Abstracts: Schizophrenia: Advances in Understanding and Treatment
Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program
Am J Psychiatry 2016; 173:362–372
OBJECTIVE: The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life.METHOD: Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and≤6 months of antipsychotic treatment (N=404) were enrolled and followed for≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities.RESULTS: The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups.CONCLUSIONS: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.
Reprinted with permission from American Psychiatric Association Publishing.
Concurrent and Sustained Cumulative Effects of Adolescent Marijuana Use on Subclinical Psychotic Symptoms
Am J Psychiatry (Epub ahead of print, May 3, 2016)
OBJECTIVE: Adolescents who regularly use marijuana may be at heightened risk of developing subclinical and clinical psychotic symptoms. However, this association could be explained by reverse causation or other factors. To address these limitations, the current study examined whether adolescents who engage in regular marijuana use exhibit a systematic increase in subclinical psychotic symptoms that persists during periods of sustained abstinence.METHOD: The sample comprised 1,009 boys who were recruited in 1st and 7th grades. Self-reported frequency of marijuana use, subclinical psychotic symptoms, and several time-varying confounds (e.g. other substance use, internalizing/externalizing problems) were recorded annually from age 13 to 18. Fixed-effects (within-individual change) models examined whether adolescents exhibited an increase in their subclinical psychotic symptoms as a function of their recent and/or cumulative history of regular marijuana use and whether these effects were sustained following abstinence. Models controlled for all time-stable factors (default) and several time-varying covariates as potential confounds.RESULTS: For each year adolescent boys engaged in regular marijuana use, their expected level of subsequent subclinical psychotic symptoms rose by 21% and their expected odds of experiencing subsequent subclinical paranoia or hallucinations rose by 133% and 92%, respectively. The effect of prior regular marijuana use on subsequent subclinical psychotic symptoms persisted even when adolescents stopped using marijuana for a year. These effects were after controlling for all time-stable and several time-varying confounds. No support was found for reverse causation.CONCLUSIONS: These results suggest that regular marijuana use may significantly increase the risk that an adolescent will experience persistent subclinical psychotic symptoms.
Reprinted with permission from American Psychiatric Association Publishing.
Social Cognition in Schizophrenia
Nat Rev Neurosci 2015; 16:620–631
Individuals with schizophrenia exhibit impaired social cognition, which manifests as difficulties in identifying emotions, feeing connected to others, inferring people's thoughts and reacting emotionally to others. These social cognitive impairments interfere with social connections and are strong determinants of the degree of impaired daily functioning in such individuals. Here, we review recent findings from the fields of social cognition and social neuroscience and identify the social processes that are impaired in schizophrenia. We also consider empathy as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia. This information may guide interventions to improve social cognition in patients with this disorder.
Reprinted with permission from Nature Publishing Group.
Common or Distinct Pathways to Psychosis? A Systematic Review of Evidence From Prospective Studies for Developmental Risk Factors and Antecedents of the Schizophrenia Spectrum Disorders and Affective Psychoses
BMC Psychiatry 2015; 15:205
BACKGROUND: Identifying the unique and shared premorbid indicators of risk for the schizophrenia spectrum disorders (SSD) and affective psychoses (AP) may refine aetiological hypotheses and inform the delivery of universal versus targeted preventive interventions. This systematic review synthesizes the available evidence concerning developmental risk factors and antecedents of SSD and AP to identify those with the most robust support, and to highlight remaining evidence gaps.METHODS: A systematic search of prospective birth, population, high-risk, and case-control cohorts was conducted in Medline and supplemented by hand searching, incorporating published studies in English with full text available. Inclusion/exclusion decisions and data extraction were completed in duplicate. Exposures included three categories of risk factors and four categories of antecedents, with case and comparison groups defined by adult psychiatric diagnosis. Effect sizes and prevalence rates were extracted, where available, and the strength of evidence synthesized and evaluated qualitatively across the study designs.RESULTS: Of 1775 studies identified by the search, 127 provided data to the review. Individuals who develop SSD experience a diversity of subtle premorbid developmental deficits and risk exposures, spanning the prenatal period through early adolescence. Those of greatest magnitude (or observed most consistently) included obstetric complications, maternal illness during pregnancy (especially infections), other maternal physical factors, negative family emotional environment, psychopathology and psychotic symptoms, and cognitive and motor dysfunctions. Relatively less evidence has accumulated to implicate this diversity of exposures in AP, and many yet remain unexamined, with the most consistent or strongest evidence to date being for obstetric complications, psychopathology, cognitive indicators and motor dysfunction. Among the few investigations affording direct comparison between SSD and AP, larger effect sizes and a greater number of significant associations are commonly reported for SSD relative to AP.CONCLUSIONS: Shared risk factors for SSD and AP may include obstetric complications, childhood psychopathology, cognitive markers and motor dysfunction, but the capacity to distinguish common versus distinct risk factors/antecedents for SSD and AP is limited by the scant availability of prospective data for AP, and inconsistency in replication. Further studies considering both diagnoses concurrently are needed. Nonetheless, the prevalence of the risk factors/antecedents observed in cases and controls helps demarcate potential targets for preventative interventions for these disorders.
The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and Description of Psychosocial Components
Psychiatr Serv 2015; 66:680–690
Comprehensive coordinated specialty care programs for first-episode psychosis have been widely implemented in other countries but not in the United States. The National Institute of Mental Health's Recovery After an Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first-episode treatment programs designed for the U.S. health care system. This article describes the background, rationale, and nature of the intervention developed by the RAISE Early Treatment Program project-known as the NAVIGATE program-with a particular focus on its psychosocial components. NAVIGATE is a team-based, multicomponent treatment program designed to be implemented in routine mental health treatment settings and aimed at guiding people with a first episode of psychosis (and their families) toward psychological and functional health. The core services provided in the NAVIGATE program include the family education program (FEP), individual resiliency training (IRT), supported employment and education (SEE), and individualized medication treatment. NAVIGATE embraces a shared decision-making approach with a focus on strengths and resiliency and on collaboration with clients and family members in treatment planning and reviews. The NAVIGATE program has the potential to fill an important gap in the U.S. health care system by providing a comprehensive intervention specially designed to meet the unique treatment needs of persons recovering from a first episode of psychosis. A cluster-randomized controlled trial comparing NAVIGATE with usual community care has recently been completed.
Reprinted with permission from American Psychiatric Association Publishing.
Insight and Subjective Measures of Quality of Life in Chronic Schizophrenia
Schizophr Res Cogn 2015; 2:127–132
Lack of insight is a well-established phenomenon in schizophrenia, and has been associated with reduced rater-assessed functional performance but increased self-reported well-being in previous studies. The objective of this study was to examine factors that might influence insight (as assessed by the Insight and Treatment Attitudes Questionnaire [ITAQ] or PANSS item G12) and subjective quality-of-life (as assessed by Lehman QoL Interview [LQOLI]), using the large National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset. Uncooperativeness was assessed by PANSS item G8 (“Uncooperativeness”). In the analysis, we found significant moderating effects for insight on the relationships of subjective life satisfaction assessment to symptom severity (as assessed by CGI-S score), objective everyday functioning (as assessed by rater-administered Heinrichs-Carpenter Quality of Life scale), clinically rated uncooperativeness (as assessed by PANSS G8), and discontinuation of treatment for all causes (all p>0.05 for statistical interaction between insight and subject QoL). Patients with chronic schizophrenia who reported being “pleased” or “delighted” on LQOLI were found to have significantly lower neurocognitive reasoning performance and poorer insight (ITAQ total score). Our findings underscore the importance of reducing cognitive and insight impairments for both treatment compliance and improved functional outcomes.
From Adversity to Psychosis: Pathways and Mechanisms From Specific Adversities to Specific Symptoms
Soc Psychiatry Psychiatr Epidemiol 2014; 49:1011–1022
PURPOSE: Although there is considerable evidence that adversities in childhood such as social deprivation, sexual abuse, separation from parents, neglect and exposure to deviant parental communication are associated with psychosis in later life, most studies have considered broad diagnoses as outcomes. In this review we consider evidence for pathways between specific types of adversity and specific symptoms of psychosis.METHODS: We present theoretical arguments for expecting some degree of specificity (although by no means perfect specificity) between different kinds of adversity and different symptoms of psychosis. We review studies that have investigated social-environmental risk factors for thought disorder, auditory-verbal hallucinations and paranoid delusions, and consider how these risk factors may impact on specific psychological and biological mechanisms.RESULTS: Communication deviance in parents has been implicated in the development of thought disorder in offspring, childhood sexual abuse has been particularly implicated in auditory-verbal hallucinations, and attachment-disrupting events (e.g. neglect, being brought up in an institution) may have particular potency for the development of paranoid symptoms. Current research on psychological mechanisms underlying these symptoms suggests a number of symptom-specific mechanisms that may explain these associations.CONCLUSIONS: Few studies have considered symptoms, underlying mechanisms and different kinds of adversity at the same time. Future research along these lines will have the potential to elucidate the mechanisms that lead to severe mental illness, and may have considerable clinical implications.
Reprinted with permission from Springer-Verlag.
Biological Insights From 108 Schizophrenia-Associated Genetic Loci
Nature 2014; 511:421–427
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multistage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into etiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
Reprinted with permission from Nature Publishing Group.
New Options for the Treatment of Schizophrenia: A Clinical Review of the Three Most Recent Antipsychotic Drugs
Focus 2014; 12:127–135
This clinical review summarizes the pharmacological characteristics, efficacy, and tolerability of asenapine, iloperidone, and lurasidone, the most recently approved antipsychotics in the treatment of schizophrenia.
Newer agents have the task of distinguishing themselves for clinical use based on patient-relevant characteristics; some provide specialized features. The agents reviewed here are similar in overall clinical efficacy and tolerability, as well as being in a low risk for weight gain and metabolic syndrome, but are different in terms of formulation, schedule of administration, and particular side effects. Based on these distinguishing characteristics, we offer recommendations for the optimal clinical use of each drug.
Reprinted with permission from American Psychiatric Association Publishing.
