Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.

First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses.

The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.

The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact.

We aimed to identify unmet treatment needs for improving social and occupational functioning in early schizophrenia using a data-driven causal discovery analysis.

Demographic, clinical, and psychosocial measures were obtained for 276 participants from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) trial at baseline and 6-months, along with measures of social and occupational functioning from the Quality of Life Scale. The Greedy Fast Causal Inference algorithm was used to learn a partial ancestral graph modeling causal relationships across baseline variables and 6-month functioning. Effect sizes were estimated using a structural equation model. Results were validated in an independent dataset (N = 187).

In the data-generated model, greater baseline socio-affective capacity was a cause of greater baseline motivation [Effect size (ES) = 0.77], and motivation was a cause of greater baseline social and occupational functioning (ES = 1.5 and 0.96, respectively), which in turn were causes of their own 6-month outcomes. Six-month motivation was also identified as a cause of occupational functioning (ES = 0.92). Cognitive impairment and duration of untreated psychosis were not direct causes of functioning at either timepoint. The graph for the validation dataset was less determinate, but otherwise supported the findings.

In our data-generated model, baseline socio-affective capacity and motivation are the most direct causes of occupational and social functioning 6 months after entering treatment in early schizophrenia. These findings indicate that socio-affective abilities and motivation are specific high-impact treatment needs that must be addressed in order to promote optimal social and occupational recovery.

To explore factors associated with work impairment at 2 years following an acute episode.

European Mania in Bipolar disorder Longitudinal Evaluation of Medication (EMBLEM) is a prospective, observational study on the outcomes of patients with a manic/mixed episode. Work impairment was measured using a Longitudinal Interval Follow-up Evaluation (slice of LIFE) item and patients were categorised with either low or high work impairment at each observation. Baseline factors associated with work impairment at 2 years were assessed using multivariate modelling.

At baseline (n = 2289), 69% of patients had high work impairment. At 2 years (n = 1393), high impairment reduced to 41%. Modelling identified rapid cycling as the strongest disease-related factor associated with high work impairment at 2 years, although high work impairment at baseline had the strongest association overall. Lower levels of education, recent admissions, CGI-BP overall severity in the 12 months prior to baseline and CGI-BP mania at baseline all predicted higher work impairment. Living together in a relationship and independent housing were both significantly associated with having low work impairment at 2 years.

Work impairment in bipolar disorder is maintained over long periods, and is strongly associated with relationship status, living conditions and various disease-related factors.

This post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.

Data were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0–3), moderate (4–6), and marked/extreme (7–10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.

Greater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (all p ≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (all p<0.0001).

Treatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.

Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting individual differences in functional outcomes.

We used data from the Dutch TRAILS study in which 1778 youths were followed from pre-adolescence into young adulthood (retention 80%). Of those, 1584 youths were successfully interviewed, at age 19, using the World Health Organization Composite International Diagnostic Interview (CIDI 3.0) to assess current and past CIDI-DSM-IV mental disorders. Four outcome domains were assessed at the same time: economic (e.g. academic achievement, social benefits, financial difficulties), social (early motherhood, interpersonal conflicts, antisocial behavior), psychological (e.g. suicidality, subjective well-being, loneliness), and health behavior (e.g. smoking, problematic alcohol, cannabis use).

Out of the 19 outcomes, 14 were predicted by both current and past disorders, three only by past disorders (receiving social benefits, psychiatric hospitalization, adolescent motherhood), and two only by current disorder (absenteeism, obesity). Which type of disorders was most important depended on the outcome. Adjusted for current disorder, past internalizing disorders predicted in particular psychological outcomes while externalizing disorders predicted in particular health behavior outcomes. Economic and social outcomes were predicted by a history of co-morbidity of internalizing and externalizing disorder. The risk of problematic cannabis use and alcohol consumption dropped with a history of internalizing disorder.

To understand current functioning, it is necessary to examine both current and past psychiatric status.

The consequences of minor trauma involving a head injury (MT-HI) in independent older adults are largely unknown. This study assessed the impact of a head injury on the functional outcomes six months post-injury in older adults who sustained a minor trauma.

This multicenter prospective cohort study in eight sites included patients who were aged 65 years or older, previously independent, presenting to the emergency department (ED) for a minor trauma, and discharged within 48 hours. To assess the functional decline, we used a validated test: the Older Americans’ Resources and Services Scale. The cognitive function of study patients was also evaluated. Finally, we explored the influence of a concomitant injury on the functional decline in the MT-HI group.

All 926 eligible patients were included in the analyses: 344 MT-HI patients and 582 minor trauma without head injury. After six months, the functional decline was similar in both groups: 10.8% and 11.9%, respectively (RR=0.79 [95% CI: 0.55–1.14]). The proportion of patients with mild cognitive disabilities was also similar: 21.7% and 22.8%, respectively (RR=0.91 [95% CI: 0.71–1.18]). Furthermore, for the group of patients with a MT-HI, the functional outcome was not statistically different with or without the presence of a co-injury (RR=1.35 [95% CI: 0.71–2.59]).

This study did not demonstrate that the occurrence of a MT-HI is associated with a worse functional or cognitive prognosis than other minor injuries without a head injury in an elderly population, six months after injury.

Whether an association exists between cerebral microbleeds (CMBs) and functional recovery after ischemic stroke is unclear. We aimed to evaluate the association between CMBs and functional outcome after acute ischemic stroke.

Consecutive patients with acute stroke were enrolled, and all patients were stratified into good and poor functional outcome groups at discharge and 6 months after ischemic stroke by using a modified Rankin Scale score. Cardiovascular risk factors, CMBs, and white matter hyperintensities were compared between these two outcome groups. Logistic regression analysis was used to estimate the risk of poor functional outcomes.

A total of 225 patients were enrolled, 121 of whom were classified as having a good functional outcome at discharge and 142 as having a good 6-month functional outcome. The presence of CMBs was associated with a poor functional outcome at discharge [CMBs (+) patients in poor vs. good functional group; 48.1% vs. 30.6%; p=0.007] and 6 months [53.0% vs. 30.3%; p=0.001]. After adjustment for confounding factors, only the presence of infratentorial CMBs was associated with a poor functional outcome at discharge and 6 months. The poor functional outcome group had more CMBs than the good outcome group at 6 months.

Infratentorial cerebral microbleeds were significantly associated with worse functional outcomes not only in the early phase of ischemic stroke but also in the chronic phase. These findings suggest that the presence of infratentorial CMBs can predict poor functional outcome after acute ischemic stroke.

Improvements in long-term survival of children undergoing the Norwood staged procedure and the arterial switch operation have resulted in the need to prepare these at-risk children for each stage of their developmental trajectory, including school readiness. This study describes and compares functional outcomes following the Norwood staged procedure and arterial switch operations.

This prospective inception cohort study comprised a sample of 73 children (71% boys) who had the Norwood staged procedure (n = 28) or the arterial switch operation (n = 45) at the age of 6 weeks or younger at the Stollery Children’s Hospital, Edmonton, Alberta, between 2002 and 2005. We excluded children who had chromosomal abnormalities or cerebral palsy. When children were 18–24 months of age, parents completed the Adaptive Behavioral Assessment System II. Standard scores for the domains are mean 100, standard deviation (15); skill area scaled scores, 10 (3). Student’s t-test with Bonferonni correction was used to compare groups.

This population has greater than four times the number of children delayed on the General Adaptive Composite than the normative group. Functional outcomes were similar in the two groups other than those of home living (Norwood: 8.8 (2.8) compared with arterial switch: 11.2 (3.1), t = 3.389, p = 0.001) and self-care (Norwood: 5.9 (3.5) versus arterial switch: 8.1 (2.6), t = 3.140, p = 0.002).

These survivors are at increased risk for delayed functional abilities. Self-care, necessary for independence and confidence as children reach school age, was particularly low in the Norwood group. Reasons for low self-care abilities require further study.