For each outcome, growth mixture models identified two latent classes. Approximately 31% of HCWs experienced persistently high symptoms of probable common mental disorders, while 69% experienced persistently low symptoms. Similar patterns were observed for secondary outcomes, with small subgroups demonstrating worsening symptoms followed by improvement. Logistic regression analyses showed that being female, younger, single, working as a nurse, or having a pre-existing mental health diagnosis increased the odds of belonging to a high symptom class. Perceived support from colleagues and managers was protective. CONCLUSIONS: While many HCWs reported consistently low mental health symptom levels, almost a third belonged to a latent class characterized by persistently high symptoms across all time points. These findings underscore the need for mental health support for vulnerable HCW groups, embedded within routine NHS practice rather than limited to crisis periods.
Smartphone CBT engagement and depressive symptoms: secondary analysis of the RESiLIENT trial using a time-varying exposure approach.
Luo Y, Inoue K, Tajika A … +6 more , Toyomoto R, Sakata M, Akechi T, Horikoshi M, Noma H, Furukawa TA
Psychol Med · 2026 May · PMID 42124392 · Full text
BACKGROUND: Smartphone-based cognitive behavioral therapy (CBT) programs offer accessible interventions for subthreshold depression, yet engagement needed for meaningful benefit remains unclear. We examined how lesson an...
BACKGROUND: Smartphone-based cognitive behavioral therapy (CBT) programs offer accessible interventions for subthreshold depression, yet engagement needed for meaningful benefit remains unclear. We examined how lesson and worksheet engagement relate to depressive symptom improvements in a behavioral activation (BA) intervention, accounting for time-varying confounders. METHODS: This secondary analysis included 298 adults assigned to the BA arm of the RESiLIENT trial, a randomized controlled trial in Japan. Lesson and worksheet completion were treated as time-varying exposures, each yielding four engagement patterns: , , , and Outcomes were depressive symptom changes measured by the Patient Health Questionnaire-9 (PHQ-9) at weeks 6 and 26. We applied the parametric g-formula to estimate counterfactual PHQ-9 changes under each pattern, adjusting for baseline and time-varying confounders. RESULTS: Early lesson engagement during weeks 0-3 was associated with larger PHQ-9 reductions at both weeks 6 and 26, even when later engagement declined ( vs. : week 6: -1.47 [95% CI -2.52 to -0.53]; week 26: -1.27 [-2.53 to -0.17]). In contrast, higher worksheet engagement was linked to improved PHQ-9 at week 6, with maximal benefit among consistently high engagers ( vs. : -1.25 [-2.17 to -0.44]) and late engagers ( vs. : -1.18 [-2.20 to -0.08]), but not persist to week 26. CONCLUSIONS: Greater engagement with smartphone-delivered BA is associated with larger symptom reductions. Early lesson engagement drives sustained benefit, whereas worksheet engagement did not persist. These findings may guide digital CBT design by emphasizing early lesson completion alongside concurrent skill practice.
Multimodal fusion of brain imaging and proteomics reveals a brain-body pathway linking depression and metabolic dysfunction.
Lian Z, Liu Z, Fan H … +14 more , Wang J, Zhang K, Liu Y, Kuang N, Yu G, Cheng W, Becker B, Sahakian BJ, Robbins TW, Calhoun VD, Sui J, Wu X, Zhang J, Feng J
Psychol Med · 2026 May · PMID 42124391 · Full text
BACKGROUND: Depression is associated with pathological dysregulations affecting both the brain and the body, with the latter being reflected in plasma proteins. While plasma protein signatures of depression have been inc...
BACKGROUND: Depression is associated with pathological dysregulations affecting both the brain and the body, with the latter being reflected in plasma proteins. While plasma protein signatures of depression have been increasingly recognized, a holistic examination of interactions with brain features is lacking. METHODS: Leveraging data from 3,966 UK Biobank participants, we identified a multimodal neuroimaging-plasma protein component of depression (NeuroPro-Dep) by integrating plasma proteins and five brain modalities via an ICD-10 diagnosis-constrained multimodal fusion approach. RESULTS: Notably, NeuroPro-Dep demonstrates detectable associations with depression symptoms across datasets from diverse populations, underscoring its clinical potential. This capability is anchored in its five brain modalities alterations, including hippocampal atrophy, reduced cortical sensorimotor network functional connectivity, and impaired internetwork structural connectivity of the frontoparietal network. The multimodal neuroimaging-derived plasma protein modality of NeuroPro-Dep is enriched in metabolic pathways, as further supported by association analysis linking this modality to body mass index (BMI), type 2 diabetes, and other metabolic indicators. Crucially, two-step Mendelian randomization analysis revealed that the NeuroPro-Dep plasma protein modality exerts a causal effect on depression through BMI (plasma protein to BMI: or=0.28, p=0.035; BMI to depression: or=1.14, p=4.37×10). CONCLUSIONS: Overall, this study underscores metabolic dysfunction as a bridge between brain changes, depression, and physical diseases, while providing a novel multimodal biological signature and valuable insights that may inform future treatment strategies.
Commonalities in frailty and psychopathology predict chronotype across severe mental disorders from a comorbidity perspective.
Sánchez-Ortí JV, Correa-Ghisays P, Balanzá-Martínez V … +11 more , Selva-Vera G, M Victor V, San Martin Valenzuela C, Soldevila-Matías P, Flores-Rodero M, Sánchez-Valle J, Forés-Martos J, Macías Saint-Gerons D, Fuentes-Durá I, Valencia A, Tabarés-Seisdedos R
Psychol Med · 2026 May · PMID 42116816 · Full text
BACKGROUND: Individuals with severe mental illness (SMI) have increased risk of physical comorbidities, linked to worse outcomes such as greater psychopathology, frailty, and neurocognitive impairment. Mechanisms underly...
BACKGROUND: Individuals with severe mental illness (SMI) have increased risk of physical comorbidities, linked to worse outcomes such as greater psychopathology, frailty, and neurocognitive impairment. Mechanisms underlying this burden remain unclear. This study examined whether frailty and psychopathology predict evening chronotype, especially in SMI with comorbidities. METHODS: A longitudinal study assessed 165 participants at two time points over one year: schizophrenia ( = 30), bipolar disorder ( = 42), major depressive disorder ( = 35), and healthy controls ( = 58). The SMI group ( = 107) was divided into SMI with comorbidities (SMI-C; = 47) and without (SMI; = 60). Measures included psychopathology, frailty, chronotype, neurocognitive and functional performance, and hematological biomarkers. RESULTS: Neurocognitive and functional impairments were greater in SMI groups than controls ( = 10.3-31.4; < 0.0001; η² = 0.12-0.34). The SMI-C group showed worse frailty than controls at T1 ( = 4.3; < 0.01; η² = 0.05) and than SMI at T2 ( = 8.5; < 0.0001; η² = 0.12), and elevated MCV/MCH ( = 3.8-9.4; < 0.05-0.0001; η² = 0.04-0.11). Chronotype distribution did not differ. Frailty and psychopathology predicted chronotype in SMI ( < 0.05-0.01); in controls, frailty and performance did so (p < 0.05). CONCLUSIONS: Psychopathological and hematological profiles are associated with chronotype and may help identify subgroups for chronobiology-informed interventions. These findings support more personalized treatment approaches.
Risk factors associated with blood dyscrasia during clozapine treatment: a systematic review and meta-analysis.
Casetta C, Loane E, Taylor D … +2 more , Emsley R, MacCabe JH
Psychol Med · 2026 May · PMID 42112559 · Full text
Clozapine is the only effective treatment for treatment-resistant schizophrenia, but concerns over blood dyscrasia and need for monitoring limit its use. Evidence suggests many hematological abnormalities may result from...
Clozapine is the only effective treatment for treatment-resistant schizophrenia, but concerns over blood dyscrasia and need for monitoring limit its use. Evidence suggests many hematological abnormalities may result from surveillance bias, with agranulocytosis being the primary adverse effect directly induced by clozapine. This systematic review (PROSPERO: CRD42024487199) investigates non-genetic risk factors associated with blood dyscrasia during clozapine treatment, focusing on neutropenia and agranulocytosis. Random-effect meta-analyses were performed on studies reporting quantitative risk data. Due to inconsistent neutropenia definitions, analyses used absolute neutrophil count (ANC) thresholds of <2000/mm, <1500/mm, and <500/mm. Forty-four studies were included in the systematic review, 15 in meta-analyses. No significant association was found between agranulocytosis and female gender (OR = 1.48, 95% CI: 0.92-2.38; p = 0.106) or age (pooled standardized mean difference [SMD] = 0.32, 95% CI: -0.26 to 0.90, p = 0.285), whilst a modest inverse association with clozapine dose (SMD = -0.32, 95%CI: -0.50 to -0.14, p < 0.001) and baseline white cell count (SMD = -0.21, 95%CI: -0.40 to -0.03, p = 0.026) was found. Neutropenia (ANC < 2000/mm) was positively associated with concomitant psychotropic use (OR = 2.15, 95% CI: 1.13-4.07, p = 0.019). Clozapine rechallenge studies revealed no significant associations with gender, age, duration of initial clozapine trial, or length of discontinuation period prior to rechallenge. No strong predictors of clozapine-associated blood dyscrasia were identified. Findings may be limited by study variability, surveillance bias, and lack of consistent differentiation between agranulocytosis and milder neutropenia, highlighting limitations in current evidence.
Cortical morphometric inverse divergence in attention-deficit/hyperactivity disorder correlates with cell-type-specific, laminar-specific and developmental transcriptomic signatures.
Zeng Y, Yang L, Cui Z … +1 more , Cao Q
Psychol Med · 2026 May · PMID 42112549 · Full text
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with widespread brain structure alterations. However, the relationship between macroscale cortical organization and microscale...
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with widespread brain structure alterations. However, the relationship between macroscale cortical organization and microscale molecular mechanisms remains unclear, particularly regarding the neurobiological mechanisms shared between the full ADHD cohort and its combined subtype (ADHD-C). METHODS: We analyzed 176 patients with ADHD (105 ADHD-C, 71 ADHD inattentive subtype) and 176 matched typically developing (TD) controls from the ADHD-200 dataset. Morphometric Inverse Divergence (MIND) networks quantified cortical similarity. Partial least squares (PLS) regression linked case-control MIND differences to cortical gene expression, assessing functional enrichment, cell-type specificity, and developmental trajectories. RESULTS: Neuroanatomically, the ADHD-C subtype exhibited widespread increases in regional MIND values, particularly in temporal and parietal cortices, reflecting greater inter-regional morphological homogeneity. PLS regression revealed that these MIND alterations were spatially correlated with a specific transcriptomic signature (PLS1+). These PLS1+ genes were significantly enriched in mitochondria-related metabolic pathways and showed distinct cortical layer specificity (notably layer V) and developmental stage specificity (from late fetal to late infancy stages). Regarding cell-type specificity, while PLS1+ genes in the full ADHD cohort were significantly enriched in excitatory and inhibitory neurons, the ADHD-C subtype showed similar but trend-level associations. Importantly, the full ADHD cohort and the ADHD-C group shared numerous PLS1-related genes and broad functional pathway enrichment commonalities. CONCLUSIONS: This study links macroscale cortical abnormalities to microscale transcriptional regulation, with pronounced alterations in ADHD-C. The shared genetic and functional profiles between ADHD and its combined subtype underscore common pathological processes, providing novel insights into the neurodevelopmental mechanisms of ADHD.
Safe and supported: Mitigating psychotic experiences in Irish adolescents - A population-based study.
Hoey J, Szank T, Ohland J … +7 more , Fleury R, Staines L, Dooley N, Power E, Kelleher I, Cotter D, Cannon M
Psychol Med · 2026 May · PMID 42112536 · Full text
BACKGROUND: Psychotic experiences (PEs) in are associated with elevated risk for mental health difficulties. This study examined predictors of PEs, inclusive of the role of gender, ethnicity, and protective factors. METH...
BACKGROUND: Psychotic experiences (PEs) in are associated with elevated risk for mental health difficulties. This study examined predictors of PEs, inclusive of the role of gender, ethnicity, and protective factors. METHODS: Data were drawn from a 2021 Planet Youth survey of adolescents (n = 4,005). PEs were measured using the adolescent psychotic symptom screener. Effects of psychosocial predictors on PEs were measured by fitting multivariable logistic regression main effect and joint exposure models. RESULTS: 29.8% reported PEs. Black/Asian/Other minorities had elevated odds (a = 1.59, 95% CI 1.26-2.02, < .001). Increased odds in males, females, undisclosed gender and non-binary/transgender with elevated emotional/behavioural difficulties (a = 4.47, 95% CI 3.53-5.67, < .001; a = 3.25, 95% CI 2.59-4.08, < .001; a = 4.83, 95% CI 2.58-9.02, p < .001; a = 4.33, 95% CI 2.69-6.97, < .001 respectively). High odds in undisclosed gender with low emotional/behavioural difficulties (a = 4.36, 95% CI 1.50-12.66, = .007). Lower odds from perceived school/home safety (a = 0.69, 95% CI 0.58-0.83, < .001 and (a = 0.81, 95% CI 0.66-0.99, = .038, respectively). Elevated odds from recent adversities (a = 1.91, 95% CI 1.47-2.49, = .011) attenuated by parental support (a = 1.76, 95% CI 1.17-2.65, < .001). Each additional adversity (>12 months) increased odds (a = 1.12, 95% CI 1.07-1.17, < .001). CONCLUSIONS: Findings highlight the interplay of risk and protective factors in adolescent PEs, with increased vulnerability among minoritized youth. Results support targeted interventions to reduce mental health disparities.
Attenuated dynamic impulse control in risky action under the escalating risk and reward in gambling disorder.
Zhong G, Chen T, Liu J … +7 more , Wei Y, Zhang X, Yang P, Zhang RY, Voon V, Du J, Zhao M
Psychol Med · 2026 May · PMID 42112535 · Full text
BACKGROUND: Gambling disorder (GD) involves persistent risky choices despite losses, suggesting impaired impulse control. While static paradigms reveal inhibition deficits in GD, they cannot model dynamic risk-reward esc...
BACKGROUND: Gambling disorder (GD) involves persistent risky choices despite losses, suggesting impaired impulse control. While static paradigms reveal inhibition deficits in GD, they cannot model dynamic risk-reward escalations during real gambling. This study aims to investigate whether GD involves impaired dynamic impulse control during escalating stakes and to dissociate contributions of subjective risk evaluation and trait impulsivity to this deficit. METHODS: Using a sequential gambling task with 83 male patients with GD and 62 matched healthy controls (HCs), this study investigated dynamic impulse control deficits under escalating stakes. We quantified dynamic impulse control via the reward-reaction time (RT) coupling for 'continue' choices (dynamic impulse control index [DICI]) using Bayesian modeling. Risk sensitivity and risk preference were derived from stop/continue decisions. Trait impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Regression analyses examined the modulation of DICI by risk sensitivity and trait impulsivity. RESULTS: Patients with GD exhibited significantly attenuated DICI versus HCs, reflecting failure to increase deliberation with escalating stakes. Computational modeling revealed markedly reduced risk sensitivity in GD despite comparable risk preference. Critically, trait impulsivity positively modulated DICI in HCs but not in GD, indicating pathological decoupling. Risk sensitivity positively predicted DICI in both groups, though significantly weaker in GD. CONCLUSIONS: These findings establish a triadic impairment in GD: (1) attenuated adaptive impulse control during escalation (impaired DICI), (2) deficient subjective risk weighting (reduced sensitivity), and (3) breakdown of impulsivity-based modulation of control. This reveals a dynamic, mechanism-focused pathology beyond static trait models.
The longitudinal association between adverse childhood experiences and persistence of psychotic-like experiences in young people: evidence from the ALSPAC birth cohort.
Hudson G, Baldwin JR, Sykes K … +4 more , Mackie CS, Hiller R, Powell C, Kirkbride JB
Psychol Med · 2026 May · PMID 42112533 · Full text
BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of psychotic-like experiences (PLEs), but the relationship between specific adversities and the persistence of PLEs in young people rema...
BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of psychotic-like experiences (PLEs), but the relationship between specific adversities and the persistence of PLEs in young people remains unclear. We examined associations between distinct ACEs and the persistence of PLEs until 24 years old. METHODS: Using longitudinal data from participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort with at least one PLE datapoint, we used group-based trajectory modeling to estimate longitudinal trajectories of PLEs from age 12-24. We examined their associations with bullying victimization, maltreatment, parental mental health problems, parental substance abuse, parental separation, and parental intimate partner violence prior to first PLE experiences. RESULTS: Among 4,448 participants, a three-group trajectory model provided the best fit, revealing low, increasing and persistent PLE groups from ages 12-24. In fully adjusted multinomial logistic regression models, those exposed to bullying were more likely to belong to either the increasing (relative risk ratio [RRR]: 1.83, 95%CIs: 1.26-2.66) or high (RRR: 1.78, 95%CIs: 1.07-2.93) PLEs group than the low PLE group; those exposed to maltreatment were more likely to be in the increasing PLE group (RRR: 1.47, 95%CIs: 1.03-2.10). No other ACEs were associated with PLE trajectories. CONCLUSIONS: Bullying was associated with persistent PLEs up to 24 years old, independent of other forms of childhood adversity, with timing-specific effects of maltreatment on increasing symptoms emerging later in adolescence. Findings provide further evidence for the importance of prioritizing bullying and maltreatment reduction as public health targets.
A visual cortex origin of trauma memory intrusions: integrated evidence from TMS and fMRI.
Dai J, Xu Z, Guo J … +2 more , Yu K, Wang Y
Psychol Med · 2026 May · PMID 42112531 · Full text
BACKGROUND: Intrusive trauma memories - vivid, distressing recollections that occur involuntarily and may feel present - is a defining symptom of post-traumatic stress disorder (PTSD). While traditional models emphasize...
BACKGROUND: Intrusive trauma memories - vivid, distressing recollections that occur involuntarily and may feel present - is a defining symptom of post-traumatic stress disorder (PTSD). While traditional models emphasize dysregulation within limbic-prefrontal circuits, emerging evidence implicates visual sensory systems in the formation of trauma-memory intrusions. However, direct causal evidence remains lacking. METHODS: We combined functional MRI with repetitive transcranial magnetic stimulation (rTMS) to examine the causal role of visual sensory cortices in intrusive memory formation. Healthy participants underwent a trauma-film paradigm, followed by fMRI scanning during memory encoding and a post-encoding resting phase during which spontaneous intrusions were recorded. One group received 1-Hz rTMS targeting early visual cortex (V1/V2); a control group received stimulation at the Vertex. Intrusive memories were recorded over the subsequent 7 days. RESULTS: rTMS to V1/V2 significantly reduced the frequency, vividness, and emotional intensity of intrusive memories, while preserving recognition of episodic gist. fMRI analyses showed that intrusive episodes were associated with heightened activation and stable neural representations within the occipital visual cortex (OVC). Functional and effective connectivity analyses further revealed that the occurrence of intrusions was predicted by interactions between the middle frontal gyrus (MFG) and OVC. Dynamic causal modeling confirmed direct, bidirectional MFG-OVC interactions that coexisted with, but tracked the intrusion dynamics more closely than, the traditional prefrontal-limbic circuits. CONCLUSIONS: These findings provide the first causal evidence for the direct involvement of the early visual cortex in trauma-memory intrusions. They highlight the visual system as a novel neuromodulation target for therapeutic intervention on PTSD.
Insomnia severity impact dynamic connectivity and modulate connectivity-cognitive links in major depressive disorder.
Bao W, Gao Y, Li H … +5 more , Zhou Z, Wang Y, Hu X, Gong Q, Huang X
Psychol Med · 2026 May · PMID 42108953 · Full text
BACKGROUND: Insomnia is common in major depressive disorder (MDD), and varying severity of insomnia may be associated with distinct neural alterations in MDD. Dynamic functional connectivity can capture time-varying brai...
BACKGROUND: Insomnia is common in major depressive disorder (MDD), and varying severity of insomnia may be associated with distinct neural alterations in MDD. Dynamic functional connectivity can capture time-varying brain network interactions and may help disentangle insomnia-related mechanisms in MDD. METHODS: We recruited 203 drug-naïve adult MDD patients, divided into high- (HI-MDD, = 133) and low-insomnia (LI-MDD, = 70) groups using the Hamilton Depression Rating Scale insomnia subscale, along with 122 health controls (HCs). Independent component analysis and a sliding-window approach were applied to explore static and dynamic functional network connectivity (FNC). RESULTS: While static FNC revealed no significant group difference, dynamic analysis identified distinct connectivity states between two groups. Compared to HCs, HI-MDD displayed more frequent occurrence of state I and less of state IV, a pattern was absent in LI-MDD. Both MDD groups showed increased default mode network (DMN)-lateral ventral attention network (VAN) connectivity in states I and II, accompanied by decreased dorsal attention network-cerebellar/DMN connectivity in state I relative to HCs. Compared with LI-MDD, HI-MDD exhibited enhanced DMN-medial VAN connectivity in state II, along with increased DMN connectivity with visual and sensorimotor networks in state I, suggesting insomnia-related changes. In addition, we identified insomnia-related memory deficits and depression-related processing speed impairment in MDD. Insomnia significantly moderated the association between altered DMN-lateral VAN connectivity in state I and logical memory impairment in MDD. CONCLUSIONS: These findings suggest that insomnia severity in MDD is associated with distinct temporal patterns of brain network alterations beyond shared depression-related changes and moderate cognitive functions in MDD.
Cognitive effects of intravenous Ketamine in treatment-resistant depression: A systematic review.
Chavigny LA, Desbeaumes Jodoin V, Garel N … +4 more , Sob Ndongo M, Osborne L, Turecki G, Richard Devantoy S
Psychol Med · 2026 May · PMID 42100880 · Full text
Intravenous (IV) low-dose ketamine has emerged as a promising treatment for patients with treatment-resistant depression (TRD). However, its impact on cognitive functioning remains unclear. This systematic review examine...
Intravenous (IV) low-dose ketamine has emerged as a promising treatment for patients with treatment-resistant depression (TRD). However, its impact on cognitive functioning remains unclear. This systematic review examines the cognitive and executive effects of IV ketamine in TRD, focusing on their relationship to depressive and suicidal outcomes. A systematic search of Cochrane, MEDLINE, Embase, and PsycINFO databases was conducted up to May 15, 2025, using the terms depression, cognition, and ketamine. This review was conducted in accordance with the PRISMA guidelines, and the protocol was registered in PROSPERO (ID: 1160487). Risk of bias was evaluated using the Cochrane RoB 2 tool for randomized trials and the ROBINS-I tool for non-randomized studies. Twenty-one studies, comprising approximately 900-1,180 participants with TRD, assessed cognitive domains of processing speed, working memory, attention, verbal and visual memory, cognitive flexibility, and executive control. Procognitive effects were frequently observed in processing speed and working memory, while attention results were preserved or modestly improved, and verbal and visual memory results were heterogeneous. Executive control, particularly inhibitory performance on Stroop paradigms, improved in several trials. Two studies directly examined cognition as it relates to suicidal behaviors. No cognitive deterioration was reported. Subanesthetic IV ketamine appears to preserve and enhance specific cognitive functions in TRD, notably across processing speed, working memory, and executive control. These procognitive effects, particularly in executive control, may mediate ketamine's antisuicidal action. Standardized longitudinal studies are warranted to clarify their durability and clinical significance.
Childhood environment clusters reveal heterogeneous associations between large-scale brain networks and youth mental health symptoms.
Hardi FA, Keding TJ, Holt-Gosselin B … +2 more , Goldfarb EV, Gee DG
Psychol Med · 2026 May · PMID 42100879 · Full text
BACKGROUND: Youth mental health and brain development are profoundly shaped by highly heterogeneous childhood environments. However, research often operates under the assumption that neural networks linked to psychopatho...
BACKGROUND: Youth mental health and brain development are profoundly shaped by highly heterogeneous childhood environments. However, research often operates under the assumption that neural networks linked to psychopathology function in the same way across different individuals, with limited consideration of how brain-behavior associations themselves may vary across environmental contexts. This poses challenges for identifying the precise neural correlates of risk or resilience to psychopathology. METHODS: In a large, longitudinal sample ( = 8,078), we examined differences in psychological symptoms and their associations with brain network functional connectivity across three clusters of youth identified by their home, school, and community environments. RESULTS: Child environment groups differed in mental health symptoms, as well as the links between large-scale functional network connectivity and symptoms. Youth exposed to high trauma and familial risk showed the highest symptom levels over time compared to those youth in low-risk or economically disadvantaged environments. Moreover, youth in the high trauma and familial risk group showed stronger functional connectivity between the salience and frontoparietal networks with increased symptoms, whereas youth in the high disadvantage group showed the opposite pattern. Notably, these brain and mental health associations were not observed when examined across the entire sample, and group differences were more pronounced in female and older youth. CONCLUSIONS: The same neural patterns of functional network connectivity can have different implications for mental health depending on the environment. These findings highlight the importance of context-sensitive approaches for developing personalized interventions in supporting youth mental health.
Inflammatory markers in the emergency department and PTSD symptoms in the AURORA Study: A longitudinal cohort study.
Nishimi K, Linnstaedt SD, Neylan TC … +36 more , McKibben LA, Albertorio-Sáez LM, Zhao Y, House SL, Beaudoin FL, An X, Stevens JS, Clifford GD, Jovanovic T, Germine LT, Rauch SL, Haran JP, Storrow AB, Musey PI, Hendry PL, Sheikh S, Punches BE, Swor RA, Pascual JL, Seamon MJ, Datner EM, Pearson C, Peak DA, Merchant RC, Domeier RM, Rathlev NK, O'Neil BJ, Sergot P, Sanchez LD, Bruce SE, Harte SE, Kessler RC, Koenen KC, Ressler KJ, McLean SA, O'Donovan A
Psychol Med · 2026 May · PMID 42100824 · Full text
BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. W...
BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months. METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), and generally anti-inflammatory IL-10. PTSD symptoms were self-reported at 2 weeks, 8 weeks, 3 months, and 6 months post-ED. Covariate-adjusted repeated-measures regressions estimated associations between inflammation and PTSD symptoms, overall and sex-stratified. RESULTS: Among 742 participants (age = 40.0 [13.7]; 479 [64.6%] female), PTSD symptoms were elevated then modestly decreased over follow-up. Higher ED inflammation was associated with higher PTSD symptoms across follow-up (standardized symptoms = 0.05, 95% CI: 0.01-0.09), adjusted for potential confounders. Higher pro-inflammatory index levels and IL-6, IL-8, and TNF-α were associated with higher PTSD symptoms in males only, while higher IL-10 was associated with higher PTSD symptoms in females only. CONCLUSIONS: Pro-inflammatory levels shortly after traumatic stress are associated with heightened PTSD symptoms, particularly among males. Inflammatory markers may prove useful additions to prediction models for PTSD following trauma, with attention to sex differences.
Do antidepressants change our interpretations of facial emotions?
McKenzie N, Bone J, Duffy L … +2 more , Mufano M, Lewis G
Psychol Med · 2026 May · PMID 42087774 · Full text
BACKGROUND: Cognitive neuropsychological models propose that antidepressants exert their therapeutic effects by modifying negative emotional processing biases early in treatment. However, evidence from large, long-term c...
BACKGROUND: Cognitive neuropsychological models propose that antidepressants exert their therapeutic effects by modifying negative emotional processing biases early in treatment. However, evidence from large, long-term clinical samples is limited. METHODS: We conducted a mechanistic analysis within the Antidepressants to Prevent Relapse in Depression randomized controlled trial, which compared maintenance antidepressant treatment with placebo substitution in adults with recurrent depression who were currently well (N = 478). Participants completed a computerized facial emotion recognition task at baseline, 12 weeks, and 52 weeks, in which faces morphed from happy to sad. The primary outcome was the number of faces classified as happy (0-45). Linear and longitudinal mixed-effects models were used to compare treatment groups and examine associations with depressive (PHQ-9) and anxiety (GAD-7) symptoms. RESULTS: Of the 462 participants completing at least one task, there was no evidence that discontinuing antidepressants altered performance compared with maintenance at 12 weeks (adjusted mean difference = 0.23, 95% CI -0.5 to 1.0, p = 0.5) or 52 weeks (0.29, -0.5 to 1.2, p = 0.5). Depressive symptoms were negatively associated with happy face classifications both cross sectionally (β = -0.20 per PHQ-9 point, p = 0.02) and longitudinally (β = -0.09, p = 0.05). Anxiety symptoms were positively associated with happy classifications (β = 0.11, p = 0.047). CONCLUSIONS: Maintenance antidepressant treatment did not sustain positive emotional processing biases as indexed by facial emotion recognition, despite robust associations between such biases and depressive symptoms. These findings challenge the generalizability of laboratory evidence on emotional bias modification to long-term clinical treatment and highlight the need for further mechanistic research on antidepressant action.
Clusters of social and substance use-related risks are associated with the duration of untreated psychosis.
Edelhoff H, van Os J, van Amelsvoort T … +20 more , Simons CJP, de Haan L, van der Pluijm M, GROUP Investigators, Sideli L, Tarricone I, Ferraro L, Tosato S, Berardi D, Arango C, Bernardo M, Menezes PR, Del-Ben CM, Schürhoff F, Selten JP, Rutten BPF, Murray RM, Morgan C, Schirmbeck F, Reininghaus U
Psychol Med · 2026 May · PMID 42083874 · Full text
BACKGROUND: The duration of untreated psychosis (DUP) is still considerably long in patients with psychotic disorders worldwide. Social determinants, such as the socioeconomic status, can influence DUP, exacerbating heal...
BACKGROUND: The duration of untreated psychosis (DUP) is still considerably long in patients with psychotic disorders worldwide. Social determinants, such as the socioeconomic status, can influence DUP, exacerbating health inequalities in access to timely care. We investigated whether subpopulations with shared characteristics are associated with longer DUP. METHODS: We performed latent class analyses to investigate whether classes with shared configurations of social and substance use-related risks can be identified in two large cohorts with psychotic disorders: = 780 patients from the GROUP project and = 847 patients from the EU-GEI project. Subsequently, we conducted survival analyses to analyze whether identified classes are associated with DUP. RESULTS: We identified three classes in both samples. Membership of the class with predominantly younger men, higher proportion of cannabis use, and supported living was associated with longer DUP compared with a class with predominantly White ethnicity, higher education, and current employment in GROUP (HR = 1.28, 95% CI: 1.06-1.56, = .011) and in EU-GEI (HR = 1.27, 95% CI: 1.07-1.51, = .007). In GROUP, membership of a third class with predominantly White women, without cannabis use, was associated with the shortest DUP (HR = 0.78, 95% CI: 0.63-0.95, = .016). CONCLUSIONS: Results suggest that specific populations differ in their risk distributions for prolonged DUP and highlight the importance of considering configurations of social determinants in context. Public mental health programs need to establish their differential impact for diverse populations and facilitate more targeted pathways to care.
Brain network representations of placebo analgesia.
Zhang X, Sun X, Huang W … +7 more , An K, Zhao X, Zhang D, Zhang W, Yu Y, Qian Y, Zhu J
Psychol Med · 2026 May · PMID 42083871 · Full text
BACKGROUND: Prior neuroimaging studies and meta-analyses investigating brain correlates of placebo analgesia (PA) have yielded neuroanatomically heterogeneous findings, which may be reconciled from a connectomics perspec...
BACKGROUND: Prior neuroimaging studies and meta-analyses investigating brain correlates of placebo analgesia (PA) have yielded neuroanatomically heterogeneous findings, which may be reconciled from a connectomics perspective. The objective of this study was to examine network localization of brain functional alterations related to PA. METHODS: We initially identified PA-induced brain activation alterations (hyper-activation and hypo-activation separately) during experimental pain from 29 published studies with 674 individuals. By combining these implicated dysfunctional brain regions with large-scale discovery (N = 1113) and validation (N = 1093) resting-state functional magnetic resonance imaging datasets, we then employed a novel functional connectivity network mapping approach to construct PA hyper-activation and hypo-activation networks, respectively. RESULTS: The PA hyper-activation network manifested as a pattern of circumscribed brain regions mainly involving the limbic, default, and frontoparietal networks. By contrast, the PA hypo-activation network comprised a broadly distributed set of brain regions primarily implicating the ventral attention, somatomotor, and subcortical networks. CONCLUSIONS: Our findings regarding the brain network representations of PA may contribute to a deeper understanding of its action mechanisms and provide a neural framework that may inform future clinical translation.
A review and integration of models on delusion maintenance.
Lincoln TM, Romberg H, Torrents-Rodas D … +1 more , Bott A
Psychol Med · 2026 May · PMID 42083868 · Full text
Contemporary definitions of delusions highlight their resistance to conflicting evidence as the core feature. However, most etiological models of delusions have focused on delusion formation rather than maintenance and w...
Contemporary definitions of delusions highlight their resistance to conflicting evidence as the core feature. However, most etiological models of delusions have focused on delusion formation rather than maintenance and we lack a coherent understanding of why delusions persist. We conducted a systematic literature search of models on delusion maintenance, extracted their core postulates, point to explanatory gaps, and derive an integrated framework. We identified 74 published accounts that include postulated mechanisms of delusion maintenance. We classified the models into six core perspectives that informed them: Bayesian inference (17 models), associative learning theory (6 models), neurobiological (11 models), cognitive-behavioral (23 models), motivational (7 models), and social (6 models). Most models highlight a mechanistic role of avoidance and operant learning, converging on the idea that a delusional explanation is reinforced. Another repeatedly suggested mechanism is that the delusional belief, once formed, influences the way further information is processed. In addition, most models propose a key role of individual deficits and biases. The proposed factors can be combined in temporal progression, including early risk factors and resulting vulnerability, the common proposed mechanism of formation (i.e. search for explanation of ambiguous experiences), and the short- and long-term consequences of the delusional explanation along with feedback loops. By considering numerous factors and their interactions, the integrative model provides a considerably more compelling account of why delusions persist than any single perspective alone. It can help to identify novel directions for research and intervention, such as addressing short-term benefits of delusion maintenance.
Psychiatric safety of methylphenidate in adults with major depressive disorder: a 1-year retrospective cohort study of 6,422 patients.
Liu TH, Huang YL, Wu JY … +3 more , Lin CH, Jang FL, Lai CC
Psychol Med · 2026 May · PMID 42083867 · Full text
BACKGROUND: Methylphenidate is sometimes used to address residual symptoms of major depressive disorder (MDD), but concerns about psychiatric destabilization and limited long-term evidence have constrained its use. We ex...
BACKGROUND: Methylphenidate is sometimes used to address residual symptoms of major depressive disorder (MDD), but concerns about psychiatric destabilization and limited long-term evidence have constrained its use. We examined the psychiatric safety of methylphenidate in adults with MDD in a large, real-world cohort. METHODS: Using the TriNetX Global Collaborative Network, we identified adults with MDD who initiated methylphenidate and matched them 1:1 with controls who did not receive methylphenidate. Patients with attention-deficit/hyperactivity disorder, bipolar disorder, mania, or recent psychiatric destabilization were excluded. The primary outcome was a composite of all-cause hospitalization or emergency room visits; secondary outcomes included hospitalization, emergency visits, suicidal behavior, manic episodes, and recurrence of MDD. Hazard ratios (HRs) were estimated with Cox proportional hazards models after propensity score matching. RESULTS: Of 425,190 eligible patients, 3,211 matched pairs were included (mean age, 55.8 years; 58% female). Over 1 year, the composite outcome occurred less frequently in the methylphenidate group than in controls (574 vs. 694; HR, 0.85; 95% CI, 0.76-0.95). No significant differences were observed for hospitalization, emergency visits, suicidal behavior, manic episodes, or MDD recurrence. Results were consistent across subgroups defined by sex, age, and antidepressant class. CONCLUSIONS: In adults with MDD, methylphenidate use was associated with a lower risk of hospitalization or emergency visits and was not linked to increased risk of suicidality, mania, or recurrence. These findings support the psychiatric safety of methylphenidate as an adjunctive treatment for selected patients, though longer follow-up is needed.
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