Racial Disparities Among Clinical High-Risk and First-Episode Psychosis Multisite Research Participants: A Systematic Review.

OBJECTIVE: The NIH has mandated equal representation of Black, Indigenous, and people of color (BIPOC) individuals in clinical research, but it is unclear whether such inclusion has been achieved in multisite research studies of individuals at clinical high risk for psychosis or with first-episode psychosis (FEP). An assessment of inclusion rates is important for understanding the social determinants of psychosis and psychosis risk that specifically affect BIPOC individuals. METHODS: The authors conducted a systematic review of the literature published between 1993 and 2022 of multisite research studies of clinical high risk for psychosis and FEP in North America to determine ethnoracial inclusion rates. Using an online systematic review tool, the authors checked 2,278 studies for eligibility. Twelve studies met all inclusion criteria. Data were extracted, and demographic characteristics, socioeconomic status, study design, and recruitment strategies used by each study were analyzed. RESULTS: Most (62%) of the participants in studies of clinical high risk for psychosis were White. Compared with national data, the demographic characteristics of individuals with clinical high risk were representative across most ethnoracial groups. Black participants (43%) made up the largest ethnoracial group in FEP studies and were overrepresented compared with their representation in the U.S. population. FEP studies were more likely to recruit participants from community mental health centers than were the studies of clinical high risk. CONCLUSIONS: Although these results suggest high representation of BIPOC individuals in psychosis research, opportunities exist for an improved focus on ethnoracial representation. The authors offer recommendations for practices that may increase ethnoracial diversity in future psychosis study samples.

Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial.

BACKGROUND: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). METHOD: In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150-600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. RESULTS: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (ß=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes. CONCLUSIONS: Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.

Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial.

INTRODUCTION: Mild cognitive impairment (MCI) is common in older adults and represents a high-risk group for progression to Alzheimer's disease (AD). Medication trials in MCI have generally failed, but new discoveries with brain plasticity in ageing have led to the study of cognitive training as a potential treatment to improve cognitive abilities. Computerised cognitive training (CCT) involves computerised cognitive exercises that target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity. METHODS AND ANALYSIS: In a two-site study (New York State Psychiatric Institute/Columbia University Medical Center and Duke University Medical Center), we will randomise 100 patients with MCI (Wechsler Memory Scale-III Logical Memory II score 0-11; Folstein Mini Mental State Examination ≥23) to home-based CCT (suite of exercises: memory, matching, spatial recognition, processing speed) or a home-based active control condition (computerised crossword puzzle training (CPT)) with 12 weeks of intensive training followed by regular booster sessions up to 78 weeks. All patients will receive standard neuropsychological and functional assessments in clinic as well as structural/functional brain MRI scans at study entry and endpoint. We will test if CCT, versus CPT, leads to improved cognitive functioning, transfers to functional ability and tasks of everyday life and impacts hippocampal volume changes and changes in the default mode network of the brain measured by resting-state functional MRI. ETHICS AND DISSEMINATION: The study will be conducted following ethics approval and written informed consent will be obtained from all subjects. Study results will be disseminated via publication, clinicaltrials.gov, media and conference presentations. This will be the first controlled long-term trial to evaluate the effects of home-based CCT versus computerised CPT on cognitive abilities and functional measures and neural outcomes as determined by MRI indices in patients with MCI. Positive results from trial may support further development of home-based CCT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier (NCT03205709).