The development of psychotic disorders in adolescence: a potential role for hormones.

This article is part of a Special Issue "Puberty and Adolescence". The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of "prodromal" manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis.

Developmental mechanisms in the prodrome to psychosis.

Psychotic disorders continue to be among the most disabling and scientifically challenging of all mental illnesses. Accumulating research findings suggest that the etiologic processes underlying the development of these disorders are more complex than had previously been assumed. At the same time, this complexity has revealed a wider range of potential options for preventive intervention, both psychosocial and biological. In part, these opportunities result from our increased understanding of the dynamic and multifaceted nature of the neurodevelopmental mechanisms involved in the disease process, as well as the evidence that many of these entail processes that are malleable. In this article, we review the burgeoning research literature on the prodrome to psychosis, based on studies of individuals who meet clinical high risk criteria. This literature has examined a range of factors, including cognitive, genetic, psychosocial, and neurobiological. We then turn to a discussion of some contemporary models of the etiology of psychosis that emphasize the prodromal period. These models encompass the origins of vulnerability in fetal development, as well as postnatal stress, the immune response, and neuromaturational processes in adolescent brain development that appear to go awry during the prodrome to psychosis. Then, informed by these neurodevelopmental models of etiology, we turn to the application of new research paradigms that will address critical issues in future investigations. It is expected that these studies will play a major role in setting the stage for clinical trials aimed at preventive intervention.

Confronting the dialectic between quality and access in early psychosis care in the United States: Finding the synthesis by leveraging psychological expertise.

Coordinated specialty care (CSC) is the dominant model for early psychosis care in the United States, representing a proactive recovery-oriented approach to serious mental illness in its early stages. CSC involves broad multidisciplinary support for participants, including from psychologists in some CSC teams, encompassing educational and vocational support, medication management, psychotherapy, case management, peer support, and family interventions. CSC programs have proliferated in the last 20 years, leading to a quality-access dialectic, where increasing access to treatment simultaneously prompts concerns about care quality, particularly in the context of staffing shortages and funding limits. Evidence-based psychosocial treatment, including psychotherapy, is an integral part of CSC, yet workforce training deficits, workforce turnover, and CSC financing pose threats to intervention fidelity and thus CSC participants' ability to access high-quality care. We propose an enhanced role for psychologists as a way of resolving the quality-access dialectic in the area of psychosocial treatment, specifically evidence-based therapy. We describe the potential of psychologists' skills in clinical supervision, formulation, evidence-based interventions and measurement-based care, drawing on practice examples. After considering possible limitations, we outline implementation models, for example, drawing on Early Psychosis Intervention Network and Project Extension for Community Healthcare Outcomes. We conclude with four recommendations: Psychologists should be placed in CSC team or network-leadership roles; psychological expertise should be made available to CSC teams for training, consultation, and technical assistance; psychological expertise should be used to address CSC implementation challenges; and research is needed to demonstrate psychologists' value to stakeholders. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pathways Through Early Psychosis Care for U.S. Youths From Ethnically and Racially Minoritized Groups: A Systematic Review.

OBJECTIVE: The authors of this systematic review examined service utilization and outcomes among youths from ethnoracially minoritized groups after the youths initiated treatment for a psychotic disorder-that is, the youths' "pathway through care." Also examined were potential moderating variables in pathways through care for these youths at the clinic, family, and cultural levels. The goal was to describe methodologies, summarize relevant findings, highlight knowledge gaps, and propose future research on pathways through care for young persons from ethnoracially minoritized groups who experience early psychosis. METHODS: The PubMed, PsycInfo, and Web of Science literature databases were systematically searched for studies published between January 1, 2010, and June 1, 2021. Included articles were from the United States and focused on young people after they initiated treatment for early psychosis. Eighteen studies met inclusion criteria. RESULTS: Sixteen of the 18 studies were published in the past 5 years, and 11 had an explicit focus on race and ethnicity as defined by the studies' authors. Studies varied in terminology, outcomes measures, methodologies, and depth of analysis. Being an individual from an ethnoracially minoritized group appeared to affect care utilization and outcomes. Insufficient research was found about potential moderating variables at the clinic, family, and cultural levels. CONCLUSIONS: Studies of pathways through care for persons from minoritized groups warrant further funding and attention.

The association between mental health stigma and face emotion recognition in individuals at risk for psychosis.

Self-stigma has been associated with reduced accuracy of face emotion recognition in individuals at clinical high risk for psychosis (CHR). Stigma may also relate to slowing of performance during cognitive tasks for which a negative stereotype is relevant. This study aimed to investigate the association of mental illness stigma with face emotion recognition among CHR individuals. Participants were 143 CHR individuals identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Face emotion recognition was assessed using the Penn Emotion Recognition Task (ER-40). Stigma was assessed using discrimination, stereotype awareness, and stereotype agreement subscales of the Mental Health Attitudes Interview for CHR. We tested associations of ER-40 accuracy and response times with these stigma variables, including the role of clinical and demographic factors. Racial/ethnic minoritized participants had higher attenuated positive symptoms than non-minoritized participants. Longer ER-40 response times were correlated with greater stereotype agreement (r=.17, p=.045) and discrimination (r=.22, p=.012). A regression model predicting ER-40 response times revealed an interaction of stereotype agreement with minoritized status (p=.008), with slower response times for minoritized participants as stereotype agreement increased. Greater disorganized symptoms and male gender also predicted longer response times. ER-40 accuracy was not associated with stigma. Overall, minoritized CHR individuals with greater internalized stigma took longer to identify face emotions. Future research is needed to assess whether slower response times are specific to social cues, and if internalized stigma interferes with performance in real-world social situations. Reducing stigma may be an important target for interventions that aim to improve social skills.

Emotional and stigma-related experiences relative to being told one is at risk for psychosis.

OBJECTIVE: Despite the appeal of early intervention in psychosis, there is concern that identifying youth as having high psychosis risk (PR) may trigger stigma. This study employed a pre-post design to measure change in PR participants' emotions about PR upon being told of their PR status and according to whether this was the first time receiving this information. METHODS: Participants (n = 54) identified as at PR via structured interview rated their emotions about PR before and after being told they were at PR. Qualitative analyses explored the valence of participant reflections on being given this information. RESULTS: Participants reported significantly less negative emotion after being told of their PR status (p < .001), regardless of whether they were hearing this for the first time (p = .72). There was no change in positive emotions or the predominant belief that they should keep their PR status private. Most participants commented positively about the process of feedback but negatively about its impact on their self-perceptions and/or expectations of others' perceptions of them. CONCLUSION: This is the first study to collect pre-post data related to being told one is at PR and to examine quantitative and qualitative responses across and within individuals. For a majority of participants, clinical feedback stimulated negative stereotypes even as it relieved some distress. To actively address internalized stigma, clinicians providing feedback to PR youth must attend to the positive and negative impacts on how youth think about themselves as well as how they feel.

Impact of "psychosis risk" identification: Examining predictors of how youth view themselves.

BACKGROUND: Identifying young people as at clinical high-risk (CHR) for psychosis affords opportunities for intervention to possibly prevent psychosis onset. Yet such CHR identification could plausibly increase stigma. We do not know whether these youth already perceive themselves to be at psychosis-risk (PR) or how their being told they are at PR might impact how they think about themselves. METHODS: 148 CHR youth were asked about labels they had been given by others (labeling by others) or with which they personally identified (self-labeling). They were then asked which had the greatest impact on how they thought about themselves. We evaluated whether being told vs. thinking they were at PR had stronger effects. FINDINGS: The majority identified nonpsychotic disorders rather than PR labels as having the greatest impact on sense of self (67.6% vs. 27.7%). However, participants who identified themselves as at PR had an 8.8 (95% CI = 2.0-39.1) increase in the odds of the PR label having the greatest impact (p < 0.01). Additionally, having been told by others that they were at PR was associated with a 4.0 increase in odds (95% CI = 1.1-15.0) that the PR label had the most impact (p < 0.05). INTERPRETATION: Nonpsychotic disorder labels appear to have a greater impact on CHR youth than psychosis-risk labels. However, thinking they are at PR, and, secondarily, being told they are at PR, appears to increase the relative impact of the PR label. Understanding self- and other-labeling may be important to how young people think of themselves, and may inform early intervention strategies.

A comparison of conversion rates, clinical profiles and predictors of outcomes in two independent samples of individuals at clinical high risk for psychosis in China.

OBJECTIVE: In a previous epidemiological study, we reported on the ascertainment and outcomes of "clinical high risk" (CHR) individuals at the Shanghai Mental Health Center (SMHC, "2011 cohort"). The current study compares demographic and clinical characteristics, including conversion rates, of this sample with a subsequently recruited, independent CHR sample and with published data from western samples. METHOD: A new sample of 100 CHR subjects ("2013 cohort") was selected based on screening and semi-structured interviews. Both studies used the Structured Interview for Prodromal Syndromes (SIPS) for CHR assessment and conducted a naturalistic two-year follow-up. The two cohorts were compared on conversion rates, demographic and clinical characteristics, psychosis risk symptoms, and risk factors for psychotic conversion. RESULTS: Ninety one (91%) of the 2013 cohort subjects completed the clinical two-year follow-up and 25 (27.5% of the 91) converted to a psychotic disorder over the follow-up period. A comparison of conversions to full psychosis between the 2013 and the 2011 cohorts showed no significant difference in time to conversion (Pairwise comparison: χ2=0.3, p=0.562). Both cohort studies showed that CHR subjects with more severe clinical symptoms at baseline and decline in functioning were more likely to convert to psychosis. CONCLUSIONS: Conversion rates in this new, independent Chinese sample are similar to those reported in non-Chinese samples and to the 2011 cohort. Future research is needed to examine whether the implementation of early intervention for CHR/prodromal symptoms reduces the risk of psychosis and decreases the conversion rate.

Progress and Future Directions in Research on the Psychosis Prodrome: A Review for Clinicians.

LEARNING OBJECTIVES: After participating in this activity, learners should be better able to: ABSTRACT: The psychosis prodrome, or period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanisms of psychosis onset and for testing early-intervention strategies. We summarize major findings and emerging directions in prodromal research and provide recommendations for clinicians working with individuals suspected to be at high risk for psychosis. The past two decades of research have led to three major advances. First, tools and criteria have been developed that can reliably identify imminent risk for a psychotic disorder. Second, longitudinal clinical and psychobiological data from large multisite studies are strengthening individual risk assessment and offering insights into potential mechanisms of illness onset. Third, psychosocial and pharmacological interventions are demonstrating promise for delaying or preventing the onset of psychosis in help-seeking, high-risk individuals. The dynamic psychobiological processes implicated in both risk and onset of psychosis, including altered gene expression, cognitive dysfunction, inflammation, gray and white matter brain changes, and vulnerability-stress interactions suggest a wide range of potential treatment targets and strategies. The expansion of resources devoted to early intervention and prodromal research worldwide raises hope for investigating them. Future directions include identifying psychosis-specific risk and resilience factors in children, adolescents, and non-help-seeking community samples, improving study designs to test hypothesized mechanisms of change, and intervening with strategies that, in order to improve functional outcomes, better engage youth, address their environmental contexts, and focus on evidence-based neurodevelopmental targets. Prospective research on putatively prodromal samples has the potential to substantially reshape our understanding of mental illness and our efforts to combat it.

Association of Neurocognition With Transition to Psychosis: Baseline Functioning in the Second Phase of the North American Prodrome Longitudinal Study.

IMPORTANCE: Neurocognition is a central characteristic of schizophrenia and other psychotic disorders. Identifying the pattern and severity of neurocognitive functioning during the "near-psychotic," clinical high-risk (CHR) state of psychosis is necessary to develop accurate risk factors for psychosis and more effective and potentially preventive treatments. OBJECTIVES: To identify core neurocognitive dysfunctions associated with the CHR phase, measure the ability of neurocognitive tests to predict transition to psychosis, and determine if neurocognitive deficits are robust or explained by potential confounders. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study across 8 sites, baseline neurocognitive data were collected from January 2009 to April 2013 in the second phase of the North American Prodrome Longitudinal Study (NAPLS 2). The dates of analysis were August 2015 to August 2016. The setting was a consortium of 8 university-based, outpatient programs studying the psychosis prodrome in North America. Participants were 264 healthy controls (HCs) and 689 CHR individuals, aged 12 to 35 years. MAIN OUTCOMES AND MEASURES: Neurocognitive associations with transition to psychosis and effects of medication on neurocognition. Nineteen neuropsychological tests and 4 factors derived from factor analysis were used: executive and visuospatial abilities, verbal abilities, attention and working memory abilities, and declarative memory abilities. RESULTS: This study included 264 HCs (137 male and 127 female) and 689 CHR participants (398 male and 291 female). In the HCs, 145 (54.9%) were white and 119 (45.1%) were not, whereas 397 CHR participants (57.6%) were white and 291 (42.3%) were not. In the HCs, 45 (17%) were of Hispanic origin, whereas 127 CHR participants (18.4%) were of Hispanic origin. The CHR individuals were significantly impaired compared with HCs on attention and working memory abilities and declarative memory abilities. The CHR converters had large deficits in attention and working memory abilities and declarative memory abilities (Cohen d, approximately 0.80) compared with controls and performed significantly worse on these dimensions than nonconverters (Cohen d, 0.28 and 0.48, respectively). These results were not accounted for by general cognitive ability or medications. In Cox proportional hazards regression, time to conversion in those who transitioned to psychosis was significantly predicted by high verbal (premorbid) abilities (ß = 0.40; hazard ratio [HR], 1.48; 95% CI, 1.08-2.04; P = .02), impaired declarative memory abilities (ß = -0.87; HR, 0.42; 95% CI, 0.31-0.56; P < .001), age (ß = -0.10; HR, 0.90; 95% CI, 0.84-0.97; P = .003), site, and a combined score of unusual thought content or delusional ideas and suspiciousness or persecutory ideas items (ß = 0.44; HR, 1.56; 95% CI, 1.36-1.78; P < .001). CONCLUSIONS AND RELEVANCE: Neurocognitive impairment, especially in attention and working memory abilities and declarative memory abilities, is a robust characteristic of CHR participants, especially those who later develop psychosis. Interventions targeting the enhancement of neurocognitive functioning are warranted in this population.

A prospective study of the efficacy of the N-Lite laser for the treatment of facial wrinkles.

BACKGROUND: Despite early studies supporting the efficacy of the N-Lite laser (ICN Pharmaceuticals, Costa Mesa, CA) for nonablative treatment of facial wrinkles, clinical reports of treatment results have been disappointing. OBJECTIVE: We devised a prospective, double-blinded study to evaluate the efficacy of this laser, based upon a protocol submitted by the manufacturer. METHODS: A total of 89 patients underwent 2 treatments by 2 treating physicians 2 weeks apart. At the end of 4 months, pretreatment and posttreatment photographs were evaluated by 3 plastic surgeons in a blinded fashion. Patients also completed a questionnaire to record their opinions regarding the success of the laser treatments. RESULTS: Twentysix patients (29.1%) expressed a positive opinion regarding their results. Physicians thought that only 9 patients (10%) showed clinical improvement. Variables such as Fitzpatrick skin type, pulses administered, and pretreatment with microdermabrasion did not seem to affect the final result. In those patients where wrinkle reduction was seen, changes were subtle and not impressive. CONCLUSIONS: We did not find the N-Lite 585-nm nonablative laser to be a predictable or efficacious way to treat facial wrinkles. More extensive studies of the laser and treatment protocols must be performed to justify acceptance of this product in the marketplace.

The prodrome and clinical risk for psychotic disorders.

The psychosis prodrome offers great promise for identifying neural mechanisms involved in psychotic disorders and offers an opportunity to implement empirical interventions to delay, and ultimately ameliorate, illness onset. This article summarizes the literature on individuals in the putatively prodromal phase of psychosis/deemed at clinical high risk (CHR) for psychosis onset. Standardized measurement and manifestation of the CHR syndromes are discussed, followed by empirical findings that highlight the psychological deficits and biological abnormalities seen in CHR syndromes and psychotic disorders. Current controversies surrounding the diagnosis of CHR syndromes and issues related to the treatment of CHR individuals are also presented.

Stress and the prodromal phase of psychosis.

Stress plays a role in most conceptualizations of the etiology of psychotic disorders. This is based on extensive research showing an association between the incidence of psychosis and psychosocial stress exposure (e.g., stressful life events and trauma) both in childhood and the weeks preceding a psychotic episode. There is also evidence of increased sensitivity to stressful events and dysregulation of biological stress systems. To better understand the relation of stress with the initial emergence of psychosis, research has increasingly focused on the psychosis prodrome, the period of functional decline that precedes clinical illness. Preliminary results suggest that increased incidence of early childhood trauma, heightened sensitivity to psychosocial stress, and dysregulation of biological stress response systems are present in the prodrome and associated with the onset and severity of psychosis. The current paper reviews this research and discusses the possible mechanisms responsible for these associations. This discussion includes the possible effect of stress on the hypothalamic-pituitary-adrenal [HPA] axis and hippocampus, and the role adolescent developmental changes may play in mediating this effect. Further longitudinal research combining clinical and biological measures of stress with techniques designed to assess developmental change in neural structure and function, cellular mechanisms, and genetic and epigenetic factors are critical for elucidating the role stress plays in the pathophysiology of psychotic illness.