Barbara K. Stuart

Modeling the role of negative symptoms in determining social functioning in individuals at clinical high risk of psychosis

A priority for improving outcome in individuals at clinical high risk (CHR) is enhancing our understanding of predictors of psychosis as well as psychosocial functioning. Social functioning, in particular, is a unique indicator of risk as well as an important outcome in itself. Negative symptoms are a significant determinant of social functioning in CHR individuals; yet, it is unclear which specific negative symptoms drive functional outcome and how these symptoms function relative to other predictors, such as neurocognition and mood/anxiety symptoms. In a sample of 85 CHR individuals, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential vs expressive symptoms) would be replicated in a CHR sample; and tested the degree to which specific negative symptoms predict social functioning, relative to neurocognition and mood/anxiety symptoms, which are known to predict functioning. The two-factor negative symptom solution was replicated in this CHR sample. Negative symptom severity was found to be uniquely predictive of social functioning, above and beyond depression/anxiety and neurocognition. Experiential symptoms were more strongly associated with social functioning, relative to expression symptoms. In addition, experiential symptoms mediated the relationship between expressive negative symptoms and social functioning. These results suggest that experiences of motivational impairment are more important in determining social functioning, relative to affective flattening and alogia, in CHR individuals, thereby informing the development of more precise therapeutic targets. Developing novel interventions that stimulate goal-directed behavior and reinforce rewarding experiences in social contexts are recommended.

Auditory Cortex Responsiveness During Talking and Listening: Early Illness Schizophrenia and Patients at Clinical High-Risk for Psychosis

OBJECTIVE The corollary discharge mechanism is theorized to dampen sensations resulting from our own actions and distinguish them from environmental events. Deficits in this mechanism in schizophrenia may contribute to misperceptions of self-generated sensations as originating from external stimuli. We previously found attenuated speech-related suppression of auditory cortex in chronic patients, consistent with such deficits. Whether this abnormality precedes psychosis onset, emerges early in the illness, and/or progressively worsens with illness chronicity, is unknown. METHODS Event-related potentials (ERPs) were recorded from schizophrenia patients (SZ; n = 75) and age-matched healthy controls (HC; n = 77). A subsample of early illness schizophrenia patients (ESZ; n = 39) was compared with patients at clinical high-risk for psychosis (CHR; n = 35) and to a subgroup of age-matched HC (n = 36) during a Talk-Listen paradigm. The N1 ERP component was elicited by vocalizations as subjects talked (Talk) and heard them played back (Listen). RESULTS As shown previously, SZ showed attenuated speech-related N1 suppression relative to HC. This was also observed in ESZ. N1 suppression values in CHR were intermediate to HC and ESZ and not statistically distinguishable from either comparison group. Age-corrected N1 Talk-Listen difference z scores were not correlated with illness duration in the full SZ sample. CONCLUSIONS Putative dysfunction of the corollary discharge mechanism during speech is evident early in the illness and is stable over its course. The intermediate effects in CHR patients may reflect the heterogeneity of this group, requiring longitudinal follow-up data to address if speech-related N1 suppression abnormalities are a risk marker for conversion to psychosis.

Functions of non-suicidal self-injury in adolescents and young adults with Borderline Personality Disorder symptoms.

Rates of deliberate non-suicidal self-injury (NSSI) increase during adolescence and young adulthood, particularly in clinical samples, making these important developmental stages for understanding the functions of NSSI. Borderline Personality Disorder (BPD) symptoms also begin to emerge in adolescence, though little research has examined relationships between BPD symptoms and the functions of NSSI in youth, the primary goal of the present study. Adolescents and young adults recruited from an outpatient psychotherapy clinic (N=36) endorsed a range of NSSI functions on the Inventory of Statements about Self-Injury (Klonsky and Glenn, 2009). Participants engaged in NSSI to serve intrapersonal functions (e.g., regulate affect, punish oneself) more frequently than interpersonal functions (e.g., bond with peers, establish autonomy). As predicted, linear regression analyses indicated that BPD affective dysregulation symptoms were associated with the intrapersonal but not the interpersonal functions of NSSI. In contrast, BPD interpersonal dysfunction symptoms were differentially associated with the interpersonal rather than intrapersonal functions of NSSI. These preliminary data indicate that clusters of BPD symptoms show unique relationships with functions of NSSI in treatment-seeking adolescents and young adults, relationships that can be used to target specific functions of NSSI in treatment planning.

The Role of Trauma and Stressful Life Events among Individuals at Clinical High Risk for Psychosis: A Review

The experience of childhood trauma (CT) and stressful life events (SLEs) is associated with subsequent development of a variety of mental health conditions, including psychotic illness. Recent research identifying adolescents and young adults at clinical high risk (CHR) for psychosis allows for prospective evaluation of the impact of trauma and adverse life events on psychosis onset and other outcomes, addressing etiological questions that cannot be answered in studies of fully psychotic or non-clinical populations. This article provides a comprehensive review of the current emerging literature on trauma and adverse life events in the CHR population. Up to 80% of CHR youth endorse a lifetime history of childhood traumatic events and victimization (e.g., bullying). Several studies have shown that the experience of CT predicts psychosis onset among CHR individuals, while the literature on the influence of recent SLEs (e.g., death of a loved one) remains inconclusive. Multiple models have been proposed to explain the link between trauma and psychosis, including the stress-vulnerability and stress-sensitivity hypotheses, with emphases on both cognitive processes and neurobiological mechanisms (e.g., the hypothalamic–pituitary–adrenal axis). Despite the preponderance of CHR individuals who endorse either CT or SLEs, no clinical trials have been conducted evaluating interventions for trauma in CHR youth to date. Furthermore, the current process of formal identification and assessment of trauma, SLEs, and their impact on CHR youth is inconsistent in research and clinical practice. Recommendations for improving trauma assessment, treatment, and future research directions in the CHR field are provided.

Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis

OBJECTIVE Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. METHODS In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). RESULTS Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. CONCLUSIONS CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5.

Dynamic functional connectivity impairments in early schizophrenia and clinical high-risk for psychosis

ABSTRACT Individuals at clinical high‐risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full‐blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time‐varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting‐state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG‐ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease‐related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR‐specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations.

Diminished emotion expressivity but not experience in men and women with schizophrenia.

Prior studies indicate that men with schizophrenia are less outwardly expressive but report similar emotion experience as healthy people. However, it is unclear whether women with schizophrenia show this same disconnect between expressivity and experience. Men (n = 24) and women (n = 25) with schizophrenia or schizoaffective disorder and women without schizophrenia (n = 25) viewed emotionally evocative film clips and were video recorded to assess facial expressivity. Participants also reported their emotion experience after each clip. Men and women with schizophrenia did not significantly differ from one another in the frequency of facial expressions, but both groups exhibited fewer expressions than women without schizophrenia. People with schizophrenia also reported lower levels of trait expressivity compared with women without schizophrenia. Overall, people with schizophrenia did not differ from controls on self-reported emotion experience with one exception: Women with schizophrenia reported more unpleasant emotion than controls. These results indicate that both women and men with schizophrenia exhibit fewer outward expressions but experience comparable emotion experience as people without schizophrenia.

Symptom assessment in early psychosis: The use of well-established rating scales in clinical high-risk and recent-onset populations

Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical-high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms; for the CHR group only, we included the Scale of Prodromal Symptoms. For investigators selecting symptom measures in intervention or longitudinal studies, we also examined the relationship of symptom scales with psychosocial functioning. In both samples, symptom subscales in the same domain, across measures, were moderately to highly intercorrelated. Within all measures, positive symptoms were not correlated with negative symptoms, but disorganized symptoms overlapped with both positive and negative symptoms. Functioning was significantly related to negative and disorganized, but not positive, symptoms in both samples on most measures. Findings suggest strong overlap in symptom severity ratings among the most common scales. In recent-onset samples, each has strengths and weaknesses. In CHR samples, they appear to add little information above and beyond the SOPS.

Identifying functional network changing patterns in individuals at clinical high-risk for psychosis and patients with early illness schizophrenia: A group ICA study

Although individuals at clinical high risk (CHR) for psychosis exhibit a psychosis-risk syndrome involving attenuated forms of the positive symptoms typical of schizophrenia (SZ), it remains unclear whether their resting-state brain intrinsic functional networks (INs) show attenuated or qualitatively distinct patterns of functional dysconnectivity relative to SZ patients. Based on resting-state functional magnetic imaging data from 70 healthy controls (HCs), 53 CHR individuals (among which 41 subjects were antipsychotic medication-naive), and 58 early illness SZ (ESZ) patients (among which 53 patients took antipsychotic medication) within five years of illness onset, we estimated subject-specific INs using a novel group information guided independent component analysis (GIG-ICA) and investigated group differences in INs. We found that when compared to HCs, both CHR and ESZ groups showed significant differences, primarily in default mode, salience, auditory-related, visuospatial, sensory-motor, and parietal INs. Our findings suggest that widespread INs were diversely impacted. More than 25% of voxels in the identified significant discriminative regions (obtained using all 19 possible changing patterns excepting the no-difference pattern) from six of the 15 interrogated INs exhibited monotonically decreasing Z-scores (in INs) from the HC to CHR to ESZ, and the related regions included the left lingual gyrus of two vision-related networks, the right postcentral cortex of the visuospatial network, the left thalamus region of the salience network, the left calcarine region of the fronto-occipital network and fronto-parieto-occipital network. Compared to HCs and CHR individuals, ESZ patients showed both increasing and decreasing connectivity, mainly hypo-connectivity involving 15% of the altered voxels from four INs. The left supplementary motor area from the sensory-motor network and the right inferior occipital gyrus in the vision-related network showed a common abnormality in CHR and ESZ groups. Some brain regions also showed a CHR-unique alteration (primarily the CHR-increasing connectivity). In summary, CHR individuals generally showed intermediate connectivity between HCs and ESZ patients across multiple INs, suggesting that some dysconnectivity patterns evident in ESZ predate psychosis in attenuated form during the psychosis risk stage. Hence, these connectivity measures may serve as possible biomarkers to predict schizophrenia progression.

The assessment of attenuated psychotic symptoms in adolescents: concepts, practical approaches and prediction of risk

The assessment of attenuated psychotic symptoms in adolescents: concepts, practical approaches and prediction of risk Rahel Pearson, Barbara Stuart, Rachel Loewy Abstract: Early detection of those at risk for developing psychotic disorders is a growing field that creates an opportunity for intervention early in the course of illness, with potential for improved prognosis. In the last two decades a number of instruments aimed at assessing clinical risk for psychosis were developed, using various approaches. These instruments are reviewed in this paper, as well as diagnostic and clinical challenges that mental health professionals often face during the assessment of attenuated psychotic symptoms, a core syndrome indicating psychosis risk. A case example illustrates assessment and feedback techniques. Keywords: assessment, diagnosis, high risk, prodromal, psychosis University of California at San Francisco 401 Parnassus Ave, Box 0984 San Francisco, CA. 94143