Psychological Medicine[JOURNAL]
Sun
200 papers
Slower motor speed as a predictor of suicide attempts in high-risk youth.
Jia-Richards M, Ksheeraja S, Riston S … +10 more , Goodfriend E, Melhem AZ, Recker-Mohn K, Murthy V, Luskin A, Toukhy N, Chen K, Douaihy A, Brent DA, Melhem NM
Psychol Med · 2026 May · PMID 42083860 · Full text
BACKGROUND: Predicting suicide risk remains a challenge. We examined whether neurocognitive performance on implicit associations toward suicide, motor speed, response inhibition, and executive functioning predicts suicid...
BACKGROUND: Predicting suicide risk remains a challenge. We examined whether neurocognitive performance on implicit associations toward suicide, motor speed, response inhibition, and executive functioning predicts suicide attempt and behavior in high-risk psychiatric patients. METHOD: Our sample ( = 298) consisted of inpatients ( = 161) and outpatients ( = 83) admitted for a suicide attempt (SA; = 78), for suicidal ideation (SI; = 76), or were non-suicidal psychiatric controls (PC; = 90), and healthy controls (HC; = 54). Participants were followed for 12 months, with follow-up assessments at 3-, 6-, and 12-months. Neurocognitive tasks were administered at baseline. Clinical symptom measures, suicidality, and electronic health record data were collected at each timepoint. ANCOVA was used to compare groups on neurocognitive performance, and logistic and Cox regressions examined whether neurocognitive performance predicted future actual suicide attempt and suicidal behaviors. RESULTS: Participants had a mean age of 24.34 years ( = 3.71). A total of 19 participants made an actual suicide attempt during the study. On neurocognitive tasks at baseline, the SA group had stronger implicit associations with death- and suicide-related words compared to the HC ( = 0.88, < 0.001) and SI ( = 0.63, = 0.005) groups and poorer executive functioning than the SI ( = 0.44, = 0.043) group in multivariate models. Stronger implicit associations with death/suicide predicted higher risk of suicide attempts at the univariate ( 1.68 = 000), but not multivariate level ( 1.17 = 000), while slower motor speed predicted actual suicide attempts ( 1.81 = 000) at the multivariate level. CONCLUSIONS: Slower motor speed predicts actual suicide attempt and may help identify psychiatric patients who are at high risk for suicidal behavior.
Objective sleep efficiency links to cortisol stress recovery via dorsolateral prefrontal-hippocampal regulation.
Luo X, Zhao X, Liu Y … +7 more , Ma Y, Ren Y, Wei Z, Tang Z, Guo K, Luo J, Yang J
Psychol Med · 2026 May · PMID 42083449 · Full text
BACKGROUND: Existing evidence highlights sleep's critical role in regulating cortisol stress recovery; the underlying neural pathways remain unclear. To address this gap, the current study aims to elucidate the neurobiol...
BACKGROUND: Existing evidence highlights sleep's critical role in regulating cortisol stress recovery; the underlying neural pathways remain unclear. To address this gap, the current study aims to elucidate the neurobiological pathway linking objective sleep efficiency to cortisol stress recovery using functional magnetic resonance imaging (fMRI), with a focus on the functional connectivity (FC) between prefrontal cortex (PFC) and hippocampus. METHODS: Seventy-seven participants completed an acute stress task during a task-dependent and resting-state fMRI scanning. Salivary samples were collected and analyzed as an indicator of cortisol stress recovery. Objective sleep efficiency was measured the night before the fMRI scanning. Using Seed-based gPPI and resting-state FC analysis, we examined the mediating role of PFC-hippocampus FC in the association between objective sleep efficiency and cortisol stress recovery, both during the stress task and in the post-stress resting-state. RESULTS: Objective sleep efficiency was significantly related to cortisol stress recovery but not with cortisol reactivity. Neurologically, higher sleep efficiency was linked to enhanced prefrontal activity and increased the left dlPFC-hippocampus FC during the acute stress task. Importantly, objective sleep efficiency promoted cortisol stress recovery by the weakened resting-state left dlPFC-hippocampus FC. CONCLUSIONS: This study highlights the pivotal role of left dlPFC-hippocampus regulation underlying sleep's effect on HPA axis recovery to acute stress. These results suggest a model whereby high objective sleep efficiency promotes adaptive stress recovery through dynamic reallocation of neural resources across acute stress process, characterized by task-dependent coupling and post-stress decoupling of frontal-hippocampal circuitry.
Changes in cannabis potency and cannabis-related psychiatric harms: a 23-year ecological study in Denmark.
Rømer Thomsen K, Thylstrup B, Hesse M … +7 more , Lindholst C, Reitzel LA, Eriksen TS, Erlangsen A, Englund A, Freeman TP, Hjorthøj C
Psychol Med · 2026 May · PMID 42076896 · Full text
BACKGROUND: In recent decades, the potency of cannabis resin increased globally, raising concerns, as higher potency has been associated with increased risk of psychiatric harms at the individual level. The aim here was...
BACKGROUND: In recent decades, the potency of cannabis resin increased globally, raising concerns, as higher potency has been associated with increased risk of psychiatric harms at the individual level. The aim here was to examine whether changes over time in the potency of seized cannabis resin samples were associated with psychiatric harms at the population level. METHODS: Data on ∆-9-tetrahydrocannabinol (THC) concentration in seized cannabis resin were obtained from forensic departments in Denmark (2000-2022), the country reporting the highest potency in Europe. Data on admissions to cannabis treatment, incidence of cannabis-induced psychosis, and dual diagnosis (schizophrenia and cannabis use disorder) were obtained from national registers. Time-dependent associations between potency and the outcomes were examined with mixed-effects linear regression models and associations across age and sex were explored. Candidate time lags were 0-10 years. RESULTS: THC concentration increased almost fourfold: mean 8.3-31.2% from 2000 to 2022. In fully adjusted models, THC was positively associated with first-time cannabis treatment entry at lags of 0-6, strongest at year 0 ( 0.0001); incidence of cannabis-induced psychosis at lags of 0-4, strongest at year 0 ( < 0.0001); and incidence of dual diagnosis at lags of 0-1, strongest at year 0 ( 0.01). No positive associations were found in unadjusted models. Subgroup analyses indicated associations in older patients and women. CONCLUSIONS: Potency of seized cannabis resin increased almost fourfold from 2000 to 2022. Changes in cannabis potency were positively associated with psychiatric harms at the population level across all outcomes.
Modulating empathy with tDCS: dissociable roles of rTPJ and lDLPFC.
Li X, Guo Z, Ye J … +3 more , Yang X, Lu X, Peng W
Psychol Med · 2026 Apr · PMID 42047109 · Full text
BACKGROUND: Empathy relies on distinct but interacting processes for representing others' states and regulating self-oriented affect. Neuroimaging studies implicate the right temporoparietal junction (rTPJ) in perspectiv...
BACKGROUND: Empathy relies on distinct but interacting processes for representing others' states and regulating self-oriented affect. Neuroimaging studies implicate the right temporoparietal junction (rTPJ) in perspective-taking and the left dorsolateral prefrontal cortex (lDLPFC) in emotion regulation, yet causal evidence from neuromodulation remains limited. This study compared the effects of rTPJ- and lDLPFC-targeted transcranial direct current stimulation (tDCS) on empathy across multiple contexts and modalities. METHODS: In Study 1, participants performed a static pain empathy task following anodal or sham tDCS over the rTPJ or lDLPFC, with electroencephalography recorded. In Study 2, participants viewed autobiographical videos depicting positive, negative, and neutral events before and after stimulation, while heart rate variability (HRV) was assessed. Machine learning-based decoding integrated behavioral and physiological data to evaluate the 'readability' of empathic states. RESULTS: rTPJ-tDCS enhanced cognitive empathy across tasks, increasing empathic ratings and late positive potential amplitudes in the pain empathy task, and enhancing the subjective sense of content and emotion understanding in the video task. lDLPFC-tDCS selectively increased HRV in the video task, consistent with greater autonomic flexibility, without altering explicit ratings. Decoding analyses converged with these findings: rTPJ stimulation increased classification accuracy of targets' emotional states, indicating stronger alignment between empathic responses and others' emotional cues, whereas lDLPFC stimulation reduced accuracy, suggesting regulation-related attenuation of overt emotional signals. CONCLUSIONS: These findings provide causal evidence for rTPJ supporting cross-context cognitive empathy and lDLPFC modulating autonomic regulation. Multi-context, multimodal assessment delineated distinct target-specific profiles, informing precision neuromodulation strategies for empathy-related deficits and regulation needs.
Sex differences in the latent structure of suicide risk among patients with mood disorders: taxometric analyses using the ideation-to-action framework.
Park C, Lee E, Cho M … +1 more , Park CHK
Psychol Med · 2026 Apr · PMID 42047103 · Full text
BACKGROUND: Previous taxometric studies have yielded inconsistent findings regarding the empirical support for the common clinical practice of categorizing patients into discrete suicide risk groups (low versus high risk...
BACKGROUND: Previous taxometric studies have yielded inconsistent findings regarding the empirical support for the common clinical practice of categorizing patients into discrete suicide risk groups (low versus high risk). Furthermore, potential sex differences in these latent structures have not been adequately explored. This study aimed to investigate the latent structure of suicide risk based on motivational and volitional phase symptoms from the ideation-to-action framework, and to explore potential sex differences in these latent structures, in order to determine whether the clinical practice of categorizing patients into low versus high suicide risk categories is empirically valid. METHODS: We employed taxometric procedures to examine whether suicide risk should be understood as dimensional or categorical. Our analysis distinctly evaluated motivational and volitional phase symptoms across separate samples of male and female outpatients with mood disorders. RESULTS: Our research revealed significant sex differences in the latent structure of suicide risk. For motivational phase symptoms, an ambiguous structure was revealed in the male group, whereas a clearly dimensional latent structure was observed in the female group. For volitional phase symptoms, a categorical structure emerged in males, while a dimensional structure was found in females. CONCLUSIONS: Given the 'gender paradox' in suicidal behavior, which highlights higher rates of fatal suicide attempts among males, early identification of the high-volitional-risk group and focused allocation of intervention resources are particularly crucial for males. Our findings underscore the necessity for sex-specific approaches to suicide risk assessments, research applying the ideation-to-action framework, and targeted intervention development.
Linking brain structure to stress reactivity: cingulate surface area predicts acute cortisol responses - CORRIGENDUM.
Serin E, Schill LS, Bärtl C … +9 more , Giglberger M, Konzok J, Peter HL, Speicher N, Kreuzpointner L, Kudielka BM, Wüst S, Walter H, Henze GI
Psychol Med · 2026 Apr · PMID 42047098 · Full text
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Distinct and common subcortical functional connectivity revealed across three major psychiatric disorders.
Chang WC, Hung DP, Chen MH … +4 more , Su TP, Bai YM, Chen YY, Tu PC
Psychol Med · 2026 Apr · PMID 42046888 · Full text
BACKGROUND: Subcortical nuclei - including the thalamus, basal ganglia, and hippocampus-amygdala complex - are key regions in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). While cortical...
BACKGROUND: Subcortical nuclei - including the thalamus, basal ganglia, and hippocampus-amygdala complex - are key regions in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). While cortical-subcortical connectivity is well studied, fine intra- and inter-subcortical patterns are less known. This study aimed to identify shared and distinct functional connectivity alterations across SZ, BD, and MDD using a high-resolution subcortical atlas. METHODS: Resting-state functional magnetic resonance imaging data from 800 participants (200 per group: SZ, BD, MDD, and healthy controls) in a single-site cohort were analyzed. Subcortical structures were parcellated into 27 regions per hemisphere - thalamus (8 regions), hippocampus (5 regions), amygdala (2 regions), and striatum (12 regions) - based on the a priori atlas. Pairwise functional connectivity among the 54 regions was computed for each participant, and group differences were assessed using general linear models. RESULTS: Patients with SZ exhibited significantly reduced intra-thalamic connectivity and increased intra-striatal connectivity, as well as enhanced connectivity between the thalamus, striatum, and limbic regions. Patients with BD showed reduced intra-thalamic and intra-striatal connectivity, along with decreased thalamus-amygdala and thalamus-striatum connectivity. In MDD, the predominant finding was reduced intra-limbic connectivity, accompanied by mild reductions in intra-thalamic and striatum-limbic connectivity. CONCLUSION: The results suggest that intra-thalamic hypoconnectivity appears common to SZ, BD, and MDD, with graded degrees of severity. In contrast, distinct alterations in intra-striatal and striatum-limbic connectivity may differentiate mood disorders from SZ. These shared and disorder-specific subcortical connectivity patterns enhance the understanding of psychiatric neurobiology and may guide the development of targeted, disorder-tailored interventions.
The effects of rTMS over orbitofrontal cortex on cognitive functions in first-episode schizophrenia.
Hu Q, Jiao X, Ding Y … +13 more , Wei Y, Tang X, Xu L, Cui H, Tang Y, Liu H, Gao J, Zeng L, Yi Z, Li C, Chen J, Wang J, Zhang T
Psychol Med · 2026 Apr · PMID 42046881 · Full text
BACKGROUND: Cognitive impairment in first-episode schizophrenia (FES) is a major contributor to functional decline, but antipsychotics provide limited cognitive improvement, and few repetitive transcranial magnetic stimu...
BACKGROUND: Cognitive impairment in first-episode schizophrenia (FES) is a major contributor to functional decline, but antipsychotics provide limited cognitive improvement, and few repetitive transcranial magnetic stimulation (rTMS) studies have targeted the orbitofrontal cortex (OFC). This study investigated whether right OFC rTMS enhances specific cognitive functions in FES and its relationship with symptom reduction. METHODS: Ninety drug-naive FES patients were enrolled, with 48 receiving active right OFC rTMS and 42 sham stimulation for 20 sessions over 8 weeks, while all patients took olanzapine (10-20 mg/day). Cognitive function was assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) at baseline and week 4, and psychotic symptoms were rated with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Repeated-measures analysis of variance (RMANOVA) demonstrated a significant Time×Group interaction for visuospatial memory (assessed via the Brief Visuospatial Memory Test-Revised, BVMT; F = 5.079, df = 1, 83, p = 0.027, η2 = 0.058). Post hoc tests revealed significant BVMT improvement in the active group (p < 0.001) but not in the sham group (p = 0.312). In the active group, improvements in BVMT and Neuropsychological Assessment Battery (NAB) scores were significantly correlated with lower PANSS total scores after Bonferroni correction. CONCLUSIONS: These findings indicate that right OFC rTMS improves specific cognitive functions in FES, with cognitive benefits associated with symptom alleviation, supporting the right OFC as a promising target for cognitive intervention in FES.
Crosstalk of peripheral cytokine-white matter alteration-insomnia during methadone maintenance treatment.
Yang L, Yang W, Tang Y … +5 more , Zeng Y, Liu S, Gao Z, Li X, Liu J
Psychol Med · 2026 Apr · PMID 42037510 · Full text
BACKGROUND: Insomnia is commonly seen in opioid use disorder (OUD) patients receiving methadone maintenance treatment (MMT) and might be related to high heroin relapse risk. This study aims to identify potential mediatio...
BACKGROUND: Insomnia is commonly seen in opioid use disorder (OUD) patients receiving methadone maintenance treatment (MMT) and might be related to high heroin relapse risk. This study aims to identify potential mediation pathways among peripheral cytokines, neuroimaging characteristics, and insomnia in MMT patients, and explore diagnostic markers and therapeutic targets for MMT-related insomnia. METHODS: A total of 121 OUD individuals (OUDs) and 109 healthy controls were recruited, including MMT individuals (MMT group, = 53), short-term abstinent (median: 30 days) heroin users at baseline (OUD1, = 68), and around 10-month follow-up (OUD2, = 61) without MMT, healthy controls-cohort 1 (HC1, = 53, age/gender/education match MMT), and healthy controls-cohort 2 (HC2, = 56, age/gender match OUD1). Multimodal datasets, including cerebral diffusion tensor imaging (DTI), peripheral hematologic indicators, and neuropsychological assessments, were collected from the MMT group and HC1. Within the MMT group, we revealed relationships among cytokines, DTI metrics, and neuropsychological assessments via partial correlation and mediation analyses. Mendelian randomization (MR) analyses between OUD and white matter (WM)-related imaging-derived phenotypes were used to further confirm Tract-Based Spatial Statistics (TBSS) results. Besides, the results of TBSS among OUD1, OUD2, and HC2 hypothetically served as baseline WM alteration before MMT. RESULTS: Through comparisons among OUD1, OUD2, and HC2, WM aberrances could return to normal after 10-month abstinence, and we used the results as baseline alterations before MMT. MMT patients exhibited a broad imbalance in peripheral immune cells and cytokines, as well as presented insomnia, anxiety, and depression symptoms. After Bonferroni correction, mean diffusivity and radial diffusivity in extensive WM regions were higher in MMT patients than those of HC1. Ultimately, through multimodal correlation analysis, the ‘Interferon-γ (IFN-γ)-WM aberrance-insomnia’ axis was discovered in the MMT group. CONCLUSIONS: Together, these results primarily link cytokines and WM injury for OUDs with MMT to insomnia, implicating pharmacological IFN-γ target as a latent strategy to improve the insomnia of MMT patients.
A common symptom geometry of mood improvement under sertraline and placebo associated with distinct neural patterns - CORRIGENDUM.
Berkovitch L, Lee K, Ji J … +12 more , Helmer M, Rahmati M, Demsar J, Kraljic A, Matkovic A, Tamayo Z, Murray J, Repovs G, Krystal J, Martin W, Fonteneau C, Anticevic A
Psychol Med · 2026 Apr · PMID 42037509 · Full text
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Intrinsic regional brain activity differences and its relationship with neurotransmitter and gene expression in postpartum depression: a voxel-based meta-analysis.
Chen G, Tang X, Chen P … +11 more , Chen R, Chen C, Zhang Y, Wang Z, Li F, Fei J, Lu D, Wang X, Xiao X, Wang Y, Huang X
Psychol Med · 2026 Apr · PMID 42037507 · Full text
BACKGROUND: Inconsistent findings persist across resting-state functional imaging studies of regional brain alterations in postpartum depression (PPD), while connections to transcriptional profiles and neurotransmitter s...
BACKGROUND: Inconsistent findings persist across resting-state functional imaging studies of regional brain alterations in postpartum depression (PPD), while connections to transcriptional profiles and neurotransmitter systems remain largely uncharacterized. METHODS: We performed a whole-brain voxel-wise meta-analysis of resting-state functional imaging studies comparing PPD patients and healthy controls using SDM-PSI software. JuSpace toolbox analyzed atlas-based nuclear imaging-derived neurotransmitter maps, and transcriptional data were sourced from the Allen Human Brain Atlas. RESULTS: Our systematic review identified 12 functional imaging studies (475 PPD patients, 504 controls). Patients with PPD displayed increased resting-state functional activity in the left inferior occipital gyrus and left precuneus as well as decreased resting-state functional activity in the right amygdala and left precentral gyrus. These functional alterations spatially overlapped with serotonergic, dopaminergic, and VAChT systems. Transcriptional analysis revealed PPD-related gene enrichments in ion channel function (transmembrane transport, gated/passive channels) and channel complexes. CONCLUSIONS: The meta-analysis revealed functional alterations within the DMN, limbic, and primary sensorimotor systems in PPD patients. These changes were linked to neurotransmitter alterations and genetic modulations underlying brain dysfunction. Collectively, these findings advance mechanistic understanding of PPD pathophysiology.
Occupational stress, burnout, and depression: an exploration from a network analysis perspective.
Qiao Y, Xu H, Li Y … +4 more , Shi L, Zhen S, He S, Zhang X
Psychol Med · 2026 Apr · PMID 42037499 · Full text
BACKGROUND: Occupational stress triggers psychological/physical health issues, elevating the risk of burnout and depression. This study explored the interrelationships among these constructs via network analysis (undirec...
BACKGROUND: Occupational stress triggers psychological/physical health issues, elevating the risk of burnout and depression. This study explored the interrelationships among these constructs via network analysis (undirected/directed graphs). METHODS: A total of 1363 participants from Beijing hospitals and a university completed House and Rizzo's Work Stress Scale, Zung's Self-Report Depression Scale, and Maslach Burnout Inventory-General Survey. Graphical Gaussian Model and directed acyclic graphs (DAG) identified core/bridge/upstream nodes and causal pathways. RESULTS: Emotional exhaustion (EE) was the core node (expected influence = 2.11). The strongest edge was D11-D12 (weight = 0.46). EE, occupational stress 11, cynicism (CY), and personal accomplishment (PA) served as key bridging nodes. The network showed high stability (0.75). DAG identified upstream occupational stress 1/7/8, confirming direct occupational stress to depression pathways (emotional dysregulation model) and CY/PA mediated pathways (burnout structural theory). CONCLUSIONS: Targeted interventions on core/bridge/upstream nodes may prevent depression onset and progression in occupational settings.
Cognitive reserve in non-affective first-episode psychosis: contributions of polygenic scores, early clinical features, and environment.
Forte MF, Segura ÀG, Serra-Navarro M … +13 more , Mezquida G, Torrent C, Gonzalez-Peñas J, Mas S, Vieta E, Andreu-Bernabeu A, Cuesta MJ, Mané A, de la Serna E, Allott K, Bernardo M, Amoretti S, PEPs Group
Psychol Med · 2026 Apr · PMID 42037495 · Full text
BACKGROUND: Cognitive reserve (CR) is a protective factor in first-episode psychosis (FEP), influencing cognitive, clinical, and functional outcomes. CR is shaped by a combination of genetic, clinical, and environmental...
BACKGROUND: Cognitive reserve (CR) is a protective factor in first-episode psychosis (FEP), influencing cognitive, clinical, and functional outcomes. CR is shaped by a combination of genetic, clinical, and environmental factors, yet the extent of their respective contributions remains unclear. This study investigates the influence of polygenic risk scores (PRS), clinical and environmental variables on CR in FEP. METHODS: A cohort of 174 individuals with non-affective FEP, aged 25.5 (SD=5.3), was analyzed. CR was assessed using a socio-behavioral proxy. PRS for educational attainment (PRS), intelligence (PRS), cognitive performance (PRS), occupational attainment (PRS), physical activity (PRS), and schizophrenia (PRS) were calculated. Age at onset, socioeconomic status, birth weight, and family history of psychosis were considered. Multiple regression models were employed to evaluate the impact of the different predictors on CR. RESULTS: PRS (p=0.002), age at onset (p=5.32x10), and family history of psychosis (p=0.001) emerged as the strongest contributors to CR. Higher PRS was associated with higher levels of CR, while earlier age at onset and positive family history were associated with lower CR. The model incorporating environmental, clinical, and genetic variables explained 17.7% of the variance in CR, and the one without PRS explained 13.5%. The inclusion of PRS in the model improved the explanatory power (Δadj.R=0.042) and predictive accuracy (ΔRMSE=-0.288). CONCLUSIONS: These findings highlight the role of precision psychiatry in better understanding CR. Early identification of individuals with earlier onset, family history of psychosis, and lower genetic predisposition to educational attainment may help characterize those with lower CR.
Unraveling reward processing in schizophrenia and bipolar disorder: a multilevel examination of the positive valence system.
van der Weijden-Germann M, van Haren NEM, Meijer MN … +7 more , Broer MI, Vreeker A, van den Brink-Steinmann LJ, Paludanus S, Ophoff R, Bilder RM, Barendse MEA
Psychol Med · 2026 Apr · PMID 42037492 · Full text
BACKGROUND: The positive valence systems (PVS) domain, a key focus of the Research Domains Criteria framework, divides reward-related processes into three constructs: reward responsiveness, reward learning, and reward va...
BACKGROUND: The positive valence systems (PVS) domain, a key focus of the Research Domains Criteria framework, divides reward-related processes into three constructs: reward responsiveness, reward learning, and reward valuation. Difficulties with several of these reward constructs have been reported in people with mood-psychosis spectrum disorders. This study aims to examine how performance on tasks corresponding to these three constructs covaries, and how performance relates to mood and psychotic symptoms in adults with mood-psychosis spectrum disorders, those at familial risk, and controls. METHODS: Data from two studies ( = 278 and = 332) were analyzed, which both included people with a psychotic disorder or bipolar disorder (patients), their first-degree relatives (FDRs), and controls. PVS constructs were measured using the Multi-Armed Bandit Task, Effort-Expenditure for Rewards Task, and Monetary Incentive Delay Task. Depression, mania, and psychosis symptoms were measured with self-report and interview instruments. Confirmatory factor analysis was used to examine covariation, and path analysis to test associations with symptoms. RESULTS: The three reward constructs showed weak (nonsignificant) covariance in all groups. There were a few impairments in reward-related performance in patients or FDRs, none that survived multiple-comparison correction. There were no associations between symptoms and performance on the PVS constructs after multiple comparisons correction. CONCLUSIONS: The findings showed no evidence that performance on any of the three PVS constructs could constitute an endophenotype of mood-psychosis spectrum disorders. We recommend future research examining the contribution of specific cognitive skills to reward-related behavior, and to sources of heterogeneity in reward functioning within the patient group.
Cognitive performance in offspring of parents with severe mental illness: a meta-analysis.
Adane AA, Dadi A, Jegnie A … +4 more , Tadesse AW, Abate BB, Shepherd CCJ, Dachew B
Psychol Med · 2026 Apr · PMID 42037487 · Full text
Parental severe mental illnesses (SMIs), including schizophrenia, bipolar disorder, and major depressive disorder (MDD), can impact children's well-being, yet existing meta-analyses are limited in scope and methodology a...
Parental severe mental illnesses (SMIs), including schizophrenia, bipolar disorder, and major depressive disorder (MDD), can impact children's well-being, yet existing meta-analyses are limited in scope and methodology and do not comprehensively assess cognitive and academic performance in offspring across SMIs. This meta-analysis aimed to synthesize the existing evidence on the association between parental SMIs and offspring cognitive and academic performance. MEDLINE, EMBASE, PsycINFO, and CINAHL were searched from their inception to December 2025. We included studies assessing associations between parental SMIs and offspring cognitive/academic performance at any age, including attention, memory, language, executive function, processing speed, IQ, social cognition, and academic performance. Standardized mean differences (SMDs) between offspring of parents with SMIs and controls were calculated. Differences in cognitive performance between affected offspring and controls were pooled using random-effects meta-analyses, with robust variance estimation. The meta-analysis included 109 studies (1,586,339 participants). Parental schizophrenia was strongly associated with several cognitive domains, including general cognition (SMD = -1.07, 95% CI: -1.92, -0.22), language (-0.70; -1.20, -0.20), and IQ (-0.53; -0.72, -0.34). Parental bipolar disorder was associated with general cognition (SMD = -0.45, 95% CI = -0.79, -0.12), memory (-0.40; -0.60, -0.19), executive function (-0.34; -0.51, -0.16), IQ (-0.32; -0.48, -0.17), and language (-0.18, 95% CI -0.34, -0.02). Parental MDD showed weaker but statistically significant associations with executive function, general cognition, and language development. Children of parents with SMIs, particularly schizophrenia or bipolar disorder, are at increased risk of cognitive difficulties. Population-level early intervention strategies targeting these families may improve offspring's cognitive performance.
Treatment effect modifiers of virtual reality-based versus standard cognitive behavioral therapy for paranoia in schizophrenia spectrum disorders: an exploratory moderator analysis of clinical and demographic characteristics in the FaceYourFears trial.
Christensen MJ, Vernal DL, Jeppesen UN … +8 more , Hjorthøj C, Mainz J, Pinkham A, Austin S, Veling W, Ward T, Nordentoft M, Glenthøj LB
Psychol Med · 2026 Apr · PMID 42037481 · Full text
BACKGROUND: This exploratory study examined baseline characteristics modifying treatment effects on paranoia in individuals diagnosed with schizophrenia spectrum disorders following a 10-session virtual reality-based cog...
BACKGROUND: This exploratory study examined baseline characteristics modifying treatment effects on paranoia in individuals diagnosed with schizophrenia spectrum disorders following a 10-session virtual reality-based cognitive behavioral therapy for psychosis (VR-CBTp) or standard CBTp. METHODS: All participants in the FaceYourFears trial were included (=254; CBTp =128; VR-CBTp =126). General linear and logistic regression models examined baseline variables associated with end-of-treatment paranoia. In covariate analyses, regression coefficients quantified associations across treatments. In moderation analyses, interaction terms (randomization x moderator) were tested, with corresponding regression coefficients estimated and assessed at the 25th (low), 50th (medium), and 75th (high) percentiles of continuous variables. RESULTS: Across treatments, higher baseline avolition, safety behavior, delusion severity, and cognitive biases were associated with end-of-treatment paranoia. Moderation analyses revealed interactions for avolition, delusion severity, and negative other-beliefs. Although avolition and delusion severity were associated with poorer outcomes overall, individuals with high avolition and those with moderate-to-high delusion severity improved more in VR-CBTp than CBTp, whereas participants with lower delusion severity showed better outcomes in CBTp. No demographic (age, gender, education, and occupation) or other clinical characteristics (diagnosis, paranoia, social anxiety, depression, anhedonia, total negative symptoms, functioning, core beliefs, or interpersonal trauma) were significantly associated with outcome. CONCLUSIONS: This exploratory study generates hypotheses for future research, including VR-CBTp's potential to engage individuals with high avolition. Given the modest effects and largely nonsignificant findings, both CBTp and VR-CBTp appear suitable for a wide range of individuals with paranoia, highlighting the importance of considering patient preferences.
Characterizing executive dysfunctions in patients with schizo-obsessive comorbidity: comparing schizophrenia with obsessive-compulsive disorder.
Chu MY, Zhu NJ, Li SB … +7 more , Wang Y, Yi ZH, Zhang Y, Lv QY, Lui SSY, Wang Z, Chan RCK
Psychol Med · 2026 Apr · PMID 42037477 · Full text
BACKGROUND: The term 'schizo-obsessive comorbidity (SOC)' is used to describe the presence of obsessive-compulsive symptoms or obsessive-compulsive disorder (OCD) in patients with schizophrenia (SOC). Recent studies have...
BACKGROUND: The term 'schizo-obsessive comorbidity (SOC)' is used to describe the presence of obsessive-compulsive symptoms or obsessive-compulsive disorder (OCD) in patients with schizophrenia (SOC). Recent studies have found overlapped executive dysfunctions in SCZ and OCD implicating shared pathophysiology. However, specific deficits in the components of executive function (EF) in patients with SOC remains unclear. METHODS: We recruited 37 patients with SOC, 68 patients with SCZ, 70 patients with OCD, and 59 healthy controls (HCs). All participants completed a battery of measures for EF components, namely initiation, sustained attention, online updating, switching, disinhibition, and planning. Apart from traditional group-mean analysis, we applied machine learning approaches to identify the unique patterns of EF among different clinical groups. RESULTS: The results showed that the three clinical groups could be distinguished from HCs. The feature importance analysis showed that, to classify clinical groups from HC, online updating was the core feature of SCZ patients, whereas disinhibition and online updating jointly determine classification between OCD patients and HC. In differentiating SOC from HC, online updating, planning, and disinhibition collectively served as key features. Machine learning algorithms classified SOC and OCD with acceptable performance but classified SOC and SCZ with lower performance. CONCLUSIONS: Deficits of EF are shared features among patients with SOC, SCZ, and OCD. However, the specific components of executive dysfunction in these clinical groups appeared distinct.
Proneness to infections and familial risk of tic disorders.
Pol-Fuster J, Vasiljevic S, Fernández de la Cruz L … +13 more , Beucke JC, Hesselmark E, Crowley JJ, Brikell I, de Schipper E, D'Onofrio BM, Chang Z, Larsson H, Tedroff K, Lichtenstein P, Kuja-Halkola R, Idring S, Mataix-Cols D
Psychol Med · 2026 Apr · PMID 42015626 · Full text
BACKGROUND: Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this n...
BACKGROUND: Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders. METHODS: Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose-response associations using logistic regression models. RESULTS: Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40-1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12-1.19) in cousins to 1.31 (1.25-1.37) in first-degree relatives. There was a dose-response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives. CONCLUSIONS: Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.
AVATAR versus cognitive-behavioral therapy for medication-resistant auditory hallucination: a systematic review and network meta-analysis.
Hsu TW, Liang CS, Changchien TC … +9 more , Tseng PT, Carvalho AF, Stubbs B, Thompson T, Böge K, Hsu CW, Yang FC, Tu YK, Lin YH
Psychol Med · 2026 Apr · PMID 41969063 · Full text
Auditory hallucinations (AH) frequently persist in schizophrenia spectrum disorder despite antipsychotic treatment. Cognitive behavioral therapy (CBT) remains an established psychological intervention, whereas AVATAR (Au...
Auditory hallucinations (AH) frequently persist in schizophrenia spectrum disorder despite antipsychotic treatment. Cognitive behavioral therapy (CBT) remains an established psychological intervention, whereas AVATAR (Audio Visual Assisted Therapy Aid for Refractory auditory hallucinations) therapy has recently been introduced as a novel approach integrating interactive digital avatars. This meta-analysis compared the efficacy of AVATAR therapy with CBT for medication-resistant AH. A systematic search of five major databases up to June 1, 2025 identified randomized controlled trials (RCTs) that evaluated either therapy. The primary outcome was AH severity, and secondary outcomes included psychotic symptoms, mood measures, and all-cause discontinuation. Twenty-six RCTs (n = 2273; 65.0% male; mean age 39.3 [SD 4.1] years) met inclusion criteria. Compared with CBT, AVATAR therapy showed no significantly greater reduction in AH severity (standardized mean difference [SMD] = -0.23, 95% confidence interval [CI] = -0.55 to 0.10). However, it demonstrated superior sustained improvement three months post-treatment (SMD = -0.37, 95% CI = -0.69 to -0.05) and greater reduction in overall psychotic symptoms (SMD = -0.41, 95% CI = -0.75 to -0.06). No significant differences were observed in positive, negative, depressive, anxiety, or quality-of-life outcomes, and discontinuation rates were comparable. Interpretation should be cautious given evidence of small-study effects (Egger's tests < 0.01 for AH severity) and predominantly moderate-to-high risk of bias across included trials. AVATAR therapy therefore shows lasting efficacy, comparable or slightly superior to CBT, and may serve as an alternative for patients with medication-resistant AH.
What is being measured by formal thought disorder scales? An item-level content analysis.
Sreeraj VS, Voppel A, Venkatasubramanian G … +1 more , Palaniyappan L
Psychol Med · 2026 Apr · PMID 41969055 · Full text
BACKGROUND: Formal thought disorder (FTD), characterized by disruptions in the flow and form of thought, is a core feature of psychosis. But its measurement is fragmented across numerous rating scales, leading to its con...
BACKGROUND: Formal thought disorder (FTD), characterized by disruptions in the flow and form of thought, is a core feature of psychosis. But its measurement is fragmented across numerous rating scales, leading to its continued neglect in both research and clinical practice. To determine if different FTD scales measure the same underlying construct, we need to assess the degree to which the content of commonly used FTD scales overlaps with each other. METHODS: We conducted a systematic review to identify all standardized, clinician-rated scales used to measure FTD in psychotic disorders. From this set, we extracted individual items and derived a consensus list of 56 discrete FTD phenomena. Two independent clinical experts conducted item-to-item mapping for every scale item onto these FTD phenomena. Content overlap between scales was quantified using Jaccard Similarity Index (JSI). We determined the overall coverage achieved via several combinations of FTD scales. RESULTS: The 15 scales, comprising 207 items, showed weak content overlap. The mean JSI across all scale pairs was low, and no single phenomenon featured across all scales. While some core FTD phenomena (e.g. 'incoherence', 'poor speech content', 'drifting-off') were represented in many scales, 20% of all identified features were idiosyncratic, appearing in only one scale. CONCLUSIONS: Existing FTD rating scales capture a wide but heterogeneous array of symptoms with poor content overlap. This lack of harmonization challenges the comparability of mechanistic and interventional studies. We highlight the need for a consensus-based, standardized measurement of FTD and provide a comprehensive checklist to advance the research and clinical practice.
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