After decades of research, schizophrenia and related psychotic disorders are still among the most debilitating disorders in medicine. The chronic illness course in most individuals, greater treatment responsiveness during the first episode, progressive gray matter decline during early disease stages, and retrospective accounts of 'prodromal' or early illness signs and symptoms formed the basis for research on the psychosis risk syndrome (PRS), known variably as 'clinical high risk' (CHR), or 'ultra-high risk' (UHR), or 'prodromal'. The pioneering era of research on PRS focused on the development and validation of specific assessment tools and the delineation of high risk criteria. This was followed by the examination of conversion rates in psychosis risk cohorts followed naturalistically, identification of predictors of conversion to psychosis, and investigation of interventions able to abort or delay the development of full psychosis. Despite initially encouraging results concerning the predictive validity of PRS criteria, recent findings of declining conversion rates demonstrate the need for further investigations. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioral therapy, are encouraging, but are currently still insufficient to make treatment recommendations for this early, relatively non-specific illness phase. The next phase of research on PRS, just now beginning, has moved to larger, 'multisite' projects to increase generalizability and to ensure that sufficiently large samples at true risk for psychosis are included. Emphasis in these emerging studies is on: 1) identification of biomarkers for conversion to psychosis; 2) examination of non-antipsychotic, neuroprotective and low-risk pharmacologic and non-pharmacologic interventions; 3) testing of potentially phase-specific interventions; 4) examination of the relationship between treatment response during PRS and prognosis for the course of illness; 5) follow-up of patients who developed schizophrenia despite early interventions and comparison of illness trajectories with patients who did not receive early interventions; 6) characterization of individuals with outcomes other than schizophrenia-spectrum disorders, such as bipolar disorder and remission from PRS, including false positive cases; and 7) assessment of meaningful social and role functioning outcomes. While the research conducted to date has already yielded crucial information, the translation of the concept of a clinically identifiable PRS into clinical practice does not seem justified at this point.

Research in people with psychosis risk syndrome: a review of the current evidence and future directions

Objectives:Cannabis use is prevalent among people with first episode psychosis and the epidemiology of its use in early psychosis is unclear. We performed a meta-analysis of observational studies to determine; (1) the interval between age at initiation of cannabis use and age at onset of first episode psychosis, (2) the prevalence of cannabis use at time of first episode psychosis, and (3) the odds of continuing cannabis following treatment for first episode psychosis.Data sources:Search of electronic databases MEDLINE, EMBASE, PsycINFO, Web of Science and CINAHL for English-language papers using search terms (psychosis OR schizophrenia) AND (cannabis OR marijuana) IN (title OR keyword OR abstract), current to October 2014.Study selection:Studies were included if they reported on prevalence of current cannabis use in first episode psychosis cohorts. A total of 37 samples were included for meta-analysis.Data extraction:Rates of cannabis use in each sample were extracted to determine prevalence estimates. T...

Cannabis use in first episode psychosis: Meta-analysis of prevalence, and the time course of initiation and continued use:

A recent meta-analysis showed that the mean age of onset of psychosis among cannabis users was almost three years earlier than that of non-cannabis users. However, because cannabis users usually smoke tobacco, the use of tobacco might independently contribute to the earlier onset of psychosis. We aimed to use meta-analysis to compare the extent to which cannabis and tobacco use are each associated with an earlier age at onset of schizophrenia and other psychoses. We also examined other factors that might have contributed to the finding of an earlier age of onset among cannabis users, including the proportion of males in the samples, the diagnostic inclusion criteria and aspects of study quality. The electronic databases MEDLINE, EMBASE, PsycINFO and ISI Web of Science, were searched for English-language peer-reviewed publications that reported age at onset of schizophrenia and other psychoses separately for cannabis users and non-users, or for tobaccosmokers and non-smokers. Meta-analysis showed that the age at onset of psychosis for cannabis users was 32 months earlier than for cannabis non-users (SMD=- 0.399, 95%CI -0.493 - -0.306, z=-8.34, p < 0.001), and was two weeks later in tobacco smokers compared with non-smokers (SMD=0.002, 95%CI -0.094 - 0.097, z=0.03, p=0.974). The main results were not affected by subgroup analyses examining studies of a single sex, the methods for making psychiatric diagnoses and measures of study quality. The results suggest that the association between cannabis use and earlier onset of psychosis is robust and is not the result either of tobacco smoking by cannabis using patients or the other potentially confounding factors we examined. This supports the hypothesis that, in some patients, cannabis use plays a causal role in the development of schizophrenia and raises the possibility of treating schizophrenia with new pharmacological treatments that have an affinity for endo-cannabinoid receptors.

The Association between Cannabis Use and Earlier Age at Onset of Schizophrenia and other Psychoses: Meta-analysis of Possible Confounding Factors

Aim

Negative symptoms (NS) have been associated with poor outcome and remain difficult to treat in patients with psychosis. This study examined the association of NS with clinical features at first presentation to mental health services for psychosis and with outcomes at 1-year follow-up.
Methods

Clinical data were utilized from five London Early Intervention Services (EIS) included in the MiData audit database. The sample comprised 484 first-episode psychosis patients with complete Positive and Negative Syndrome Scale data at baseline and 1-year follow-up. Multiple imputation (N = 50) was conducted to account for missing follow-up data.
Results

Baseline NS were associated with male gender (B = −1.63, P < .05), younger age at onset (B = −.15, P <. 05), a higher level of impairment on the Global Assessment of Functioning (disability) Scale at baseline (B = −.19, P <. 010), an absence of reported substance misuse prior to baseline assessment (B = −3.05, P <. 001) and unemployment at baseline (B = −.93, P <. 01). At 1-year follow-up, NS at presentation were associated with worse Global Assessment of Functioning Scale for symptom (B = −.28, P < .01) and disability (B = −.27, P <. 05) and with hospital admission (OR = 1.06, P < .01).
Conclusions

Negative symptoms at presentation to EIS were associated with worse functioning at entry and poorer outcomes 1 year later. Future research is required to better understand the aetiology and trajectories of NS in early psychosis and propose novel targeted interventions.

/pdf/negative-symptoms-in-first-episode-psychosis-clinical-32fwbdd6zb.pdf

Negative symptoms in first‐episode psychosis: Clinical correlates and 1‐year follow‐up outcomes in London Early Intervention Services

The pathway to receiving specialty care for first episode psychosis (FEP) among Black youth in the US has received little attention despite documented challenges that negatively impact engagement in care and clinical outcomes. We conducted a systematic review of US-based research, reporting findings related to the pathway experiences of Black individuals with FEP and their family members. A systematic search of PubMed, PsycInfo, and Embase/Medline was performed with no date restrictions up to April 2021. Included studies had samples with at least 75% Black individuals and/or their family members or explicitly examined racial differences. Of the 80 abstracts screened, 28 peer-reviewed articles met the inclusion criteria. Studies were categorized into three categories: premordid and prodromal phase, help-seeking experiences, and the duration of untreated psychosis (DUP). Compounding factors such as trauma, substance use, and structural barriers that occur during the premorbid and prodromal contribute to delays in treatment initiation and highlight the limited use of services for traumatic childhood experiences (e.g., sexual abuse). Studies focused on help-seeking experiences demonstrated the limited use of mental health services and the potentially traumatic entry to services (e.g., law enforcement), which is associated with a longer DUP. Although the majority of studies focused on help-seeking experiences and predictors of DUP, findings suggests that for Black populations, there is a link between trauma and substance use in the pathway to care that impacts the severity of symptoms, initiation of treatment, and DUP. The present review also identifies the need for more representative studies of Black individuals with FEP.

Systematic review of pathways to care in the U.S. for Black individuals with early psychosis.

OBJECTIVE: On the basis of limited prior research on associations between symptoms and substance use in first-episode psychosis, a retrospective chart review was conducted to test 2 hypotheses: (1) the presence of positive symptoms is associated with alcohol use prior to admission and (2) the absence of prominent negative symptoms is associated with cannabis use prior to admission. METHOD: Eligible patients included those admitted for a first episode of psychosis in a public-sector, university-affiliated hospital that serves a predominantly African American, socially disadvantaged, urban population. The 72 patients included in the analysis were 18 to 40 years of age, and all were African American. Using a structured data collection instrument, discharge summaries of consecutively admitted patients from January 2002 to March 2005 were reviewed to extract data on basic demographic and clinical characteristics, the presence of 11 symptoms, and alcohol and cannabis use within 6 months prior to hospitalization. RESULTS: Alcohol use in the 6 months prior to hospitalization was associated with a higher frequency of positive psychotic symptoms among first-episode patients. Cannabis use was associated with a lower likelihood of having prominent negative symptoms. These associations remained even after controlling for relevant covariates in logistic regression models. CONCLUSION: Although the direction of causality cannot be established, the association between positive psychotic symptoms and alcohol use may represent a self-medication effect, whereas the association between lesser negative symptoms and cannabis use may result from the fact that interpersonal deficits and reduced hedonic capacity minimize drug-seeking activities. Language: en

Alcohol and cannabis use in Urban, African American, first-episode schizophrenia-spectrum patients: associations with positive and negative symptoms.

Cerebrospinal fluid levels of 5-HIAA and dopamine in people with HIV and depression.

Rationale: The clinical utility of routinely conducted computed tomography (CT) brain imaging during the evaluation of first-episode psychosis is often very limited, results typically relegated to ruling out gross intracranial pathology. Little is known about whether more commonplace findings and variants, often unreported in the radiological summary, could provide prognostic information. This study, focused on a low-income, predominantly African-American sample of public-sector, first-episode patients, addressed the understudied question of whether or not findings on routine clinical CT scans are associated with variables that may have prognostic importance. Methods: The sample included seventy-five consecutively admitted patients, aged 18-40 years, who were hospitalized for a first episode of psychosis. Sociodemographic and clinical data were obtained by a psychiatrist through a structured retrospective chart review based on dictated discharge summaries. Radiological variables were recorded by a neurora...

An Exploratory Study of the Potential Prognostic Usefulness of the Routinely Conducted Computed Tomography Scan in Patients Hospitalized for a First Episode of Psychosis

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Alcohol and cannabis use in Urban, African American, first-episode schizophrenia-spectrum patients: associations with positive and negative symptoms.

Cerebrospinal fluid levels of 5-HIAA and dopamine in people with HIV and depression.

An Exploratory Study of the Potential Prognostic Usefulness of the Routinely Conducted Computed Tomography Scan in Patients Hospitalized for a First Episode of Psychosis