Suicide Reduction in Schizophrenia via Exercise (SUnRISE): study protocol for a multi-site, single-blind, randomized clinical trial of aerobic exercise for suicide risk reduction in individuals with schizophrenia.

BACKGROUND: Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5-10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk. METHODS: Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will include suicide risk (Columbia Suicide Severity Rating Scale, C-SSRS) and aerobic fitness (VO2max), along with additional measures of suicide risk, mood, emotion regulation, sleep, cognition, and physical activity, with assessments completed at baseline and after 6 and 12 weeks of interventions. DISCUSSION: It is hypothesized that AE will reduce suicide risk among individuals with SZ. This study may offer support for a more efficacious treatment method for this population in addition to the pre-existing pharmacological and psychotherapeutic treatment regimens. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03270098 . Registered on September 1, 2017.

Correlates of loneliness among persons with psychotic disorders.

INTRODUCTION: Persons diagnosed with schizophrenia spectrum disorders (SSDs) often experience pervasive feelings of loneliness, which are considered a significant barrier to treatment and recovery. AIM: As impaired social cognition may contribute to increased loneliness and less skillful social interactions, this study examines the relationships between loneliness and measures of social cognition and functional outcome from the Social Cognition Psychometric Evaluation (SCOPE) study. METHODS: This study evaluated the relationship between loneliness, social cognitive ability, and social functioning in the context of a large-scale psychometric investigation. We also explored the associations of select demographic characteristics and clinical variables on the endorsement of loneliness in persons diagnosed with a psychotic disorder. RESULTS: Seventy-four stable outpatients with SSDs and 58 healthy controls completed the UCLA Loneliness Scale in addition to the standard SCOPE battery. Our findings support prior research indicating persons diagnosed with a psychotic disorder experience greater levels of loneliness than normative groups. However, the results also indicate that self-reported loneliness is not associated with social cognitive abilities or functional outcome in psychosis. Regression analyses indicate that roughly half the variance in loneliness endorsed by persons with SSDs is accounted for by clinical variables, with loneliness most strongly associated with guilt and self-esteem. CONCLUSION: These findings suggest that treatments aiming to reduce perceived social isolation in psychosis should incorporate techniques to bolster selfesteem, reduce guilt, and improve depressive symptoms.

Improving Cognition via Exercise (ICE): Study Protocol for a Multi-Site, Parallel-Group, Single-Blind, Randomized Clinical Trial Examining the Efficacy of Aerobic Exercise to Improve Neurocognition, Daily Functioning, and Biomarkers of Cognitive Change in Individuals with Schizophrenia.

Individuals with schizophrenia (SZ) display cognitive deficits that have been identified as major determinants of poor functioning and disability, representing a serious public health concern and an important target for interventions. At present, available treatments offer only minimal to moderate benefits to ameliorate cognitive deficits. Thus, there remains an urgent need to identify novel interventions to improve cognition in people with SZ. Emerging evidence from animal and basic human research suggests aerobic exercise training (AE) has beneficial effects on cognition. Preliminary findings suggest that AE is efficacious in improving cognitive functioning in SZ, however the extant studies have been limited by small samples, a dearth of information on biologically-relevant covariates, and limited information on impact on daily functioning. Additionally, while AE-related cognitive benefits have been linked to Brain-Derived Neurotrophic Factor (BDNF) upregulation, this putative mechanism needs confirmation. The present report describes a study protocol designed to address these limitations-we review and summarize the current literature on treatment of cognitive deficits in SZ, state the rationale for employing AE to target these deficits, and describe the current protocol-a multi-site, single-blind, randomized clinical trial aiming to recruit 200 community-dwelling individuals with SZ. Participants are randomized to one of two 12-week interventions: AE using active-play video games (i.e., Xbox Kinect) and traditional cardiovascular exercise equipment or a stretching-and-toning (ST) control intervention. Participants undergo assessments of aerobic fitness, cognition, and daily functioning, as well as BDNF and other biomarkers of cognitive change, at baseline and after 6-and 12-weeks.

Alternative pharmacologic targets for the treatment of schizophrenia: results from phase I and II trials.

PURPOSE OF REVIEW: The current article provides a brief review of the clinical efficacy and safety outcomes from selected phase I and II clinical trials of compounds in development acting on targets beyond the dopamine D2 receptor in patients with schizophrenia. RECENT FINDINGS: A number of experimental pharmacological targets have been studied in clinical trials. Among those, glutamatergic and nicotinergic pathways have received most attention. Glycine transporter 1 inhibitors used adjunctively with antipsychotics suggest efficacy for negative symptoms of schizophrenia. Adjunctive alpha7 nicotinic acetylcholine receptor agonists and minocycline may improve negative symptoms and cognitive deficits. Adjunctive oxytocin may benefit psychotic symptoms and social cognitive deficits. Adjunctive erythropoietin may improve cognitive function. SUMMARY: Experimental therapeutic research for schizophrenia is rapidly expanding and a number of compounds with novel mechanisms of action are demonstrating encouraging evidence for efficacy across a range of symptoms. However, much work still needs to be conducted before these new agents can be considered for routine clinical treatment. In particular, further assessment of efficacy and longer term safety and tolerability monitoring are required.

Heterogeneity of auditory verbal working memory in schizophrenia.

The heterogeneity of schizophrenia remains an obstacle for understanding its pathophysiology. Studies using a tone discrimination screening test to classify patients have found evidence for 2 subgroups having either a specific deficit in verbal working memory (WM) or deficits in both verbal and nonverbal memory. This study aimed to (a) replicate in larger samples differences between these subgroups in auditory verbal WM; (b) evaluate their performance on tests of explicit memory and sustained attention; (c) determine the relation of verbal WM deficits to auditory hallucinations and other symptoms; and (d) examine medication effects. The verbal WM and tone discrimination performance did not differ between medicated (n = 45) and unmedicated (n = 38) patients. Patients with schizophrenia who passed the tone screening test (discriminators; n = 60) were compared with those who did not (nondiscriminators; n = 23) and healthy controls (n = 47). The discriminator subgroup showed poorer verbal WM than did controls and a deficit in verbal but not visual memory on the Wechsler Memory Scale-Revised (Wechsler, 1987), whereas the nondiscriminator subgroup showed overall poorer performance on both verbal and nonverbal tests and a marked deficit in sustained attention. Verbal WM deficits in discriminators were correlated with auditory hallucinations but not with negative symptoms. The results are consistent with a verbal memory deficit in a subgroup of schizophrenia having intact auditory perception, which may stem from dysfunction of language-related cortical regions, and a more generalized cognitive deficit in a subgroup having auditory perceptual and attentional dysfunction.

Current source density (CSD) old/new effects during recognition memory for words and faces in schizophrenia and in healthy adults.

We previously reported a preserved 'old-new effect' (enhanced parietal positivity 300-800 ms following correctly-recognized repeated words) in schizophrenia over mid-parietal sites using 31-channel nose-referenced event-related potentials (ERP) and reference-free current source densities (CSD). However, patients showed poorer word recognition memory and reduced left lateral-parietal P3 sources. The present study investigated whether these abnormalities are specific to words. High-density ERPs (67 channels) were recorded from 57 schizophrenic (24 females) and 44 healthy (26 females) right-handed adults during parallel visual continuous recognition memory tasks using common words or unknown faces. To identify and measure neuronal generator patterns underlying ERPs, unrestricted Varimax-PCA was performed using CSD estimates (spherical spline surface Laplacian). Two late source factors peaking at 442 ms (lateral parietal maximum) and 723 ms (centroparietal maximum) accounted for most of the variance between 250 and 850 ms. Poorer (76.6+/-20.0% vs. 85.7+/-12.4% correct) and slower (824+/-170 vs. 755+/-147 ms) performance in patients was accompanied by reduced stimulus-locked parietal sources. However, both controls and patients showed mid-frontal (442 ms) and left parietal (723 ms) old/new effects in both tasks. Whereas mid-frontal old/new effects were comparable across groups and tasks, later left parietal old/new effects were markedly reduced in patients over lateral temporoparietal but not mid-parietal sites, particularly for words, implicating impaired phonological processing. In agreement with prior results, ERP correlates of recognition memory deficits in schizophrenia suggest functional impairments of lateral posterior cortex (stimulus representation) associated with conscious recollection. This deficit was more pronounced for common words despite a greater difficulty to recall unknown faces, indicating that it is not due to a generalized cognitive deficit in schizophrenia.