Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes.

Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups.

The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning.

CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

Evidence suggests a link between smaller hippocampal volume (HV) and post-traumatic stress disorder (PTSD). However, there has been little prospective research testing this question directly and it remains unclear whether smaller HV confers risk or is a consequence of traumatization and PTSD.

U.S. soldiers (N = 107) completed a battery of clinical assessments, including structural magnetic resonance imaging pre-deployment. Once deployed they completed monthly assessments of traumatic-stressors and symptoms. We hypothesized that smaller HV would potentiate the effects of traumatic stressors on PTSD symptoms in theater. Analyses evaluated whether total HV, lateral (right v. left) HV, or HV asymmetry (right – left) moderated the effects of stressor-exposure during deployment on PTSD symptoms.

Findings revealed no interaction between total HV and average monthly traumatic-stressors on PTSD symptoms b = −0.028, p = 0.681 [95% confidence interval (CI) −0.167 to 0.100]. However, in the context of greater exposure to average monthly traumatic stressors, greater right HV was associated with fewer PTSD symptoms b = −0.467, p = 0.023 (95% CI −0.786 to −0.013), whereas greater left HV was unexpectedly associated with greater PTSD symptoms b = 0.435, p = 0.024 (95% CI 0.028–0.715).

Our findings highlight the importance of considering the complex role of HV, in particular HV asymmetry, in predicting the emergence of PTSD symptoms in response to war-zone trauma.

Previous Scandinavian studies have shown increased levels of psychiatric morbidity in young refugees and international adoptees with an origin outside Europe. This study investigated their risk of non-affective psychotic disorders (NAPD) and whether this risk is influenced by early childhood adversity, operationalised as age at adoption/residency, and/or gender.

Register study in Swedish national cohorts born 1972–1990 including 21 615 non-European international adoptees, 42 732 non-European refugees that settled in Sweden at age 0–14 years and 1 610 233 Swedish born. The study population was followed from age 18 to year 2016 for hospitalisations with a discharge diagnosis of NAPD. Hazard ratios (HRs) were calculated in gender stratified Cox regression models, adjusted for household income at age 17.

The adjusted risks of NAPD were 2.33 [95% confidence interval (CI) 2.07–2.63] for the international adoptees and 1.92 (1.76–2.09) for the former child refugees, relative to the Swedish-born population. For the international adoptees there was a stepwise gradient for NAPD by age of adoption from adjusted HR 1.66 (1.29–2.03) when adopted during the first year of life to adjusted HR 4.56 (3.22–6.46) when adopted at ages 5–14 years, with a similar risk pattern in women and men. Age at residency did not influence the risk of NAPD in the refugees, but their male to female risk ratio was higher than in Swedish-born and the adoptees.

The risk pattern in the international adoptees gives support to a link between early childhood adversity and NAPD. Male gender increased the risk of NAPD more among the refugees.

Depression is characterised by a heightened self-focus, which is believed to be associated with differences in emotion and reward processing. However, the precise relationship between these cognitive domains is not well understood. We examined the role of self-reference in emotion and reward processing, separately and in combination, in relation to depression.

Adults experiencing varying levels of depression (n = 144) completed self-report depression measures (PHQ-9, BDI-II). We measured self, emotion and reward processing, separately and in combination, using three cognitive tasks.

When self-processing was measured independently of emotion and reward, in a simple associative learning task, there was little association with depression. However, when self and emotion processing occurred in combination in a self-esteem go/no-go task, depression was associated with an increased positive other bias [b = 3.51, 95% confidence interval (CI) 1.24–5.79]. When the self was processed in relation to emotion and reward, in a social evaluation learning task, depression was associated with reduced positive self-biases (b = 0.11, 95% CI 0.05–0.17).

Depression was associated with enhanced positive implicit associations with others, and reduced positive learning about the self, culminating in reduced self-favouring biases. However, when self, emotion and reward processing occurred independently there was little evidence of an association with depression. Treatments targeting reduced positive self-biases may provide more sensitive targets for therapeutic intervention and potential biomarkers of treatment responses, allowing the development of more effective interventions.

Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology.

The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS.

Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040–0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062).

PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.

Prior work supports delayed gastric emptying in anorexia nervosa and bulimia nervosa (BN) but not binge-eating disorder, suggesting that neither low body weight nor binge eating fully accounts for slowed gastric motility. Specifying a link between delayed gastric emptying and self-induced vomiting could offer new insights into the pathophysiology of purging disorder (PD).

Women (N = 95) recruited from the community meeting criteria for DSM-5 BN who purged (n = 26), BN with nonpurging compensatory behaviors (n = 18), PD (n = 25), or healthy control women (n = 26) completed assessments of gastric emptying, gut peptides, and subjective responses over the course of a standardized test meal under two conditions administered in a double-blind, crossover sequence: placebo and 10 mg of metoclopramide.

Delayed gastric emptying was associated with purging with no main or moderating effects of binge eating in the placebo condition. Medication eliminated group differences in gastric emptying but did not alter group differences in reported gastrointestinal distress. Exploratory analyses revealed that medication caused increased postprandial PYY release, which predicted elevated gastrointestinal distress.

Delayed gastric emptying demonstrates a specific association with purging behaviors. However, correcting disruptions in gastric emptying may exacerbate disruptions in gut peptide responses specifically linked to the presence of purging after normal amounts of food.

Although the DSM-5 was adopted in 2013, the validity of the new substance use disorder (SUD) diagnosis and craving criterion has not been investigated systematically across substances.

Adults (N = 588) who engaged in binge drinking or illicit drug use and endorsed at least one DSM-5 SUD criterion were included. DSM-5 SUD criteria were assessed for alcohol, tobacco, cannabis, cocaine, heroin, and opioids. Craving was considered positive if “wanted to use so badly that could not think of anything else” (severe craving) or “felt a very strong desire or urge to use” (moderate craving) was endorsed. Baseline information on substance-related variables and psychopathology was collected, and electronic daily assessment queried substance use for the following 90 days. For each substance, logistic regression estimated the association between craving and validators, i.e. variables expected to be related to craving/SUD, and whether association with the validators differed for DSM-5 SUD diagnosed with craving as a criterion v. without.

Across substances, craving was associated with most baseline validators (p values<0.05); neither moderate nor severe craving consistently showed greater associations. Baseline craving predicted subsequent use [odds ratios (OR): 4.2 (alcohol) – 234.3 (heroin); p's ⩽ 0.0001], with stronger associations for moderate than severe craving (p's < 0.05). Baseline DSM-5 SUD showed stronger associations with subsequent use when diagnosed with craving than without (p's < 0.05).

The DSM-5 craving criterion as operationalized in this study is valid. Including craving improves the validity of DSM-5 SUD diagnoses, and clinical relevance, since craving may cause impaired control over use and development and maintenance of SUD.

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.

We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.

There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).

Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

It remains unknown whether coronavirus disease 2019 (COVID-19) patients with bipolar disorders (BDs) are at an increased risk of mortality. We aimed to establish whether health outcomes and care differed between patients infected with COVID-19 with BD and patients without a diagnosis of severe mental illness.

We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. We used propensity score matching to control for confounding factors.

In total, 50 407 patients were included, of whom 480 were patients with BD. Patients with BD were 2 years older, more frequently women and had more comorbidities than controls without a diagnosis of severe mental illness. Patients with BD had an increased in-hospital mortality rate (26.6% v. 21.9%; p = 0.034) and similar ICU admission rate (27.9% v. 28.4%, p = 0.799), as confirmed by propensity analysis [odds ratio, 95% confidence interval (OR, 95% CI) for mortality: 1.30 (1.16–1.45), p < 0.0001]. Significant interactions between BD and age and between BD and social deprivation were found, highlighting that the most important inequalities in mortality were observed in the youngest [OR, 95% CI 2.28 (1.18–4.41), p = 0.0015] and most deprived patients with BD [OR, 95% CI 1.60 (1.33–1.92), p < 0.001].

COVID-19 patients with BD were at an increased risk of mortality, which was exacerbated in the youngest and most deprived patients with BD. Patients with BD should thus be targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies.

Exposure to trauma is common and can have a profoundly negative impact on mental health. Interventions based on trauma-focused cognitive behavioural therapy have shown promising results to facilitate recovery. The current trial evaluated whether a novel, scalable and digital early version of the intervention, Condensed Internet-Delivered Prolonged Exposure (CIPE), is effective in reducing post-traumatic stress symptoms.

A single-site randomised controlled trial with self-referred adults (N = 102) exposed to trauma within the last 2 months. The participants were randomised to 3 weeks of CIPE or a waiting list (WL) for 7 weeks. Assessments were conducted at baseline, week 1–3 (primary endpoint), week 4–7 (secondary endpoint) and at 6-month follow-up. The primary outcome measure was PTSD Checklist for DSM-5 (PCL-5).

The main analysis according to the intention-to-treat principle indicated statistically significant reductions in symptoms of post-traumatic stress in the CIPE group as compared to the WL group. The between-group effect size was moderate at week 3 (bootstrapped d = 0.70; 95% CI 0.33–1.06) and large at week 7 (bootstrapped d = 0.83; 95% CI 0.46–1.19). Results in the intervention group were maintained at the 6-month follow-up. No severe adverse events were found.

CIPE is a scalable intervention that may confer early benefits on post-traumatic stress symptoms in survivors of trauma. The next step is to compare this intervention to an active control group and also investigate its effects when implemented in regular care.

A subgroup of patients with anorexia nervosa (AN) undergoing involuntary treatment (IT) seems to account for most of the IT events. Little is known about these patients and their treatment including the temporal distribution of IT events and factors associated with subsequent utilization of IT. Hence, this study explores (1) utilization patterns of IT events, and (2) factors associated with subsequent utilization of IT in patients with AN.

In this nationwide Danish register-based retrospective exploratory cohort study patients were identified from their first (index) hospital admission with an AN diagnosis and followed up for 5 years. We explored data on IT events including estimated yearly and total 5-year rates, and factors associated with subsequent increased IT rates and restraint, using regression analyses and descriptive statistics.

IT utilization peaked in the initial few years starting at or following the index admission. A small percentage (1.0%) of patients accounted for 67% of all IT events. The most frequent measures reported were mechanical and physical restraint. Factors associated with subsequent increased IT utilization were female sex, lower age, previous admissions with psychiatric disorders before index admission, and IT related to those admissions. Factors associated with subsequent restraint were lower age, previous admissions with psychiatric disorders, and IT related to these.

High IT utilization in a small percentage of individuals with AN is concerning and can lead to adverse treatment experiences. Exploring alternative approaches to treatment that reduce the need for IT is an important focus for future research.

Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression.

Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions.

After Bonferroni correction, having a subthreshold psychotic (v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94–2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10–3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38–4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55–7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01–0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset.

Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.

Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.

PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.

Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.

These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers.

Reports of problematic anger were obtained from 7298 US Army soldiers who deployed to Afghanistan in 2012. A series of mixed-effects growth models estimated linear trajectories of anger over a period of 1–2 months before deployment to 9 months post-deployment, and evaluated the effects of pre-deployment factors (prior deployments and perceived resilience) on average levels and growth of problematic anger.

A model with random intercepts and slopes provided the best fit, indicating heterogeneity in soldiers' levels and trajectories of anger. First-time deployers reported the lowest anger overall, but the most growth in anger over time. Soldiers with multiple prior deployments displayed the highest anger overall, which remained relatively stable over time. Higher pre-deployment resilience was associated with lower reports of anger, but its protective effect diminished over time. First- and second-time deployers reporting low resilience displayed different anger trajectories (stable v. decreasing, respectively).

Change in anger from pre- to post-deployment varies based on pre-deployment factors. The observed differences in anger trajectories suggest that efforts to detect and reduce problematic anger should be tailored for first-time v. repeat deployers. Ongoing screening is needed even for soldiers reporting high resilience before deployment, as the protective effect of pre-deployment resilience on anger erodes over time.

We aimed to identify unmet treatment needs for improving social and occupational functioning in early schizophrenia using a data-driven causal discovery analysis.

Demographic, clinical, and psychosocial measures were obtained for 276 participants from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) trial at baseline and 6-months, along with measures of social and occupational functioning from the Quality of Life Scale. The Greedy Fast Causal Inference algorithm was used to learn a partial ancestral graph modeling causal relationships across baseline variables and 6-month functioning. Effect sizes were estimated using a structural equation model. Results were validated in an independent dataset (N = 187).

In the data-generated model, greater baseline socio-affective capacity was a cause of greater baseline motivation [Effect size (ES) = 0.77], and motivation was a cause of greater baseline social and occupational functioning (ES = 1.5 and 0.96, respectively), which in turn were causes of their own 6-month outcomes. Six-month motivation was also identified as a cause of occupational functioning (ES = 0.92). Cognitive impairment and duration of untreated psychosis were not direct causes of functioning at either timepoint. The graph for the validation dataset was less determinate, but otherwise supported the findings.

In our data-generated model, baseline socio-affective capacity and motivation are the most direct causes of occupational and social functioning 6 months after entering treatment in early schizophrenia. These findings indicate that socio-affective abilities and motivation are specific high-impact treatment needs that must be addressed in order to promote optimal social and occupational recovery.

Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia.

A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest.

The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms.

We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD.

In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment.

After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests.

rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Peer victimization is associated with a wide range of mental health problems in youth, yet few studies described its association with mental health comorbidities.

To test the association between peer victimization timing and intensity and mental health comorbidities, we used data from 1216 participants drawn from the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Peer victimization was self-reported at ages 6–17 years, and modeled as four trajectory groups: low, childhood-limited, moderate adolescence-emerging, and high-chronic. The outcomes were the number and the type of co-occurring self-reported mental health problems at age 20 years. Associations were estimated using negative binomial and multinomial logistic regression models and adjusted for parent, family, and child characteristics using propensity score inverse probability weights.

Youth in all peer victimization groups had higher rates of co-occurring mental health problems and higher likelihood of comorbid internalizing-externalizing problems [odds ratios ranged from 2.06, 95% confidence interval (CI) 1.52–2.79 for childhood-limited to 4.34, 95% CI 3.15–5.98 for high-chronic victimization] compared to those in the low victimization group. The strength of these associations was highest for the high-chronic group, followed by moderate adolescence-emerging and childhood-limited groups. All groups also presented higher likelihood of internalizing-only problems relative to the low peer victimization group.

Irrespective of timing and intensity, self-reported peer victimization was associated with mental health comorbidities in young adulthood, with the strongest associations observed for high-chronic peer victimization. Tackling peer victimization, especially when persistent over time, could play a role in reducing severe and complex mental health problems in youth.

Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT.

Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up.

Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring.

MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.

Disorders involving compulsivity, fear, and anxiety are linked to beliefs that the world is less predictable. We lack a mechanistic explanation for how such beliefs arise. Here, we test a hypothesis that in people with compulsivity, fear, and anxiety, learning a probabilistic mapping between actions and environmental states is compromised.

In Study 1 (n = 174), we designed a novel online task that isolated state transition learning from other facets of learning and planning. To determine whether this impairment is due to learning that is too fast or too slow, we estimated state transition learning rates by fitting computational models to two independent datasets, which tested learning in environments in which state transitions were either stable (Study 2: n = 1413) or changing (Study 3: n = 192).

Study 1 established that individuals with higher levels of compulsivity are more likely to demonstrate an impairment in state transition learning. Preliminary evidence here linked this impairment to a common factor comprising compulsivity and fear. Studies 2 and 3 showed that compulsivity is associated with learning that is too fast when it should be slow (i.e. when state transition are stable) and too slow when it should be fast (i.e. when state transitions change).

Together, these findings indicate that compulsivity is associated with a dysregulation of state transition learning, wherein the rate of learning is not well adapted to the task environment. Thus, dysregulated state transition learning might provide a key target for therapeutic intervention in compulsivity.