Obstetric complications (OCs) are associated with cognitive and brain abnormalities observed in patients with schizophrenia. Gyrification, a measure of cortical integrity sensitive to events occurring during the prenatal and perinatal periods, is also altered in first-episode psychosis (FEP). We examined the relationship between OCs and gyrification in FEP, as well as whether gyrification mediates the relationship between OCs and cognition.

We examined differences in the Local Gyrification Index (LGI) for the frontal, parietal, temporal, occipital, and cingulate cortices between 139 FEP patients and 125 healthy controls (HCs). Regression analyses explored whether OCs and diagnosis interact to explain LGI variation. Parametric mediation analyses were conducted to assess the effect of LGI on the relationship between OCs and cognition for FEP and HC.

Significant LGI differences were observed between FEP patients and HC in the left parietal and bilateral cingulate and occipital cortices. There was a significant interaction between OCs and diagnosis on the left cingulate cortex (LCC) that was specific to males (p = 0.04) and was driven by gestational rather than intrauterine OCs.

In HCs, OCs had a direct effect on working memory (WM) (p = 0.048) in the mediation analysis, whereas in FEP, we observed no significant effect of OCs on either verbal or WM.

OCs interact with diagnosis to predict LCC gyrification, such that males with FEP exposed to OCs exhibit the lowest LGI. OCs influence WM, and LCC gyrification may mediate this relation only in HC, suggesting a differential neurodevelopmental process in psychosis.

The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.

We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.

Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.

Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

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.

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.

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.

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.

Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients.

The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model.

In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β = −0.293, p = 0.034) and verbal memory performance (β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains.

Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders.

We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed.

Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004).

This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients.

Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.

Some studies suggest individuals with schizophrenia have an increased risk of diabetes prior to antipsychotic use. Small sample sizes and the potential for confounding by hypercortisolaemia have decreased confidence in those results.

To examine diabetes-related factors in newly diagnosed, antipsychotic-naive people with non-affective psychosis.

Participants with psychosis (the psychosis group; n = 50) and matched controls (the control group; n = 50) were given a 2 h oral glucose tolerance test. Fasting concentrations were also determined for adiponectin, interleukin-6 and C-reactive protein.

Compared with the control group, the psychosis group had significant increases in 2 h glucose and interleukin-6 concentrations, and in the prevalence of abnormal glucose tolerance (16% of psychosis group v. 0% of control group). Adiponectin and C-reactive protein concentrations did not differ significantly between the two groups. These findings could not be attributed to differences in cortisol concentrations, smoking, gender, neighbourhood of residence, body mass index, aerobic conditioning, ethnicity, socioeconomic status or age.

Individuals with non-affective psychosis appear to have an increased prevalence of abnormal glucose tolerance prior to antipsychotic treatment, as well as abnormalities in a related inflammatory molecule. These underlying problems may contribute to the metabolic side-effects of antipsychotic medications.