The association between negative wealth shocks and depression among middle-aged and older individuals remains unclear. Our study aimed to assess the association between negative wealth shocks and depression and its trajectories, and to explore cross-national differences in these associations

Our sample included 21 999 participants, of which 9519 were from the Health and Retirement Study (2012–2020), 4936 from the English Longitudinal Study of Ageing (2012–2020), 2520 from the China Health and Retirement Longitudinal Study (2011–2020), and 5024 from the Mexican Health and Aging Study (2012–2021). We used latent class trajectory models to identify depressive trajectories, alongside mixed-model logistic regression and multinomial logistic regression to evaluate associations.

In the USA (OR 1.73, 95% CI 1.40–2.16), England (OR 1.71, 95% CI 1.09–2.70), and China (OR 1.38, 95% CI 1.09–1.75), negative wealth shocks were associated with subsequent depressive symptoms, but not in Mexico (OR 1.06, 95% CI 0.86–1.29). Additionally, negative wealth shocks were associated with several depressive trajectories in the USA and China. This association occurred only in increasing–decreasing trajectory in England, while no significant association was found across any trajectory in Mexico.

Negative wealth shocks were associated with subsequent depressive symptoms, with significant associations observed in some specific depressive trajectories. These associations exhibited cross-national differences, underscoring the importance of considering country-specific contexts when addressing the mental health impacts of wealth shocks.

Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life.

We surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants' current depression/anxiety symptoms and their early-life activities (N = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants' early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) of outcome risk associated with frequency of early-life activity.

Each one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95% CI 0.38–0.77) for late-life depression and an OR of 0.94 (95% CI 0.61–1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status.

More frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.

The COVID-19 pandemic introduced unique stressors that posed significant threats to adolescent mental health. However, limited research has examined the impact of trauma exposure on vulnerability to subsequent stressor-related mental health outcomes in adolescents. Furthermore, it is unclear whether there are protective factors that promote resilience against the negative impacts of COVID-19 stressors in adolescents with prior trauma exposure. This preregistered study aimed to investigate the impact of trauma on COVID-19 stressor-related mental health difficulties in adolescents, in addition to the role of protective factors.

Aims were investigated in a sample of 9696 adolescents (mean age 12.85 ± 0.88 years) from the Adolescent Brain Cognitive Development Study. Linear mixed-effects models were employed to examine (a) the associations of early trauma exposure (exposed v. non-exposed), COVID-19 stressors, and perceived stress, sadness, and positive affect levels during the pandemic period in the US, and (b) the role of protective factors (physical activity, parental support, and improvements in family and peer relationships) in these associations.

There was a positive association between COVID-19 stressors and sadness, which was enhanced in trauma-exposed adolescents. Improvements in family and peer relationships mitigated the association between COVID-19 stressors and poor mental health outcomes, regardless of prior traumatic experience.

These findings support the hypothesis that prior trauma elevates risk of mental health difficulties in the face of future stressors. Results underscore the protective role of enhanced social relationships as targets for early prevention and intervention in those experiencing acute stressors, regardless of prior traumatic experiences.

To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system.

Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2).

We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD.

The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.

The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).

Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.

ClinicalTrials.gov Identifier: NCT02458690

Childhood trauma (CT) has been cross-sectionally associated with metabolic syndrome (MetS), a group of biological risk factors for cardiometabolic disease. Longitudinal studies, while rare, would clarify the development of cardiometabolic dysregulations over time. Therefore, we longitudinally investigated the association of CT with the 9-year course of MetS components.

Participants (N = 2958) from the Netherlands Study of Depression and Anxiety were assessed four times across 9 years. The CT interview retrospectively assessed childhood emotional neglect and physical, emotional, and sexual abuse. Metabolic outcomes encompassed continuous MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, blood pressure [BP], and glucose) and count of clinically elevated MetS components. Mixed-effects models estimated sociodemographic- and lifestyle-adjusted longitudinal associations of CT with metabolic outcomes over time. Time interactions evaluated change in these associations.

CT was reported by 49% of participants. CT was consistently associated with increased waist (b = 0.32, s.e. = 0.10, p = 0.001), glucose (b = 0.02, s.e. = 0.01, p < 0.001), and count of MetS components (b = 0.04, s.e. = 0.01, p < 0.001); and decreased HDL cholesterol (b = −0.01, s.e.<0.01, p = .020) and systolic BP (b = −0.33, s.e. = 0.13, p = 0.010). These associations were mainly driven by severe CT and unaffected by lifestyle. Only systolic BP showed a CT-by-time interaction, where CT was associated with lower systolic BP initially and with higher systolic BP at the last follow-up.

Over time, adults with CT have overall persistent poorer metabolic outcomes than their non-maltreated peers. Individuals with CT have an increased risk for cardiometabolic disease and may benefit from monitoring and early interventions targeting metabolism.

There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event.

During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses.

Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions.

Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP).

We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach.

A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval −16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery.

Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

Although risk markers for depressive disorders (DD) are dynamic, especially during adolescence, few studies have examined how change in risk levels during adolescence predict DD onset during transition to adulthood. We compared two competing hypotheses of the dynamic effects of risk. The risk escalation hypothesis posits that worsening of risk predicts DD onset beyond risk level. The chronic risk hypothesis posits that persistently elevated risk level, rather than risk change, predicts DD onset.

Our sample included 393 girls (baseline age 13.5–15.5 years) from the adolescent development of emotions and personality traits project. Participants underwent five diagnostic interviews and assessments of risk markers for DD at 9-month intervals and were re-interviewed at a 6-year follow-up. We focused on 17 well-established risk markers. For each risk marker, we examined the prospective effects of risk level and change on first DD onset at wave six, estimated by growth curve modeling using data from the first five waves.

For 13 of the 17 depression risk markers, elevated levels of risk during adolescence, but not change in risk, predicted first DD onset during transition to adulthood, supporting the chronic risk hypothesis. Minimal evidence was found for the risk escalation hypothesis.

Participants who had a first DD onset during transition to adulthood have exhibited elevated levels of risk throughout adolescence. Researchers and practitioners should administer multiple assessments and focus on persistently elevated levels of risk to identify individuals who are most likely to develop DD and to provide targeted DD prevention.

Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.

We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.

Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent–child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (β = −0.640, p = 0.005).

Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent–child reading in moderating the association between screen time and topological brain restructuring in early childhood.

While unemployment is known to increase the risk of suicide, its cumulative effect remains underexplored. This study investigates how unemployment affects suicide mortality and whether the effect varies based on the number of unemployment spells using two years of nationwide data.

Using the data from the National Statistical Office and Employment Insurance Database for 2018 and 2019, we identified an average of 2365 cases of suicide over two years among 7.76 million workers aged 25–64 years who had been employed within one year before their suicide. The number of unemployment spells was counted using the employment history of the past five years. We calculated crude suicide mortality rates per 100 000 population, age- and sex- standardized mortality rates (SMRs), and proportionate mortality rates (PMRs) for suicide.

Over the two years, the crude suicide rate was 30.0 per 100 000 among the general population and 30.5 among workers. Workers with no unemployment spells in the past five years had a significantly lower SMR (0.44; 0.42–0.46), while those with four or more unemployment spells had a significantly higher SMR (3.13; 2.92–3.35) than the general population. These findings were consistent across all sex and age groups. Additionally, workers with four or more unemployment spells had a significantly higher PMR than the general population.

The impact of unemployment on suicide mortality intensifies as the number of unemployment spells increases. These results underscore the necessity for additional social and psychological support along with economic assistance for individuals facing recurrent unemployment.

Bipolar disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed.

We apply genomic structural equation modeling (Genomic SEM) to investigate divergent genetic pathways across BD's two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 98 external traits using a Bonferroni-corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, transcriptome-wide SEM (T-SEM) was used to identify neuronal gene expression patterns associated with BD subtypes.

BD II was characterized by significantly larger genetic overlap across non-psychiatric medical and internalizing traits (e.g. heart disease, neuroticism, insomnia), while stronger associations for BD I were absent. Consistent with these findings, follow-up modeling revealed a substantial major depression component for BD II. T-SEM results revealed 35 unique genes associated with shared risk across BD subtypes.

Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR.

This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization.

One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (β = −0.24), achieving response (β = 0.86), attaining remission (β = 1.05), or reducing treatment dropout rates (β = −0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females.

The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.

Suicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk.

Data come from several waves of a prospective cohort study (2016–2022) of college students (n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this high-risk group.

5454 students ranging in age from 17–36 (s.d. = 5.346) participated; 65% female. The algorithm identified 77% of students reporting subsequent suicidal behavior in the top 15% of predicted probabilities (Sensitivity = 26.26 [95% CI 17.93–36.07]; Specificity = 97.46 [95% CI 96.21–98.38], PPV = 53.06 [95% CI 40.16–65.56]; AUC range: 0.895 [95% CIs 0.872–0.917] to 0.966 [95% CIs 0.939–0.994]). High-risk students in the Intervention Cohort showed a 41.7% reduction in probability of suicidal behavior at 12-month follow-up compared to high-risk students in the Control Cohort.

Predictive risk algorithms embedded into universal screening, coupled with telehealth intervention, offer significant potential as a suicide prevention approach for students.

Psychotic disorders are highly heritable, yet the evidence is less clear for subclinical psychosis expression, such as psychotic experiences (PEs). We examined if PEs in parents were associated with PEs in offspring.

As part of the Danish general population Lolland-Falster Health Study, families with youths aged 11–17 years were included. Both children and parents reported PEs according to the Psychotic Like Experiences Questionnaire, counting only ‘definite’ PEs. Parents additionally reported depressive symptoms, anxiety, and mental wellbeing. The associations between parental and child PEs were estimated using generalized estimating equations with an exchangeable correlation structure to account for the clustering of observations within families, adjusting for sociodemographic characteristics.

Altogether, 984 youths (mean age 14.3 years [s.d. 2.0]), 700 mothers, and 496 fathers from 766 households completed PEs-questionnaires. Offspring of parents with PEs were at an increased risk of reporting PEs themselves (mothers: adjusted risk ratio (aRR) 2.42, 95% CI 1.73–3.38; fathers: aRR 2.25, 95% CI 1.42–3.59). Other maternal problems (depression, anxiety, and poor mental well-being), but not paternal problems, were also associated with offspring PEs. In multivariate models adjusting for parental problems, PEs, but not other parental problems, were robustly associated with offspring PEs (mothers: aRR 2.25, 95% CI 1.60–3.19; fathers: aRR 2.44, 95% CI 1.50–3.96).

The current findings add novel evidence suggesting that specific psychosis vulnerability in families is expressed at the lower end of the psychosis continuum, underlining the importance of assessing youths’ needs based on psychosis vulnerability broadly within the family systems.

Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent.

Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis.

A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients.

Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.

The incidence of psychotic disorders varies in different geographic areas. As there has been no report from Turkey, this study aimed to provide the treated incidence rate of first-episode psychosis (FEP) in a defined area.

All individuals, aged 15–64 years, presenting with FEP (ICD-10 F20-29, F30-33) to mental health services in a defined catchment-area in Sinop which is located in the Black Sea region of the northern Turkey were recorded over a 4-year period (2009 to 2012). Incidence rates of psychotic disorders and their 95% confidence intervals (CIs) were estimated. Poisson regression was applied to estimate the differences in incidence rate ratio (IRR) by age, sex, and urbanicity.

One hundred and fifteen FEP participants were identified during the 4 years. Crude incidence rates of all psychoses, schizophrenia, other psychotic disorders, and affective psychotic disorders were respectively 38.5 (95% CI 27.1–49.9), 10.7 (95% CI 6.6–14.8), 10.0 (95% CI 5.7–14.3) and 17.7 (95% CI 11.3–24.2) per 100 000 person-years. After age-sex standardisation the rates increased slightly. There were no gender differences in the incidence rates. IRR of any psychotic disorder was highest in the youngest age group (15–24 years) compared to the oldest age group (55–64 years), 7.9 (95% CI 2.8–30.5). In contrast with previous studies, the incidence rate of any psychotic disorder was not significantly increased in urban areas compared with rural areas.

The current study, the first of its kind from Turkey, indicates that the risk of schizophrenia and other psychotic disorders in a lowly urbanised area of Turkey is comparable to those reported in Western European cities.

In schizophrenia (SZ), impairments in cognitive functions, such as working memory, have been associated with alterations in certain types of inhibitory neurons that utilize the neurotransmitter γ-aminobutyric acid (GABA) in the dorsolateral prefrontal cortex (DLPFC). For example, GABA neurons that express parvalbumin (PV) or somatostatin (SST) have more prominent gene expression alterations than those that express vasoactive intestinal peptide (VIP). In bipolar disorder (BD) and major depression (MD), which exhibit similar, but less severe, cognitive impairments than SZ, alterations of transcript levels in GABA neurons have also been reported. However, the extent to which GABA neuron subtype-selective transcripts in the DLPFC are affected, and the relative magnitudes of the diagnosis-associated effects, have not been directly compared across SZ, BD, and MD in the same study.

We used quantitative polymerase chain reaction to examine levels of GABA neuron subtype-selective transcripts (PV, potassium voltage-gated channel modifier subfamily-S member-3, SST, VIP, and calretinin mRNAs), as well as the pan-GABA neuron marker 67 kDa glutamate decarboxylase mRNA, in DLPFC total gray matter of 160 individuals, including those with SZ, BD, or MD and unaffected comparison (UC) individuals.

Relative to UC individuals, individuals with SZ exhibited large deficits in levels of all transcripts except for calretinin mRNA, whereas individuals with BD or MD showed a marked deficit only for PV or SST mRNAs, respectively.

These findings suggest that broader and more severe alterations in DLPFC GABA neurons might contribute to the greater cognitive impairments in SZ relative to BD and MD.

Cognitive deficits are a core feature of schizophrenia and are closely associated with poor functional outcomes. It remains unclear if cognitive deficits progress over time or remain stable. Determining patients at increased risk of progressive worsening might help targeted neurocognitive remediation approaches.

This 20-year follow-up study examined neurocognitive outcomes of 156 participants from the OPUS I trial. Neurocognition was assessed using the brief assessment of cognition in schizophrenia at the 10- and 20-year follow-up, allowing us to examine changes in neurocognition over ten years.

We found that 30.5% of patients had a declining course of neurocognition, 49.2% had a stable course of neurocognition and 20.3% experienced improvements in neurocognition. Good cognitive functioning at the 20-year follow-up was significantly associated with higher levels of social functioning (B 6.86, CI 4.71–9.02, p < 0.001) while increasing experiential negative symptoms were significantly correlated to cognitive worsening (PC-0.231, p = 0.029). Younger age at inclusion (B: 0.23 per 10-years, CI 0.00–0.045, p = 0.047) and low level of education (below ten years) (mean difference: −0.346, CI −0.616 to −0.076, p = 0.012) predicted declining neurocognition.

Our findings support the notion of different schizophrenia subtypes with varying trajectories. Neurocognitive impairment at the 20-year follow-up was associated with other poor outcomes, highlighting the importance of treatments aimed at improving neurocognition in patients with schizophrenia spectrum disorders.