Living with major depressive disorder (MDD) reduces life expectancy, with respiratory disease being a significant threat. However, evidence on respiratory disease in this population has not yet been meta-analyzed.

This meta-analysis examines respiratory disease prevalence and odds ratio (OR) in patients with MDD and treatment resistant depression (TRD). A systematic literature search was conducted, with a snowball search of reference and citation lists. Inclusion criteria covered studies in MDD and TRD patients with confirmed diagnoses of respiratory diseases (asthma, chronic obstructive pulmonary disease [COPD], pneumonia, lung cancer, and tuberculosis), comparing with a control group when possible.

From 4,138 retrieved articles, 15 (including 476,927 individuals with MDD, 50,680 with TRD, and 1,108,979 control group) met the inclusion criteria. In MDD patients, COPD prevalence was 9.0% (95% CI: 3.8–19.6%), asthma 8.6% (95% CI: 5.7–12.8%), and pneumonia 2.5% (95% CI: 2.2–2.9%). In TRD patients, COPD prevalence was 9.9% (95% CI: 4.2–21.9%) and asthma 10.9% (95% CI: 10.7–11.2%), but meta-analysis limited to those diseases showed no significant relative risk differences. Compared to the general population, individuals with MDD had significantly higher rates of COPD (OR 1.79, 95% CI: 1.49–2.16), even higher in younger populations (1.85 [95% CI: 1.74–1.97]) and more prevalent in women.

This first meta-analysis on this topic shows that MDD is associated with an increased risk of respiratory illness compared to the general population. The prevalence of asthma doubles the mean described in the general population worldwide, and in COPD, women and younger people are at particular risk. Prevention policies are urgently needed.

Assess effect of predominant polarity on efficacy of cariprazine in patients with bipolar I (BP-I) disorder. Predominant polarity may be an important clinical consideration in BP-I disorder, with predominant depressive episodes associated with delayed diagnosis and higher rates of suicidality, while predominant manic episodes are associated with younger onset, manic/psychotic first episode, and more substance abuse [1].

Data were pooled from 3 randomized, double-blind, cariprazine trials in BP-I depression and 3 trials in BP-I mania. Post hoc analyses were performed in subgroups from the bipolar depression studies with/without predominant depression (≥2:1 ratio of prior lifetime depressive to manic episodes), and in subgroups from the bipolar mania studies with and without predominant mania (≥2:1 ratio of prior lifetime manic to depressive episodes). Change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was evaluated for cariprazine 1.5 and 3 mg/d versus placebo (bipolar depression studies); change from baseline to week 3 in Young Mania Rating Scale total score was evaluated for cariprazine 3-12 mg/d versus placebo (bipolar mania studies). Change from baseline analyzed using mixed-effect model for repeated measures in pooled intent-to-treat population from each indication.

In bipolar depression studies, there were 624 patients (45% of total study population) in the predominantly depressive subgroup (placebo=197, cariprazine: 1.5 mg/d=217; 3 mg/d=210) and 750 patients (55%) in the subgroup without predominant depression (placebo=258, cariprazine: 1.5 mg/d=241; 3 mg/d=251). In the predominant depressive subgroup, LSMDs for MADRS total score change from baseline were significant versus placebo for cariprazine 1.5 mg/d (-2.49 [-4.30, -.68], P=.0071) and 3 mg/d (-2.48 [-4.31, -.65], P=.0079); in the subgroup without predominant depression, LSMDs were also significant versus placebo for both doses (1.5 mg/d=-3.30 [-5.06, -1.54], P=.0002; 3 mg/d=-2.53 [-4.29, -.77], P=.0049). In bipolar mania studies, there were 721 patients (73% of total study population) in the predominantly manic episode subgroup (placebo=307, cariprazine 3-12 mg/d =414) and 267 patients (27%) in the subgroup without predominant manic episodes (placebo=102, cariprazine 3-12 mg/d=165). In predominant mania subgroup, LSMD in YMRS total score change from baseline was significant for cariprazine 3-12 mg/d versus placebo (-4.65 [-6.29, -3.02], P<.0001); in subgroup without predominant mania, the LSMD for cariprazine versus placebo was also significant (-7.56 [-10.30, -4.82], P<.0001).

Cariprazine was efficacious in treating BP-I mood episodes regardless of predominant polarity for the presenting mood episode. Cariprazine was effective against symptoms of depression in patients with BP-I depression with/without predominant depressive episodes, and against symptoms of mania in patients with BP-I mania with/ without predominant manic episodes.

AbbVie

This data was previously presented at the Annual ECNP Congress; Barcelona, Spain; October 7-10, 2023.

Both childhood adversity (CA) and first-episode psychosis (FEP) have been linked to alterations in cortical thickness (CT). The interactive effects between different types of CAs and FEP on CT remain understudied.

One-hundred sixteen individuals with FEP (mean age = 23.8 ± 6.9 years, 34% females, 80.2% non-affective FEP) and 98 healthy controls (HCs) (mean age = 24.4 ± 6.2 years, 43% females) reported the presence/absence of CA <17 years using an adapted version of the Childhood Experience of Care and Abuse (CECA.Q) and the Retrospective Bullying Questionnaire (RBQ) and underwent magnetic resonance imaging (MRI) scans. Correlation analyses were used to assess associations between brain maps of CA and FEP effects. General linear models (GLMs) were performed to assess the interaction effects of CA and FEP on CT.

Eighty-three individuals with FEP and 83 HCs reported exposure to at least one CA. CT alterations in FEP were similar to those found in participants exposed to separation from parents, bullying, parental discord, household poverty, and sexual abuse (r = 0.50 to 0.25). Exposure to neglect (β = −0.24, 95% CI [−0.37 to −0.12], p = 0.016) and overall maltreatment (β = −0.13, 95% CI [−0.20 to −0.06], p = 0.043) were associated with cortical thinning in the right medial orbitofrontal region.

Cortical alterations in individuals with FEP are similar to those observed in the context of socio-environmental adversity. Neglect and maltreatment may contribute to CT reductions in FEP. Our findings provide new insights into the specific neurobiological effects of CA in early psychosis.

The prevalence of mental health disorders has significantly increased in recent years, posing substantial challenges to healthcare systems worldwide, particularly primary care (PC) settings. This study examines trends in mental health diagnoses in PC settings in Catalonia from 2010 to 2019 and identifies associated sociodemographic, clinical characteristics, psychopharmacological treatments, and resource utilization patterns.

Data from 947,698 individuals without prior severe mental illness, derived from the Data Analytics Program for Health Research and Innovation (PADRIS), were analyzed for this study. Sociodemographic data, diagnoses, and resource utilization were extracted from electronic health records. Descriptive statistics, chi-square tests, Mann–Whitney tests, and a multivariate binary logistic regression were employed to analyze the data.

Over the study period, 172,112 individuals (18.2%) received at least one mental health diagnosis in PC, with unspecified anxiety disorder (40.5%), insomnia (15.7%) and unspecified depressive disorder (10.2%) being the most prevalent. The prevalence of these diagnoses increased steadily until 2015 and stabilized thereafter. Significant associations were found between mental health diagnoses, female sex, lower socioeconomic status, higher BMI, and smoking status in a multivariate binary logistic regression.

This study highlights a growing burden of stress-related mental health diagnoses in PC in Catalonia, driven by demographic and socioeconomic factors. These findings may be indicative of broader trends across Europe and globally. Addressing this rising prevalence requires innovative approaches and collaborative strategies that extend beyond traditional healthcare resources. Engaging stakeholders is essential for implementing effective, sustainable solutions that promote mental health in Catalonia and potentially inform similar initiatives worldwide.

Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions.

The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder.

We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients.

Recruitment is ongoing.

This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

There is a significant contribution of genetic factors to the etiology of bipolar disorder (BD). Unaffected first-degree relatives of patients (UR) with BD are at increased risk of developing mental disorders and may manifest cognitive impairments and alterations in brain functional and connective dynamics, akin to their affected relatives.

In this prospective longitudinal study, resting-state functional connectivity was used to explore stable and progressive markers of vulnerability i.e. abnormalities shared between UR and BD compared to healthy controls (HC) and resilience i.e. features unique to UR compared to HC and BD in full or partial remission (UR n = 72, mean age = 28.0 ± 7.2 years; HC n = 64, mean age = 30.0 ± 9.7 years; BD patients n = 91, mean age = 30.6 ± 7.7 years). Out of these, 34 UR, 48 BD, and 38 HC were investigated again following a mean time of 1.3 ± 0.4 years.

At baseline, the UR showed lower connectivity values within the default mode network (DMN), frontoparietal network, and the salience network (SN) compared to HC. This connectivity pattern in UR remained stable over the follow-up period and was not present in BD, suggesting a resilience trait. The UR further demonstrated less negative connectivity between the DMN and SN compared to HC, abnormality that remained stable over time and was also present in BD, suggesting a vulnerability marker.

Our findings indicate the coexistence of both vulnerability-related abnormalities in resting-state connectivity, as well as adaptive changes possibly promoting resilience to psychopathology in individual at familial risk.

Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction are yet to be explored. This study assessed the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP.

A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study summary results, PRSEA were constructed for each individual. Two mediation models were performed. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms. The serial mediation model tested a causal chain of the three mediators: CR, NS, and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22.

A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β = −0.35, 95%CI [−0.85, −0.04], p < 0.05). The model fit the data satisfactorily (CFI = 1.00; RMSEA = 0.00; SRMR = 7.2 × 10−7). Conversely, no parallel mediation was found between the three mediators, PRSEA and functionality and the model poorly fit the data (CFI = 0.30; RMSEA = 0.25; SRMR = 0.11).

Both CR and NS mediate the relationship between PRSEA and functionality at one-year follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients.

Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances.

We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis–Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups.

FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio.

Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress.

This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP).

Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4–95.6%) and work-related stressful experiences (PARP range 76.8–86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety.

TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs.

Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis–Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia.

Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use.

Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders.

A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I2 statistic. Homogeneity was assessed using the Q-statistic (X2). The study was registered on PROSPERO (CRD42018094238).

A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = −0.89 (95% CI −1.41 to −0.37), p < 0.001] and working memory performance [Hedges' g = −1.47 (95% CI −2.89 to −0.06), p = 0.01] in a random-effect model compared to those without OCs.

OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder.

The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status.

Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001).

Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.