Emotional distress and dysregulation as treatment targets to reduce suicide in psychosis: a scoping review.

There is a pressing need for effective treatments that address the high rate of suicide observed among people with psychosis. In this scoping review we highlight two suicidogenic treatment targets that have been relatively neglected in people with psychotic disorders: emotional distress and emotion dysregulation. We review the research on these constructs in psychosis and their relationship to suicide in this population, and then make clinical recommendations based on research findings. Emotional distress and emotional dysregulation may be promising treatment targets for suicide among people with psychosis.

The impact of inflammation on neurocognition and risk for psychosis: a critical review.

Neurocognitive difficulties are highly prevalent among people with schizophrenia and have been linked to increased inflammation, as well as dysfunction and disability. Poor neurocognitive functioning has also been documented in individuals at clinical high risk for psychosis (CHR) and a burgeoning literature point to alterations in inflammation markers in this population. However, there is limited information regarding the putative link between inflammation and neurocognition in CHR individuals, and the potential role of inflammation in the development of cognitive difficulties and psychosis. As previous reports indicate that early treatment in schizophrenia is associated with better outcomes, there is an urgent need to identify neurobiological mechanisms underlying cognitive deterioration and psychosis in CHR individuals to provide them with care prior to significant cognitive and functional declines. To address this gap in the literature, we review and summarize the relevant literatures on inflammation and neurocognitive dysfunction in schizophrenia and CHR individuals, point to remaining gaps, and suggest directions for future research.

Inflammation in individuals with schizophrenia - Implications for neurocognition and daily function.

Individuals with schizophrenia display substantial deficits in neurocognition, resulting in poor daily functioning and disability. Recent reports have suggested that neurocognitive dysfunction in this population is linked to increased inflammation. However, there is paucity of evidence supporting this link, as well as lack of information about the putative link of inflammation to daily functioning. We examined neurocognition (MCCB) and daily functioning (SLOF), as well as inflammatory markers (TNF-α, IL-6, IL-1ß, and IL-12p70) in 41 individuals with schizophrenia. Poor neurocognition was significantly associated with increased peripheral TNF-α and IL-12p70 (r = -0.44 and r = -0.38, respectively, controlling for BMI, depression and antipsychotic medication). Notably, difficulties with daily functioning were significantly associated with increased peripheral TNF-α (r = -0.51) and a trend with increased IL-12p70. Our findings support previous hypotheses linking neurocognitive impairment to increased inflammation in individuals with schizophrenia. Our results extend these associations in this population, linking inflammation to poor daily functioning in this population.

Self-esteem and Symptoms in Individuals at Clinical High Risk for Psychosis.

Individuals with psychotic symptoms often report low global self-esteem (GSE). However, it remains unclear whether the low GSE is linked to the presence of psychotic symptoms or it is present before the onset of psychosis. In addition, the specific subdomains of GSE in these populations are unknown. To address this question, we conducted a cross-sectional study comparing global and SE elements among individuals at clinical high risk for psychosis (CHR; n = 36), individuals with schizophrenia (SCZ; n = 43), and healthy controls (HCs; n = 40). We then examined among CHR individuals the association between GSE, subdomains, and symptoms. CHR individuals displayed significantly lower GSE compared to HCs, at a level comparable with those for individuals with SCZ. The low GSE was driven primarily by self-perceptions of work and interpersonal relationships abilities. Lower GSE was associated with overall negative and disorganized symptoms severity, but not positive ones. The authors discuss the implications of the findings to intervention development.

Cognitive-Behavioral Therapy for Olfactory Hallucinations and Associated Delusions: A Case Report.

Olfactory hallucinations (OH) are experienced by a substantial minority of people with schizophrenia, often leading to social anxiety, depression and suffering. Yet, despite their prevalence and clinical significance, OH in schizophrenia are under-researched and poorly understood, with scarce information about potential treatments. To address this gap in the literature, the author describes a case report of successfully using Cognitive-Behavioral Therapy for psychosis (CBTp) to address OH, related delusions, as well as mood and social functioning difficulties in a male patient with schizophrenia. The results provide preliminary support for the feasibility and effectiveness of using CBTp to address OH and related delusions in individuals with schizophrenia.

Psychiatric and affective predictors of negative racial attitudes.

Negative Racial Attitudes (NRA) have been identified as major contributors to discrimination and inequalities. Previous studies of predictors of NRA have focused largely on socioeconomic, socialization, social attitudes, and personality characteristics. Yet, the potential links of psychiatric and affective indicators to NRA have received little scientific inquiry. Three-hundred-and-two participants completed measures of explicit, covert, and implicit NRA, along with indices of psychotic-like experiences (PLEs), mood symptoms, affective processing, social attitudes, and personality characteristics. Explicit and covert NRA were significantly correlated with difficulty identifying and describing feelings, use of suppression to regulate emotion, and the PLEs domains of perceptual abnormalities, bizarre experiences, and persecutory ideation, along with social attitudes and personality characteristics. Implicit NRA was not associated with any indicators. Next, employing hierarchical multiple linear regression analyses, the affective and psychiatric indicators accounted 5.2% and 10.4% of the explicit and covert NRA variance, respectively, controlling for previously identified predictors including demographics, social attitudes, and personality characteristics. Our results point to newly identified predictors of NRA including difficulties identifying and describing emotions, use of suppression to regulate emotions, as well as PLEs, specifically perceptual abnormalities. We discuss the implications of the findings to the development and adaptation of anti-racism interventions.

Engagement of individuals with serious mental illness in outpatient mental health services and telehealth use during the COVID-19 pandemic.

Questions remain regarding whether the transition and continued use of telehealth was associated with changes in treatment engagement among patients with serious mental illness (SMI). Using NYS Medicaid claims, we identified 116,497 individuals with SMI receiving outpatient mental health services from September 1, 2019-February 28, 2021 and a comparison cohort of 101,995 from September 1, 2017-February 28, 2019 to account for unmeasured and seasonal variation. We characterized engagement in three 6-month increments (T0-T1-T2) using clinically meaningful measures of high, partial, low, and none. Subgroup differences were compared, and telehealth users were compared to those with only in-person visits. Engagement, as characterized, was largely maintained during COVID. The 19.0 % with only in-person visits during COVID had different characteristics than telehealth users. Telehealth use was greater among younger people by T2 (33.1 %), women (57.7 %), non-Hispanic White people (38.9 %), and those with MDD (18.0 %), but lower among non-Hispanic Black people, in NYC, and those with schizophrenia or SUD. Most telehealth users were highly engaged (77.1 %); most using only in-person services had low engagement (47.5 %). The shift to telehealth preserved access to many outpatient services for this SMI population. Exploring reasons for not using telehealth may identify opportunities to increase care access.

The Impact of Sleep on Neurocognition and Functioning in Schizophrenia-Is It Time to Wake-Up?

People with schizophrenia (SZ) display substantial neurocognitive deficits that have been implicated as major contributors to poor daily functioning and disability. Previous reports have identified a number of predictors of poor neurocognition in SZ including demographics, symptoms, and treatment adherence, as well as body mass index, aerobic fitness, and exercise activity. However, the putative impact of sleep has received relatively limited consideration, despite sleep disturbances, which are pervasive in this population, resulting in symptoms that are strikingly similar to the neurocognitive deficits commonly observed in SZ. Here we argue for the consideration of the impact of sleep on neurocognition in people with SZ and propose recommendations for future research to elucidate the links between sleep parameters, neurocognition and daily functioning.

Exercise Intervention in Individuals at Clinical High Risk for Psychosis: Benefits to Fitness, Symptoms, Hippocampal Volumes, and Functional Connectivity.

BACKGROUND AND HYPOTHESIS: Individuals at clinical high risk for psychosis (CHR-p) are less fit than nonclinical peers and show hippocampal abnormalities that relate to clinical symptoms. Exercise generates hippocampal neurogenesis that may ameliorate these hippocampal abnormalities and related cognitive/clinical symptoms. This study examines the impact of exercise on deficits in fitness, cognitive deficits, attenuated psychotic symptoms, hippocampal volumes, and hippocampal connectivity in individuals at CHR-p. STUDY DESIGN: In a randomized controlled trial, 32 individuals at CHR-p participated in either an exercise (n = 17) or waitlist (no exercise) (n = 15) condition. All participants were sedentary at use and absent of current antipsychotic medication, psychosis diagnoses, or a substance use disorder. The participants completed a series of fitness, cognitive tasks, clinical assessments, and an MRI session preintervention and postintervention. The exercise intervention included a high-intensity interval exercise (80% of VO2max) with 1-minute high-intensity intervals (95% of VO2max) every 10 minutes) protocol twice a week over 3 months. STUDY RESULTS: The exercise intervention was well tolerated (83.78% retention; 81.25% completion). The exercising CHR-p group showed that improved fitness (pre/post-d = 0.53), increased in cognitive performance (pre/post-d = 0.49), decrease in positive symptoms (pre/post-d = 1.12) compared with the waitlist group. Exercising individuals showed stable hippocampal volumes; waitlist CHR-p individuals showed 3.57% decreased hippocampal subfield volume. Exercising individuals showed that increased exercise-related hippocampal connectivity compared to the waitlist individuals. CONCLUSIONS: The exercise intervention had excellent adherence, and there were clear signs of mechanism engagement. Taken together, evidence suggests that high-intensity exercise can be a beneficial therapeutic tool in the psychosis risk period.

Development of the First Episode Digital Monitoring mHealth Intervention for People With Early Psychosis: Qualitative Interview Study With Clinicians.

BACKGROUND: Mobile health (mHealth) technologies have been used extensively in psychosis research. In contrast, their integration into real-world clinical care has been limited despite the broad availability of smartphone-based apps targeting mental health care. Most apps developed for treatment of individuals with psychosis have focused primarily on encouraging self-management skills of patients via practicing cognitive behavioral techniques learned during face-to-face clinical sessions (eg, challenging dysfunctional thoughts and relaxation exercises), reminders to engage in health-promoting activities (eg, exercising, sleeping, and socializing), or symptom monitoring. In contrast, few apps have sought to enhance the clinical encounter itself to improve shared decision-making (SDM) and therapeutic relationships with clinicians, which have been linked to positive clinical outcomes. OBJECTIVE: This qualitative study sought clinicians' input to develop First Episode Digital Monitoring (FREEDoM), an app-based mHealth intervention. FREEDoM was designed to improve the quality, quantity, and timeliness of clinical and functional data available to clinicians treating patients experiencing first-episode psychosis (FEP) to enhance their therapeutic relationship and increase SDM. METHODS: Following the app's initial development, semistructured qualitative interviews were conducted with 11 FEP treatment providers at 3 coordinated specialty care clinics to elicit input on the app's design, the data report for clinicians, and planned usage procedures. We then generated a summary template and conducted matrix analysis to systematically categorize suggested adaptations to the evidence-based intervention using dimensions of the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) and documented the rationale for adopting or rejecting suggestions. RESULTS: The clinicians provided 31 suggestions (18 adopted and 13 rejected). Suggestions to add or refine the content were most common (eg, adding questions in the app). Adaptations to context were most often related to plans for implementing the intervention, how the reported data were displayed to clinicians, and with whom the reports were shared. Reasons for suggestions primarily included factors related to health narratives and priorities of the patients (eg, focus on the functional impact of symptoms vs their severity), providers' clinical judgment (eg, need for clinically relevant information), and organizations' mission and culture. Reasons for rejecting suggestions included requests for data and procedures beyond the intervention's scope, concerns regarding dilution of the intervention's core components, and concerns about increasing patient burden while using the app. CONCLUSIONS: FREEDoM focuses on a novel target for the deployment of mHealth technologies in the treatment of FEP patients-the enhancement of SDM and improvement of therapeutic relationships. This study illustrates the use of the FRAME, along with methods and tools for rapid qualitative analysis, to systematically track adaptations to the app as part of its development process. Such adaptations may contribute to enhanced acceptance of the intervention by clinicians and a higher likelihood of integration into clinical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04248517; https://tinyurl.com/tjuyxvv6.

Inflammation and emotion regulation: Findings from the MIDUS II study.

Emotion regulation (ER) strategies are thought to contribute to mental as well as physical health outcomes. Two common ER strategies include expressive suppression, or inhibition of emotional expression, and cognitive reappraisal, which involves changing how to think about an emotion-eliciting event in order to change its emotional impact. Recent reports have hypothesized that one potential way in which ER may be linked to health outcomes is via the immune system. However, information on this putative link is scarce. The present study aims to explore whether peripheral inflammatory biomarkers are associated with individual differences in ER-strategy use. Participants (n = 117) from the Midlife in the United States II (MIDUS II) study completed the Emotion Regulation Questionnaire (ERQ), and provided a blood sample for immune biomarker extraction including interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), E-selectin, Intercellular Adhesion Molecule-1 (ICAM-1), and fibrinogen. Results showed higher levels of expressive suppression were associated with decreased IL-10, TNF-α, and ICAM-1 levels (controlling for age, sex, BMI, total prescribed medications, and depressive symptoms). Consistent with these findings, hierarchical regression results identified TNF-α as a significant predictor of expressive suppression use. In contrast, no inflammatory markers were associated with predicted use of cognitive reappraisal. Our findings suggest a link between inflammation and specific ER-strategy use. Future research should consider the effects of pro-vs. anti-inflammatory cytokines on adaptive ER and subsequent mental and physical health.

Social Isolation-Mediated Exacerbation of Negative Affect in Young Drinkers during the COVID-19 Pandemic.

Emerging research on psychological adjustment during the COVID-19 outbreak has suggested that young people may be particularly vulnerable to increases in negative affect during the pandemic. However, the association between alcohol use in youth and change in negative affect during this unprecedented time is not clear. Using an online survey, this study obtained scores on negative affect (before and during the COVID-19 pandemic), pandemic-related stress, change in drinking frequency, and traits including resilience, impulsivity and anhedonia, from a sample of drinkers and non-drinkers, up to the age of 21. Young drinkers experienced a greater increase in negative affect during the pandemic compared to non-drinkers, and this differential rise in negative affect was mediated by the pandemic-related stress of social isolation. Young drinkers also experienced a decrease in alcohol use during the pandemic, but this was not associated with a change in negative affect. Interestingly, young drinkers with greater resilience and lower anhedonia reported less increase in negative affect during the COVID-19 pandemic. Taken together, these results show that the greater increase in negative affect that young drinkers experienced during the COVID-19 pandemic, compared to their non-drinking counterparts, was mediated by pandemic-related social isolation. Moreover, greater resilience and lower anhedonia may have served as protective factors for mitigating the social isolation-induced worsening of negative affect in young drinkers during the pandemic. These findings may inform future studies investigating potential indicators of maladaptive affective responses to public health crises in vulnerable adolescent populations.

An integrative study of the microbiome gut-brain-axis and hippocampal inflammation in psychosis: Persistent effects from mode of birth.

The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-section birth are presented. METHOD: Study subjects undergo research diagnostic interviews and symptom assessments to be categorized into one of 3 study groups: psychosis, nonpsychotic affective disorder or healthy control. Hippocampal volume and metabolite concentrations are assessed using 3-dimensional, multi-voxel H1 Magnetic Resonance Imaging (MRSI) encompassing all gray matter in the entire hippocampal volume. Rich self-report information is obtained with the PROMIS interview, which was developed by the NIH Commons for research in chronic conditions. Early trauma is assessed and cognition is quantitated using the MATRICS. The method also includes the most comprehensive autonomic nervous system (ANS) battery used to date in psychiatric research. Stool and oral samples are obtained for microbiome assessments and cytokines and other substances are measured in blood samples. RESULTS: Group level preliminary data shows that C-section birth is associated with higher concentrations of GLX, a glutamate related hippocampal neurotransmitter in psychotic cases, worse symptoms in affective disorder cases and smaller hippocampal volume in controls. CONCLUSION: Mode of birth appears to have persistent influences through adulthood. The methodology described for this study will define pathways through which the MGBA may influence the risk for psychiatric disorders.

Psychosis risk individuals show poor fitness and discrepancies with objective and subjective measures.

Exercise is a promising intervention for individuals at clinical high-risk for psychosis (CHR). However, these youth may not be reliable reporters on fitness. There have been no investigations that utilized objective fitness assessment in this population. The present study objectively characterizes the level of fitness in CHR youth, compares the accuracy of self-report measures to objective fitness indices, and explores clinical factors that may influence the accuracy of self-reported measures of fitness. Forty CHR individuals completed an exercise survey and objective indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed objective indices of fitness and a structured clinical interview ruling out the presence of psychiatric illness. CHR youth showed greater BMI and lowered VO2max compared to healthy volunteers. In the CHR group, self-report items (perceived fitness) did not reflect objective indices of fitness, whereas specific exercise behaviors (intensity of exercise) showed stronger correlations with objective fitness measurements. Exploratory analyses suggested that symptoms (grandiosity and avolition) related to errors in self-perception. Results indicate that CHR individuals are less fit than controls as indexed by objective measures of fitness and that it is important to consider unique population clinical characteristics when employing self-report data.

Alexithymia, Affective Lability, Impulsivity, and Childhood Adversity in Borderline Personality Disorder.

Long-standing theories of borderline personality disorder (BPD) suggest that symptoms develop at least in part from childhood adversity. Emotion dysregulation may meaningfully mediate these effects. The current study examined three factors related to emotion dysregulation-alexithymia, affective lability, and impulsivity-as potential mediators of the relation between childhood adversity and BPD diagnosis in 101 individuals with BPD and 95 healthy controls. Path analysis compared three distinct models informed by the literature. Results supported a complex mediation model wherein (a) alexithymia partially mediated the relation of childhood adversity to affective lability and impulsivity; (b) affective lability mediated the relation of childhood adversity to BPD diagnosis; and (c) affective lability and impulsivity mediated the relation of alexithymia to BPD diagnosis. Findings suggest that affective lability and alexithymia are key to understanding the relationship between childhood adversity and BPD. Interventions specifically targeting affective lability, impulsivity, and alexithymia may be particularly useful for this population.

Combating the Dangers of Sedentary Activity on Child and Adolescent Mental Health During the Time of COVID-19.

Although the impact of the coronavirus disease 2019 (COVID-19) pandemic, subsequent quarantine, and social distancing on physical activity has been covered extensively, there has been limited focus on the resulting sedentary behavior1 on existing and emerging psychopathology. This is particularly disconcerting regarding children and adolescents, who rely on the ability to play to meet developmental milestones and who require more exercise than adults. Youth populations have been significantly disrupted by school closures and home confinement and are in developmental periods that overlap with the emergence of serious mental illness. Therefore, it is important to consider the mental health consequences for youths, and also explore ways to combat sedentary activity for this vulnerable population.

Considering the Microbiome in Stress-Related and Neurodevelopmental Trajectories to Schizophrenia.

Early life adversity and prenatal stress are consistently associated with an increased risk for schizophrenia, although the exact pathogenic mechanisms linking the exposures with the disease remain elusive. Our previous view of the HPA stress axis as an elegant but simple negative feedback loop, orchestrating adaptation to stressors among the hypothalamus, pituitary, and adrenal glands, needs to be updated. Research in the last two decades shows that important bidirectional signaling between the HPA axis and intestinal mucosa modulates brain function and neurochemistry, including effects on glucocorticoid hormones and brain-derived neurotrophic factor (BDNF). The intestinal microbiome in earliest life, which is seeded by the vaginal microbiome during delivery, programs the development of the HPA axis in a critical developmental window, determining stress sensitivity and HPA function as well as immune system development. The crosstalk between the HPA and the Microbiome Gut Brain Axis (MGBA) is particularly high in the hippocampus, the most consistently disrupted neural region in persons with schizophrenia. Animal models suggest that the MGBA remains influential on behavior and physiology across developmental stages, including the perinatal window, early childhood, adolescence, and young adulthood. Understanding the role of the microbiome on critical risk related stressors may enhance or transform of understanding of the origins of schizophrenia and offer new approaches to increase resilience against stress effects for preventing and treating schizophrenia.

Suicide Reduction in Schizophrenia via Exercise (SUnRISE): study protocol for a multi-site, single-blind, randomized clinical trial of aerobic exercise for suicide risk reduction in individuals with schizophrenia.

BACKGROUND: Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5-10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk. METHODS: Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will include suicide risk (Columbia Suicide Severity Rating Scale, C-SSRS) and aerobic fitness (VO2max), along with additional measures of suicide risk, mood, emotion regulation, sleep, cognition, and physical activity, with assessments completed at baseline and after 6 and 12 weeks of interventions. DISCUSSION: It is hypothesized that AE will reduce suicide risk among individuals with SZ. This study may offer support for a more efficacious treatment method for this population in addition to the pre-existing pharmacological and psychotherapeutic treatment regimens. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03270098 . Registered on September 1, 2017.

The impact of emotion awareness and regulation on psychotic symptoms during daily functioning.

Emotion regulation (ER) difficulties are ubiquitous among individuals with schizophrenia and have been hypothesized to contribute to stress sensitivity and exacerbation of psychotic symptoms in this population. However, the evidence supporting this link is equivocal, potentially due to previous studies' reliance on retrospective assessments of ER and psychosis, as well as lack of consideration of putative moderators such as emotion awareness. To address these limitations, we employed experience sampling method using mobile electronic devices to investigate the links between momentary in vivo use of ER strategies (mER), emotion awareness, and psychotic symptoms during daily functioning. Fifty-four individuals with schizophrenia completed assessment of mER and psychotic symptoms, along with traditional retrospective measures of ER and symptoms. Use of mER suppression predicted significant increases in momentary experiences of thought insertion, mind reading, auditory and visual hallucinations. Use of mER reappraisal predicted significant increases in momentary experiences of suspiciousness, thought insertion, and mind reading. Emotion awareness, driven primarily by difficulties identifying feelings, moderated the impact of ER on psychotic symptoms. There were no associations between retrospective measures of ER and symptoms. Our results indicate that, among individuals with schizophrenia, emotion awareness significantly impacts the relationship between use of ER and exacerbations in psychotic symptoms during the course of daily functioning. Our results highlight the need to incorporate emotion awareness and regulation difficulties into the development of treatment models and interventions for psychosis. In addition, our results underscore the need to employ in vivo, high time-resolution assessment methods to study dynamic clinical phenomena such as ER and psychotic symptoms.

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests.