Evaluating and treating the prodromal stage of schizophrenia

Identification of a person in the prodromal stage of schizophrenia, before the onset of the first episode of psychosis, provides an opportunity for early, potentially preventative, interventions. Recent attempts to develop "at risk" or " prodromal syndrome" diagnostic criteria have proved to be successful at identifying individuals at high risk for psychosis. Preliminary investigations find that pharmacologic and psychotherapeutic interventions may reduce the risk of psychosis in "at risk" individuals, but until more is known, current treatment guidelines recommend close monitoring, therapeutic interventions that address identified problems, including supportive or cognitive therapies to reduce the functional consequences of the presenting symptoms, family interventions to reduce family distress and improve coping, and intervention with schools to decrease likelihood of school failure. Pharmacologic intervention targeting the prodromal symptoms is not recommended, given the uncertain risk-benefit ratio

Reproducibility and Visual Inspection of Data

In 2011, Moreau et al. reported in Biological Psychiatry findings concerning patterns of microRNA (miRNA) expression in postmortem samples from prefrontal cortex (Brodmann area 9) from the Stanley Medical Research Institute (SMRI) (Chevy Chase, Maryland). They used advanced statistical techniques and miRNA assays by real-time quantitative polymerase chain reaction (TaqMan probes; Applied Biosystems, Foster City, California) for the canonical sequences in early versions of miRBase (http://www.mirbase.org/). All demographics, sample processing, and data analysis steps were carefully described in their article. The main conclusion was that certain miRNAs were distinguished in comparisons of samples from unaffected control subjects versus samples from subjects with schizophrenia and versus samples from subjects with bipolar disorder. They identified 24 miRNAs in particular with distinctive fold changes [Figure 1 in Moreau et al. (1)]

Clinician Recognition of First Episode Psychosis

Purpose: Psychotic disorders develop during mid-adolescence through early adulthood, with the initial few months a “critical period” offering the greatest promise for recovery. However, the duration of untreated psychosis is typically over a year. This study aimed to identify aspects of care episodes contributing to delays in diagnosis of a first psychotic episode. Methods: Study subjects included 161 adolescents and young adults referred to a first episode psychosis treatment program. We captured the various ways that people who experience a severe mental illness engage in treatment using standardized interviews with patients and informants (e.g., family member) and medical record review. Results: A psychotic disorder diagnosis was not given for 38% of subjects at their initial episode of care. Time to first care episode was virtually the same for subjects that did and did not receive a psychosis diagnosis; 50% within 1 month and 84% within 6 months. Compared to initial care episodes with a psychosis diagnosis, those without a psychosis diagnosis less often involved emergency services (80% vs. 38%, respectively; p value = 1 × 10−7) and more often outpatient primary care (6% vs. 18%; p value = .032) and mental health (32% vs. 49%; p value = .045) services. However, dangerousness indicators were similar (29% vs. 28%; p value = 1). Dangerousness indicators increased to 54% (p value = .002) by the time of eventual diagnosis for those requiring multiple care episodes. Conclusions: Clinicians were important contributors to delays in diagnosis and treatment of psychosis. Interventions targeting outpatient health care providers may be fruitful in reducing the duration of untreated psychosis

Premorbid social adjustment and association with attenuated psychotic symptoms in clinical high-risk and help-seeking youth

Background Attenuated positive symptom syndrome (APSS), characterized by 'putatively prodromal' attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of 'true' prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals. Method Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis. Results Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria. Conclusions Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals

Personal Beliefs about Experiences in those at Clinical High Risk for Psychosis

Background: Negative beliefs about illness in early psychosis have been shown to have an unfavourable impact on one's quality of life. A shift of focus in psychosis research has been on the detection of individuals considered to be at clinical high risk (CHR) of developing psychosis. Little is known about the impact that beliefs about psychotic like experiences or attenuated psychotic symptoms may have on CHR individuals. Aim: To explore these beliefs in a large sample of young people at CHR of developing psychosis using the Personal Beliefs about Experiences Questionnaire (PBEQ). Method: Beliefs about unusual experiences were assessed in 153 CHR individuals with the PBEQ. Prodromal symptoms (measured by the SIPS) and depression (measured by the CDSS) were also assessed. Results: In CHR individuals, holding more negative beliefs was associated with increased severity in depression and negative symptoms. Higher scores on suspiciousness were associated with increased negative beliefs, and higher levels of grandiosity were associated with decreased negative beliefs. Those who later transitioned to psychosis agreed significantly more with statements concerning control over experiences (i.e. my experiences frighten me, I find it difficult to cope). Conclusions: The results suggest that targeting negative beliefs and other illness related appraisals is an important objective for intervention strategies

Neurocognitive predictors of metacognition in individuals at clinical high risk for psychosis

Background:Metacognition refers to the ability to evaluate and control our cognitive processes. While studies have investigated metacognition in schizophrenia and clinical high risk for psychosis (CHR), less is known about the potential mechanisms which result in metacognitive deficits.Aims:We aimed to investigate whether neurocognitive functions including attention, working memory, verbal learning and executive functions predicted the tendency to focus on one's thoughts (cognitive self-consciousness) and beliefs in the efficacy of one's cognitive skills (cognitive confidence).Method:Participants (130 CHR individuals) were recruited as part of the multi-site PREDICT study. They were assessed using the Metacognitions Questionnaire (MCQ) as well as measures of executive function (WCST), attention (N-Back), working memory (LNS) and verbal learning (AVLT).Results:Cognitive competence was negatively correlated with N-Back while cognitive self-consciousness was positively correlated with N-Back and LNS. Linear regression analysis with N-Back, AVLT, LNS and WCST as predictors showed that neurocognition significantly predicted cognitive self-consciousness, with N-Back, LNS and WCST as significant predictors. The model accounted for 14% of the variance in cognitive self-consciousness. However, neurocognition did not result in a significant predictive model of cognitive competence.Conclusions:Neurocognition was associated with an increased focus on one's thoughts, but it was not associated with higher confidence in one's cognitive skills. Neurocognition accounted for less than one-sixth of the variance in metacognition, suggesting that interventions that target neurocognition are unlikely to improve metacognitive abilities

Impaired neural synchrony in the theta frequency range in adolescents at familial risk for schizophrenia

Puberty is a critical period for the maturation of the fronto-limbic and fronto-striate brain circuits responsible for executive function and affective processing. Puberty also coincides with the emergence of the prodromal signs of schizophrenia, which may indicate an association between these two processes.Time-domain analysis and wavelet based time-frequency analysis was performed on electroencephalographic (EEG) data of 30 healthy control (HC) subjects and 24 individuals at familial risk(FR) for schizophrenia. All participants were between the ages of 13 and 18 years and were carefully matched for age, gender, ethnicity, education, andTanner Stage. Electrophysiological recordings were obtained from 32 EEG channels while participants performed a visual oddball task, where they identified rare visual targets among standard "scrambled" images and rare aversive and neutral dis-tracter pictures. The time-domain analysis showed that during target processing the FR group showed smaller event-related potentials in the P2 and P3 range as compared to the HC group. In addition, EEG activity in the theta (4-8 Hz) frequency range was significantly reduced during target processing in the FR group. Inefficient cortical information processing during puberty may be an early indicator of altered brain function in adolescents at FR for schizophrenia and may represent a vulnerability marker for illness onset. Longitudinal assessments will have to determine their predictive value for illness onset in populations at FR for psychotic illness

Latent class cluster analysis of symptom ratings identifies distinct subgroups within the clinical high risk for psychosis syndrome

© 2017 The clinical-high-risk for psychosis (CHR-P) syndrome is heterogeneous in terms of clinical presentation and outcomes. Identifying more homogenous subtypes of the syndrome may help clarify its etiology and improve the prediction of psychotic illness. This study applied latent class cluster analysis (LCCA) to symptom ratings from the North American Prodrome Longitudinal Studies 1 and 2 (NAPLS 1 and 2). These analyses produced evidence for three to five subgroups within the CHR-P syndrome. Differences in negative and disorganized symptoms distinguished among the subgroups. Subgroup membership was found to predict conversion to psychosis. The authors contrast the methods employed within this study with previous attempts to identify more homogenous subgroups of CHR-P individuals and discuss how these results could be tested in future samples of CHR-P individuals

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire–Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3–5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC = 0.899 ± 0.001). The EPS-26 outperformed the PQ-B (AUC = 0.834 ± 0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway

Enhancing stress reactivity and wellbeing in early schizophrenia: A pilot study of individual coping awareness therapy (I-CAT)

Dear Editors: Positive psychology strategies and mindfulness are two non-traditional approaches to psychotherapy increasingly employed to aid recovery from psychosis (Shonin et al. 2014; Slade 2010). Positive psy-chology interventions focus on increasing experiences of positive emo-tions to improve wellbeing (Rashid 2015), while mindfulness interventions reduce stress reactivity, and facilitate experiences of pos-itive emotions (Geschwind et al. 2011; Gu et al., 2015)