Despite known deficits in postural control in patients with schizophrenia, this domain has not been investigated in youth at ultra high-risk (UHR) for psychosis. This is particularly relevant as postural control implicates dysfunction in the cerebellum-a region implicated in cognitive dysmetria conceptions of schizophrenia but poorly understood in the prodrome. Here, we extended our understanding of movement abnormalities in UHR individuals to include postural control, and have linked these deficits to both symptom severity and cerebello-cortical network connectivity. UHR and healthy control participants completed an instrumentally-based balance task to quantify postural control along with a resting state brain imaging scan to investigate cerebellar networks. We also quantified positive and negative symptom severity with structured clinical interviews. The UHR group showed overall increased postural sway and decreased cerebello-cortical resting state connectivity, relative to controls. The decreased cerebello-cortical connectivity was seen across multiple networks. Postural sway was also correlated with cerebellar connectivity in this population and uniquely positively correlated with the severity of negative symptoms. Finally, symptom severity was also associated with cerebellar connectivity. Together, our results point to a potential deficit in sensory integration as an underlying contributor to the increased postural sway, and provide evidence of cerebellar abnormalities in UHR individuals. These results extend our understanding of the motor abnormalities of UHR individuals beyond striatum-based dyskinesias to include postural control and sensory integration deficits, and implicate the cerebellum as a distinct neural substrate preceding the onset of psychosis. Taken together, our results extend the cognitive dysmetria framework to UHR populations.

Findings of abnormal white matter development provide direct empirical evidence to support prominent neurodevelopmental theories. The predictive relationships between NSS and longitudinal cerebellar-thalamic tract integrity and negative symptom course provide insight into the role of cognitive dysmetria in the high-risk period and inform on a unique biomarker tied to core features underlying psychosis.

Background Sleep dysfunction is a pervasive, distressing characteristic of psychosis, yet little is known regarding sleep quality prior to illness onset. At present, it is unclear whether sleep dysfunction precedes the emergence of psychotic symptoms, signifying a core feature of the disorder, or if it represents a consequence of prolonged contact with aspects of schizophrenia and its treatment (e.g., medication use or neurotoxicity) or co-morbid symptoms (e.g., depressive and manic symptomatology). The current study examined sleep dysfunction in adolescents at ultra high-risk (UHR) for psychosis, relationships between sleep disturbances and psychosis symptoms, volume of an integral sleep-structure (thalamus), and associations between thalamic abnormalities and sleep impairment in UHR youth. Method Thirty-three UHR youth and 33 healthy controls (HC) participated in a self-assessment of sleep functioning (Pittsburgh Sleep Quality Index; PSQI), self and parent-report clinical interviews, and structural magnetic resonance imaging (MRI). Results UHR adolescents displayed increased latency to sleep onset and greater sleep disturbances/disrupted continuity compared to HC youth, over and above concurrent mood symptoms. Among UHR youth, increased sleep dysfunction was associated with greater negative symptom severity but not positive symptoms. Compared to HC adolescents, UHR participants displayed decreased bilateral thalamus volume, which was associated with increased sleep dysfunction. Conclusions Sleep dysfunction occurs during the pre-psychotic period, and may play a role in the etiology and pathophysiology of psychosis. In addition, the relationship of disrupted sleep to psychosis symptoms in UHR youth indicates that prevention and intervention strategies may be improved by targeting sleep stabilization in the pre-psychotic period.

A growing body of evidence suggests that moderate to vigorous activity levels can affect quality of life, cognition, and brain structure in patients diagnosed with schizophrenia. However, physical activity has not been systematically studied during the period immediately preceding the onset of psychosis. Given reports of exercise-based neurogenesis in schizophrenia, understanding naturalistic physical activity levels in the prodrome may provide valuable information for early intervention efforts. The present study examined 29 ultra high-risk (UHR) and 27 matched controls to determine relationships between physical activity level, brain structure (hippocampus and parahippocampal gyrus), and symptoms. Participants were assessed with actigraphy for a 5-day period, magnetic resonance imaging (MRI), and structured clinical interviews. UHR participants showed a greater percentage of time in sedentary behavior while healthy controls spent more time engaged in light to vigorous activity. There was a strong trend to suggest the UHR group showed less total physical activity. The UHR group exhibited smaller medial temporal volumes when compared to healthy controls. Total level of physical activity in the UHR group was moderately correlated with smaller parahippocampal gyri bilaterally (right: r=.44, left: r=.55) and with occupational functioning (r=−.36; of negative symptom domain), but not positive symptomatology. Results suggest that inactivity is associated with medial temporal lobe health. Future studies are needed to determine if symptoms are driving inactivity, which in turn may be affecting the health of the parahippocampal structure and progression of illness. Although causality cannot be determined from the present design, these findings hold important implications for etiological conceptions and suggest promise for an experimental trial.

Impaired ability to maintain an upright posture may reflect impairment in the cerebellum, a critical structure for the fluid coordination of neural information, thought to be disrupted in psychosis. The current study utilized an instrumental measure of posture in individuals at ultrahigh risk (UHR) for psychosis (n=43) and healthy controls (n=44). Positive and negative symptoms were assessed twice over 12-months. Results showed that increased postural sway in the UHR group predicted changes in negative symptoms. This study provides an important prospective view on the relationship between cerebellar-sensitive behavior and integral symptoms, which until now has received limited biomarker research.

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 preto-post reductions in symptoms (depression, anxiety, and subclinical psychotic symptoms, ps < 0.004) and improvements in resilience-promoting capacities (selfcompassion 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).

Despite evidence suggesting a role for cerebellar abnormalities in the pathogenesis of psychosis, the structure has yet to receive attention in individuals at ultrahigh risk for psychosis (UHR). Accumulating research has suggested that the cerebellum helps modulate cognition and movement, domains in which UHR individuals show impairment; understanding putative markers of risk, such as structural abnormalities and behavioral correlates, is essential. In this study, participants underwent a high-resolution structural brain scan and participated in a pursuit rotor experiment. Cerebellar regions associated with movement (anterior cerebellum) and cognition (crus I) were subsequently analyzed. UHR participants showed impaired performance on the pursuit rotor task, learned at a slower rate, and showed smaller cerebellar volumes compared with control participants. Left crus I volume was significantly associated with poor rate of learning. The present results suggest that cerebellar abnormalities and their behavioral correlates (poor learning and motor control) precede the onset of psychosis.

Many investigations have demonstrated that negative symptoms and social cognitive deficits in schizophrenia play a large role in determining functional outcomes and ultimately long-term prognosis. Given this, there is increasing interest in understanding the relationship between these two symptom domains, particularly since studies have consistently found moderate to large associations between them. This shared variance raises a key question: to what degree do these two categories of symptoms arise from overlapping or identical changes in brain function? In other words, do some or all negative symptoms represent merely the downstream effects of social cognition deficits on daily functioning? In this commentary, the evidence for and against this possibility, limitations of currently validated empirical measurements of these symptoms, and directions for further investigation of this hypothesis are discussed. Understanding the shared and distinct mechanisms of these disabling deficits will have important implications for the design of novel, personalized treatments for psychotic illness.