Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID.

We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations.

Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21–1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36–1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78–0.88).

Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.

Controlled research examining maintenance treatments for responders to acute interventions for binge-eating disorder (BED) is limited. This study tested efficacy of lisdexamfetamine (LDX) maintenance treatment amongst acute responders.

This prospective randomized double-blind placebo-controlled single-site trial, conducted March 2019 to September 2023, tested LDX as maintenance treatment for responders to acute treatments with LDX-alone or with cognitive-behavioral therapy (CBT + LDX) for BED with obesity. Sixty-one (83.6% women, mean age 44.3, mean BMI 36.1 kg/m2) acute responders were randomized to LDX (N = 32) or placebo (N = 29) for 12 weeks; 95.1% completed posttreatment assessments. Mixed-models and generalized-estimating equations comparing maintenance LDX v. placebo included main/interactive effects of acute (LDX or CBT + LDX) treatments to examine their predictive/moderating effects.

Relapse rates (to diagnosis-level binge-eating frequency) following maintenance treatments were 10.0% (N = 3/30) for LDX and 17.9% (N = 5/28) for placebo; intention-to-treat binge-eating remission rates were 59.4% (N = 19/32) and 65.5% (N = 19/29), respectively. Maintenance LDX and placebo did not differ significantly in binge-eating but differed in weight-loss and eating-disorder psychopathology. Maintenance LDX was associated with significant weight-loss (−2.3%) whereas placebo had significant weight-gain (+2.2%); LDX and placebo differed significantly in weight-change throughout treatment and at posttreatment. Eating-disorder psychopathology remained unchanged with LDX but increased significantly with placebo. Acute treatments did not significantly predict/moderate maintenance-treatment outcomes.

Adults with BED/obesity who respond to acute lisdexamfetamine treatment (regardless of additionally receiving CBT) had good maintenance during subsequent 12-weeks. Maintenance lisdexamfetamine, relative to placebo, did not provide further benefit for binge-eating but was associated with significantly better eating-disorder psychopathology outcomes and greater weight-loss.

There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI).

Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks.

Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular–left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure.

These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse.

Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction.

After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak.

We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Extensive research has focused on the potential benefits of education on various mental and physical health outcomes. However, whether the associations reflect a causal effect is harder to establish.

To examine associations between educational duration and specific aspects of well-being, anxiety and mood disorders, and cardiovascular health in a sample of European Ancestry UK Biobank participants born in England and Wales, we apply four different causal inference methods (a natural policy experiment leveraging the minimum school-leaving age, a sibling-control design, Mendelian randomization [MR], and within-family MR), and assess if the methods converge on the same conclusion.

A comparison of results across the four methods reveals that associations between educational duration and these outcomes appears predominantly to be the result of confounding or bias rather than a true causal effect of education on well-being and health outcomes. Although we do consistently find no associations between educational duration and happiness, family satisfaction, work satisfaction, meaning in life, anxiety, and bipolar disorder, we do not find consistent significant associations across all methods for the other phenotypes (health satisfaction, depression, financial satisfaction, friendship satisfaction, neuroticism, and cardiovascular outcomes).

We discuss inconsistencies in results across methods considering their respective limitations and biases, and additionally discuss the generalizability of our findings in light of the sample and phenotype limitations. Overall, this study strengthens the idea that triangulation across different methods is necessary to enhance our understanding of the causal consequences of educational duration.

The age-related heterogeneity in major depressive disorder (MDD) has received significant attention. However, the neural mechanisms underlying such heterogeneity still need further investigation. This study aimed to explore the common and distinct functional brain abnormalities across different age groups of MDD patients from a large-sample, multicenter analysis.

The analyzed sample consisted of a total of 1238 individuals including 617 MDD patients (108 adolescents, 12–17 years old; 411 early-middle adults, 18–54 years old; and 98 late adults, > = 55 years old) and 621 demographically matched healthy controls (60 adolescents, 449 early-middle adults, and 112 late adults). MDD-related abnormalities in brain functional connectivity (FC) patterns were investigated in each age group separately and using the whole pooled sample, respectively.

We found shared FC reductions among the sensorimotor, visual, and auditory networks across all three age groups of MDD patients. Furthermore, adolescent patients uniquely exhibited increased sensorimotor-subcortical FC; early-middle adult patients uniquely exhibited decreased visual-subcortical FC; and late adult patients uniquely exhibited wide FC reductions within the subcortical, default-mode, cingulo-opercular, and attention networks. Analysis of covariance models using the whole pooled sample further revealed: (1) significant main effects of age group on FCs within most brain networks, suggesting that they are decreased with aging; and (2) a significant age group × MDD diagnosis interaction on FC within the default-mode network, which may be reflective of an accelerated aging-related decline in default-mode FCs.

To summarize, these findings may deepen our understanding of the age-related biological and clinical heterogeneity in MDD.

Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history.

We used data from the Estonian Biobank cohort (N = 111 261) and generated polygenic risk scores (PRS) for ADHD (PRSADHD) based on the ADHD genome-wide association study. We performed a phenome-wide association study (PheWAS) to test for associations between standardized PRSADHD and 1515 EHR-based ICD-10 diagnoses in the full and sex-stratified sample. We compared the observed significant ICD-10 associations to associations with (1) ADHD diagnosis and (2) questionnaire-based high ADHD risk analyses.

After Bonferroni correction (p = 3.3 × 10−5) we identified 80 medical conditions associated with PRSADHD. The strongest evidence was seen with chronic obstructive pulmonary disease (OR 1.15, CI 1.11–1.18), obesity (OR 1.13, CI 1.11–1.15), and type 2 diabetes (OR 1.11, CI 1.09–1.14). Sex-stratified analysis generally showed similar associations in males and females. Out of all identified associations, 40% and 78% were also observed using ADHD diagnosis or questionnaire-based ADHD, respectively, as the predictor.

Overall our findings indicate that ADHD genetic liability is associated with an increased risk of a substantial number of medical conditions in undiagnosed individuals. These results highlight the need for timely detection and improved management of ADHD symptoms in adults.

Epidemiologic research suggests that youth cannabis use is associated with psychotic disorders. However, current evidence is based heavily on 20th-century data when cannabis was substantially less potent than today.

We linked population-based survey data from 2009 to 2012 with records of health services covered under universal healthcare in Ontario, Canada, up to 2018. The cohort included respondents aged 12–24 years at baseline with no prior psychotic disorder (N = 11 363). The primary outcome was days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder according to validated diagnostic codes. Due to non-proportional hazards, we estimated age-specific hazard ratios during adolescence (12–19 years) and young adulthood (20–33 years). Sensitivity analyses explored alternative model conditions including restricting the outcome to hospitalizations and ED visits to increase specificity.

Compared to no cannabis use, cannabis use was significantly associated with psychotic disorders during adolescence (aHR = 11.2; 95% CI 4.6–27.3), but not during young adulthood (aHR = 1.3; 95% CI 0.6–2.6). When we restricted the outcome to hospitalizations and ED visits only, the strength of association increased markedly during adolescence (aHR = 26.7; 95% CI 7.7–92.8) but did not change meaningfully during young adulthood (aHR = 1.8; 95% CI 0.6–5.4).

This study provides new evidence of a strong but age-dependent association between cannabis use and risk of psychotic disorder, consistent with the neurodevelopmental theory that adolescence is a vulnerable time to use cannabis. The strength of association during adolescence was notably greater than in previous studies, possibly reflecting the recent rise in cannabis potency.

The aims were to investigate patterns of labour market integration following an adult diagnosis of attention-deficit/hyperactivity disorder (ADHD) and its relation to sociodemographic factors and comorbid disorders.

Multiple Swedish nationwide registers were used to identify 8045 individuals, aged 20–29, with an incident diagnosis of ADHD 2006–2011. Labour market integration was conceptualized according to the core-peripheral model as a continuum from a strong (core) to a weak (peripheral) connection to the labour market. Sequence analyses categorized clusters of labour market integration, from 1 year before to 5 years after their ADHD diagnosis for individuals diagnosed with ADHD and a matched control group without ADHD. Multinomial logistic regression computed odds ratios (ORs) with 95% confidence intervals (CIs) between sociodemographic factors and comorbid disorders and the identified clusters.

About one-fourth of the young adults diagnosed with ADHD belonged to clusters characterized by a transition to a mainly peripheral labour market position, which was approximately four-times higher compared to controls without ADHD. Foremost, those living in small cities/villages (OR 1.9; CI 1.5–2.2), those having comorbid autism-spectrum disorder (OR 13.7; CI 6.8–27.5) or schizophrenia/psychoses (OR 7.8; CI 3.8–15.9) were associated with a transition towards a peripheral labour market position throughout the study period. Those with a high educational level (OR 0.1; CI 0.1–0.1), and men (OR 0.7; CI 0.6–0.8) were less likely to have a peripheral labour market position.

Young adults diagnosed with ADHD are four-times more likely to be in the peripheral labour market position compared to those without ADHD. To increase labour market participation, special attention is warranted to those with low educational level, those living outside big cities and those with comorbid mental disorders.

Structural anomalies in the frontal lobe and basal ganglia have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, these findings have been not always consistent because of ADHD diversity. This study aimed to identify ADHD subtypes based on cognitive function and find their distinct brain structural characteristics.

Using the data of 656 children with ADHD from the Adolescent Brain Cognitive Development (ABCD) Study, we applied unsupervised machine learning to identify ADHD subtypes using the National Institutes of Health Toolbox Tasks. Moreover, we compared the regional brain volumes between each ADHD subtype and 6601 children without ADHD (non-ADHD).

Hierarchical cluster analysis automatically classified ADHD into three distinct subtypes: ADHD-A (n = 212, characterized by high-order cognitive ability), ADHD-B (n = 190, characterized by low cognitive control, processing speed, and episodic memory), and ADHD-C (n = 254, characterized by strikingly low cognitive control, working memory, episodic memory, and language ability). Structural analyses revealed that the ADHD-C type had significantly smaller volumes of the left inferior temporal gyrus and right lateral orbitofrontal cortex than the non-ADHD group, and the right lateral orbitofrontal cortex volume was positively correlated with language performance in the ADHD-C type. However, the volumes of the ADHD-A and ADHD-B types were not significantly different from those of the non-ADHD group.

These results indicate the presence of anomalies in the lateral orbitofrontal cortex associated with language deficits in the ADHD-C type. Subtype specificity may explain previous inconsistencies in brain structural anomalies reported in ADHD.

Anxiety disorders are highly prevalent and debilitating conditions that show high comorbidity rates in adolescence. The present article illustrates how Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) was adapted for Iranian adolescents with anxiety disorders.

A total of 54 adolescents with comorbid anxiety disorders participated in a randomized, waitlist-controlled trial of group weekly sessions of either UP-A or waitlist control (WLC). Primary and process of change outcomes were assessed at baseline, posttreatment, and 1-month follow-up.

Significant changes were observed over time on major DSM-5 anxiety disorder symptoms (F(2, 51) = 117.09, p < 0.001), phobia type symptoms (F(2, 51) = 100.67, p < 0.001), and overall anxiety symptoms (F(2, 51) = 196.29, p < 0.001), as well as on emotion regulation strategies of reappraisal (F(2, 51) = 17.03, p < 0.001), and suppression (F(2, 51) = 21.13, p < 0.001), as well as on intolerance of uncertainty dimensions including prospective (F(2, 51) = 74.49, p < 0.001), inhibitory (F(2, 51) = 45.94, p < 0.001), and total intolerance of uncertainty (F(2, 51) = 84.42, p < 0.001), in favor of UP-A over WLC.

Overall, results provide a cultural application of the UP-A and support the protocol as useful for improving anxiety disorders as well as modifying of emotion regulation strategies and intolerance of uncertainty dimensions in Iranian adolescents. Future directions and study limitations are discussed.

Aberrant reward functioning is implicated in depression. While attention precedes behavior and guides higher-order cognitive processes, reward learning from an attentional perspective – the effects of prior reward-learning on subsequent attention allocation – has been mainly overlooked.

The present study explored the effects of reward-based attentional learning in depression using two separate, yet complimentary, studies. In study 1, participants with high (HD) and low (LD) levels of depression symptoms were trained to divert their gaze toward one type of stimuli over another using a novel gaze-contingent music reward paradigm – music played when fixating the desired stimulus type and stopped when gazing the alternate one. Attention allocation was assessed before, during, and following training. In study 2, using negative reinforcement, the same attention allocation pattern was trained while substituting the appetitive music reward for gazing the desired stimulus type with the removal of an aversive sound (i.e. white noise).

In study 1 both groups showed the intended shift in attention allocation during training (online reward learning), while generalization of learning at post-training was only evident among LD participants. Conversely, in study 2 both groups showed post-training generalization. Results were maintained when introducing anxiety as a covariate, and when using a more powerful sensitivity analysis. Finally, HD participants showed higher learning speed than LD participants during initial online learning, but only when using negative, not positive, reinforcement.

Deficient generalization of learning characterizes the attentional system of HD individuals, but only when using reward-based positive reinforcement, not negative reinforcement.

Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores.

In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery.

VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls.

Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.

Psychological treatments for young people with sub-threshold or full-syndrome borderline personality disorder (BPD) are found to be effective. However, little is known about the age at which adolescents benefit from early intervention. This study investigated whether age affects the effectiveness of early intervention for BPD.

N = 626 participants (M age = 15 years, 82.7% female) were consecutively recruited from a specialized outpatient service for early intervention in BPD in adolescents aged 12- to 17-years old. DSM-IV BPD criteria were assessed at baseline, one-year (n = 339) and two-year (n = 279) follow-up.

Older adolescents presented with more BPD criteria (χ2 (1) = 58.23, p < 0.001) and showed a steeper decline of BPD criteria over the 2-year follow-up period compared with younger adolescents (χ2 (2) = 13.53, p = 0.001). In an attempt to disentangle effects of early intervention from the natural course of BPD, a parametrized regression model was used. An exponential decrease (b = 0.10, p < 0.001) in BPD criteria was found when starting therapy over the 2-year follow-up. This deviation from the natural course was impacted by age at therapy commencement (b = 0.06, p < 0.001), although significant across all ages: older adolescents showed a clear decrease in BPD criteria, and young adolescents a smaller decrease.

Early intervention appears effective across adolescence, but manifests differently: preventing the normative increase of BPD pathology expected in younger adolescents, and significantly decreasing BPD pathology in older adolescents. The question as to whether developmentally adapted therapeutic interventions could lead to an even increased benefit for younger adolescents, should be explored in future studies.

We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England.

108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models.

Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71–0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74–0.87, p < 0.0001). Referral to substance use services and ‘other’ services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78–0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79–0.94, p = 0.001).

SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.

The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).

The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Cardiovascular disease (CVD) is excessively prevalent and premature in bipolar disorder (BD), even after controlling for traditional cardiovascular risk factors. The increased risk of CVD in BD may be subserved by microvascular dysfunction. We examined coronary microvascular function in relation to youth BD.

Participants were 86 youth, ages 13–20 years (n = 39 BD, n = 47 controls). Coronary microvascular reactivity (CMVR) was assessed using quantitative T2 magnetic resonance imaging during a validated breathing-paradigm. Quantitative T2 maps were acquired at baseline, following 60-s of hyperventilation, and every 10-s thereafter during a 40-s breath-hold. Left ventricular structure and function were evaluated based on 12–15 short- and long-axis cardiac-gated cine images. A linear mixed-effects model that controlled for age, sex, and body mass index assessed for between-group differences in CMVR (time-by-group interaction).

The breathing-paradigm induced a significant time-related increase in T2 relaxation time for all participants (i.e. CMVR; β = 0.36, p < 0.001). CMVR was significantly lower in BD v. controls (β = −0.11, p = 0.002). Post-hoc analyses found lower T2 relaxation time in BD youth after 20-, 30-, and 40 s of breath-holding (d = 0.48, d = 0.72, d = 0.91, respectively; all pFDR < 0.01). Gross left ventricular structure and function (e.g. mass, ejection fraction) were within normal ranges and did not differ between groups.

Youth with BD showed evidence of subclinically impaired coronary microvascular function, despite normal gross cardiac structure and function. These results converge with prior findings in adults with major depressive disorder and post-traumatic stress disorder. Future studies integrating larger samples, prospective follow-up, and blood-based biomarkers are warranted.

One in eight children experience early life stress (ELS), which increases risk for psychopathology. ELS, particularly neglect, has been associated with reduced responsivity to reward. However, little work has investigated the computational specifics of this disrupted reward response – particularly with respect to the neural response to Reward Prediction Errors (RPE) – a critical signal for successful instrumental learning – and the extent to which they are augmented to novel stimuli. The goal of the current study was to investigate the associations of abuse and neglect, and neural representation of RPE to novel and non-novel stimuli.

One hundred and seventy-eight participants (aged 10–18, M = 14.9, s.d. = 2.38) engaged in the Novelty task while undergoing functional magnetic resonance imaging. In this task, participants learn to choose novel or non-novel stimuli to win monetary rewards varying from $0 to $0.30 per trial. Levels of abuse and neglect were measured using the Childhood Trauma Questionnaire.

Adolescents exposed to high levels of neglect showed reduced RPE-modulated blood oxygenation level dependent response within medial and lateral frontal cortices particularly when exploring novel stimuli (p < 0.05, corrected for multiple comparisons) relative to adolescents exposed to lower levels of neglect.

These data expand on previous work by indicating that neglect, but not abuse, is associated with impairments in neural RPE representation within medial and lateral frontal cortices. However, there was no association between neglect and behavioral impairments on the Novelty task, suggesting that these neural differences do not necessarily translate into behavioral differences within the context of the Novelty task.

The Hierarchical Taxonomy of Psychopathology (HiTOP) offers a promising framework to identify the neurobiological mechanisms of psychopathology. Many forms of psychopathology are characterized by dysfunctional emotional reactivity. The late positive potential (LPP) is an event-related potential component that provides an index of neurobiological emotional reactivity. Several categorical disorders have demonstrated a similar association with the emotion-modulated LPP. It is possible that higher-order dimensional representations of psychopathology might explain the comparable results. The present study examined the association between HiTOP-consistent pathological personality dimensions across multiple levels of the hierarchy and neurobiological emotional reactivity.

The sample included 215 18–35-year-old adults (86% female) who were oversampled for psychopathology. Participants completed the emotional interrupt task while electroencephalography was recorded to examine the LPP. Participants also completed the Comprehensive Assessment of Traits relevant to Personality Disorders to assess pathological personality.

At the spectra level, higher negative emotionality was associated with a larger emotion-modulated LPP, while higher detachment was associated with a smaller emotion-modulated LPP. There were no associations between higher-order psychopathology levels and the emotion-modulated LPP. Compared to categorical diagnoses, spectra-level personality pathology dimensions significantly improved the prediction of the emotion-modulated LPP.

The present study indicates that HiTOP spectra levels of negative emotionality and detachment demonstrate unique associations with neurobiological emotional reactivity. The study highlights the utility of examining dimensional and hierarchical, rather than categorical, representations of psychopathology in the attempt to identify the neurobiological origins of psychopathology.

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.

Longitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010–2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence (low, n = 5225 [87.8%]); early increasing, then chronic high prevalence (early-chronic, n = 157 [2.6%]); low, then increasing prevalence (late-increasing, n = 247 [4.2%]); and remitting prevalence (remitting, n = 323 [5.4%]).

After a median follow-up of 7.0 years (range 1.0–11.0), 806 (13.5%) individuals had incident clinically relevant depressive symptoms. After full adjustment, a larger CRAE and CRVE were each associated with a lower risk of clinically relevant depressive symptoms (hazard ratios [HRs] per standard deviation [s.d.]: 0.89 [95% confidence interval (CI) 0.83–0.96] and 0.93 [0.86–0.99], respectively), while a lower flicker light-induced retinal dilation was associated with a higher risk of clinically relevant depressive symptoms (HR per s.d.: 1.10 [1.01–1.20]). Compared to the low trajectory, a larger CRAE was associated with lower odds of belonging to the early-chronic trajectory (OR: 0.83 [0.69–0.99]) and a lower flicker light-induced retinal dilation was associated with higher odds of belonging to the remitting trajectory (OR: 1.23 [1.07–1.43]).

These findings support the hypothesis that cerebral microvascular dysfunction contributes to the development of depressive symptoms.