Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. Results: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. Conclusions: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Changes in responses of the amygdala and hippocampus during fear conditioning are associated with persecutory beliefs.

The persecutory delusion is the most common symptom of psychosis, yet its underlying neurobiological mechanisms are poorly understood. Prior studies have suggested that abnormalities in medial temporal lobe-dependent associative learning may contribute to this symptom. In the current study, this hypothesis was tested in a non-clinical sample of young adults without histories of psychiatric treatment (n = 64), who underwent classical Pavlovian fear conditioning while fMRI data were collected. During the fear conditioning procedure, participants viewed images of faces which were paired (the CS+) or not paired (the CS-) with an aversive stimulus (a mild electrical shock). Fear conditioning-related neural responses were measured in two medial temporal lobe regions, the amygdala and hippocampus, and in other closely connected brain regions of the salience and default networks. The participants without persecutory beliefs (n = 43) showed greater responses to the CS- compared to the CS+ in the right amygdala and hippocampus, while the participants with persecutory beliefs (n = 21) failed to exhibit this response. These between-group differences were not accounted for by symptoms of depression, anxiety or a psychosis risk syndrome. However, the severity of subclinical psychotic symptoms overall was correlated with the level of this aberrant response in the amygdala (p = .013) and hippocampus (p = .033). Thus, these findings provide evidence for a disruption of medial temporal lobe-dependent associative learning in young people with subclinical psychotic symptoms, specifically persecutory thinking.

Efficacy of a transdiagnostic, prevention-focused program for at-risk young adults: a waitlist-controlled trial.

BACKGROUND: Prevention programs that are 'transdiagnostic' may be more cost-effective and beneficial, in terms of reducing levels of psychopathology in the general population, than those focused on a specific disorder. This randomized controlled study evaluated the efficacy of one such intervention program called Resilience Training (RT). METHODS: College students who reported mildly elevated depressive or subclinical psychotic symptoms ('psychotic experiences' (PEs)) (n = 107) were randomized to receiving RT (n = 54) or to a waitlist control condition (n = 53). RT consists of a four-session intervention focused on improving resilience through the acquisition of mindfulness, self-compassion, and mentalization skills. Measures of symptoms and these resilience-enhancing skills were collected before and after the 4-week RT/waitlist period, with a follow-up assessment 12-months later. RESULTS: Compared to the waitlist control group, RT participants reported significantly greater reductions in PEs, distress associated with PEs, depression, and anxiety, as well as significantly greater improvements in resilience, mindfulness, self-compassion, and positive affect, following the 4-week RT/waitlist period (all p < 0.03). Moreover, improvements in resilience-promoting skills were significantly correlated with symptom reductions (all p < 0.05). Lastly, the RT-related reductions in PEs and associated distress were maintained at the 12-month follow-up assessment. CONCLUSIONS: RT is a brief, group-based intervention associated with improved resilience and reduced symptoms of psychopathology, with sustained effects on PEs, in transdiagnostically at-risk young adults. Follow-up studies can further assess the efficacy of RT relative to other interventions and test whether it can reduce the likelihood of developing a serious mental illness.

The role of anhedonia in predicting risk-taking behavior in university students.

There is a growing interest in understanding symptoms of psychological distress, such as anhedonia, not just as related to individual psychological disorders, but transdiagnostically. This broader focus allows for the investigation of the effects of symptoms across disorders, or in non-clinical samples. Previous work has linked anhedonia and risk-taking behavior in clinical samples, though the exploration of this relationship in healthy adolescents and early adults is still a relatively new area of research. The current study explored the relationship between variability in anhedonia and risk-taking behavior by breaking each into separable parts (i.e. anhedonia into deficits in anticipatory and consummatory pleasure; risk-taking into risk propensity, sub-optimal risky behavior, and response to punishment). A sample of 81 university students completed two Chapman scales of anhedonia, the Temporal Experience of Pleasure Scale (TEPS), and the Balloon Analogue Risk Task (BART). Hierarchical linear regression analyses were completed to assess the predictive power of each anhedonia measure on each outcome measure on the BART. TEPS score significantly negatively predicted all three outcome measures, with anticipatory pleasure having more predictive power than consummatory pleasure. Physical anhedonia was also a significant predictor of sub-optimal risky behavior and response to punishment. These findings present a broader and more complex view of the associations between anhedonia and risk than have previously been reported, and merit further study to continue to elucidate how they are related to one another.

Socioemotional mechanisms of loneliness in subclinical psychosis.

Loneliness is an important predictor of physical and mental health in the general population and in individuals across the psychosis spectrum, including those experiencing subclinical psychotic-like experiences (PLEs). However, the mechanisms underlying loneliness in the psychosis spectrum are not well understood. Emotion processing deficits are well described across the psychosis spectrum, and socioemotional processing biases are critical for the development and maintenance of loneliness through altered social appraisal, including judgements of rejection. Therefore, we propose that PLEs are associated with increased loneliness, and the relationship is mediated by alterations in socioemotional processing. We also explored how this pathway may be affected by mood and anxiety symptoms, which have been associated with loneliness across the psychosis spectrum. As part of the Human Connectome Project, generally healthy adults (n = 1180) reported symptomatology and social functioning and completed the Penn Emotion Recognition Task to assess efficiency in identifying emotions. We found that higher reported PLEs were associated with elevated levels of loneliness and perceived rejection and that these factors were linked by multiple independent pathways. First, anxiety/depression and emotion processing efficiency independently mediated the PLE-loneliness relationship. Second, we found that the association between PLEs and loneliness was serially mediated through inefficient emotion recognition then higher levels of perceived rejection. These separable mechanisms of increased loneliness in subclinical psychosis have implications for treatment and continued study of social functioning in the psychosis spectrum.

Adolescent Neurodevelopment and Vulnerability to Psychosis.

Adolescence is characterized by significant changes in several domains, including brain structure and function, puberty, and social and environmental factors. Some of these changes serve to increase the likelihood of psychosis onset during this period, while others may buffer this risk. This review characterizes our current knowledge regarding the unique aspects of adolescence that may serve as risk factors for schizophrenia spectrum disorders. In addition, we provide potential future directions for research into adolescent-specific developmental mechanisms that impart vulnerability to psychosis and the possibility of interventions that capitalize on adolescents' unique characteristics. Specifically, we explore the ways in which gray and white matter develop throughout adolescence in typically developing youth as well as in those with psychosis spectrum disorders. We also discuss current views on the function that social support and demands, as well as role expectations, play in risk for psychosis. We further highlight the importance of considering biological factors such as puberty and hormonal changes as areas of unique vulnerability for adolescents. Finally, we discuss cannabis use as a factor that may have a unique impact during adolescent neurodevelopment, and subsequently potentially impact psychosis onset. Throughout, we include discussion of resilience factors that may provide unique opportunities for intervention during this dynamic life stage.

Rationale, Methods, Feasibility, and Preliminary Outcomes of a Transdiagnostic Prevention Program for At-Risk College Students.

PURPOSE: Early adulthood represents one period of increased risk for the emergence of a serious mental illness. The college campus provides a unique opportunity to assess and monitor individuals in this at-risk age group. However, there are no validated early detection programs that are widely implemented on college campuses. In an effort to address this gap, we designed and tested an early detection and prevention program tailored to college students. A transdiagnostic approach was employed because of evidence for shared risk factors across major mental illnesses. DESIGN: Single arm, prospective study evaluating outcomes following a 4-week intervention. METHOD: Three in-person mental health screenings were conducted on the campus of one university. Undergraduate students with at least mildly elevated, self-reported levels of depressive or subclinical psychotic symptoms, who were not receiving treatment for these symptoms, were invited to participate in a 4-session workshop focused on increasing self- and other- awareness and emotion regulation using established mindfulness, self-compassion, and mentalization principles and experiential exercises. Symptoms, resilience-promoting capacities, and aspects of social functioning were assessed pre- and post- intervention. RESULTS: 416 students were screened and a total of 63 students participated in the workshop. 91% attended at least 3 of the 4 sessions. The majority of participants found the workshop interesting and useful and would recommend it to a friend. Significant pre-to-post reductions in symptoms (depression, anxiety, and subclinical psychotic symptoms, ps < 0.004) and improvements in resilience-promoting capacities (self-compassion and self-efficacy, ps < 0.006) and indices of social functioning (social motivation, activity, and a measure of comfort with the physical presence of others, ps < 0.04) were observed. Moreover, the significant increases in resilience-promoting capacities correlated with the reductions in affective symptoms (ps < 0.03). CONCLUSIONS: These findings suggest that an on-campus mental health screening and early intervention program is feasible, acceptable, and may be associated with improvements in resilience-related capacities and symptom reductions in young adults with non-impairing, subclinical symptoms of psychopathology. Follow-up work will determine whether this program can improve both shorter and longer-term mental health and functional outcomes in this at-risk population.