Zachary B. Millman

Sleep dysfunction and thalamic abnormalities in adolescents at ultra high-risk for 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.

Physical Activity Level and Medial Temporal Health in Youth at Ultra High-Risk for Psychosis

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, 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 with healthy controls. Total level of physical activity in the UHR group was moderately correlated with 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.

Evidence-based early interventions for individuals at clinical high risk for psychosis: a review of treatment components.

Abstract Youth and young adults at clinical high risk (CHR) for psychosis experience a broad range of difficulties, including attenuated psychotic symptoms, comorbid concerns, functional impairments, and family and interpersonal stress. Given emerging evidence that early interventions may improve functioning and reduce symptomatology while also lowering risk of transition to full-threshold psychosis, several randomized controlled trials have systematically evaluated the efficacy of CHR treatment approaches. This article describes and summarizes psychosocial intervention approaches that have demonstrated efficacy in treating people at CHR, with a focus on distilling individual components of these treatments. On the basis of the existing literature, we propose an empirically based, flexible, and comprehensive modularized approach to early intervention that meets the varying needs of individuals experiencing CHR-related distress and dysfunction, many of whom may be on a trajectory toward psychosis.

Mismatch and lexical retrieval gestures are associated with visual information processing, verbal production, and symptomatology in youth at high risk for psychosis

INTRODUCTION Gesture is integrally linked with language and cognitive systems, and recent years have seen a growing attention to these movements in patients with schizophrenia. To date, however, there have been no investigations of gesture in youth at ultra high risk (UHR) for psychosis. Examining gesture in UHR individuals may help to elucidate other widely recognized communicative and cognitive deficits in this population and yield new clues for treatment development. METHOD In this study, mismatch (indicating semantic incongruency between the content of speech and a given gesture) and retrieval (used during pauses in speech while a person appears to be searching for a word or idea) gestures were evaluated in 42 UHR individuals and 36 matched healthy controls. Cognitive functions relevant to gesture production (i.e., speed of visual information processing and verbal production) as well as positive and negative symptomatologies were assessed. RESULTS Although the overall frequency of cases exhibiting these behaviors was low, UHR individuals produced substantially more mismatch and retrieval gestures than controls. The UHR group also exhibited significantly poorer verbal production performance when compared with controls. In the patient group, mismatch gestures were associated with poorer visual processing speed and elevated negative symptoms, while retrieval gestures were associated with higher speed of visual information-processing and verbal production, but not symptoms. CONCLUSIONS Taken together these findings indicate that gesture abnormalities are present in individuals at high risk for psychosis. While mismatch gestures may be closely related to disease processes, retrieval gestures may be employed as a compensatory mechanism.

Emotion recognition and social/role dysfunction in non-clinical psychosis

As researchers continue to understand non-clinical psychosis (NCP-brief psychotic-like experiences occurring in 5-7% of the general population; van Os et al., 2009), it is becoming evident that functioning deficits and facial emotion recognition (FER) impairment characterize this phenomenon. However, the extent to which these domains are related remains unclear. Social/role functioning and FER were assessed in 65 adolescents/young adults exhibiting low and high-NCP. Results indicate that FER and social/role functioning deficits were present in the High-NCP group, and that the domains were associated in this group alone. Taken together, findings suggest that a core emotive deficit is tied to broader social/role dysfunction in NCP.

Beat and metaphoric gestures are differentially associated with regional cerebellar and cortical volumes

Gestures represent an integral aspect of interpersonal communication, and they are closely linked with language and thought. Brain regions for language processing overlap with those for gesture processing. Two types of gesticulation, beat gestures and metaphoric gestures are particularly important for understanding the taxonomy of co‐speech gestures. Here, we investigated gesture production during taped interviews with respect to regional brain volume. First, we were interested in whether beat gesture production is associated with similar regions as metaphoric gesture. Second, we investigated whether cortical regions associated with metaphoric gesture processing are linked to gesture production based on correlations with brain volumes. We found that beat gestures are uniquely related to regional volume in cerebellar regions previously implicated in discrete motor timing. We suggest that these gestures may be an artifact of the timing processes of the cerebellum that are important for the timing of vocalizations. Second, our findings indicate that brain volumes in regions of the left hemisphere previously implicated in metaphoric gesture processing are positively correlated with metaphoric gesture production. Together, this novel work extends our understanding of left hemisphere regions associated with gesture to indicate their importance in gesture production, and also suggests that beat gestures may be especially unique. This provides important insight into the taxonomy of co‐speech gestures, and also further insight into the general role of the cerebellum in language. Hum Brain Mapp 36:4016–4030, 2015.

Childhood dyspraxia predicts adult-onset nonaffective–psychosis-spectrum disorder

Several neurological variables have been investigated as premorbid biomarkers of vulnerability for schizophrenia and other related disorders. The current study examined whether childhood dyspraxia predicted later adult nonaffective-psychosis-spectrum disorders. From a standardized neurological examination performed with children (aged 10-13) at genetic high risk of schizophrenia and controls, several measures of dyspraxia were used to create a scale composed of face/head dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to other psychiatric disorders and no mental illness outcomes, even after controlling for genetic risk, χ2 (4, 244) = 18.61, p < .001. Findings that symptoms of dyspraxia in childhood (reflecting abnormalities spanning functionally distinct brain networks) specifically predict adult nonaffective-psychosis-spectrum disorders are consistent with a theory of abnormal connectivity, and they highlight a marked early-stage vulnerability in the pathophysiology of nonaffective-psychosis-spectrum disorders.

High-risk diagnosis, social stress, and parent-child relationships: A moderation model

Stress is related to symptom severity among youth at clinical high-risk (CHR) for psychosis, although this relation may be influenced by protective factors. We explored whether the association of CHR diagnosis with social stress is moderated by the quality of parent-child relationships in a sample of 96 (36 CHR; 60 help-seeking controls) adolescents and young adults receiving mental health services. We examined self-reported social stress and parent-child relationships as measured by the Behavior Assessment System for Children, Second Edition (BASC-2), and determined CHR status from the clinician-administered Structured Interview for Psychosis-Risk Syndrome (SIPS). The social stress subscale, part of the clinical domain of the BASC-2, assesses feelings of stress and tension in personal relationships and the relations with parents subscale, part of the adaptive domain of the BASC-2, assesses perceptions of importance in family and quality of parent-child relationship. There was a modest direct relation between risk diagnosis and social stress. Among those at CHR, however, there was a significant relation between parent-child relationships and social stress (b=-0.73, t[92]=-3.77, p<0.001, f(2)=0.15) that was not observed among non-CHR individuals, suggesting that a positive parent-child relationship may be a protective factor against social stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent-child relationships might be relevant for adolescents and young adults at clinical high-risk for psychosis.

Orbitofrontal cortex volume and intrinsic religiosity in non-clinical psychosis.

Research indicates that religiosity plays a complex role in mental illness. Despite this link, little work has been done to clarify the role of religiosity in persons exhibiting non-clinical psychosis (NCP, individuals experiencing fleeting psychotic-like symptoms in the absence of a formal psychotic disorder). Further, there are no NCP investigations into whether abnormalities exist in brain structures that are associated with religiosity. Understanding these relationships in NCP is important to clarify the role of religiosity and brain structural anomalies in psychosis. Twenty individuals experiencing NCP and twenty controls were assessed for intrinsic religiosity (IR; motivation/commitment to religious beliefs and/or practices) using a well-validated self-report scale. Structural magnetic resonance imaging was used to determine volumes of the orbitofrontal cortex (OFC), a critical region that has been associated with increased religiosity. Results indicate that IR is elevated in the NCP group, and that these individuals exhibit bilateral volume reduction in both the lateral and medial OFC. Sample-wide correlations are non-significant, but show notable relationships between smaller OFC regions and increased IR. Significant negative relationships were found between OFC volume and depressive and negative symptoms. Overall, results suggest that brain abnormalities associated with NCP may also confer a heightened susceptibility for religiosity.

Differential relations of locus of control to perceived social stress among help-seeking adolescents at low vs. high clinical risk of psychosis

Research suggests that perceived social stress influences illness presentation and course among youth in the clinical high-risk (CHR) phase of psychosis. Little is known, however, about the social cognitive factors associated with social stress perception in this population, particularly relative to youth with non-CHR psychopathology. Individuals with psychosis tend to endorse an external locus of control (LOC), which is associated with the stress response in healthy individuals. LOC may therefore be related to perceived social stress in youth at CHR. We examined the differential relations of self-reported LOC and perceived social stress, as measured by the Behavior Assessment System for Children, Second Edition, across 45 CHR and 65 help-seeking control (HSC) participants. Youth at CHR reported more social stress (F[1, 107]=6.28, p=0.01) and a more external LOC (F[1, 107]=4.98, p=0.03) than HSCs. Further, external LOC was more strongly associated with feelings of social stress in the CHR group relative to the HSC group (interaction: b=0.35, t[105]=2.32, p<0.05, f2=0.05). Group differences in social stress, however, were nonsignificant at internal levels of LOC (b=-2.0, t[105]=-0.72, p=0.48; f2=0.00). Results suggest that perceptions of uncontrollability over ones social environment may more often induce or exacerbate feelings of stress and tension in CHR youth relative to HSCs. A better understanding of the social cognition-stress relation may improve understanding of CHR phenomenology, etiology, and treatment.