Auditory hallucinations, childhood sexual abuse, and limbic gray matter volume in a transdiagnostic sample of people with psychosis.

Childhood sexual abuse (CSA) is a potentially unique risk factor for auditory hallucinations (AH), but few studies have examined the moderating effects of sex or the association of CSA with limbic gray matter volume (GMV) in transdiagnostic samples of people with psychotic disorders. Here we found that people with psychotic disorders reported higher levels of all surveyed maltreatment types (e.g., physical abuse) than healthy controls, but people with psychotic disorders with AH (n = 41) reported greater CSA compared to both those without AH (n = 37; t = -2.21, p = .03) and controls (n = 37; t = -3.90, p < .001). Among people with psychosis, elevated CSA was most pronounced among females with AH (sex × AH status: F = 4.91, p = .009), held controlling for diagnosis, medications, and other maltreatment (F = 3.88, p = .02), and correlated with the current severity of AH (r = .26, p = .03) but not other symptoms (p's > .16). Greater CSA among patients related to larger GMV of the left amygdala accounting for AH status, diagnosis, medications, and other maltreatment (t = 2.12, p = .04). Among people with psychosis, females with AH may represent a unique subgroup with greater CSA. Prospective high-risk studies integrating multiple measures of maltreatment and brain structure/function may help elucidate the mechanisms linking CSA with amygdala alterations and AH.

Linking Salience Signaling With Early Adversity and Affective Distress in Individuals at Clinical High Risk for Psychosis: Results From an Event-Related fMRI Study.

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few studies have examined the intersection of stress exposure and affective distress with prediction error (PE) signals among youth at clinical high-risk (CHR). Here, 26 individuals at CHR and 19 healthy volunteers (HVs) completed a monetary incentive delay task in conjunction with fMRI. We compared these groups on the amplitudes of neural responses to surprising outcomes-PEs without respect to their valence-across the whole brain and in two regions of interest, the anterior insula and amygdala. We then examined relations of these signals to the severity of depression, anxiety, and trauma histories in the CHR group. Relative to HV, youth at CHR presented with aberrant PE-evoked activation of the temporoparietal junction and weaker deactivation of the precentral gyrus, posterior insula, and associative striatum. No between-group differences were observed in the amygdala or anterior insula. Among youth at CHR, greater trauma histories were correlated with stronger PE-evoked amygdala activation. No associations were found between affective symptoms and the neural responses to PE. Our results suggest that unvalenced PE signals may provide unique information about the neurobiology of CHR syndromes and that early adversity exposure may contribute to neurobiological heterogeneity in this group. Longitudinal studies of young people with a range of risk syndromes are needed to further disentangle the contributions of distinct aspects of salience signaling to the development of psychopathology.

Psychosis-Spectrum Screening and Assessment Within a College Counseling Center: A Pilot Study Exploring Feasibility and Clinical Need.

Evidence supports the use of brief psychosis-spectrum screening tools for identifying individuals at an increased risk of developing a psychotic disorder. Screening has not been well studied in general mental health settings that serve young adults in the age range associated with highest risk for psychosis. This study explored the feasibility of psychosis-risk screening and assessment among help-seeking students at a university counseling center. The PRIME Screen-Revised was administered to students at clinic intake. Participants who screened positively were offered a follow-up assessment using the Structured Interview for Psychosis-risk Syndromes (SIPS). At intake, 510 students completed the PRIME Screen-Revised, with 132 (25.9%) screening positive. Comprehensive psychosis-spectrum evaluations were completed with 38 participants, and 22 met criteria for a psychosis-spectrum disorder, representing 57.9% of this subsample. Findings suggest that psychosis-risk screening in a college clinic is a promising approach to identifying those at high risk for or in the early stages of psychosis.

Neuropsychological Performance Among Individuals at Clinical High-Risk for Psychosis vs Putatively Low-Risk Peers With Other Psychopathology: A Systematic Review and Meta-Analysis.

BACKGROUND AND HYPOTHESIS: Youth at clinical high-risk (CHR) for psychosis present with neuropsychological impairments relative to healthy controls (HC), but whether these impairments are distinguishable from those seen among putatively lower risk peers with other psychopathology remains unknown. We hypothesized that any excess impairment among CHR cohorts beyond that seen in other clinical groups is minimal and accounted for by the proportion who transition to psychosis (CHR-T). STUDY DESIGN: We performed a systematic review and meta-analysis of studies comparing cognitive performance among CHR youth to clinical comparators (CC) who either sought mental health services but did not meet CHR criteria or presented with verified nonpsychotic psychopathology. STUDY RESULTS: Twenty-one studies were included representing nearly 4000 participants. Individuals at CHR showed substantial cognitive impairments relative to HC (eg, global cognition: g = -0.48 [-0.60, -0.34]), but minimal impairments relative to CC (eg, global cognition: g = -0.13 [-0.20, -0.06]). Any excess impairment among CHR was almost entirely attributable to CHR-T; impairment among youth at CHR without transition (CHR-NT) was typically indistinguishable from CC (eg, global cognition, CHR-T: g = -0.42 [-0.64, -0.19], CHR-NT: g = -0.09 [-0.18, 0.00]; processing speed, CHR-T: g = -0.59 [-0.82, -0.37], CHR-NT: g = -0.12 [-0.25, 0.07]; working memory, CHR-T: g = -0.42 [-0.62, -0.22], CHR-NT: g = -0.03 [-0.14, 0.08]). CONCLUSIONS: Neurocognitive impairment in CHR cohorts should be interpreted cautiously when psychosis or even CHR status is the specific clinical syndrome of interest as these impairments most likely represent a transdiagnostic vs psychosis-specific vulnerability.

Categorical versus dimensional models of early psychosis.

AIM: Early psychosis is typically operationalized as a categorical construct by dividing people into one of three diagnostic statuses: low-risk, clinical high-risk, and first episode psychosis. We empirically assess whether an alternative dimensional approach focused on observed symptom severity may be more desirable for clinical and research purposes. METHODS: Participants were 152 help-seeking youths ages 12-22 years old. Structured interview for psychosis risk syndromes interviews were used to obtain dimensional psychosis symptom severity ratings, and to classify participants by categorical psychosis risk status. Twenty-five participants were classified as having a diagnosable psychotic disorder, 52 participants as clinical high-risk, and 75 participants as help-seeking controls. We assessed the relation between categorical and dimensional measurements of psychosis severity, and then compared categorical versus dimensional psychosis severity in their ability to predict social and role functioning. RESULTS: On average, dimensional psychosis symptom severity increased along with categorical risk status (help-seeking control < clinical high-risk < diagnosable psychotic disorder). There was, however, considerable overlap between categories, with people at clinical high-risk being particularly hard to distinguish from people with diagnosable psychotic disorders on the basis of symptom severity. Dimensional symptom severity was more predictive of functioning than categorical risk status. CONCLUSIONS: Categorical risk status and psychosis symptom severity are related but not interchangeable, and dimensional models of psychosis may be more predictive of functional outcomes. Adopting a dimensional rather than categorical approach to the psychosis risk spectrum may facilitate better predictive models and a richer theoretical understanding of early psychosis.

Changes in community providers' screening behaviours, referral practices, and clinical confidence following participation in an early psychosis educational campaign.

AIM: Successful delivery of care to individuals with early psychosis depends on the ability of community providers to identify and refer appropriate candidates for services. Although specialty centres commonly rely upon education and outreach campaigns to building bridges with community providers, few studies have examined the effectiveness of these campaigns or the mechanisms by which they may achieve their intended effects. METHODS: We surveyed community clinicians (N = 39) about their screening behaviours, referral practices, and confidence in managing early psychosis just before and 3-6 months after attending an educational event designed to promote recognition and quality treatment of early psychosis. RESULTS: Three to six months following attendance, providers reported screening a greater proportion of clients for early psychosis, referring a greater number of clients to specialty services, and feeling more confident in their ability to respond to clients with early psychosis. Increases in confidence following attendance were associated with corresponding increases in screening behaviour. CONCLUSIONS: The results suggest that outreach campaigns designed to enhance community providers' knowledge about early psychosis assessment and resources may be effective in promoting screening, referrals, and confidence in managing psychosis. Gains in provider confidence may contribute to increases in screening. Given the lack of control group and relatively short follow-up period, more research is needed to determine the effects of early psychosis educational events and the mechanisms by which they may promote successful treatment delivery for young people in need.

The Intersection Between Childhood Trauma, the COVID-19 Pandemic, and Trauma-related and Psychotic Symptoms in People With Psychotic Disorders.

INTRODUCTION: People with psychotic disorders may be disproportionately affected by the traumatic effects of the COVID-19 pandemic. Childhood trauma, which also increases vulnerability to subsequent stressors, is common in individuals with psychosis. In this study, we investigated the intersection of the pandemic, childhood trauma, and psychotic and trauma-related symptoms in individuals with psychotic disorders. METHODS: We administered a cross-sectional survey to 151 participants [47 schizophrenia (SZ), 53 psychotic bipolar disorder (BP)], 51 healthy control (HC)] during the COVID-19 pandemic. Participants were asked about exposure to the pandemic's impacts, childhood trauma, and post-traumatic stress, dissociative, and psychotic symptoms. RESULTS: BP reported greater negative impacts to emotional health than SZ and HC and to non-COVID physical health than HC. SZ reported less impact on work and employment during the pandemic. There were no other group differences in pandemic-related adversities. We also found that cumulative exposure to the pandemic's negative impacts was significantly associated with PTSD symptoms but not psychotic or dissociative symptoms. Moreover, the number of adversities an individual experienced during the pandemic was strongly associated with the cumulative number of traumatic experiences they had in childhood. DISCUSSION: Our results suggest that having a psychotic disorder does not, in and of itself, increase susceptibility to the pandemic's negative impacts. Instead, we provide evidence of a graded relationship between cumulative exposure to the pandemic's negative impacts and PTSD symptom severity, as well as a graded relationship between cumulative childhood traumatic experiences and the number pandemic adversities, across diagnoses.

White matter in prolonged glucocorticoid response to psychological stress in schizophrenia.

Stress is implicated in psychosis etiology and exacerbation, but pathogenesis toward brain network alterations in schizophrenia remain unclear. White matter connects limbic and prefrontal regions responsible for stress response regulation, and white matter tissues are also vulnerable to glucocorticoid aberrancies. Using a novel psychological stressor task, we studied cortisol stress responses over time and white matter microstructural deficits in schizophrenia spectrum disorder (SSD). Cortisol was measured at baseline, 0-, 20-, and 40-min after distress induction by a psychological stressor task in 121 SSD patients and 117 healthy controls (HC). White matter microstructural integrity was measured by 64-direction diffusion tensor imaging. Fractional anisotropy (FA) in white matter tracts were related to cortisol responses and then compared to general patterns of white matter tract deficits in SSD identified by mega-analysis. Differences between 40-min post-stress and baseline, but not acute reactivity post-stress, was significantly elevated in SSD vs HC, time × diagnosis interaction F2.3,499.9 = 4.1, p = 0.013. All SSD white matter tracts were negatively associated with prolonged cortisol reactivity but all tracts were positively associated with prolonged cortisol reactivity in HC. Individual tracts most strongly associated with prolonged cortisol reactivity were also most impacted in schizophrenia in general as established by the largest schizophrenia white matter study (r = -0.56, p = 0.006). Challenged with psychological stress, SSD and HC mount similar cortisol responses, and impairments arise in the resolution timeframe. Prolonged cortisol elevations are associated with the white matter deficits in SSD, in a pattern previously associated with schizophrenia in general.

Relations Among Anhedonia, Reinforcement Learning, and Global Functioning in Help-seeking Youth.

Dysfunction in the neural circuits underlying salience signaling is implicated in symptoms of psychosis and may predict conversion to a psychotic disorder in youth at clinical high risk (CHR) for psychosis. Additionally, negative symptom severity, including consummatory and anticipatory aspects of anhedonia, may predict functional outcome in individuals with schizophrenia-spectrum disorders. However, it is unclear whether anhedonia is related to the ability to attribute incentive salience to stimuli (through reinforcement learning [RL]) and whether measures of anhedonia and RL predict functional outcome in a younger, help-seeking population. We administered the Salience Attribution Test (SAT) to 33 participants who met criteria for either CHR or a recent-onset psychotic disorder and 29 help-seeking youth with nonpsychotic disorders. In the SAT, participants must identify relevant and irrelevant stimulus dimensions and be sensitive to different reinforcement probabilities for the 2 levels of the relevant dimension ("adaptive salience"). Adaptive salience attribution was positively related to both consummatory pleasure and functioning in the full sample. Analyses also revealed an indirect effect of adaptive salience on the relation between consummatory pleasure and both role (αß = .22, 95% CI = 0.02, 0.48) and social functioning (αß = .14, 95% CI = 0.02, 0.30). These findings suggest a distinct pathway to poor global functioning in help-seeking youth, via impaired reward sensitivity and RL.

Sleep quality moderates the association between psychotic-like experiences and suicidal ideation among help-seeking university students.

Suicide is a leading cause of death for young adults, and college-enrolled students are at markedly high risk for suicide. Psychotic-like experiences (PLEs) and sleep difficulties are prevalent among college students and have been linked to increased suicidal ideation (SI). This cross-sectional study examined the relation between PLEs and SI, moderated by sleep quality, in a sample of 442 students at a university counseling center. The Behavioral Health Measure-43 (BHM-43) was used to evaluate mental health symptoms, including sleep quality and SI. The PRIME Screen-Revised was used to measure PLEs. Regression results indicated that higher PRIME scores statistically predicted greater SI. There was a significant interaction between PRIME and sleep quality in predicting SI. Among individuals with greater sleep difficulties, PLEs were positively, significantly associated with SI. The PRIME was not a significant predictor of SI at lower levels of sleep difficulties (i.e. better sleep quality). This interaction effect remained significant when controlling for age and the BHM-43 depression and bipolar subscales. Findings suggest that sleep difficulties may be linked to increased SI for individuals with PLEs, and better sleep may be protective. Further research is needed to explore treatment targeting PLEs and/or sleep to mitigate suicide risk among university students.

Telepsychotherapy with Youth at Clinical High Risk for Psychosis: Clinical Issues and Best Practices during the COVID-19 Pandemic.

Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.

Evidence of reward system dysfunction in youth at clinical high-risk for psychosis from two event-related fMRI paradigms.

Abnormal reward processing is thought to play an important role in the development of psychosis, but relatively few studies have examined reward prediction errors, reinforcement learning (RL), and the reward circuitry that subserves these interconnected processes among individuals at clinical high-risk (CHR) for the disorder. Here, we present behavioral and functional neuroimaging results of two experimental tasks designed to measure overlapping aspects of reward processing among individuals at CHR (n = 22) and healthy controls (n = 19). We found no group differences in response times to positive, negative, or neutral outcome-signaling cues, and no significant differences in brain activation during reward anticipation or receipt. Youth at CHR, however, displayed clear RL impairments, as well as attenuated responses to rewards and blunted prediction error signals in the ventral striatum, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). Greater contrasts for cue valence (gain-loss) and outcome magnitude (large-small) in the vmPFC were associated with more severe negative symptoms, and deficits in dACC signaling during RL were associated with more depressive symptoms. Our results provide evidence for RL deficits and abnormal prediction error signaling in the brain's reward circuitry among individuals at CHR, while also suggesting that reward motivation may be relatively preserved at this stage in development. Longitudinal studies, medication-free participants, and comparison of neurobehavioral measures against both healthy and clinical controls are needed to better understand the role of reward system abnormalities in the development of psychosis.

Evidence for Differential Predictive Performance of the Prime Screen Between Black and White Help-Seeking Youths.

OBJECTIVE: Self-report screening instruments for emerging psychosis have the potential to improve early detection efforts by increasing the number of true positives among persons deemed to be at "clinical high risk" of the disorder, but their practical utility depends on their validity across race. This study sought to examine whether a commonly used self-report screening tool for psychosis risk performed equally among black and white youths in its ability to predict clinical high-risk status. METHODS: Black (N=58) and white (N=50) help-seeking individuals ages 12-25 (61% female) were assessed with the Prime Screen and the Structured Interview for Psychosis-Risk Syndromes (SIPS). A logistic regression model estimated race differences in the strength of the relation between Prime Screen scores and SIPS-defined risk status. RESULTS: Higher Prime Screen scores significantly predicted clinical high-risk status among white (p<.01) but not black participants. Among black youths without clinical high risk, self-reported Prime Screen scores more closely resembled scores for youths (black or white) with clinical high risk than scores of white peers who were also without clinical high risk. CONCLUSIONS: Results suggest that consideration of race or ethnicity and associated cultural factors is important when screening for clinical high-risk status. Findings support the need to develop culturally valid early psychosis screening tools to promote appropriately tailored early intervention efforts.

Using the K-SADS psychosis screen to identify people with early psychosis or psychosis risk syndromes.

BACKGROUND: Current methods to identify people with psychosis risk involve administration of specialized tools such as the Structured Interview for Psychosis-Risk Syndromes (SIPS), but these methods have not been widely adopted. Validation of a more multipurpose assessment tool-such as the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS)-may increase the scope of identification efforts. METHODS: We assessed the correspondence between SIPS-determined clinical high risk/early psychosis (CHR/early psychosis) status and K-SADS psychosis screen (child and parent reports and their combination) in a sample of 147 help-seeking individuals aged 12-25. Detailed classification results are reported. RESULTS: Both the child and parent interviews on the K-SADS psychosis screen were strongly predictive of CHR/early psychosis status, although parent reports contributed no significant additional information beyond child reports. Across informants, the presence of either subthreshold hallucinations or subthreshold delusions was highly suggestive of CHR/early psychosis status as determined by SIPS interview (78% (child) and 74% (parent) accuracy). CONCLUSIONS: Subthreshold scores on the two-item K-SADS psychosis screen may be good indicators of the presence or absence of early signs of psychosis. The option of using a non-specialized assessment such as the K-SADS as a staged approach to assess for CHR/early psychosis status could increase rates of early psychosis screening and treatment.

Sociodemographic disparities in corticolimbic structures.

This study sought to examine the interactive relations of socioeconomic status and race to corticolimbic regions that may play a key role in translating stress to the poor health outcomes overrepresented among those of lower socioeconomic status and African American race. Participants were 200 community-dwelling, self-identified African American and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN study. Brain volumes were derived using T1-weighted MP-RAGE images. Socioeconomic status by race interactions were observed for right medial prefrontal cortex (B = .26, p = .014), left medial prefrontal cortex (B = .26, p = .017), left orbital prefrontal cortex (B = .22, p = .037), and left anterior cingulate cortex (B = .27, p = .018), wherein higher socioeconomic status Whites had greater volumes than all other groups. Additionally, higher versus lower socioeconomic status persons had greater right and left hippocampal (B = -.15, p = .030; B = -.19, p = .004, respectively) and amygdalar (B = -.17, p = .015; B = -.21; p = .002, respectively) volumes. Whites had greater right and left hippocampal (B = -.17, p = .012; B = -.20, p = .003, respectively), right orbital prefrontal cortex (B = -.34, p < 0.001), and right anterior cingulate cortex (B = -.18, p = 0.011) volumes than African Americans. Among many factors, the higher levels of lifetime chronic stress associated with lower socioeconomic status and African American race may adversely affect corticolimbic circuitry. These relations may help explain race- and socioeconomic status-related disparities in adverse health outcomes.

The impact of age on the validity of psychosis-risk screening in a sample of help-seeking youth.

Self-report screening instruments offer promise in furthering early identification of at-risk youth, yet current efforts are limited by false positive rates. Identifying moderators of accuracy is a potential step towards improving identification and prevention efforts. We investigated the moderating effect of age on self-reported attenuated positive symptoms from the Prime Screen and clinician diagnosed clinical high-risk/early psychosis (CHR/EP) status. Participants (N = 134) were racially diverse, lower-income, help-seeking adolescents and young adults from a primarily urban community. The overall model predicting CHR/EP status was significant, with results suggesting the presence of a trending interaction between age and Prime Screen symptoms. Analyses indicated that number of items endorsed to predict CHR/EP decreased with age (youngest group [M = 12.99] cut off = 6 items; middle age group [M = 14.97] cut off = 3; oldest age group [M = 18.40] cut off = 1). Although younger participants endorsed more risk items on average, follow up analyses suggested that the Prime Screen was a more accurate predictor of clinician-diagnosed-risk among older participants relative to their younger peers. The current study builds on the literature identifying moderators of psychosis-risk screening measure accuracy, highlighting potential limitations of CHR/EP screening tools in younger populations.

The Critical Need for Help-Seeking Controls in Clinical High-Risk Research.

Despite rapidly growing knowledge of the clinical high-risk (CHR) state for psychosis, the vast majority of case-control studies have relied on healthy volunteers as a reference point for drawing inferences about the CHR construct. Researchers have long recognized that results generated from this design are limited by significant interpretive concerns, yet little attention has been given to how these concerns affect the growing field of CHR research. We argue that overreliance on healthy controls in CHR research threatens the validity of inferences concerning group differences, hinders advances in understanding the development of psychosis, and limits clinical progress. We suggest that the combined use of healthy and help-seeking (i.e., psychiatric) controls is a necessary step for the next generation of CHR research. We then evaluate methods for help-seeking control studies, identify the available CHR studies that have used such designs, discuss select findings in this literature, and offer recommendations for research.