Accelerated ageing indexed by telomere attrition is suggested in schizophrenia spectrum- (SCZ) and bipolar disorders (BD). While inflammation may promote telomere shortening, few studies have investigated the association between telomere length (TL) and markers of immune activation and inflammation in severe mental disorders.

Leucocyte TL defined as telomere template/amount of single-copy gene template (T/S ratio), was determined in participants with SCZ (N = 301) or BD (N = 211) and a healthy control group (HC, N = 378). TL was analysed with linear regressions for associations with levels of 12 immune markers linked to SCZ or BD. Adjustments were made for a broad range of potential confounding variables. TL was measured by quantitative polymerase chain reaction (qPCR) and the immune markers were measured by enzyme immunoassays.

A positive association between levels of soluble tumour necrosis factor receptor 1A (sTNF-R1) and TL in SCZ (β = 0.191, p = 0.012) was observed. Plasma levels of the other immune markers were not significantly associated with TL in the BD, SCZ or HC groups.

There was limited evidence of association between immune markers and TL in SCZ and BD. The results provide little support for involvement of immune dysregulation, as reflected by current systemic markers, in telomere attrition-related accelerated ageing in severe mental disorders.

While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship.

Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups.

There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation – lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation – higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course.

Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap.

FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year).

In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none.

In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.

Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery—no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups.

Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the “Remission in Schizophrenia Working Group” criteria and TR on adaptations of the “Treatment Response and Resistance in Psychosis” (TRRIP) working group criteria.

97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects.

The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

Intellectual functioning (IQ) is lower in schizophrenia patients compared to healthy controls, with bipolar patients intermediate between the two. Declines in IQ mark the onset of schizophrenia, while stability is generally found post-onset. There are to date few studies on long-term IQ development in bipolar disorder. This study presents 10-year follow-up data on IQ, including premorbid IQ estimates, to track the developmental course from pre-onset levels to long-term outcomes in both patient groups compared to healthy controls.

We included 139 participants with schizophrenia, 76 with bipolar disorder and 125 healthy controls. Mixed model analyses were used to estimate developmental slopes for IQ scores from estimated premorbid level (NART IQ) through baseline (WASI IQ) measured within 12 months post-onset, to 10-year follow-up (WASI IQ), with pairwise group comparisons. The best fit was found using a model with a breakpoint at baseline assessment.

Only the schizophrenia group had significant declines from estimated premorbid to baseline IQ levels compared to controls. When comparing patient groups, schizophrenia patients had steeper declines than the bipolar group. Increases in IQ were found in all groups over the follow-up period.

Trajectories of IQ from premorbid level to 10-year follow-up indicated declines from estimated premorbid level to illness onset in both patient groups, followed by increases during the follow-up period. Schizophrenia patients had a steeper decline than bipolar patients. During follow-up, increases indicate developmental improvement for both patient groups, but with a maintained lag compared to healthy controls due to lower premorbid levels.

Cardiometabolic risk is increased in severe mental disorders (SMDs), and there appears to be a relationship between childhood trauma and cardiometabolic risk, possibly related to adverse health behavior. The current study examined the association between childhood trauma and serum lipids and adiposity in SMDs and the potential mediating role of cognitive and personality characteristics.

Participants with schizophrenia and bipolar spectrum disorders (N = 819) were included, cardiometabolic risk factors (serum lipids, body mass index, and waist circumference) were measured, and history of childhood trauma was assessed by the Childhood Trauma Questionnaire. Cognitive and personality characteristics were available in subsamples, with assessments of cognitive control, impulsiveness, self-esteem, and affective lability. Linear regressions and mediation analyses with Hayes’ PROCESS were performed, adjusting for age, sex, antipsychotic agent propensity of metabolic side-effect, and diagnostic group.

Experience of three or more subtypes of childhood trauma was positively associated with waist circumference in patients with SMDs (p = 0.014). There were no other significant associations between trauma variables and lipid or adiposity measures in the total sample. Cognitive control was a significant mediator between experience of one or two subtypes of childhood trauma and waist circumference.

The results indicate childhood trauma as a predisposing factor for increased waist circumference in individuals with SMDs. Poorer cognitive control, suggestive of adverse health behavior, might be a mediating factor of the association, and the findings indicate the potential importance of increased focus on these factors in prevention and treatment regimens targeting cardiometabolic health.

The etiology of schizophrenia (SZ) is proposed to include an interplay between a genetic risk for disease development and the biological environment of pregnancy and birth, where early adversities may contribute to the poorer developmental outcome. We investigated whether a history of birth asphyxia (ASP) moderates the relationship between intracranial volume (ICV) and intelligence in SZ, bipolar disorder (BD) and healthy controls (HC).

Two hundred seventy-nine adult patients (18–42 years) on the SZ and BD spectrums and 216 HC were evaluated for ASP based on information from the Medical Birth Registry of Norway. Participants underwent structural magnetic resonance imaging (MRI) to estimate ICV and intelligence quotient (IQ) assessment using the Wechsler Abbreviated Scale of Intelligence (WASI). Multiple linear regressions were used for analyses.

We found a significant three-way interaction (ICV × ASP × diagnosis) on the outcome variable, IQ, indicating that the correlation between ICV and IQ was stronger in patients with SZ who experienced ASP compared to SZ patients without ASP. This moderation by ASP was not found in BD or HC groups. In patients with SZ, the interaction between ICV and a history of the ASP was specifically related to the verbal subcomponent of IQ as measured by WASI.

The significant positive association between ICV and IQ in patients with SZ who had experienced ASP might indicate abnormal neurodevelopment. Our findings give support for ICV together with verbal intellectual abilities as clinically relevant markers that can be added to prediction tools to enhance evaluations of SZ risk.

Cognitive dysfunction cut across diagnostic categories and is present in both schizophrenia and bipolar disorder, although with considerable heterogeneity in both disorders. This study examined if distinct cognitive subgroups could be identified across schizophrenia and bipolar disorder based on the intellectual trajectory from the premorbid phase to after illness onset.

Three hundred and ninety-eight individuals with schizophrenia (n = 223) or bipolar I disorder (n = 175) underwent clinical and neuropsychological assessment. Hierarchical and k-means cluster analyses using premorbid (National Adult Reading Test) and current IQ (Wechsler Abbreviated Scale of Intelligence) estimates were performed for each diagnostic category, and the whole sample collapsed. Resulting clusters were compared on neuropsychological, functional, and clinical variables. Healthy controls (n = 476) were included for analyses of neuropsychological performance.

Cluster analyses consistently yielded three clusters: a relatively intact group (36% of whole sample), an intermediate group with mild cognitive impairment (44%), and an impaired group with global deficits (20%). The clusters were validated by multinomial logistic regression and differed significantly for neuropsychological, functional, and clinical measures. The relatively intact group (32% of the schizophrenia sample and 42% of the bipolar sample) performed below healthy controls for speeded neuropsychological tests.

Three cognitive clusters were identified across schizophrenia and bipolar disorder using premorbid and current IQ estimates. Groups differed for clinical, functional, and neuropsychological variables, implying their meaningfulness. One-third of the schizophrenia sample belonged to the relatively intact group, highlighting that neuropsychological assessment is needed for the precise characterization of the individual.

Despite apparent clinical remission, individuals with psychotic disorders often experience significant impairments across functional domains. Thus, there is a need to search beyond management of core symptoms to optimize treatment outcomes. Affective dysregulation is considered a risk factor for poor clinical and functional outcomes in many mental disorders, but research investigating such features in psychosis, particularly in schizophrenia, is limited. We aimed to investigate the level of affective lability (AL) in participants with schizophrenia- and bipolar spectrum disorders (n = 222) compared to healthy controls (n = 140), as well as clinical correlates of AL in the diagnostic groups.

The Affective Lability Scale (ALS-SF) was used to measure total score of AL and subscores covering the domains of anxiety/depression, depression/elation, and anger. An analysis of covariance was performed to compare the ALS-SF total score between groups, correcting for potential confounders, as well as standard multiple regression analyses for diagnosis-specific investigations of the relationship between AL and demographic and clinical features.

Both the schizophrenia- and bipolar spectrum group had significantly higher ALS-SF total score compared to controls (p < 0.001), and no significant differences between the patient groups were found. In the schizophrenia group, current psychotic and depressive symptoms were significantly and independently associated with AL (p = 0.012 and p = 0.024, respectively).

The findings indicate that AL is elevated in psychotic disorders and that it transcends diagnostic boundaries. Further research into the causal relationship between psychotic and affective symptoms and AL, as well as its role as a potential therapeutic target in psychosis spectrum disorders, is warranted.

Whether severe obstetric complications (OCs), which harm neural function in offspring, contribute to impaired cognition found in psychiatric disorders is currently unknown. Here, we sought to evaluate how a history of severe OCs is associated with cognitive functioning, indicated by Intelligence Quotient (IQ).

We evaluated the associations of a history of OCs and IQ in 622 healthy controls (HC) and 870 patients on the schizophrenia (SCZ) – bipolar disorder (BIP) spectrum from the ongoing Thematically Organized Psychosis study cohort, Oslo, Norway. Participants underwent assessments using the NART (premorbid IQ) and the WASI (current IQ). Information about OCs was obtained from the Medical Birth Registry of Norway. Multiple linear regression models were used for analysis.

Severe OCs were equally common across groups. SCZ patients with OCs had lower performances on both premorbid and current IQ measures, compared to those without OCs. However, having experienced more than one co-occurring severe OC was associated with lower current IQ in all groups.

Severe OCs were associated with lower IQ in the SCZ group and in the BIP and HC groups, but only if they had experienced more than one severe OC. Low IQ might be a neurodevelopmental marker for SCZ; wherein, severe OCs influence cognitive abilities and increase the risk of developing SCZ. Considering OCs as a variable of neurodevelopmental risk for severe mental illness may promote the development of neuroprotective interventions, improve outcome in vulnerable newborns and advance our ability to make clinical prognoses.