Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness.

Our aim was to determine if NMDAR availability was lower in patients with first episode psychosis compared to healthy controls.

To address this, we studied 40 volunteers (21 patients with first episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Striatal glutamatergic indices (glutamate and Glx) were measured simultaneously using magnetic resonance spectroscopy imaging (1H-MRS).

Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p=0.02, Cohen’s d=0.81; p=0.15, Cohen’s d=0.49), and negatively associated with total (rho=-0.47, p= 0.04), depressive (rho=-0.67, p=0.002), and general symptom severity (rho=-0.74, p<0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). We found an inverse relationship between hippocampal NMDAR availability and striatal glutamate levels in people with first-episode psychosis (rho = -0.74, p <0.001) but not in healthy controls (rho = -0.22, p = 0.44).

These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality.

No significant relationships.

Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.

The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.

We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.

We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls.

Neuroanatomical investigation of BSD in a UHR sample

To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations.

32 HR subjects (27 antipsychotics-naïve) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex).

Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05).

This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.

Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.

Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.

Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).

In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.