Since 2008, the Improving Access to Psychological Therapies (IAPT) programme has offered adults in England evidence-based psychological treatments for common mental disorders (CMDs) such as depression and anxiety disorders. However, inequalities in access have not been explored at the national level.

Using a unique individual patient dataset that linked 2011 Census information of English residents to national IAPT data collected between April 2017 and March 2018, we estimated the rate of access by a wide range of socio-demographic characteristics that are not routinely available. A large household survey was used to estimate the prevalence of probable CMDs by these socio-demographic characteristics. We estimated the probability of access to IAPT amongst people with CMDs by comparing the rates of access from IAPT data and the estimates of prevalence of CMDs from the household survey. Both unadjusted and adjusted (for important patient characteristics) access rates were estimated in logistic regression models.

As a proportion of those with a probable CMD, access to IAPT varied markedly by socio-demographic characteristics. Older adults, males, people born outside of the UK, people with religious beliefs, people from Asian ethnic backgrounds, people reporting a disability and those without any academic or professional qualifications were underrepresented in IAPT services nationally, in adjusted models.

The identification of patients who may be underrepresented in IAPT provides an opportunity for services to target outreach and engagement with these groups. Further understanding of barriers to access should help increase equity in access.

Midlife adults are experiencing a crisis of deaths of despair (i.e. deaths from suicide, drug overdose, and alcohol-related liver disease). We tested the hypothesis that a syndrome of despair-related maladies at midlife is preceded by psychopathology during adolescence.

Participants are members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972–73 and followed to age 45 years, with 94% retention. Adolescent mental disorders were assessed in three diagnostic assessments at ages 11, 13, and 15 years. Indicators of despair-related maladies across four domains – suicidality, substance misuse, sleep problems, and pain – were assessed at age 45 using multi-modal measures including self-report, informant-report, and national register data.

We identified and validated a syndrome of despair-related maladies at midlife involving suicidality, substance misuse, sleep problems, and pain. Adults who exhibited a more severe syndrome of despair-related maladies at midlife tended to have had early-onset emotional and behavioral disorders [β = 0.23, 95% CI (0.16–0.30), p < 0.001], even after adjusting for sex, childhood SES, and childhood IQ. A more pronounced midlife despair syndrome was observed among adults who, as adolescents, were diagnosed with a greater number of mental disorders [β = 0.26, 95% CI (0.19–0.33), p < 0.001]. Tests of diagnostic specificity revealed that associations generalized across different adolescent mental disorders.

Midlife adults who exhibited a more severe syndrome of despair-related maladies tended to have had psychopathology as adolescents. Prevention and treatment of adolescent psychopathology may mitigate despair-related maladies at midlife and ultimately reduce deaths of despair.

Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?

In over 9000 twins from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, the occurrence of all nine DSM symptomatic criteria for MD in the last year was assessed at personal interview and then grouped by their temporal co-occurrence. The DSM criteria which occurred outside (OUT) v. inside of (IN) MD episodes were then separated. We calculated tetrachoric correlations for OUT and IN depressive criteria in monozygotic (MZ) and dizygotic (DZ) pairs and fitted univariate and bivariate ACE twin models using OpenMx.

The mean twin correlations (±95% CIs) for IN depressive criteria were substantially higher than for OUT depressive criteria in both MZ [+0.35 (0.32–0.38) v. 0.20 (0.17–0.24)] and DZ pairs [0.20 (0.17–0.24) v. 0.10 (0.04–0.16]. The mean IN–OUT cross-correlation in MZ and DZ pairs was modest [+0.15 (0.07–0.24) and +0.07 (0.03–0.12)]. The mean heritability estimates for the nine In v. Out depressive criteria was 0.31 (0.22–0.41) and 0.15 (0.08–0.21), in MZ and DZ pairs, respectively. The mean genetic correlation between the nine IN and OUT depressive criteria was +0.07 (−0.07 to 0.21).

Depressive criteria occurring outside depressive episodes are less heritable than those occurring within. These two ways criteria can manifest are not closely genetically related. Current depressive symptoms – most of which are occurring outside of depressive episodes – are not, for genetic studies, good proxies for MD.

Losing a parent or spouse in adulthood may result in prolonged grief disorder (PGD) symptoms. PGD levels in parents may affect PGD levels in their adult offspring and the other way around. However, research on transmission of PGD in parent–child dyads is lacking. Consequently, we aimed to examine temporal associations between PGD levels in parent and adult children.

In doing so, we analyzed longitudinal self-report data on PGD levels (using the PG-13) assessed at 2, 11, 18, and 26 months after loss in 257 adult parent–child dyads from Denmark. Cross-lagged panel modeling was used for data-analyses.

Changes in PGD levels in parents significantly predicted PGD levels in adult children, but not vice versa. Small through moderate cross-lagged effects (β = 0.05 through 0.07) were found for PGD levels in parents predicting PGD levels in adult children at a subsequent time-point. These cross-lagged effects were found while taking into account the association between PGD levels in parents and adult children at the same time-point as well as the associations between the same construct over time and relevant covariates.

Pending replication of these findings in clinical samples and younger families, our findings offer tentative support for expanding our focus in research and treatment of PGD from the individual to the family level.

Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.

Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.

In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.

This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

Dissociative symptoms can emerge after trauma and interfere with attentional control and interoception; disruptions to these processes are barriers to mind-body interventions such as breath-focused mindfulness (BFM). To overcome these barriers, we tested the use of an exteroceptive augmentation to BFM, using vibrations equivalent to the amplitude of the auditory waveform of the actual breath, delivered via a wearable subwoofer in real time (VBFM). We tested whether this device enhanced interoceptive processes, attentional control and autonomic regulation in trauma-exposed women with dissociative symptoms.

65 women, majority (82%) Black American, aged 18–65 completed self-report measures of interoception and 6 BFM sessions, during which electrocardiographic recordings were taken to derive high-frequency heart rate variability (HRV) estimates. A subset (n = 31) of participants completed functional MRI at pre- and post-intervention, during which they were administered an affective attentional control task.

Compared to those who received BFM only, women who received VBFM demonstrated greater increases in interoception, particularly their ability to trust body signals, increased sustained attention, as well as increased connectivity between nodes of emotion processing and interoceptive networks. Intervention condition moderated the relationship between interoception change and dissociation change, as well as the relationship between dissociation and HRV change.

Vibration feedback during breath focus yielded greater improvements in interoception, sustained attention and increased connectivity of emotion processing and interoceptive networks. Augmenting BFM with vibration appears to have considerable effects on interoception, attention and autonomic regulation; it could be used as a monotherapy or to address trauma treatment barriers.

Previous research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups.

We conducted a nationwide Danish register-based cohort study including all individuals aged 16–49 at some point during 1972–2021. CUD and schizophrenia status was obtained from the registers. Hazard ratios (HR), incidence risk ratios (IRR), and PARFs were estimated. Joinpoint analyses were applied to sex-specific PARFs.

We examined 6 907 859 individuals with 45 327 cases of incident schizophrenia during follow-up across 129 521 260 person-years. The overall adjusted HR (aHR) for CUD on schizophrenia was slightly higher among males (aHR = 2.42, 95% CI 2.33–2.52) than females (aHR = 2.02, 95% CI 1.89–2.17); however, among 16–20-year-olds, the adjusted IRR (aIRR) for males was more than twice that for females (males: aIRR = 3.84, 95% CI 3.43–4.29; females: aIRR = 1.81, 95% CI 1.53–2.15). During 1972–2021, the annual average percentage change in PARFs for CUD in schizophrenia incidence was 4.8 among males (95% CI 4.3–5.3; p < 0.0001) and 3.2 among females (95% CI 2.5–3.8; p < 0.0001). In 2021, among males, PARF was 15%; among females, it was around 4%.

Young males might be particularly susceptible to the effects of cannabis on schizophrenia. At a population level, assuming causality, one-fifth of cases of schizophrenia among young males might be prevented by averting CUD. Results highlight the importance of early detection and treatment of CUD and policy decisions regarding cannabis use and access, particularly for 16–25-year-olds.

Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.

Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.

The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.

Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.

We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.

Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.

Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.

Difficulties in the context-dependent modulation of conditioned fear are known for posttraumatic stress disorder and may explain the occurrence of intrusive memories in safe contexts. The current study therefore investigated if reduced context-dependent modulation of conditioned fear and its underlying neural circuitry constitute risk factors for the development of analog intrusions in response to an experimental trauma.

Eighty-five healthy women participated in the trauma film paradigm to investigate the development of analog intrusions as well as explicit memory for an experimental trauma after one week and three months, respectively. Before, participants underwent a context-dependent fear conditioning paradigm during functional magnetic resonance imaging with fear acquisition in context A and extinction training in context B on a first day, as well as extinction recall in context B and fear renewal in a novel context C one day later. Skin conductance responses (SCRs) and blood oxygen level dependent responses were main outcome measures.

In addition to stronger fear acquisition in context A, stronger conditioned fear responses in the safe context B, as indicated by stronger conditioned SCRs or stronger activation of fear expressing regions during extinction learning and recall, predicted the development of long-term analog intrusions.

Stronger fear responses in safe and danger contexts were risk factors for the development of long-term analog intrusions and point to decontextualized fear memories and difficulties in the context-dependent modulation of conditioned fear. Altered fear conditioning processes and reduced storage of contextual information may cause the occurrence of fear independent of context.

Lower cognitive functioning has been documented across psychiatric disorders and hypothesized to be a core deficit of mental disorders. Situating psychopathology and cognition as part of a unitary construct is therefore important to understanding the etiology of psychiatric disorders. The current study aims to test competing structural models of psychopathology and cognition in a large national cohort of adolescents.

The analytic sample consisted of 1189 participants aged 16–17 years, screened by the Israeli Draft Board. Psychopathology was assessed using a modified version of the Brief Symptom Inventory, and cognition was assessed based on four standardized test scores ((1) mathematical reasoning, concentration, and concept manipulation; (2) visual-spatial problem-solving skills and nonverbal abstract reasoning; (3) verbal understanding; (4) categorization and verbal abstraction). Confirmatory factor analysis was implemented to compare competing structural models of psychopathology with and without cognition. Sensitivity analyses examined the models in different subpopulations.

Confirmatory factor analysis indicated a better model fit of psychopathological symptoms without cognition (RMSEA = 0.037; TLI = 0.991; CFI = 0.992) than with cognition (RMSEA = 0.04–0.042; TLI = 0.987–0.988; CFI = 0.988–0.989). Sensitivity analyses supported the robustness of these results with a single exception. Among participants with low cognitive abilities (N = 139), models that integrated psychopathological symptoms with cognition had a better fit compared to models of psychopathology without cognition.

The current study suggests that cognition and psychopathology are, generally, independent constructs. However, within low cognitive abilities, cognition was integral to the structure of psychopathology. Our results point toward an increased vulnerability to psychopathology in individuals with low cognitive abilities and may provide valuable information for clinicians.

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

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

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

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

Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD.

We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity.

Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11–1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12–2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24–1.60).

In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.

Obsessive–compulsive disorder (OCD) is a psychiatric condition leading to significant distress and poor quality of life. Successful treatment of OCD is restricted by the limited knowledge about its pathophysiology. This study aimed to investigate the pathophysiology of OCD using electroencephalographic (EEG) event-related potentials (ERPs), elicited from multiple tasks to characterise disorder-related differences in underlying brain activity across multiple neural processes.

ERP data were obtained from 25 OCD patients and 27 age- and sex-matched healthy controls (HCs) by recording EEG during flanker and go/nogo tasks. Error-related negativity (ERN) was elicited by the flanker task, while N200 and P300 were generated using the go/nogo task. Primary comparisons of the neural response amplitudes and the topographical distribution of neural activity were conducted using scalp field differences across all time points and electrodes.

Compared to HCs, the OCD group showed altered ERP distributions. Contrasting with the previous literature on ERN and N200 topographies in OCD where fronto-central negative voltages were reported, we detected positive voltages. Additionally, the P300 was found to be less negative in the frontal regions. None of these ERP findings were associated with OCD symptom severity.

These results indicate that individuals with OCD show altered frontal neural activity across multiple executive function-related processes, supporting the frontal dysfunction theory of OCD. Furthermore, due to the lack of association between altered ERPs and OCD symptom severity, they may be considered potential candidate endophenotypes for OCD.

Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models.

We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later.

The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave.

The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.

The psychosis continuum implies that subclinical psychotic experiences (PEs) can be differentiated from clinically relevant expressions since they are not accompanied by a ‘need for care’.

Using data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 34 653), the current study examined variation in functioning, symptomology and aetiological risk across the psychosis phenotype [i.e. variation from (i) no PEs, ‘No PEs’ to (ii) non-distressing PEs, ‘PE-Experienced Only’ to (iii) distressing PEs, ‘PE-Impaired’ to (iv) clinically defined psychotic disorder, ‘Diagnosed’].

A graded trend was present such that, compared to those with no PEs, the Diagnosed group had the poorest functioning, followed by the PE-Impaired then PE-Experienced Only groups. In relation to symptom expression, the PE-Impaired group were more likely than the PE-Experienced Only and the Diagnosed groups to endorse most PEs. Predictors of group membership tended to vary quantitatively rather than qualitatively. Trauma, current mental health diagnoses (anxiety and depression) and drug use variables differentiated between all levels of the continuum, with the exception of the extreme end (PE-Impaired v. Diagnosed). Only a few variables distinguished groups at the upper end of the continuum: female sex, older age, unemployment, parental mental health hospitalisation and lower likelihood of having experienced physical assault.

The findings highlight the importance of continuum-based interpretations of the psychosis phenotype and afford valuable opportunities to consider if and how impairment, symptom expression and risk change along the continuum.

The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis.

One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS).

The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05).

Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.