Non-suicidal self-injury (NSSI) is associated with mental disorders, yet work regarding the direction of this association is inconsistent. We examined the prevalence, comorbidity, time–order associations with mental disorders, and sex differences in sporadic and repetitive NSSI among emerging adults.

We used survey data from n = 72,288 first-year college students as part of the World Mental Health-International College Student Survey Initiative (WMH-ICS) to explore time–order associations between onset of NSSI and mental disorders, based on retrospective age-of-onset reports using discrete-time survival models. We distinguished between sporadic (1–5 lifetime episodes) and repetitive (≥6 lifetime episodes) NSSI in relation to DSM-5 mood, anxiety, and externalizing disorders.

We estimated a lifetime NSSI rate of 24.5%, with approximately half reporting sporadic NSSI and half repetitive NSSI. The time–order associations between onset of NSSI and mental disorders were bidirectional, but mental disorders were stronger predictors of the onset of NSSI (median RR = 1.94) than vice versa (median RR = 1.58). These associations were stronger among individuals engaging in repetitive rather than sporadic NSSI. While associations between NSSI and mental disorders generally did not differ by sex, repetitive NSSI was a stronger predictor for the onset of subsequent substance use disorders among females compared to males. Most mental disorders marginally increased the risk for persistent repetitive NSSI (median RR = 1.23).

Our findings offer unique insights into the temporal order between NSSI and mental disorders. Further work exploring the mechanism underlying these associations will pave the way for early identification and intervention of both NSSI and mental disorders.

Observational studies indicate that higher educational attainment (EA) is associated with a lower risk of many mental health conditions (MHC). We assessed to what extent this association is influenced by genetic nurture and demographic factors (i.e., assortative mating and population structure).

We conducted a within-sibship Mendelian randomization (MR) study. The sample consisted of 61 880 siblings (27 507 sibships) from the Trøndelag Health Study-HUNT (Norway) and UK Biobank (United Kingdom). MHC outcomes included symptom scores for anxiety, depression, and neuroticism, measured using the Hospital Anxiety and Depression Scale, the 7-item Generalized Anxiety Disorder Scale, the 9-item Patient Health Questionnaire, and the Eysenck Personality Questionnaire, along with self-reported psychotropic medication use.

One standard deviation (SD) increase in liability to EA was associated with lower anxiety (−0.20 SD [95% CI: −0.26, −0.14]), depression (−0.11 SD [−0.43, −0.22]), and neuroticism scores (−0.30 SD [−0.53, −0.06]), as well as lower odds of psychotropic medication use (OR: 0.60 [0.52, 0.69]). Within-sibship MR estimates remained consistent with population-based estimates: anxiety (−0.17 SD [−0.33, −0.00]); depression (−0.18 SD [−1.26, 0.89]); neuroticism (−0.29 SD [−0.43, −0.15]); psychotropic medication use (OR, 0.52 [0.34, 0.82]).

Higher EA or genetic liability to education reduces symptoms of anxiety, neuroticism, and psychotropic medication use. These mental health benefits do not seem to be explained by EA-linked genetic nurture or demographic factors. Regarding depression, results were less conclusive due to imprecise estimates, though beneficial effects of genetic liability to higher EA are possible and warrant further investigation.

Contemporary society faces significant challenges that can lead to stress-induced tunnel vision. Positive affect can counteract these effects by expanding humans’ attentional scope, potentially promoting resilience and creativity. This preregistered triple-blind study investigated the role of endogenous opioids in mediating attentional broadening following reward receipt.

Using a placebo-controlled crossover design, 40 volunteers underwent two sessions separated by at least 1 week, receiving either 50 mg of naltrexone or a placebo. Participants completed a Navon letters task designed to contrast the effects of reward receipt versus reward anticipation on attentional scope.

As predicted, our results show that the attentional broadening observed after reward receipt under placebo was eliminated when opioid receptors were blocked. Naltrexone did not result in blunted reward anticipation effects on task performance or attentional narrowing.

This study highlights the role of endogenous opioids in attentional breadth and their potential for cognitive flexibility and resilience through natural positive experiences, with potential implications for mental health and stress management.

Psychomotor disturbance (PmD) is prevalent in major depressive disorder (MDD), with neural substrates implicated in disrupted motor circuits and the interaction to non-motor cortex. Our objective is to explore the functional connectivity pattern underlying PmD using functional magnetic resonance imaging (fMRI).

A total of 150 patients with MDD and 91 healthy controls (HCs) were included in this study. The patients were categorized into psychomotor (pMDD, n = 107) and non-psychomotor (npMDD, n = 43) groups based on the Hamilton Depression Rating Scale. Seed-based connectivity (SBC) analysis was conducted using predefined somatomotor and cerebellar network (SMN and CN) coordinates as seeds, to assess group differences and symptom correlations. Subsequently, we correlated the group-contrast SBC map with existing neurotransmitter maps to explore the neurochemical basis.

In pMDD patients compared to HC, we observed decreased connectivity, especially between the SMN and frontal cortex, within the bilateral SMN, and between the CN and right precentral cortex. Meanwhile, connectivity increased between the SMN and the middle cingulate cortex and between the CN and left precentral cortex in pMDD relative to npMDD and HC. Connectivity between the SMN and angular gyrus was positively correlated with the severity of PmD. Additionally, the aberrant SBC patterns in pMDD were linked to the distribution of dopamine D1 and D2 receptors.

This study provides insights into the aberrant connectivity within the motor circuits and its interactions with non-motor regions in PmD. It also suggests a potential role for dopaminergic dysregulation in the connectivity abnormalities associated with PmD.

Genetic risk scores hold potential for predicting depression in the general population. These scores must be validated for their associations with relevant characteristics of depression-related phenotypes, such as severity. We validated a genome-wide risk score (GRS) and a restricted polygenic risk score (PRS) for depression based on a meta-analysis of three genome-wide association studies and assessed their associations with depression in three subcohorts of middle-aged and older adults from the Dutch population-based Rotterdam Study.

Of participants with genotype data, 9,198 had longitudinally measured data (mean follow-up: 11.3 years) on three depression-related phenotypes (depressive symptoms, depressive syndrome, and major depressive disorder). Generalized linear models estimated the associations of standardized GRS and PRS with depression phenotypes per subcohort and were then meta-analyzed. One unit of the GRS/PRS represents 1 standard deviation, following z-transformation per cohort.

A one unit higher GRS and PRS were associated with any longitudinally measured depression phenotype (odds ratio (OR)GRS = 1.20 [1.15–1.26], ORPRS = 1.10 [1.05–1.16]). Effect sizes were highest for episodes of major depressive disorder: for individuals with the 10% highest GRS and PRS, the ORs were 1.99 [1.53–2.57] and 1.51 [1.13–1.99], respectively, compared to the middle 50% of the distribution.

The GRS and PRS for depression showed modest associations across multiple depression-related phenotypes in a population-based setting. The strength of associations generally increased with the severity of the phenotype. While effect sizes were generally larger for GRS compared to PRS, the difference was mostly not statistically significant.

Schizophrenia spectrum disorders confer an increased and earlier dementia diagnosis risk, but the relative timing and course of cognitive decline compared to individuals with affective disorders is unclear.

This retrospective study used de-identified electronic patient records to compare cognitive trajectories from the first recorded MMSE, representing the earliest cognitive concerns in relation to a possible dementia syndrome, and subsequent dementia risk between patients with a schizophrenia spectrum and primary affective disorder diagnosis. Patients had at least two MMSE scores recorded at least 6 months apart. We examined annual MMSE change from the first recorded MMSE, dementia risk, dementia subtypes, and rates of dementia assessment and treatment.

Compared to affective disorders (n = 2,264; 71.1 years), schizophrenia spectrum disorders (n = 1,217; 65.0 years) showed earlier initial MMSE scores (by 6.1 years, 95% CI = 5.2–7.0), earlier dementia diagnoses (by 2.3 years, 95% CI = 0.9–3.7) but lower dementia risk (adjusted HR = 0.81; 95% CI = 0.69–0.95). Cognitive decline rates and dementia subtype diagnoses did not differ between affective and schizophrenia spectrum disorders, but it took longer for schizophrenia spectrum disorder patients to receive a dementia diagnosis (5.6 vs. 4.4 years). Anti-dementia medication was less likely to be prescribed in patients with schizophrenia versus depression.

Cognitive concerns in older individuals with schizophrenia spectrum disorders arise from around 63 years and are associated with earlier dementia risk versus older individuals with affective disorders. Findings emphasize the importance of targeted dementia prevention and treatment strategies in these individuals and the need to reduce the existing inequity of access to dementia services.

Pharmacological efforts to treat anorexia nervosa (AN) have predominantly repurposed medications that treat conditions with overlapping symptoms and yielded generally disappointing results. Despite limited empirical support, SSRIs are often prescribed to patients with AN. Whether SSRIs are effective in a subgroup of individuals with AN, such as those with depression, is not known.

A secondary analysis of a randomized trial of fluoxetine versus placebo for relapse prevention in AN was conducted. Participants (n = 92) were weight-restored women with AN who completed the Beck Depression Inventory (BDI) at the time of randomization. BDI scores were dichotomized to reflect moderate/severe depression (BDI > 20, n = 26). A Cox Proportional Hazards model estimated the association of the level of depression, medication, and their interaction with time to relapse. Mixed effects models examined the effects of medication on symptom trajectories in high versus low depression groups and whether depression severity modified the effect of the drug on symptom trajectory.

There was a significant interaction between medication and depression severity in time to relapse (hazard ratio = 0.46, 95% CI: [0.25, 0.85], p = .01). Depression severity modified the effect of fluoxetine on the time course of symptoms of depression (β = −0.27, 95% CI: [−0.42,-0.12], p = 0.001) and bulimia (β = −0.15, 95% CI: [−0.25,-0.05], p = 0.004) in the twelve month follow-up period.

Fluoxetine was more effective than placebo in reducing relapse among more depressed, weight-restored individuals with AN. These results require replication but provide support for the use of antidepressant medication for patients with AN who remain depressed following weight restoration.

Psychometric methods are used to remove underperforming items and reduce error in existing measures, albeit different approaches can produce different results. This study aimed to determine the implications of applying different psychometric methods for clinical trial outcomes.

Individual participant data from 15 antidepressant treatment trials from Vivli.org were analyzed. Baseline (pretreatment) and 8-week (range 4–12 weeks) outcome data from the Montgomery-Asberg Depression Rating Scale were subjected to best-practice factor analysis (FA), item response theory (IRT), and network analysis (NA) approaches. Trial outcomes for the original summative scores and psychometric-model scores were assessed using multilevel models. Percentage differences in Cohen’s d effect sizes for the original summative and psychometrically modeled scores were the effects of interest.

Each method produced unidimensional models, but the modified scales varied from 7 to 10 items. Treatment effects (d = 0.072) were unchanged for IRT (10 items), decreased by 1.3%–2.8% (eight-item abbreviated d = 0.070; weighted score d = 0.071) for NA, and increased by 11%–12.5% (seven-item abbreviated model d = 0.081; weighted score d = 0.080) for FA.

IRT and NA yielded negligible differences in effect outcomes relative to original trials. FA increased effect sizes and may be the most effective method for identifying the items on which placebo and treatment group outcomes differ.

The co-occurrence of cannabis use and internalizing symptoms, such as depression and anxiety, during emerging adulthood (18–25 years) is well documented. However, while bidirectional relationships are often assumed, empirical evidence is mixed. This study investigates bidirectional longitudinal relationships between cannabis frequency and consequences and internalizing symptoms (depressive and anxiety) among high-risk emerging adults.

Data came from seven assessments collected over a 2-year period among 961 (54% female) high-risk emerging adults participating in two longitudinal cohorts (Ontario, Canada; Tennessee, USA). Assessments were at 4-month intervals spanning 2018–2020. Latent curve models with structured residuals were used to explore bidirectional between- and within-person relationships between cannabis-related variables and internalizing symptoms.

At baseline, higher levels of cannabis frequency and consequences were associated with higher internalizing symptoms. In between-person model components, cannabis-related and internalizing variables decreased across emerging adulthood. Significant within-person bidirectional relationships were observed, partially supporting both symptom-driven and substance-induced pathways, but the findings were specific to negative cannabis consequences, not frequency, and for depressive symptoms, not anxiety symptoms, for symptom-driven pathways. These bidirectional relationships were more pronounced among females and those surpassing clinical thresholds for internalizing symptoms at baseline.

This study found evidence of bidirectional relationships between cannabis consequences and internalizing symptoms across emerging adulthood, with the prevailing direction from cannabis-related negative consequences to increases in internalizing symptoms. These findings highlight the importance of cannabis intervention in emerging adults, both to reduce consequences and to prevent internalizing disorders, especially targeting females and those with clinically elevated internalizing symptoms.

Childhood irritability and harsh parenting are associated with youth suicide attempts. Parents’ harsh reactions have been associated with children’s irritable behavior. While studies have shown individual associations of irritability and parenting behaviors with suicide risk, few have considered these factors jointly. We aimed to identify profiles of children based on irritability and parenting during childhood and examine their associations with youth suicide attempt.

Participants (N = 1626) were from the Québec Longitudinal Study of Child Development. Mothers reported on childhood irritability, harsh parenting, and positive parenting between ages 3.5 and 8; youth self-reported suicide attempt between ages 13 and 23.

We identified four profiles based on the joint development of irritability and parenting during childhood: (1) low irritability, low harsh parenting, and high positive parenting (30.3%); (2) moderate irritability, moderate harsh parenting, and high positive parenting (28.4%); (3) moderate irritability, moderate harsh parenting, and low positive parenting (26.6%); and (4) high irritability, high harsh parenting, and low positive parenting (14.8%). In logistic regression analyses, only children in the high irritability, high harsh parenting, and low positive parenting profile had higher odds of attempting suicide (OR = 2.51; 95% CI = 1.55–4.09) compared to those in the low irritability, low harsh parenting, and high positive parenting profile. This association remained significant (OR = 1.80; 95% CI = 1.03–3.15) in models adjusting for covariates.

Children with chronically high irritability were also those experiencing the harshest parenting and the least positive parenting, as well as those most at risk of suicide attempt. Targeting both child and parental behavior may maximize suicide prevention efforts among children with high irritability.

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

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

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

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

Although mental disorders have long been considered complex dynamic systems, our understanding of the mutual interactions and temporal patterns of their symptoms remains limited.

In this longitudinal study, we examined the structure and dynamics of four key mental health indicators – depression, anxiety, post-traumatic stress disorder, and insomnia – in a representative sample of the Slovak population (effective N = 3,874) over 10 waves spanning 3.5 years. For each construct, a longitudinal panel network model was estimated.

The temporal relationships between symptoms were mostly weak, with the autoregressive effects typically being stronger. In depression, anxiety, and insomnia, some causal chains and feedback loops were identified. In all constructs, both contemporaneous and between-person networks showed dense connections.

The findings provide critical insights into the complexity of mental health development, offering potential targets for intervention and prevention strategies.

There is a considerable overlap in clinical features and genetics between schizophrenia (SZ) and bipolar disorder (BD). Previous neuroimaging research has demonstrated common and distinct brain damage patterns between relatives (RELs) of SZ and BD patients, suggesting shared and differential genetic influences on the brain. Despite an increasing recognition that disorders localize better to distributed brain networks than individual brain regions, studies investigating network localization of genetic risk for SZ and BD are still lacking.

To address this gap, we initially identified brain functional and structural damage locations in SZ- and BD-RELs from 103 published studies with 2364 SZ-RELs, 864 BD-RELs, and 4114 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional MRI datasets, we mapped these affected brain locations to four disorder-susceptibility networks.

SZ-susceptibility functional damage network primarily involved the executive control and salience networks, while its BD-counterpart principally implicated the default mode and basal ganglia networks. SZ-susceptibility structural damage network predominantly involved the auditory and default mode networks, yet its BD-counterpart mainly implicated the language and executive control networks. Although these networks showed cross-disorder inconsistencies when focusing on either imaging modality alone, the combined SZ- and BD-susceptibility brain damage networks had a substantially increased spatial similarity.

These findings may support the concept that SZ and BD represent distinct diagnostic categories from a neurobiological perspective, helping to clarify the common network substrates via which the shared genetic mechanisms underlying both disorders give rise to their overlapping clinical phenotypes.

With the increased prevalence of major depressive episodes with mixed features specifier (MDE-MFS), the pharmacological treatment for MDE-MFS has attracted great clinical attention. This study aimed to investigate the efficacy and safety of medication use for MDE-MFS.

Commonly used databases were searched for the meta-analysis. Primary efficacy outcomes included response rate and the change in the Young Mania Rating Scale scores; the primary safety outcome was the rate of treatment-emergent hypomania/mania. Effects were expressed as relative risk (RR) or standardized mean difference (SMD).

In patients with MDE-MFS, antipsychotics significantly improved depressive (RR = 1.46 [95% CI: 1.31, 1.61]) and manic (SMD = −0.35 [95% CI: −0.53, −0.17]) symptoms without increasing the risk of manic switch (RR = 0.91 [95% CI: 0.53, 1.55]). However, subgroup analysis of bipolar disorder (BD) patients with MDE-MFS indicated that antipsychotics had limited effects on manic symptoms. Mood stabilizers, especially valproate, demonstrated significant effects in BD patients with MDE-MFS by relieving depressive and manic symptoms. For MDE-MFS in patients with major depressive disorder, trazodone has shown potential effectiveness in retrospective studies, while the effectiveness of antidepressants on BD patients with MDE-MFS lacked evidence.

While antipsychotics are first options for MDE-MFS, their effect on manic symptoms in BD patients with MDE-MFS is still unclear. Mood stabilizers may also be considered, and the use of antidepressants remains a topic of controversy. Since our findings are mostly based on post-hoc analyses, the evidence remains preliminary, highlighting the need for further research to produce more conclusive evidence.

Cortical thickness reductions associated with chronic methamphetamine use exhibit a non-uniform spatial distribution across brain regions. A potential neurobiological mechanism underlying for this heterogeneous pattern may involve the structural and functional organization of cortical connectivity networks, which could mediate the propagation of neuroanatomical alterations. Here, we aimed to explore how brain network architecture constrains cortical thickness alterations and their clinical relevance.

The 3D-T1 images were acquired from 139 patients with methamphetamine use disorder (MUD) and 119 sex- and age-matched healthy controls. We first characterized distributed cortical thinning patterns in patients with MUD, then evaluated the relationships between regional atrophy and (1) multimodal nodal centrality measures (structural, morphological, and functional) and (2) atrophy profiles of structural connected neighbors. Individual network-weighted cortical abnormality maps were used to identify distinct MUD biotypes and related to clinical features through k-means clustering and partial least squares regression.

Cortical thinning patterns demonstrated significant associations with nodal centrality across all modalities, as well as cortical thinning of connected neighbors revealing a network-dependent atrophy architecture. Fronto-temporal regions emerged as critical epicenters, showing both high nodal centrality and strong correlations with connected neighbors’ thinning severity. We found that the individual differences in network-weighted cortical abnormality corresponded to clinical symptom variability, and distinguished two MUD biotypes associated with drug use.

Our findings suggest that cortical thinning in MUD is influenced by the brain connectome architecture, providing a mechanistic framework for understanding individual variability in addiction progression.

Reward can influence cognitive control; however, dysfunctional interactions between reward and cognitive control in adolescents with major depressive disorder (MDD) remain unclear.

We recruited 35 adolescents with MDD and 29 healthy controls (HC) who completed the AX version of the Continuous Performance Test (AX-CPT) under reward and non-reward conditions, while undergoing functional Near-Infrared Spectroscopy (fNIRS).

Adolescents with MDD exhibited slower response times and higher error rates compared to healthy controls. Under reward conditions, they responded more quickly but made more errors. Hierarchical Drift Diffusion Modeling (HDDM) revealed that adolescents with MDD showed a reduced starting bias toward more rewarding responses and a broader decision threshold in reward contexts. Neuroimaging results indicated that the MDD group showed diminished activation differences in the left dorsolateral prefrontal cortex (DLPFC), left ventrolateral prefrontal cortex (VLPFC), and right VLPFC in response to cues requiring high versus low cognitive control. Additionally, they exhibited weaker functional connectivity between these regions during reward-related cognitive control. Correlation analyses further showed that greater anhedonia severity was associated with poorer behavioral performance and less flexible activation in the prefrontal cortex.

Cognitive control impairments in depressed adolescents may be related to dysfunction in the motivational system. Our findings provide behavioral, computational, and neural evidence for the Expected Value of Control (EVC) theory. Diminished reward sensitivity and inflexible cognitive control may jointly contribute to these deficits, highlighting the importance of considering motivational factors in the diagnosis and intervention of cognitive control impairments in adolescents with depression.

The use of cannabis in adolescence and early adulthood, critical phases for brain development, is linked to psychotic-like experiences (PLEs). The underlying mechanisms, however, remain unclear. This research examined the relationship between recreational cannabis use and PLEs, emphasizing the connectivity of the salience network (SN), which plays a role in salience processing and psychosis. To determine whether this relationship reflects shared genetic or environmental contributions, twin modeling was used.

We included 232 healthy adolescent Turkish twins who underwent diffusion MRI and psychometric assessment. SN connectivity was quantified using graph theory metrics. Linear mixed models were used to examine the associations among cannabis use, SN factors, and PLEs. Mediation analyses assessed whether SN parameters explained the cannabis–PLEs association. Twin models disentangle genetic and environmental contributions to these traits and their covariation.

Cannabis use was significantly associated with higher overall PLE frequency. A specific SN factor predicted both total and positive PLEs. However, SN connectivity did not mediate the cannabis–PLEs relationship. Twin modeling showed that cannabis use and PLEs were mainly influenced by unique environmental factors. No significant phenotypic covariations were found among cannabis use, PLEs, and SN parameters.

Recreational cannabis use during adolescence and young adulthood is associated with heightened PLEs, although this association is not mediated by SN connectivity. The environment plays an important role during adolescence in shaping these traits independently. The findings underscore the need for longitudinal and genetically informed studies to clarify the mental health effects of adolescent cannabis use.