Increasing conceptual clarity and confounders identification: a pragmatic way to enhance prognostic precision in ENIGMA clinical high risk for psychosis (CHR-P)
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Core beliefs in psychosis: a systematic review and meta-analysis
Increasing interest is growing for the identification of psychological mechanisms to account for the influence of trauma on psychosis, with core beliefs being proposed as a putative mediator to account for this relationship. A systematic review (n = 79 studies) was conducted to summarise the existing evidence base regarding the role of core beliefs/schemas in psychosis, Clinical High-Risk (CHR), and non-clinical samples with Psychotic-Like Experiences (PLEs). Compared to Healthy Controls (HCs), individuals with psychosis experiencing Auditory Hallucinations or Persecutory Delusions had significantly higher scores for negative self and negative other-beliefs and significantly lower scores for positive self and positive other-beliefs. This pattern of core beliefs was also observed for CHR individuals. In contrast, the core belief profile for grandiose delusions was in the opposite direction: higher positive self and positive other-beliefs and lower negative self-beliefs. In non-clinical samples, several factors mediated the relationship between Traumatic Life Events (TLEs) and PLEs, such as greater perceived stress, dissociation, external locus of control, and negative self and negative other-beliefs. Compared to HCs, meta-analyses revealed statistically significant large effects for negative self and negative other-beliefs in Schizophrenia. In CHR, statistically significant large and moderate effects were found for negative self and negative other-beliefs, respectively, along with a moderate negative effect for positive self-beliefs. Core beliefs were found to play a significant role in the development and maintenance of positive symptoms of psychosis. The development of psychosocial interventions that explicitly target negative self and other-beliefs, whilst also enhancing positive self-beliefs are warranted and would innovate CBTp practices.
Preventing psychosis in people at clinical high risk: an updated meta-analysis by the World Psychiatric Association Preventive Psychiatry section
Recently published large-scale randomised controlled trials (RCTs) have questioned the efficacy of preventive interventions in individuals at clinical high risk for psychosis (CHR-P). We conducted a systematic review and meta-analysis to include this new evidence and provide future directions for the field. We followed the PRISMA guidelines and a pre-registered protocol, with a literature search conducted from inception to November 2023. We included RCTs that collected data on psychosis transition (the primary outcome) in CHR-P. Secondary outcomes were symptoms severity and functioning. Investigated time points were 6,12,24,36, and +36 months. We used odd ratios (ORs) and standardised mean differences (SMD) as summary outcomes. Heterogeneity was estimated with the Higgins I2. Twenty-four RCTs, involving 3236 CHR-P individuals, were included. Active interventions were Cognitive Behavioural Therapy (CBT), family-focused therapy, Integrated Psychological Therapy, antipsychotics, omega-3 fatty acids, CBT plus risperidone, minocycline, and other non-pharmacological approaches (cognitive remediation, sleep-targeted therapy, brain stimulation). Results showed no evidence that any of the investigated active interventions had a sustained and robust effect on any of the investigated outcomes in CHR-P, when compared to control interventions, including CBT on transition to psychosis at 12 months (9 RCTs; OR: 0.64; 95% CI: 0.39–1.06; I2: 21%; P = 0.08). These results highlight the need for novel treatment approaches in CHR-P. Future studies should consider the heterogeneity of this clinical population and prioritise stratification strategies and bespoke treatments.
Association between Adverse Childhood Experiences and long-term outcomes in people at Clinical High-Risk for Psychosis
Adverse childhood experiences (ACEs) are common in people at clinical high-risk for psychosis (CHR), however, the relationship between ACEs and long-term clinical outcomes is still unclear. This study examined associations between ACEs and clinical outcomes in CHR individuals. 344 CHR individuals and 67 healthy controls (HC) were assessed using the Childhood Trauma Questionnaire (CTQ), the Bullying Questionnaire and the Childhood Experience of Care and Abuse (CECA). CHR were followed up for up to 5 years. Remission from the CHR state, transition to psychosis (both defined with the Comprehensive Assessment of an At Risk Mental State), and level of functioning (assessed with the Global Assessment of Functioning) were assessed. Stepwise and multilevel logistic regression models were used to investigate the relationship between ACEs and outcomes. ACEs were significantly more prevalent in CHR individuals than in HC. Within the CHR cohort, physical abuse was associated with a reduced likelihood of remission (OR = 3.64, p = 0.025). Separation from a parent was linked to an increased likelihood of both remission (OR = 0.32, p = 0.011) and higher level of functioning (OR = 1.77, p = 0.040). Death of a parent (OR = 1.87, p = 0.037) was associated with an increased risk of transitioning to psychosis. Physical abuse and death of a parent are related to adverse long-term outcomes in CHR. The counter-intuitive association between separation from a parent and outcomes may reflect the removal of a child from an adverse environment. Future studies should investigate whether interventions targeting the effect of specific ACEs might help to improve outcomes in this population.
Identifying neurobiological heterogeneity in clinical high-risk psychosis: a data-driven biotyping approach using resting-state functional connectivity
To explore the neurobiological heterogeneity within the Clinical High-Risk (CHR) for psychosis population, this study aimed to identify and characterize distinct neurobiological biotypes within CHR using features from resting-state functional networks. A total of 239 participants from the Shanghai At Risk for Psychosis (SHARP) program were enrolled, consisting of 151 CHR individuals and 88 matched healthy controls (HCs). Functional connectivity (FC) features that were correlated with symptom severity were subjected to the single-cell interpretation through multikernel learning (SIMLR) algorithm in order to identify latent homogeneous subgroups. The cognitive function, clinical symptoms, FC patterns, and correlation with neurotransmitter systems of biotype profiles were compared. Three distinct CHR biotypes were identified based on 646 significant ROI-ROI connectivity features, comprising 29.8%, 19.2%, and 51.0% of the CHR sample, respectively. Despite the absence of overall FC differences between CHR and HC groups, each CHR biotype demonstrated unique FC abnormalities. Biotype 1 displayed augmented somatomotor connection, Biotype 2 shown compromised working memory with heightened subcortical and network-specific connectivity, and Biotype 3, characterized by significant negative symptoms, revealed extensive connectivity reductions along with increased limbic-subcortical connectivity. The neurotransmitter correlates differed across biotypes. Biotype 2 revealed an inverse trend to Biotype 3, as increased neurotransmitter concentrations improved functional connectivity in Biotype 2 but reduced it in Biotype 3. The identification of CHR biotypes provides compelling evidence for the early manifestation of heterogeneity within the psychosis spectrum, suggesting that distinct pathophysiological mechanisms may underlie these subgroups.
Digital health for early psychosis in Ghana: patient and caregiver needs and preferences
In West Africa, the long-term consequences of poor early psychosis recovery include poverty, neglect, and community ostracization. To understand the potential for digital health approaches to support early psychosis care in Ghana, we conducted a survey study among early psychosis patients and their caregivers about mental health needs, technology use and access, and interest in digital mental health. Hospital staff at Accra Psychiatric Hospital reviewed hospital medical records from January 2023 – December 2023 identifying young adults (≥18 years old) who had experienced psychosis symptoms for the first time within the prior five years. Trained data assessors contacted these individuals via telephone and invited them and their caregivers to participate; those providing informed consent were interviewed via phone in Twi or English. Overall, 256 individuals participated in the survey, including 121 young adults experiencing early psychosis and 135 caregivers of early psychosis patients. The majority (80%) of early psychosis patients and their caregivers expressed interest in digital mental health for early psychosis and had access to a mobile phone (91%) and necessary mobile infrastructure. Early psychosis patients were most interested in information about managing stress and improving mood via a digital resource (72%). Caregivers desired a digital tool to provide information about psychosis symptoms (86%). Our study among those experiencing early psychosis and their caregivers in Ghana suggests readiness and acceptability of digital mental health for early psychosis care.
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