A multiple baseline trial of adapted prolonged exposure psychotherapy for individuals with early phase psychosis, comorbid substance misuse, and a history of adversity: A study protocol.

Background: Adversity is prevalent among people with psychotic disorders, especially those within the first 5 years of a psychotic disorder, called early phase psychosis. Although adversity can lead to many negative outcomes (e.g., posttraumatic stress symptoms), very few treatments for adversity-related sequelae have been tested with individuals with psychotic disorders, and even fewer studies have specifically tested interventions for people in early phase psychosis. Furthermore, people who misuse substances are commonly excluded from adversity treatment trials, which is problematic given that individuals with early phase psychosis have high rates of substance misuse. For the first time, this trial will examine the outcomes of an adapted 15-session prolonged exposure protocol (i.e., PE+) to observe whether reductions in adversity-related psychopathology occurs among people with early phase psychosis and comorbid substance misuse. Methods: This study will use a multiple-baseline design with randomization of participants to treatment start time. Participants will complete baseline appointments prior to therapy, engage in assessments between each of the five therapy modules, and complete a series of follow-up appointments 2 months after the completion of therapy. Primary hypothesized outcomes include clinically significant reductions in (1) negative psychotic symptoms measured using the Positive and Negative Syndrome Scale, (2) adversity-related sequelae measured using the Trauma Symptom Checklist-40, and (3) substance use frequency and overall risk score measured with the Alcohol, Smoking, and Substance Involvement Screening Test. We also anticipate that clinically significant reductions in hopelessness and experiential avoidance, measured with the Beck Hopelessness Scale and Brief Experiential Avoidance Questionnaire, the theorized mechanisms of change of PE+, will also be observed. A secondary outcome is a hypothesized improvement in functioning, measured using the Clinical Global Impression and Social and Occupational Functioning Assessment scales. Discussion: The results of this treatment trial will contribute to the advancement of treatment research for individuals in early phase psychosis who have current substance misuse and a history of adversity, and the findings may provide evidence supporting the use of hopelessness and experiential avoidance as mechanisms of change for this treatment. Clinical trial registration: Clinicaltrials.gov, NCT04546178; registered August 28, 2020, https://clinicaltrials.gov/ct2/show/NCT04546178?term=NCT04546178&draw=2&rank=1.

An Internet-Based Cognitive Behavioral Therapy Program for Anxiety and Depression (Tranquility): Adaptation Co-design and Fidelity Evaluation Study.

BACKGROUND: Internet-based cognitive behavioral therapy (iCBT) is a necessary step toward increasing the accessibility of mental health services. Yet, few iCBT programs have been evaluated for their fidelity to the therapeutic principles of cognitive behavioral therapy (CBT) or usability standards. In addition, many existing iCBT programs do not include treatments targeting both anxiety and depression, which are commonly co-occurring conditions. OBJECTIVE: This study aims to evaluate the usability of Tranquility-a novel iCBT program for anxiety-and its fidelity to CBT principles. This study also aims to engage in a co-design process to adapt Tranquility to include treatment elements for depression. METHODS: CBT experts (n=6) and mental health-informed peers (n=6) reviewed the iCBT program Tranquility. CBT experts assessed Tranquility's fidelity to CBT principles and were asked to identify necessary interventions for depression by using 2 simulated client case examples. Mental health-informed peers engaged in 2 co-design focus groups to discuss adaptations to the existing anxiety program and the integration of interventions for depression. Both groups completed web-based surveys assessing the usability of Tranquility and the likelihood that they would recommend the program. RESULTS: The CBT experts' mean rating of Tranquility's fidelity to CBT principles was 91%, indicating a high fidelity to CBT. Further, 5 out of 6 CBT experts and all mental health-informed peers (all participants: 11/12, 88%) rated Tranquility as satisfactory, indicating that they may recommend Tranquility to others, and they rated its usability highly (mean 76.56, SD 14.07). Mental health-informed peers provided suggestions on how to leverage engagement with Tranquility (eg, adding incentives and notification control). CONCLUSIONS: This preliminary study demonstrated the strong fidelity of Tranquility to CBT and usability standards. The results highlight the importance of involving stakeholders in the co-design process and future opportunities to increase engagement.

Youth Experience Tracker Instrument: A self-report measure of developmental antecedents to severe mental illness.

AIM: We sought to examine the structure, internal consistency, convergent and criterion validity of the Youth Experience Tracker Instrument (YETI), a new brief self-report measure designed to facilitate early identification of risk for severe forms of mental illness, including major depressive disorder, bipolar disorder, and schizophrenia. METHODS: We collected 716 YETIs from 315 individuals aged 8 to 27 with and without familial risk of severe mental illness. The YETI measures six developmental antecedents that precede and predict serious forms of mental illness: affective lability, anxiety, basic symptoms, depressive symptoms, psychotic-like experiences, and sleep. A battery of concurrent questionnaires and interviews measured the same constructs. RESULTS: The best-fitting bifactor model supported the validity of both total score and antecedent-specific subscales. Internal consistency was high for the total score (ω = 0.94) and subscales (ω = 0.80-0.92; ρ = 0.72). The total score captured the majority of information from the 26 YETI items (hierarchical omega ωh = 0.74). Correlations of YETI subscales with established measures of the same constructs (r = 0.45-0.80) suggested adequate convergent validity. We propose cut-offs with high negative predictive values to facilitate efficient risk screening. CONCLUSION: The YETI, a brief self-report measure of antecedents, provides an alternative to using multiple longer instruments. Future research may examine the predictive validity of the YETI for the onset of major mood and psychotic disorders.

Affective lability in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

Affective lability, defined as the propensity to experience excessive and unpredictable changes in mood, has been proposed as a potential transdiagnostic predictor of major mood and psychotic disorders. A parental diagnosis of bipolar disorder has been associated with increased affective lability in offspring. However, the association between affective lability and family history of other mood and psychotic disorders has not been examined. We measured affective lability using the self- and parent-reported Children's Affective Lability Scale in a cohort of 320 youth aged 6-17 years, including 137 offspring of a parent with major depressive disorder, 68 offspring of a parent with bipolar disorder, 24 offspring of a parent with schizophrenia, and 91 offspring of control parents. We tested differences in affective lability between groups using mixed-effects linear regression. Offspring of a parent with major depressive disorder (ß = 0.46, 95% CI 0.17-0.76, p = 0.002) or bipolar disorder (ß = 0.47, 95% CI 0.12-0.81, p = 0.008) had significantly higher affective lability scores than control offspring. Affective lability did not differ significantly between offspring of a parent with schizophrenia and offspring of control parents. Our results suggest that elevated affective lability during childhood is a marker of familial risk for mood disorders.

Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness

Background: Cortical folding is essential for healthy brain development. Previous studies have found regional reductions in cortical folding in adult patients with psychotic illness. It is unknown whether these neuroanatomical markers are present in youth with subclinical psychotic symptoms. Methods: We collected MRIs and examined the local gyrification index in a sample of 110 youth (mean age ± standard deviation 14.0 ± 3.7 yr; range 9­25 yr) with a family history of severe mental illness: 48 with psychotic symptoms and 62 without. Images were processed using the Human Connectome Pipeline and FreeSurfer. We tested for group differences in local gyrification index using mixed-effects generalized linear models controlling for age, sex and familial clustering. Sensitivity analysis further controlled for intracranial volume, IQ, and stimulant and cannabis use. Results: Youth with psychotic symptoms displayed an overall trend toward lower cortical folding across all brain regions. After adjusting for multiple comparisons and confounders, regional reductions were localized to the frontal and occipital lobes. Specifically, the medial (B = ­0.42, pFDR = 0.04) and lateral (B = ­0.39, pFDR = 0.04) orbitofrontal cortices as well as the cuneus (B = ­0.47, pFDR = 0.03) and the pericalcarine (B = ­0.45, pFDR = 0.03) and lingual (B = ­0.38, pFDR = 0.04) gyri. Limitations: Inference about developmental trajectories was limited by the cross-sectional data. Conclusion: Psychotic symptoms in youth are associated with cortical folding deficits, even in the absence of psychotic illness. The current study helps clarify the neurodevelopmental basis of psychosis at an early stage, before medication, drug use and other confounds have had a persistent effect on the brain.

Basic symptoms in offspring of parents with mood and psychotic disorders.

BACKGROUND: Basic symptoms, defined as subjectively perceived disturbances in thought, perception and other essential mental processes, have been established as a predictor of psychotic disorders. However, the relationship between basic symptoms and family history of a transdiagnostic range of severe mental illness, including major depressive disorder, bipolar disorder and schizophrenia, has not been examined. AIMS: We sought to test whether non-severe mood disorders and severe mood and psychotic disorders in parents is associated with increased basic symptoms in their biological offspring. METHOD: We measured basic symptoms using the Schizophrenia Proneness Instrument - Child and Youth Version in 332 youth aged 8-26 years, including 93 offspring of control parents, 92 offspring of a parent with non-severe mood disorders, and 147 offspring of a parent with severe mood and psychotic disorders. We tested the relationships between parent mental illness and offspring basic symptoms in mixed-effects linear regression models. RESULTS: Offspring of a parent with severe mood and psychotic disorders (B = 0.69, 95% CI 0.22-1.16, P = 0.004) or illness with psychotic features (B = 0.68, 95% CI 0.09-1.27, P = 0.023) had significantly higher basic symptom scores than control offspring. Offspring of a parent with non-severe mood disorders reported intermediate levels of basic symptoms, that did not significantly differ from control offspring. CONCLUSIONS: Basic symptoms during childhood are a marker of familial risk of psychopathology that is related to severity and is not specific to psychotic illness. DECLARATION OF INTEREST: None.

Disruptive mood dysregulation disorder in offspring of parents with depression and bipolar disorder.

BackgroundIt has been suggested that offspring of parents with bipolar disorder are at increased risk for disruptive mood dysregulation disorder (DMDD), but the specificity of this association has not been established.AimsWe examined the specificity of DMDD to family history by comparing offspring of parents with (a) bipolar disorder, (b) major depressive disorder and (c) a control group with no mood disorders.MethodWe established lifetime diagnosis of DMDD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children for DSM-5 in 180 youth aged 6-18 years, including 58 offspring of parents with bipolar disorder, 82 offspring of parents with major depressive disorder and 40 control offspring.ResultsDiagnostic criteria for DMDD were met in none of the offspring of parents with bipolar disorder, 6 of the offspring of parents with major depressive disorder and none of the control offspring. DMDD diagnosis was significantly associated with family history of major depressive disorder.ConclusionsOur results suggest that DMDD is not specifically associated with a family history of bipolar disorder and may be associated with parental depression.