Neurodevelopmental models regard impulsivity as a central risk factor for adolescent substance use. However, the practical utility of impulsivity in predicting substance use is complicated by variability among measures that encompass multiple methods and theoretical domains. Prior research has been constrained by cross-sectional designs, small sample sizes, and/or the use of a narrow subset of impulsivity measures.

Leveraging the ABCD dataset (n = 11,868), we identified and replicated correlations among impulsivity measures and assessed their prospective longitudinal and concurrent predictive utility regarding adolescent substance use outcomes before 15 years old. We then used simulation to inform how associations between impulsivity and substance use vary across sampling strategies (population vs. high-risk cohorts) and sample sizes.

Correlations between questionnaire and behavioral measures of impulsivity were small, and questionnaires significantly outperformed behavioral measures in predicting substance use initiation, largely due to the contribution of the CBCL externalizing scale. Predictions of substance use based on impulsivity were statistically detectable but small according to clinical standards (AUCs 0.6–0.76), exhibiting sensitivity to sample size and base rate of substance use, and thus, poor absolute predictive performance. Large samples (n > 1,000) were needed to achieve adequate power for impulsivity measures to predict substance use initiation.

These results support a significant but small contribution of impulsivity in predicting the onset of early adolescent substance use, indicating that these factors alone are insufficient for clinically deployable prediction. In community samples, large sample sizes are needed for reproducible impulsivity prediction of adolescent substance use.

People with schizophrenia develop more chronic diseases at a younger age and die younger than people in the general population. It has been hypothesized that this excess morbidity and mortality could be partially due to accelerated aging in schizophrenia. If true, this would motivate the development of ‘gero-protective’ interventions to reduce chronic disease burden in schizophrenia. However, it has been difficult to test this hypothesis, in part, due to the limited ability to measure aging in samples of people with schizophrenia.

We utilized a novel neuroimaging biomarker of the longitudinal pace of aging, DunedinPACNI, to test for accelerated whole-body aging in schizophrenia across four neuroimaging datasets (total N = 2,096, 48% female) accessed through the Lieber Institute for Brain Development, the University of Bari Aldo Moro, and the North American Prodrome Longitudinal Study – 3.

We found consistent evidence of faster DunedinPACNI in schizophrenia compared with controls. In contrast, youth at clinical-high risk for psychosis did not have faster DunedinPACNI compared to controls. Unaffected siblings of patients also did not have faster DunedinPACNI than controls. Faster DunedinPACNI in schizophrenia was not explained by tobacco smoking or antipsychotic medication use.

The results support the hypothesis that schizophrenia is accompanied by accelerated aging. Results were inconsistent with some of the most obvious explanations for accelerated aging in schizophrenia (familial risk, smoking, and iatrogenic medication effects). Research should aim to uncover why people who have schizophrenia age rapidly, as well as the utility of early disease-risk monitoring and anti-aging interventions in schizophrenia.

Seeking to clarify the parent-offspring transmission of Major Depression (MD) and type I Bipolar Disorder (BD), we examined offspring MD and BD risk in five informative parental pairs: Unaffected x MD, Unaffected x BD, MDxMD, MDxBD and BDxBD.

We identified 289,637 individuals born in Sweden 1970-1990, followed through 2018, from parents with MD and/or BD identified from Swedish medical registers. We quantified the MD→MD, BD→BD, MD→BD and BD→MD parent-offspring transmission and explored effects of parental illness on MD→BD conversions.

The risk for MD was modestly and similarly increased in offspring of Unaffected x MD (HR=1.64) and Unaffected x BD parents (HR=1.53), higher in MDxMD and MDxBD pairings (HRs=2.39 and 2.47) and slightly lower in BDxBD matings (HR=2.29). By contrast, risk for BD was much higher in Unaffected x BD versus Unaffected x MD matings (HRs = 5.59 vs. 1.70), further elevated modestly in MDxBD matings (HR=6.26) and very high in BDxBD matings (HR=13.61). The rate of offspring MD→BD conversions was substantially increased by parental BD but not parental MD. Offspring BD was equally predicted by paternal and maternal affective illness while offspring MD was more strongly predicted by maternal than paternal affective illness.

Examining risk for MD and BD in offspring of different parental mating types of MD and BD is an informative strategy for further clarifying the cross-generational transmission of these two partially related and partially distinct mood disorders.

Irritable bowel syndrome (IBS) commonly co-occurs with psychological distress, including depression and anxiety, but the temporal and bidirectional nature of this relationship remains unclear. Dysregulation of the gut–brain–microbiota axis has been proposed as a shared mechanism.

We conducted two retrospective, population-based cohort studies using Taiwan’s National Health Insurance Research Database (2000–2015). Cohort 1 assessed the risk of incident IBS among patients with newly diagnosed depression or anxiety, while Cohort 2 evaluated the risk of subsequent depression or anxiety among patients with newly diagnosed IBS. Propensity score matching, multivariable Cox regression, and Fine–Gray competing risk models were applied.

IBS was associated with increased risks of depression (adjusted hazard ratio [aHR] = 1.55) and anxiety (aHR = 1.68). Conversely, depression and anxiety were associated with higher risks of developing IBS (aHR = 1.45 and 1.51, respectively). Associations were stronger among females and younger adults aged 18–39 years. Sleep disorders (SDs) showed the strongest modifying effect in both directions (sub-distribution HR ≈ 1.60). Results were consistent across sensitivity analyses.

This nationwide longitudinal study demonstrates a robust bidirectional association between IBS and psychological distress, supporting integrated screening and multidisciplinary care approaches targeting gut–brain interactions.

Parenting is related to the development of callous-unemotional (CU) traits (i.e. low empathy and restricted guilt), making it an important target of interventions for childhood conduct problems (CPs). However, the relative importance of different parenting features in relation to the development of CU traits remains unclear. This study used machine learning to examine multiple parenting features assessed across infancy and early childhood as predictors of CU traits and CPs in early adolescence.

Data were from the Family Life Project (N = 1,292; 49% female, 41% Black, and 28% below the poverty line). Seventy-four parenting predictors were assessed at eight time points between children aged 6–90 months using parent-reported questionnaires and observer ratings of videotaped interactions and home visits. CU traits and CPs were assessed via parent-reported questionnaires in preadolescence (12–14 years).

Parenting features explained 8.2% of CU traits variability in preadolescence, with top predictors including early sensitive parenting and later behavior management and scaffolding practices. Prediction of CPs was weaker, with parenting explaining 4.5% of the variability.

Results highlight that disruption in close and sensitive early parent–child relationships is relevant to the development of CU traits. Results from the prediction of CPs indicate a more heterogeneous etiology. Findings support targeting parental sensitivity and behavior management within preventative interventions for CU traits and CPs.

Children with attention-deficit/hyperactivity disorder (ADHD) frequently exhibit impairing emotional dysregulation along with inattention and hyperactivity. We aim to parse the heterogeneity of behavioral and emotional dysregulation in ADHD using latent brain factors based on cortical thickness (CT), and examine associated differences in intrinsic functional connectivity (iFC).

Data were collected from 123 children (39 ADHD, 47 ADHD with impairing emotional outbursts [ADHD + IEO], 37 neurotypical controls [NT], 5–9.9 years old). First, exploratory factor analysis revealed latent behavioral factors. Using Latent Dirichlet allocation, we decomposed heterogeneous CT patterns into parsimonious latent brain factors. We further investigated the functional relevance of brain regions showing structural differences in the ADHD + IEO group and examined associations between brain and behavioral latent factors.

Among the four behavioral factors identified (Externalizing, Emotion Dysregulation, Internalizing, and Surgency/Impulsivity), the dominant factor – Externalizing behavior – significantly differentiated the ADHD + IEO from the ADHD and NT groups. A conjunction analysis of the three brain factors revealed significantly thicker CT in the dorsolateral prefrontal cortex for ADHD + IEO compared to NT. Using this region as a seed, we found reduced functional connectivity primarily in the default mode network, which differentiated ADHD + IEO and ADHD groups. Structural brain and iFC measures showed significant associations with the Externalizing behavior factor.

Parsing the neurobiology underlying the heterogeneous presentation of ADHD requires integrating multiple modalities and analytical methods. This study demonstrates that combining behavioral, structural, and functional data reveals unique neural features associated with behavioral and emotional dysregulation.

Neuroimaging studies have consistently revealed neuroanatomical abnormalities in individuals with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). However, it remains unknown whether and to what extent disorder-selective gray matter variations occur in these prominent psychiatric disorders. This study conducted a meta-analysis of 25 years of published voxel-based morphometry (VBM) research to assess the presence of selective and robust neuroanatomical substrates of gray matter variation in BD, MDD, and SZ.

Peer-reviewed experiments encompassing subjects with target disorders were systematically searched in the MEDLINE database. Additionally, peer-reviewed data on 30 other psychiatric disorders and 65 neurological diseases were obtained from the BrainMap database. Experiments reporting whole-brain group comparisons between patients and healthy controls were included if they identified significant reductions in gray matter morphometry.

The data were analyzed using the Bayes fACtor mOdeliNg algorithm. A total of 1,021 VBM experiments were included, comprising 29,540 patients and 28,177 healthy controls. Primary analyses of psychiatric data revealed strong evidence of gray matter reduction in the right middle temporal gyrus for BD and the posterior dorsal anterior cingulate cortex for SZ (P ≥ 95% selectivity). The robustness of these findings was confirmed using the fail-safe method tailored to the neuroimaging meta-analytic environment. No selective findings were observed in additional analyses that included neurological diseases.

Taken together, these findings offer a framework that underscores the significance of diagnosis-selective neural substrates in psychopathology, a new perspective that could inform distinct pathophysiological processes and assist in diagnosis and treatment.

There is evidence that the two most common subtypes of functional neurological disorder, functional seizures (FSs) and functional motor symptoms (FMDs), have differences between them beyond symptom type, creating debate as to whether they may best be considered distinct disorders. However, most research has studied FS or FMD separately, and the few studies that have directly compared them have been relatively small. We used the large TriNetX electronic health database to see whether the differences previously identified would be confirmed in a larger sample of both subtypes.

All cases of FMD without FS were compared with cases of FS without FMD, extracted from the TriNetX electronic health records database. Previously identified between-group differences in demographics, comorbidity, and antecedents were compared between groups.

Over 120,000 cases of FMD and FS were extracted. They confirmed that people with FS were significantly younger and had a younger onset than those with FMD, were more likely to be Black and less likely to be Asian, and had higher rates of all comorbid mental health diagnoses, other than somatoform diagnoses, which were more common in FMD. The onset of FS was more commonly preceded by psychological injury, as measured by preceding depression or stress reactions.

The differences between FMD and FS previously identified in small studies were confirmed in this much larger dataset. They provide indirect support for differences in etiology and mechanism, which may in turn support a nosological distinction between FMD and FS.

Functional magnetic resonance imaging (fMRI) has revealed inconsistent neural activity patterns in major depressive disorder (MDD) across cognitive and affective domains, and this study used an activation likelihood estimation (ALE) meta-analysis to examine brain function abnormalities in working memory, reward processing, and emotion processing.

A systematic search was conducted in PubMed, Embase, Web of Science, ScienceDirect, and CNKI for fMRI studies comparing MDD patients with healthy controls (HCs), including data up to 3 December 2024. ALE meta-analysis was performed to examine activation patterns. Jackknife sensitivity analysis, risk of bias, and Newcastle–Ottawa scale were used to assess robustness and publication bias. Meta-regression analyses were conducted to explore the impact of covariates on the results.

Sixty-nine studies (2,073 MDD individuals and 2,009 HCs) were included. MDD individuals showed hyperactivation in the bilateral parahippocampal gyrus, subcallosal gyrus, lentiform nucleus, left claustrum, insula, and anterior cingulate cortex, alongside hypoactivation in the right lentiform nucleus, parahippocampal gyrus, fusiform gyrus, and other regions. Domain-specific analyses revealed working memory-related hyperactivation in the right middle and superior frontal gyrus, reward-related hyperactivation in the bilateral lentiform nucleus, right claustrum, and left caudate, and emotion-related hyperactivation in the bilateral parahippocampal gyrus, bilateral lentiform nucleus, right subcallosal gyrus, right anterior cingulate cortex, and left claustrum. Jackknife sensitivity analysis confirmed robustness, with no significant publication bias or covariate impact.

Aberrant activation in the lentiform and caudate nuclei across reward and emotion tasks suggests striatal dysfunction plays a key role in emotion-motivation interplay, highlighting the striatum as a potential target for future therapies.