This confirmatory study aimed to examine whether we can foresee recurrence of depressive symptoms using personalized modeling of rises in restlessness.

Participants were formerly depressed patients (N = 41) in remission who (gradually) discontinued antidepressants. Participants completed five smartphone-based Ecological Momentary Assessments (EMA) a day, for a period of 4 months, yielding a total of 21 180 observations. Statistical Process Control by means of Exponentially Weighted Moving Average (EWMA) control charts was used to detect rises in the EMA item ‘I feel restless’, for each individual separately.

An increase in restlessness was detected in 68.3% of the participants with recurring depressive symptoms, and in 26.3% of those who stayed in remission (Fisher's exact test p = 0.01, sensitivity was 68.3%, specificity was 73.7%). In the participants with a recurrence and an increase in restlessness, this increase could be detected in the prodromal phase of depression in 93.3% of the cases and at least a month before the onset of the core symptoms of depression in 66.7% of the cases.

Restlessness is a common prodromal symptom of depression. The sensitivity and specificity of the EWMA charts was at least as good as prognostic models based on cross-sectional patient characteristics. An advantage of the current idiographic method is that the EWMA charts provide real-time personalized insight in a within-person increase in early signs of depression, which is key to alert the right patient at the right time.

Successful interventions have been developed for smoking cessation although the success of smoking relapse prevention protocols has been limited. Cognitive behavioural therapy (CBT) in particular has been hampered by a high relapse rate. Because relapse can be due to conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality cue exposure therapy (VRCE) can be a potential tool to generate 3D interactive environments that simulate risk situations for relapse prevention procedures.

To assess the effectiveness of VRCE with CBT, a comparative trial involving 100 smoking abstinent participants was designed with all required virtual environments (VE) created with an inexpensive graphic engine/game level editor.

Outcome measures confirmed the immersive and craving eliciting effect of these VEs. Results demonstrated that more participants in the VRCE group did not experience smoking relapse and that VRCE is at least as efficacious as traditional CBT in terms of craving reduction and decrease in nicotine dependence. Dropout and relapse rate in the VRCE group was noticeably lower than the CBT group. Aside from mood scores, no significant differences were found regarding the other scales.

The present clinical trial provides evidence that VRCE was effective in preventing smoking relapse. Improvement in technology and methodology for future research and applications is delineated.

Personality traits (e.g. neuroticism) and the social environment predict risk for internalizing disorders and suicidal behavior. Studying these characteristics together and prospectively within a population confronted with high stressor exposure (e.g. U.S. Army soldiers) has not been done, yet could uncover unique and interactive predictive effects that may inform prevention and early intervention efforts.

Five broad personality traits and social network size were assessed via self-administered questionnaires among experienced soldiers preparing for deployment (N = 4645) and new soldiers reporting for basic training (N = 6216). Predictive models examined associations of baseline personality and social network variables with recent distress disorders or suicidal behaviors assessed 3- and 9-months post-deployment and approximately 5 years following enlistment.

Among the personality traits, elevated neuroticism was consistently associated with increased mental health risk following deployment. Small social networks were also associated with increased mental health risk following deployment, beyond the variance accounted for by personality. Limited support was found for social network size moderating the association between personality and mental health outcomes. Small social networks also predicted distress disorders and suicidal behavior 5 years following enlistment, whereas unique effects of personality traits on these more distal outcomes were rare.

Heightened neuroticism and small social networks predict a greater risk for negative mental health sequelae, especially following deployment. Social ties may mitigate adverse impacts of personality traits on psychopathology in some contexts. Early identification and targeted intervention for these distinct, modifiable factors may decrease the risk of distress disorders and suicidal behavior.

Maternal suicide attempts are associated with adverse psychosocial outcomes in children, but the association with chronic morbidity is poorly understood. We examined the relationship between maternal suicide attempt and risk of hospitalization for potentially preventable conditions in offspring.

We analyzed a longitudinal cohort of 1 032 210 children born in Quebec, Canada between 2006 and 2019. The main exposure measure was maternal suicide attempt before or during pregnancy. Outcomes included child hospitalizations for potentially preventable conditions, including infectious diseases, dental caries, atopy, and injury up to 14 years after birth. We used adjusted Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal suicide attempt with risk of hospitalization for these outcomes.

Compared with no suicide attempt, children whose mothers attempted suicide had an increased risk of hospitalization for infectious diseases (HR 1.11, 95% CI 1.06–1.16), dental caries (HR 1.31, 95% CI 1.15–1.48), and injury (HR 1.16, 95% CI 1.03–1.31). Risk of hospitalization for any of these outcomes was greater if mothers attempted suicide by hanging (HR 1.46, 95% CI 1.22–1.75), had their first attempt between the age of 25 and 34 years (HR 1.27, 95% CI 1.13–1.42), and had 3 or more attempts (HR 1.56, 95% CI 1.27–1.91). Maternal suicide attempts were more strongly associated with child hospitalization before 10 years of age.

Children whose mothers have a history of suicide attempt have an elevated risk of hospitalization for potentially preventable conditions.

Racial/ethnic differences in mental health outcomes after a traumatic event have been reported. Less is known about factors that explain these differences. We examined whether pre-, peri-, and post-trauma risk factors explained racial/ethnic differences in acute and longer-term posttraumatic stress disorder (PTSD), depression, and anxiety symptoms in patients hospitalized following traumatic injury or illness.

PTSD, depression, and anxiety symptoms were assessed during hospitalization and 2 and 6 months later among 1310 adult patients (6.95% Asian, 14.96% Latinx, 23.66% Black, 4.58% multiracial, and 49.85% White). Individual growth curve models examined racial/ethnic differences in PTSD, depression, and anxiety symptoms at each time point and in their rate of change over time, and whether pre-, peri-, and post-trauma risk factors explained these differences.

Latinx, Black, and multiracial patients had higher acute PTSD symptoms than White patients, which remained higher 2 and 6 months post-hospitalization for Black and multiracial patients. PTSD symptoms were also found to improve faster among Latinx than White patients. Risk factors accounted for most racial/ethnic differences, although Latinx patients showed lower 6-month PTSD symptoms and Black patients lower acute and 2-month depression and anxiety symptoms after accounting for risk factors. Everyday discrimination, financial stress, past mental health problems, and social constraints were related to these differences.

Racial/ethnic differences in risk factors explained most differences in acute and longer-term PTSD, depression, and anxiety symptoms. Understanding how these risk factors relate to posttraumatic symptoms could help reduce disparities by facilitating early identification of patients at risk for mental health problems.

Among individuals with alcohol use disorder (AUD) and drug use disorder (DUD), is their genetic liability and its specificity moderated by substance availability?

Offspring (born 1960–1995) and their biological parents from three family types [not-lived-with (NLW) biological father, mother and adoptive] and their AUD and DUD diagnoses were ascertained from Swedish national registers. Parent–offspring resemblance was calculated by tetrachoric correlation.

In Swedes born from 1960 to 1995, prevalence rates of AUD were stable while DUD rates increased substantially. Best-estimate tetrachoric correlations (±95% confidence intervals) between AUD in biological parents and AUD and DUD in their offspring were, respectively, +0.19 (0.18–0.20) and +0.18 (0.17–0.20). Parallel results from DUD in parents to AUD and DUD in children were +0.12 (0.10–0.13) and +0.27 (0.26–0.28). When divided into older and younger cohorts, the specificity of DUD transmission increased substantially over time, while the genetic correlation between AUD and DUD significantly decreased.

Raised when alcohol was the preferred substance of abuse and illicit drugs highly stigmatized, AUD in parents reflected a general liability to substance use disorders, as they transmitted similar genetic risk for AUD and DUD to their children raised when both substances were widely available and relatively acceptable. DUD in parents, by contrast, reflected a more specific liability to DUD and, when transmitted to offspring, produced a considerably stronger risk for DUD than for AUD that increased over time. The magnitude and specificity of the genetic liability to psychoactive substances can be influenced by the availability of that substance.

Schizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample.

Participants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length.

Two clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group.

This study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

There is significant heterogeneity in cognitive function in patients with bipolar I disorder (BDI); however, there is a dearth of research into biological mechanisms that might underlie cognitive heterogeneity, especially at disease onset. To this end, this study investigated the association between accelerated or delayed age-related brain structural changes and cognition in early-stage BDI.

First episode patients with BDI (n = 80) underwent cognitive assessment to yield demographically normed composite global and domain-specific scores in verbal memory, non-verbal memory, working memory, processing speed, attention, and executive functioning. Structural magnetic resonance imaging data were also collected from all participants and subjected to machine learning to compute the brain-predicted age difference (brainPAD), calculated by subtracting chronological age from age predicted by neuroimaging data (positive brainPAD values indicating age-related acceleration in brain structural changes and negative values indicating delay). Patients were divided into tertiles based on brainPAD values, and cognitive performance compared amongst tertiles with ANCOVA.

Patients in the lowest (delayed) tertile of brainPAD values (brainPAD range −17.9 to −6.5 years) had significantly lower global cognitive scores (p = 0.025) compared to patients in the age-congruent tertile (brainPAD range −5.3 to 2.4 yrs), and significantly lower verbal memory scores (p = 0.001) compared to the age-congruent and accelerated (brainPAD range 2.8 to 16.1 yrs) tertiles.

These results provide evidence linking cognitive dysfunction in the early stage of BDI to apparent delay in typical age-related brain changes. Further studies are required to assess how age-related brain changes and cognitive functioning evolve over time.

Moral injury exposure (MIE) and distress (MID) may indirectly affect the relationship between trauma exposure and alterations in autonomic regulation [assessed via high-frequency heart rate variability (hfHRV)] in civilians, but this has not been tested in prior research. We conducted two exploratory studies to examine trauma types' associations with MIE and MID among civilian medical patients (Study 1) and explore how these facets may indirectly affect the relationship between trauma type and hfHRV among civilians seeking mental health services (Study 2).

Participants recruited from a public hospital and/or community advertisements (Study 1, n = 72, 87.5% Black, 83.3% women; Study 2, n = 46, 71.7% Black, 97.8% women) completed measures assessing trauma type, MIE, and MID. In Study 1, trauma types that emerged as significant correlates of MIE and MID were entered into separate linear regression analyses. Trauma types identified were included as predictors in indirect effects models with MIE or MID as the mediator and resting hfHRV (assayed via electrocardiography) as the outcome.

Childhood sexual abuse emerged as the only significant predictor of MIE, b = 0.38, p < 0.001; childhood sexual abuse, b = 0.26, p < 0.05, and adulthood sexual assault, b = 0.23, p < 0.05 were significant predictors of MID. Participants with greater MIE and MID demonstrated lower hfHRV. Adulthood sexual assault showed an indirect effect on hfHRV through MID, B = −0.10, s.e. = 0.06, 95%CI (−0.232 to −0.005).

Moral injury was uniquely associated with sexual violence and lower hfHRV in civilians. Data highlight moral injury as a pathway through which autonomic dysregulation may emerge and its salience for trauma treatment selection.

Adolescence is characterized by profound change, including increases in negative emotions. Approximately 84% of American adolescents own a smartphone, which can continuously and unobtrusively track variables potentially predictive of heightened negative emotions (e.g. activity levels, location, pattern of phone usage). The extent to which built-in smartphone sensors can reliably predict states of elevated negative affect in adolescents is an open question.

Adolescent participants (n = 22; ages 13–18) with low to high levels of depressive symptoms were followed for 15 weeks using a combination of ecological momentary assessments (EMAs) and continuously collected passive smartphone sensor data. EMAs probed negative emotional states (i.e. anger, sadness and anxiety) 2–3 times per day every other week throughout the study (total: 1145 EMA measurements). Smartphone accelerometer, location and device state data were collected to derive 14 discrete estimates of behavior, including activity level, percentage of time spent at home, sleep onset and duration, and phone usage.

A personalized ensemble machine learning model derived from smartphone sensor data outperformed other statistical approaches (e.g. linear mixed model) and predicted states of elevated anger and anxiety with acceptable discrimination ability (area under the curve (AUC) = 74% and 71%, respectively), but demonstrated more modest discrimination ability for predicting states of high sadness (AUC = 66%).

To the extent that smartphone data could provide reasonably accurate real-time predictions of states of high negative affect in teens, brief ‘just-in-time’ interventions could be immediately deployed via smartphone notifications or mental health apps to alleviate these states.

Persistent psychological distress associated with the coronavirus disease 2019 (COVID-19) pandemic has been well documented. This study aimed to identify pre-COVID brain functional connectome that predicts pandemic-related distress symptoms among young adults.

Baseline neuroimaging studies and assessment of general distress using the Depression, Anxiety and Stress Scale were performed with 100 healthy individuals prior to wide recognition of the health risks associated with the emergence of COVID-19. They were recontacted for the Impact of Event Scale-Revised and the Posttraumatic Stress Disorder Checklist in the period of community-level outbreaks, and for follow-up distress evaluation again 1 year later. We employed the network-based statistic approach to identify connectome that predicted the increase of distress based on 136-region-parcellation with assigned network membership. Predictive performance of connectome features and causal relations were examined by cross-validation and mediation analyses.

The connectome features that predicted emergence of distress after COVID contained 70 neural connections. Most within-network connections were located in the default mode network (DMN), and affective network-DMN and dorsal attention network-DMN links largely constituted between-network pairs. The hippocampus emerged as the most critical hub region. Predictive models of the connectome remained robust in cross-validation. Mediation analyses demonstrated that COVID-related posttraumatic stress partially explained the correlation of connectome to the development of general distress.

Brain functional connectome may fingerprint individuals with vulnerability to psychological distress associated with the COVID pandemic. Individuals with brain neuromarkers may benefit from the corresponding interventions to reduce the risk or severity of distress related to fear of COVID-related challenges.

Stress is associated with binge eating and emotional eating (EE) cross-sectionally. However, few studies have examined stress longitudinally, limiting understanding of how within-person fluctuations in stress influence EE over time and whether stress is a risk factor or consequence of EE. Additionally, little is known regarding how the biological stress response relates to EE.

We used an intensive, longitudinal design to examine between-person and within-person effects of major life stress, daily stress, and cortisol on EE in a population-based sample of women (N = 477; ages 15–30; M = 21.8; s.d. = 3.0) from the Michigan State University Twin Registry. Participants reported past year major life stress, then provided daily ratings of EE and stress for 49 consecutive days. Hair cortisol concentration (HCC) was collected as a longitudinal biological stress measure.

Women reported greater EE when they experienced greater mean stress across days (between-person effects) or greater stress relative to their own average on a given day (within-person effects). Daily stress was more strongly associated with EE than major life stress. However, the impact of daily stress on EE was amplified in women with greater past year major life stress. Finally, participants with lower HCC had increased EE.

Findings confirm longitudinal associations between stress and EE in women, and highlight the importance of within-person shifts in stress in EE risk. Results also highlight HCC as a novel biological stress measure that is significantly associated with EE and may overcome limitations of prior physiological stress response indicators.

Despite the significant psychosocial morbidity associated with borderline personality disorder (BPD), its underrecognition is a significant clinical problem. BPD is likely underdiagnosed, in part, because patients with BPD usually present with chief complaints associated with mood, anxiety, and substance use disorders. When patients with BPD do not exhibit self-harm behavior, we suspect that BPD is less likely to recognized. An important question is whether the absence of this criterion, which might attenuate the likelihood of recognizing and diagnosing the disorder, identifies a subgroup of patients with BPD who are ‘less borderline’ than patients with BPD who do not manifest this criterion.

Psychiatric outpatients were evaluated with a semi-structured diagnostic interview for DSM-IV BPD, 390 of whom were diagnosed with BPD. We compared the demographic and clinical characteristics of patients with BPD who do and do not engage in repeated suicidal and self-harm behavior.

Approximately half of the patients with BPD did not meet the suicidality/self-injury diagnostic criterion for the disorder. There were no differences between the patients who did and did not meet this criterion in occupational impairment, likelihood of receiving disability payments, impairment in social functioning, level of educational achievement, comorbid psychiatric disorders, history of childhood trauma, or severity of depression, anxiety, or anger upon presentation for treatment.

Repeated self-injurious and suicidal behavior is not synonymous with BPD. It is critical for clinicians to be aware that the absence of repeated self-injury and suicide threats/gestures or attempts does not rule out the diagnosis of BPD.

Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries.

Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001–2019). A self-controlled case series design was applied to control for time-invariant confounders.

A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71–5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88–1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09–1.66), p = 0.006].

This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Previous studies have found that stressful life events (SLEs) are associated with an increased risk of adult depression. However, many studies are observational in nature and limited by methodological issues, such as potential confounding by genetic factors. Genetically informative research, such as the co-twin control design, can strengthen causal inference in observational studies. Discrete-time survival analysis has several benefits and multilevel survival analysis can incorporate frailty terms (random effects) to estimate the components of the biometric model. In the current study, we investigated associations between SLEs and depression risk in a population-based twin sample (N = 2299).

A co-twin control design was used to investigate the influence of the occurrence of SLEs on depression risk. The co-twin control design involves comparing patterns of associations in the full sample and within dizygotic (DZ) and monozygotic twins (MZ). Associations were modelled using discrete-time survival analysis with biometric frailty terms. Data from two time points were used in the analyses. Mean age at Wave 1 was 28 years and mean age at Wave 2 was 38 years.

SLE occurrence was associated with increased depression risk. Co-twin control analyses indicated that this association was at least in part due to the causal influence of SLE exposure on depression risk for event occurrence across all SLEs and for violent SLEs. A minor proportion of the total genetic risk of depression reflected genetic effects related to SLEs.

The results support previous research in implicating SLEs as important risk factors with probable causal influence on depression risk.

Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression.

We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months.

General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all pFDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all pFDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all pFDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all pFDR < 0.048).

Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents.

Impaired trust in other humans is commonly seen in psychosis and it leads to poor societal functioning. However, examining trust behavior in an experimental setting is challenging. Investigators have used the trust game, a neuro-economic game to assess trust behavior in psychosis. However, the findings are inconsistent. Hence, we systematically reviewed the existing literature and conducted a meta-analysis to examine trust behavior in patients with psychosis, their relatives, and those at high risk for psychosis.

We searched electronic databases for studies that have examined trust game in patients with psychosis, published up to November 2021. The primary outcome measure was the baseline trust in a trust game by patients and controls. The meta-analysis was performed if at least three data sets of control and patient groups were available for that measure/design. We conducted meta-analyses with a random-effects model. The results were described narratively wherever meta-analysis was not possible due to paucity of studies.

The searches across the databases including cross-references yielded 465 publications of which 10 studies were included in the final analysis. Baseline trust in the trust game was significantly lower in patients with psychosis compared to controls (SMD 0.39, 95% CI −0.14 to 0.64, p −0.002). However, a similar decrease in baseline trust was not present in relatives of patients (SMD 0.08, 95% CI −0.20 to 0.36, p −0.58).

The current meta-analysis suggests significant trust deficits in patients with psychosis. Future studies with a bigger sample size are required to understand the nature of trust deficits and factors affecting this impairment.

For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years.

Participants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991–1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition.

Mental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79–0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10–1.35 per year; OR 1.20, 95% CI 1.10–1.30 respectively).

This contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.

Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response.

We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14).

There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008).

These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.

Substance-induced psychosis (SIP) is a serious condition and may predispose for schizophrenia. We know too little about SIP incidence over time and across countries, including substance-specific SIPs. We estimated annual incidence rate of SIP in Denmark, Norway, and Sweden according to substance, age, gender, and socioeconomic background.

Data were drawn from registries covering the whole adult population in the countries. Annual incidence rate per 100 000 persons of SIPs was estimated for Denmark and Sweden from 2000 to 2016 and for Norway from 2010 to 2015.

The annual incidence rate of any SIP fluctuated between 9.3 and 14.1. The most commonly occurring SIPs were those induced by alcohol, cannabis, amphetamines, and multiple substances. There was a steady decrease in the incidence rate of alcohol-induced psychosis from the first to the last year of the observation period in Denmark (from 4.9 to 1.5) and Sweden (from 4.5 to 2.2). The incidence rate of cannabis-induced psychosis increased in all countries, from 2.6 to 5.6 in Denmark, from 0.8 to 2.7 in Sweden, and from 1.8 to 3.0 in Norway. Median age of any SIP decreased in Denmark (from 36 to 29 years) and Sweden (from 41 to 31 years). Incidence rates were higher in men and in individuals on disability pension, and increased more among those with high parental education.

We found similar and stable incidence rates of any SIP in all Scandinavian countries through the observation period. The incidence of alcohol-induced psychosis decreased. The incidence of cannabis-induced psychosis increased.