Mental health awareness efforts are increasing, especially for ADHD. There is growing evidence that such efforts may also cause unnecessary self-diagnosis and worsening symptoms for some disorders; however, there are no validated approaches to avoid these potential harms without reducing the awareness efforts themselves. We developed a multifaceted intervention, called nocebo education. The intervention was based on the principles of the nocebo effect, where negative expectations may cause symptom misattribution and worsening. We tested whether teaching about the nocebo effect could mitigate the potential false self-diagnosis and symptom worsening from ADHD awareness.

In a double-blind randomized controlled trial with a week-long follow-up (NCT06638411), 215 healthy young adults (77% women) were randomized to participate in a group workshop on either ADHD awareness, ADHD combined with nocebo education, or control (sleep). We measured changes in self-diagnosis and ADHD symptoms immediately after the workshop (self-diagnosis), and 1-week later (self-diagnosis and symptoms).

ADHD group reported substantially higher self-diagnosis scores immediately $ ({\beta}_{\mathrm{standardised}}=0.80\;\left[0.58,1.02\right],p<.001 $) and 1 week after the workshop $ (\beta =0.50\;\left[0.28,0.72\right],p<.001 $) compared to controls. These effects persisted despite no changes in reported symptoms. Nocebo education halved the false self-diagnosis scores immediately after the workshop ($ \beta =0.45\;\left[0.23,0.67\right],p<.001 $) and eliminated the false self-diagnosis entirely at follow-up $ (\beta =0.16\;\left[-0.06,0.38\right],p=.08 $).

We show that being exposed to ADHD awareness reliably increases false self-diagnosis among healthy young adults for at least one week; a brief nocebo education intervention is efficacious in substantially reducing and later eliminating it. Nocebo education is a promising adjunct for balanced awareness efforts that could be applied in various contexts.

Test whether a dissonance-based transdiagnostic eating disorder treatment, body project treatment (BPT), produces greater reduction in brain reward region response to the thin ideal and behaviors used to pursue this ideal and eating disorder symptoms, and higher abstinence from eating disorder behaviors and remittance from eating disorder diagnoses than a matched transdiagnostic interpersonal psychotherapy (IPT).

Women with various eating disorders (N = 83) were randomized to 8-week group-implemented BPT or IPT and completed functional magnetic resonance imaging (fMRI) at pretest and posttest, and surveys and masked diagnostic interviews at pretest, posttest, and 6-month follow-up.

BPT versus IPT participants showed significantly greater reductions in mid cingulate cortex response to thin models, anterior cingulate cortex response to eating disorder behavior words, eating disorder symptoms (d = 0.54), and body dissatisfaction (d = 0.57), and marginally greater reductions in psychosocial impairment (d = 0.39) at posttest, as well as significantly greater reductions in body dissatisfaction (d = 0.68) and psychosocial impairment (d = 0.63), and marginally greater reductions in eating disorder symptoms (d = 0.53) at 6-month follow-up. At posttest, BPT versus IPT participants showed significantly greater abstinence from binge eating and purging (48% versus 23%, respectively) but did not differ on remittance from eating disorder diagnoses (52% versus 44%, respectively).

Results provide further evidence of target engagement for BPT and suggest that it is more effective than IPT in treating a range of eating disorders.

Early intervention (EI) for first-episode psychosis (FEP) mainly focuses on adolescents and young adults. Previous evaluation demonstrated superiority of 2-year EI program (EASY) over standard care in outcome improvement in young people (15–25 years) with FEP in Hong-Kong. However, effectiveness of territory-wide extended EASY, which provides 3-year EI service also to adult patients aged ≥26 years, has not been systematically examined.

This study adopted historical control–case design, comparing patients aged 26–55 years who had received extended EI (EI-group, n = 160) with those managed by standard psychiatric care (SC-group, n = 160) prior to an implementation of extended EI service on a comprehensive range of outcomes encompassing duration of untreated psychosis (DUP), pathway to care, symptom severity, psychosocial functioning, subjective quality of life and service utilization over 3 years of psychiatric follow-up, using systematic medical-record review and follow-up interview assessment.

Our results showed that EI-group had significantly shorter DUP than SC-group. Additionally, EI-group displayed fewer average positive symptoms in the first and second year of follow-up, lower levels of negative and depressive symptoms, better global and social functioning, and higher quality of life on physical domain than SC-group at 3 years of follow-up. Our findings indicate that adult FEP patients receiving 3-year extended EI service had better clinical and functional outcomes than those managed by standard psychiatric care.

Our results thus provide real-world evidence supporting the superiority and implementation of 3-year extended EASY program for adult FEP patients in shortening of treatment delay and improvement of symptom and functional outcomes.

Euthymic bipolar disorder (BD) is associated with general and domain-specific cognitive impairment, which predicts poor occupational and social functioning.

We searched Embase, Medline, and PsycInfo for articles published between database inception and June 2024, examining cognitive domains in euthymic BD. We conducted meta-analysis, meta-regressions, including premorbid IQ, demographic, and clinical variables. Newcastle Ottawa Scale, I2 statistic, and funnel plots/Egger’s and Begg’s Test were used to assess quality, heterogeneity, and publication bias, respectively. The Benjamini-Hochberg (BH) procedure was utilised for multiple comparisons.

We identified 95 groups from 75 studies (N = 4,404 BD & 4,037 HC). BD showed significant impairment in general cognitive functioning (Hedge’s g = −0.58, 95%CI: −0.79, −0.37, p <.01), verbal memory (Hedge’s g = −0.70, 95%CI: −0.79, −0.60, p <.01), executive function (Hedge’s g = −0.69, 95%CI: −0.78, −0.60, p <.01), visuo-spatial memory (Hedge’s g = −0.68, 95%CI: −0.83, −0.53, p <.01), attention/processing speed (Hedge’s g = −0.64, 95%CI: −0.75, −0.54, p <.01), working memory (Hedge’s g = −0.61, 95%CI: −0.74, −0.49, p <.01), and premorbid IQ (Hedge’s g = −0.24, 95%CI: −0.36, −0.12, p <.01). Demographic and clinical factors were not associated with cognitive performance, except for a statistically significant, but small positive correlation between years of education and lower impairment in verbal memory, β = .066, adjusted p <.05.

Our findings highlight cognitive domains impaired in euthymic BD, indicating targets for interventions. Substantial variance is unexplained, warranting focus on larger samples of individual-level data.

Conduct disorder and childhood head injuries frequently co-occur and are linked to a higher risk of later delinquency. While both are known to disrupt reward-related neural circuits, this study investigated whether their combined presence leads to a unique disruption in these pathways, potentially accounting for the increased risk of delinquency.

Using neuroimaging data from the baseline (age 9–10) assessment from the Adolescent Brain and Cognitive Development (ABCD) study, four groups were compared: children with conduct disorder (CD, n = 588), a mild traumatic brain injury (mTBI, n = 1,216), both (mTBI+CD, n = 252), and typically developing controls (TD, n = 705). Neural activation in eight regions of interest (amygdala, hippocampus, nucleus accumbens, caudal anterior cingulate cortex, rostral anterior cingulate cortex, medial orbitofrontal cortex, thalamus, and insula) during reward anticipation and receipt were assessed during the monetary incentive delay task.

After controlling for several covariates, including sex, ADHD, and internalizing problems, the mTBI+CD group displayed greater left amygdala and hippocampal activation during reward receipt compared to all other groups. While they displayed increased activation in the right hippocampus and thalamus compared to TD controls and the right hippocampus compared to the mTBI group, they did not differ from the CD group. No group differences emerged during reward anticipation.

Increased left amygdala and hippocampus activation in children with conduct disorder and a history of mild traumatic brain injury may reflect robust encoding of emotionally charged reward experiences, potentially reinforcing memory-guided, reward-seeking behaviors.

Adolescence is a critical period for brain maturation, influenced by stress and hormonal changes. Chronic stress can lead to increased allostatic load (AL), a cumulative measure of multisystem dysregulation, and insulin resistance (IR), both of which are linked to mental health disorders. We hypothesized that heightened AL and IR during adolescence (age 17) would predict the emergence of mood and psychotic symptoms in young adults.

This study used data from the Avon Longitudinal Study of Parents and Children, a population cohort from Bristol, United Kingdom.

Our results showed that elevated AL at age 17 was significantly associated with the development of mood disorder symptoms (MDS) and psychotic disorder symptoms (PDS) and the co-occurrence of mood and psychotic disorder symptoms (MPDS) at age 24 (p < 0.001). Mean AL increased progressively across these symptom groups, indicating a dose–response relationship between physiological dysregulation and mental health burden (MDS = 3.67, PDS = 3.89, and MPDS = 4.03). We also observed that IR was significantly elevated in the MDS, PDS, and MPDS groups compared to healthy controls (HCs). IR was most prevalent in the PDS group, suggesting a possible association between metabolic dysfunction and psychosis risk.

This study demonstrated that multisystem dysregulation in late adolescence precedes the onset of mood and psychotic symptoms in early adulthood. These results support the use of AL and metabolic markers as early indicators of psychiatric vulnerability and highlight the potential for early intervention targeting systemic dysregulation to prevent the onset of mental health disorders.

If excessive mistrust – for example, holding conspiracy beliefs or experiencing paranoia – is widespread then people should notice it in others. We aimed to assess the degree to which the general population had observed excessive mistrust. Paranoia is a particular form of excessive mistrust. How people understand paranoia, and therefore react to it, could affect its persistence. We also aimed to learn how the general population views paranoia.

A non-probability online survey was conducted in May 2024 with 1,036 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. Nine examples of excessive mistrust in others were presented. Knowledge of paranoia was also assessed.

Participants (n = 698, 67.4%) had most commonly encountered a person ‘Saying that they would not get a COVID-19 vaccination because of concerns about the real motivation behind the vaccine rollout’. Least commonly encountered by participants (n = 328, 31.7%) was a person ‘Thinking that others are targeting them in order to bully or exploit them, and so isolating from the world and refusing to leave their home’. A total of 854 (82.4%) participants had observed at least one form of excessive mistrust in the past year, most frequently in friends. More mistrustful participants were more likely to observe mistrustful behaviors. Participants endorsed multiple causes of paranoia, with the most endorsed causes being worry and illicit drugs.

The large majority of people have encountered others, primarily individuals they know, exhibiting excessive mistrust. Public understanding of paranoia varies greatly, with diverse definitions and perceived causes.

Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability.

Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals.

SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences.

SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.

Accumulating evidence suggests that stress, social relationships, and sex/gender differences in brain function, particularly of the orbitofrontal cortex (OFC), may drive problematic alcohol use. How these factors interact to effect alcohol use, and if they do so differently in men and women, has yet to be explored.

Using a subsample of the publicly available Human Connectome Project data consisting of young adults with problematic alcohol use (N = 491; 41.75% women, ≥1 symptom of alcohol abuse/dependence), we used a moderated moderation approach to test whether perceived stress and sex/gender moderated the effect of a multidimensional measure of social relationship quality on drinking levels. We subsequently tested whether OFC function moderated these effects.

We found that in women, higher friendship and companionship had a protective effect on drinking levels, particularly for women under high stress. In contrast, in men, higher friendship and companionship were linked to increased drinking levels under stress. Preliminary evidence suggested that this effect in men was driven by a subgroup of men with higher OFC reactivity to negative emotional faces.

Our findings suggest that women benefit from friendship and companionship as a form of stress-relief in the context of problematic drinking, whereas men do not, supporting the need of interventions that facilitate emotionally supportive, pro-recovery social environments particularly in men. Preliminary evidence further suggests a role of emotional dysregulation in men. Overall, our findings support the importance of developing sex/gender and neurobiologically informed interventions that target stress-related alcohol use.

Evidence on psychological side effects (PSEs) of antipsychotic medication after remission from first-episode psychosis (FEP), and their momentary impact on daily life, is limited. This study examined how Dopamine-2 (D2) affinity and antipsychotic dosage relate to momentary PSEs.

This ecological momentary assessment (EMA) study included baseline data from 56 participants in the ongoing Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment (HAMLETT) trial. Momentary mental states indicative of reduced affect intensity, stability, and variability, as well as avolition and mental fatigue, were assessed 10×/day for eight days (N = 3,005 data points). Since these PSEs may result from D2-receptor actions, antipsychotics were classified by receptor affinity and mechanism of action. Multilevel mixed-effects regression models examined serial cross-sectional associations between D2 affinity or dosage and concurrent PSEs, both overall and separately for mornings, daytimes, and evenings.

Higher antipsychotic dosages were associated with reduced affect variability (Beta [B] = −1.40 [95% confidence interval [CI]: −2.52; −0.29]) and decreased positive affect stability (B = 0.23 [95% CI: 0.04; 0.42]) and intensity (B = −1.11 [95% CI: −1.97; −0.24]). The latter was also associated with the use of high-affinity D2 antagonists versus partial D2 agonists (B = 12.98 [95% CI: 2.43; 23.53]) and versus low-affinity D2 antagonists (B = 10.04 [95% CI: 0.59; 19.49]). Other PSEs were not associated with D2 affinity/dosage. Results were relatively consistent across daytimes.

Higher antipsychotic dosage and high-affinity D2 antagonists were associated with decreased positive affect after remission from FEP, which may partly drive the frequently reported blunting of emotional experience.

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in children. Abnormalities in sleep metrics among ADHD children gradually garnered attention. However, whether significant differences existed in sleep metrics between ADHD children and their typically developing (TD) counterparts remained controversial, with inconsistent conclusions across studies. Furthermore, the potential moderating effects of age and gender on these differential patterns remained insufficiently characterized.

The current study systematically analyzed multimodal sleep monitoring data (polysomnography, actigraphy, electroencephalography, and questionnaires) from 34 articles spanning three decades (44 independent studies: 2,239 ADHD children vs. 57,181 TD children), focusing on core sleep metrics (total sleep time, sleep efficiency, sleep latency, wake after sleep onset, awakening index, and stage shifts) and their complex moderating mechanisms.

The results demonstrated that ADHD children exhibited impaired sleep continuity (reduced total sleep time, increased stage shifts), severe sleep interruption (prolonged wake after sleep onset, elevated awakening index), and abnormal sleep process effectiveness (decreased sleep efficiency, extended sleep latency). Demographic analyses revealed that maturation exacerbated ADHD-related sleep deficits, and male ADHD children had more severe sleep problems than female ADHD children. Furthermore, the moderating effect of gender composition on the awakening index showed interaction effects with other sleep metrics. In addition, slow-wave sleep acted as both a moderator and mediator in group differences of the awakening index.

These findings provided novel neurodevelopmental explanations for sleep dysregulation in ADHD and proposed clinically translatable strategies involving gender-specific interventions and neuromodulation targeting slow-wave sleep.

Anorexia nervosa has potential to influence the development and function of the gastrointestinal system. We assessed the association between maternal anorexia nervosa and risk of gastrointestinal morbidity in offspring.

We analyzed a longitudinal cohort of 1,269,370 children born in Quebec, Canada, between 2006 and 2022. The exposure was maternal anorexia nervosa. The outcome was hospitalization for pediatric gastrointestinal disorders, including hypertrophic pyloric stenosis, inflammatory bowel disease, and other digestive morbidity. Follow-up ranged from 1 to 17 years. We used adjusted Cox regression models to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal anorexia nervosa and pediatric gastrointestinal disorders.

A total of 2,447 children (0.2%) had a mother with anorexia nervosa. By age 17 years, the cumulative incidence of gastrointestinal disorders was higher among children whose mothers had anorexia nervosa than other children (165.7 vs. 129.4 per 1,000). Compared with no anorexia, maternal anorexia nervosa was associated with a greater risk of any childhood gastrointestinal disorder (HR: 1.42, 95% CI: 1.26–1.61), particularly hypertrophic pyloric stenosis (HR: 2.51, 95% CI: 1.35–4.66), inflammatory bowel disease (HR: 2.46, 95% CI: 1.67–3.64), and rectal hemorrhage (HR: 3.46, 95% CI: 1.97–6.09). Children whose mothers developed anorexia nervosa after age 20 years or were hospitalized more than once for anorexia had the greatest risk of gastrointestinal morbidity. The associations were not explained by digestive birth defects.

Maternal anorexia nervosa is associated with pediatric gastrointestinal disorders that could potentially be mitigated with psychosocial support, nutritional rehabilitation, and breastfeeding.

Adolescence marks a critical period for the onset of anxiety disorders, yet they frequently remain undiagnosed due to barriers such as reluctance to self-disclose symptoms. Objective screening methods that bypass self-report may improve early detection. Speech-derived acoustic markers have emerged as a promising avenue for identifying anxiety disorders. This study investigates associations between acoustic properties of speech, anxiety severity, and anxiety diagnoses in adolescents, evaluated cross-sectionally and longitudinally.

Speech samples from 581 adolescents were collected during the Trier Social Stress Test. Acoustic features were extracted using OpenSMILE and analyzed for cross-sectional associations with anxiety severity (Spearman’s correlations) and longitudinal predictions of future anxiety (linear regressions). Random forest (RF) classifiers with 10-fold cross-validation were used to classify anxious and healthy individuals using acoustic features. Analyses were stratified by sex.

RFs achieved the highest performance for the longitudinal classification of social anxiety disorder (SAD), with an AUC-ROC of 85% (males) and 74% (females). Adding acoustic features to baseline measures increased the variance explained in anxiety by 5.4% (males) and 10.9% (females). In males, higher anxiety was cross-sectionally correlated with reduced pitch slope, narrower pitch range, lower F1 frequency, and greater MFCC1 variability. Females with higher anxiety showed reduced variability in pitch slope. Correlations did not survive multiple testing correction.

Acoustic speech markers elicited in socially evaluative contexts can accurately recognize SAD in male adolescents three years in advance. Performance is moderate for females and other anxiety disorders, underscoring the need for sex-specific approaches to diagnostic tool development.

Major depressive disorder (MDD) patients exhibit a mood-congruent emotional processing bias within the amygdala toward negative facial stimuli at both unconscious and conscious levels. Therefore, our study aimed to investigate the temporal and spatial dynamics of amygdala along with its interactions with the whole brain during implicit and explicit conditions in MDD.

Thirty MDD patients and 26 healthy controls (HCs) underwent magnetoencephalography (MEG) recordings and performed implicit and explicit emotional face recognition tasks with happy, sad, and neutral facial expressions. Using the amygdala as a seed region, time frequency representations (TFR) and functional connectivity (FC) were calculated. Pearson correlation analyses measured the relationship between TFR and FC values with clinical symptoms.

During implicit processing, MDD patients exhibited left amygdala activation in the gamma power (60–70 Hz) before 250 ms in response to sad facial stimuli compared to HCs. In the implicit mode, there were increased FC between the right amygdala and several brain regions in the occipitoparietal lobes, as well as higher FC between the left amygdala and putamen in MDD patients. Additionally, the right amygdala was positively correlated with the severity of depression and anxiety during implicit processing.

MDD patients had lateralized amygdala activation in response to sad facial expressions during unconscious emotional recognition of facial stimuli. Our study provided valuable insights into the spatiotemporal dynamics of facial emotional recognition associated with depressive and anxiety-related cognitive bias during implicit and explicit processing.

Cardiovascular diseases (CVD) and depression frequently co-occur, yet the biological mechanisms underpinning this comorbidity remain poorly understood. This may reflect complex, non-linear associations across multiple biological pathways. We aimed to identify molecular biomarkers linking depressive symptoms and cardiovascular phenotypes using a network-based integrative approach.

Data were obtained from the Young Finns Study (N = 1,686; mean age = 37.7 years; 58.3% female), including 21 depressive symptoms (Beck Depression Inventory), 17 CVD-related indicators, 6 risk factors, 228 metabolomic, and 437 lipidomic variables. Mutual information was used to capture both linear and non-linear associations among variables. A multipartite projection network was constructed to quantify how depressive symptoms and cardiovascular phenotypes are biologically connected via shared metabolites and lipids. Biomarkers were ranked by their contribution to these projected associations. Results were validated in an independent cohort from the UK Biobank.

Specific depressive symptoms – crying, appetite changes, and loss of interest in sex – showed strong projected associations with diastolic blood pressure, systolic blood pressure, and cardiovascular health scores. Key mediators included creatinine, valine, leucine, phospholipids in very large HDL, triglycerides in small LDL, and apolipoprotein B. Important lipid mediators included sphingomyelins, phosphatidylcholines, triacylglycerols, and diacylglycerols. Replication analysis in the UK Biobank identified many overlaps in metabolite profiles, supporting generalizability.

This network-based analysis revealed symptom-specific biological pathways linking CVD and depression. The identified biomarkers may offer insights into shared mechanisms and support future prevention and treatment strategies for cardiometabolic–psychiatric comorbidity.