A Brief Resilience-Enhancing Intervention and Loneliness in At-Risk Young Adults: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial assesses whether a behavioral intervention focused on resilience is associated with feelings of loneliness among young adults.

The impact of early intervention for first episode psychosis on cognitive functioning.

IMPORTANCE: Impaired cognitive functioning is a core characteristic of schizophrenia, present from the onset of the illness and relatively stable thereafter. Despite evidence supporting the impact of early intervention services (EIS) on improving symptoms and functioning in first episode psychosis (FEP), controlled research has not examined its impact on cognitive functioning. OBJECTIVE: To evaluate the longitudinal course of cognitive functioning in FEP patients participating in a large, controlled study comparing EIS with usual services. METHODS: A total of 404 persons ages 15-40 years old with non-affective FEP participated in the Recovery After Initial Schizophrenia-Early Treatment Program. A cluster randomized controlled trial was conducted with 34 community mental health treatment centers across the U.S. randomized to provide either an EIS program (NAVIGATE) or usual Community Care (CC) to FEP patients for 2 years. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline and 1- and 2-years later. RESULTS: Older participants (≥20 years old) in both treatment groups improved on all BACS tests. Younger participants (15-19) in NAVIGATE improved significantly more on Digit Sequencing (working memory) than those in CC, whereas both groups improved on most of the other BACS tests. Improvements in cognitive functioning occurred mostly over the first year and were correlated with reductions in symptom severity. DISCUSSION: EIS do not improve cognitive functioning more than usual care for older FEP patients but may improve working memory in younger FEP patients. Interventions targeting cognition may be required to enhance cognitive functioning in most FEP patients.

A Pilot Study of Adjunctive Group Therapy to Enhance Coping With Cognitive Challenges and Support Cognitive Health After Electroconvulsive Therapy.

OBJECTIVES: Concerns about the cognitive adverse effects of electroconvulsive therapy (ECT) are common among recipients of the treatment despite its relatively small adverse effects on cognitive functioning. Interventions aimed at remediating or improving coping with cognitive adverse effects of ECT have not been developed. The Enhancing Cognitive Domains after ECT (ENCODE) program is a new group intervention aimed at teaching self-management strategies to cope with the cognitive challenges and associated anxiety that often accompanies ECT. METHODS: This pilot study used a pretest-posttest design to examine the feasibility and clinical utility of delivering ENCODE to 20 adults who had received ECT in a hospital-based ECT program. RESULTS: The program was found to be both feasible and acceptable as indicated by the attainment of recruitment targets, high rates of attendance (85% of participants attended at least 5 of the 6 group sessions), and high participant satisfaction ratings (88% reported that ENCODE helped or helped very much to manage their cognitive challenges). The clinical utility of the program was suggested by reductions in depressive symptom severity and subjective memory complaints. Nonsignificant improvements were observed in global cognitive function and cognitive self-efficacy. CONCLUSIONS: This study provides preliminary evidence for the feasibility and clinical utility of ENCODE based on program demand, strong participant satisfaction, and postgroup reductions in distress and subjective memory complaints.

Body image and Black African women: A comparative study of Kenya and Nigeria.

Very few cross-national studies on body image focus on Black African women. In this study, a comparative analytical approach and sociocultural theory framework was utilized in examining measures of body image among 209 Kenyan and Nigerian women aged 18-69 (M = 34.4, SD = 7.81). We examined both weight-related and non-weight-related aspects of appearance, including hair texture, skin tone, and other racialized features. The regional samples were compared on scores of internalized Eurocentric beauty ideals, skin color satisfaction, objectified body consciousness, racialized body image satisfaction, and other demographic metrics. Kenyan and Nigerian women showed differences across multiple body image measures. Nigerian women showed thinner body ideals compared to Kenyan women and also endorsed higher skin color satisfaction, racialized body dissatisfaction, and internalized Eurocentric beauty idealization. Kenyan women showed higher levels of objectified body consciousness. An indirect effect of nationality was observed with internalized Eurocentric beauty ideals mediating differences in racialized body dissatisfaction and objectified body shame. Attention to regional variation in appearance satisfaction may deepen understandings of the particular sociocultural influences impacting body image among populations of Black African women.

Development of a transdiagnostic, resilience-focused intervention for at-risk adolescents.

BACKGROUND: Environmental adversity and subclinical symptoms of psychopathology in adolescents increase their risk for developing a future psychiatric disorder, yet interventions that may prevent poor outcomes in these vulnerable adolescents are not widely available. AIMS: To develop and test the feasibility and acceptability of a prevention-focused program to enhance resilience in high-risk adolescents. METHOD: Adolescents with subclinical psychopathology living in a predominantly low-income, Latinx immigrant community were identified during pediatrician visits. A group-based intervention focused on teaching emotion recognition and regulation skills was piloted in three cohorts of adolescents (n = 11, 10, and 7, respectively), using a single arm design. The second and third iterations included sessions with parents. RESULTS: Eighty-eight percent of participants completed the program, which was rated as beneficial. Also, from baseline to end of treatment, there was a significant decrease in subclinical symptoms and a significant increase in the adolescents' positive social attribution bias (all p < 0.05). CONCLUSIONS: A resilience-focused intervention administered to high-risk adolescents was found to be feasible and acceptable to participants. Future work is needed to determine whether such a program can reduce the incidence of negative outcomes, such as the development of psychiatric disorders and related disability, in this population.

Efficacy of a transdiagnostic, prevention-focused program for at-risk young adults: a waitlist-controlled trial.

BACKGROUND: Prevention programs that are 'transdiagnostic' may be more cost-effective and beneficial, in terms of reducing levels of psychopathology in the general population, than those focused on a specific disorder. This randomized controlled study evaluated the efficacy of one such intervention program called Resilience Training (RT). METHODS: College students who reported mildly elevated depressive or subclinical psychotic symptoms ('psychotic experiences' (PEs)) (n = 107) were randomized to receiving RT (n = 54) or to a waitlist control condition (n = 53). RT consists of a four-session intervention focused on improving resilience through the acquisition of mindfulness, self-compassion, and mentalization skills. Measures of symptoms and these resilience-enhancing skills were collected before and after the 4-week RT/waitlist period, with a follow-up assessment 12-months later. RESULTS: Compared to the waitlist control group, RT participants reported significantly greater reductions in PEs, distress associated with PEs, depression, and anxiety, as well as significantly greater improvements in resilience, mindfulness, self-compassion, and positive affect, following the 4-week RT/waitlist period (all p < 0.03). Moreover, improvements in resilience-promoting skills were significantly correlated with symptom reductions (all p < 0.05). Lastly, the RT-related reductions in PEs and associated distress were maintained at the 12-month follow-up assessment. CONCLUSIONS: RT is a brief, group-based intervention associated with improved resilience and reduced symptoms of psychopathology, with sustained effects on PEs, in transdiagnostically at-risk young adults. Follow-up studies can further assess the efficacy of RT relative to other interventions and test whether it can reduce the likelihood of developing a serious mental illness.

"We don't get a chance to prove who we really are": A qualitative inquiry of workplace prejudice and discrimination among Black adults with serious mental illness.

OBJECTIVE: Studies focused on prejudice and discrimination have traditionally explored the impact of one kind of prejudicial experience (e.g., race, gender, criminal history) within a particular context and thus, there is weak base of understanding about the experiences of individuals who may contend with concurrent prejudicial and/or discriminatory experiences across multiple characteristics. In this study, our aim was to better understand the prejudicial and/or discriminatory work experiences of Black adults with serious mental illness (SMI). Specifically, we highlight instances where individuals endorse the salience of multiple sources of prejudice and discrimination during a given workplace incident. METHOD: Using a semistructured interview guide and a grounded theory approach, we interviewed 24 Black adults with SMI recruited from two clubhouses in the Boston metropolitan area. To validate findings, we also conducted follow-up focus groups with participants (n = 9) at each recruitment site. RESULTS: We identified 19 personal attributes/characteristics contributing to the prejudicial/discriminatory experiences of Black adults with SMI in the context of work. We also found that respondents would organize these prejudicial/discriminatory experiences in clusters whereby two or more characteristics were viewed as the reasons for prejudice and discrimination during a given workplace incident. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Black adults with SMI contend with a range of prejudicial and discriminatory experiences, often experienced simultaneously, highlighting the importance of an intersectional framework in research designs and/or clinical interventions addressing the needs of this population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Efficacy and acceptability of psychosocial interventions in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence.

Psychosocial interventions are recommended in schizophrenia and first-episode psychosis/early psychosis (EP). Nevertheless, literature is heterogeneous and often contradictory. We conducted an umbrella review of (network) meta-analyses of randomized controlled trials (RCTs) comparing psychosocial interventions vs treatment as usual (TAU)/active interventions(ACTIVE)/MIXED controls. Primary outcome was total symptoms (TS); secondary outcomes were positive/negative/depressive symptoms (PS/NS/DS), cognition, functioning, relapse, hospitalization, quality of life (QoL), treatment discontinuation. Standardized mean difference (SMD)/odds ratio (OR)/risk ratio (RR) vs TAU/ACTIVE/MIXED were summarized at end-of-treatment (EoT)/follow-up (FU). Quality was rated as high/medium/low (AMSTAR-PLUS). Eighty-three meta-analyses were included (RCTs = 1246; n = 84,925). Against TAU, regarding TS, Early Intervention Services (EIS) were superior EoT/FU in EP (SMD = -0.32/-0.21), cognitive behavioral therapy (CBT) in schizophrenia EoT/FU (SMD = -0.38/-0.19). Regarding secondary outcomes, in EP, EIS were superior for all outcomes EoT except cognition, and at FU for PS/NS/QoL, specific family interventions (FI-s) prevented relapse EoT; in schizophrenia, superiority emerged EoT for CBT for PS/NS/relapse/functioning/QoL; psychoeducation (EDU)/any FI for relapse; cognitive remediation therapy (CRT) for cognition/functioning; and hallucination-focused integrative treatment for PS. Against ACTIVE, in EP, mixed family interventions (FI-m) were superior at FU regarding TS (SMD = -0.61) and for functioning/relapse among secondary outcomes. In schizophrenia, regarding TS, mindfulness and social skills training (SST) were superior EoT, CBT at FU; regarding secondary outcomes superiority emerged at EoT for computerized cognitive drill-and-practice training for PS/DS, CRT for cognition/functioning, EDU for relapse, individual placement and support (IPS) for employment; and at FU CBT for PS/NS. Against MIXED, in schizophrenia, CRT/EDU were superior for TS EoT (d = -0.14/SMD = -0.33), CRT regarding secondary outcomes EoT for DS/social functioning, both EoT/FU for NS/cognition/global functioning; compensatory cognitive interventions for PS/functioning EoT/FU and NS EoT; CBT for PS at FU, and EDU/SST for relapse EoT. In conclusion, mental health services should consider prioritizing EIS/any FI in EP and CBT/CRT/any FI/IPS for schizophrenia, but other interventions may be helpful for specific outcomes.

The interrelationships of motivation, positive symptoms, stigma, and role functioning in early psychosis.

AIM: Avolition, or the lack of motivation, has consistently been shown to be a significant predictor of poor psychosocial outcome, with decreased overall motivation as the single strongest predictor of poor work or school outcome in first episode psychosis. This study aimed to better understand the ways in which motivation impacts work and school functioning. This study first examined the factors related to motivation in people recovering from a recent onset of psychosis, then explored the unique interrelationships between positive symptoms, stigma, and motivation and how they influence role functioning. METHODS: A total of 40 participants with early psychosis were recruited for this cross-sectional design study; with a mean of 14.5 months of treatment prior to study assessment. RESULTS: Neither experienced nor internalized stigma were related to motivation in this sample, but internalized stigma was related to work and school functioning. Positive symptoms were significantly inversely related to both work and school functioning and motivation, with mediation analyses showing that motivation significantly mediates the relationship between positive symptoms and role functioning. CONCLUSION: This relationship may shed light on the link between motivational deficits and work and school outcomes early in the course of psychosis, an area of critical importance for early intervention.

A randomized controlled trial of exercise on augmenting the effects of cognitive remediation in persons with severe mental illness.

BACKGROUND: Preliminary evidence suggests that aerobic exercise may augment the effects of cognitive remediation on improving cognitive functioning in severe mental illness. It has also been hypothesized that increases in cognitive functioning associated with adding exercise are mediated by increases in brain derived neurotrophic factor (BDNF). However, rigorous controlled trials are lacking. METHODS: A randomized controlled trial was conducted to explore whether adding a 30-h aerobic exercise program over 10 weeks to an equally intensive cognitive remediation program (CR + E) improved cognitive functioning more than cognitive remediation alone (CR-Only). Thirty-four participants with schizophrenia or bipolar disorder were randomly assigned to CR + E or CR-Only, and cognitive functioning was assessed at baseline and post-treatment. Total and mature BDNF were measured in blood serum at baseline, Week-5 pre- and post-exercise, and Week-10 pre- and post-exercise. RESULTS: Participants in both conditions had high levels of engagement in the interventions and improved significantly in cognitive functioning, but did not differ in amount of cognitive change. The groups also did not differ in changes in BDNF from pre-to post-exercise at Weeks 5 or 10, nor in resting BDNF levels. Exploratory analyses indicated that higher body mass index (BMI) significantly predicted attenuated improvement in cognitive functioning for both groups. DISCUSSION: Exercise did not augment the effects of cognitive remediation in persons with severe mental illness, possibly because the cognitive remediation program resulted in strong gains in cognitive functioning. Moderate aerobic exercise does not appear to reliably increase BDNF levels in persons with severe mental illness. CLINICALTRIALS. GOV IDENTIFIER: NCT02326389.

Prevalence and correlates of PTSD in first episode psychosis: Findings from the RAISE-ETP study.

Posttraumatic stress disorder (PTSD) in young individuals is associated with an increased risk to develop psychosis or mania, and both trauma and PTSD rates are elevated in people with schizophrenia and other severe mental illnesses. However, less research has examined PTSD in people who have recently developed a first episode of psychosis (FEP). The present study is a secondary analysis of the baseline data collected for the National Institute of Mental Health Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study to examine the rates of trauma and PTSD, and to explore the demographic and clinical correlates of PTSD in a representative sample of 404 persons with an FEP. Approximately 80% of the study sample reported experiencing at least one traumatic event during their lives, with females more likely to report childhood sexual abuse and spousal abuse than males. A total of 20 participants (5.0%) met criteria for a lifetime diagnosis of PTSD, while another 15 participants (3.7%) met subthreshold diagnostic criteria for PTSD. Significant correlations were found between lifetime PTSD and the Calgary Depression Scale, the Mental Health Recovery Measure, the Stigma Scale, and duration of untreated psychosis, with higher scores on each variable associated with a diagnosis of PTSD. The association between PTSD and more severe depression, as well as lower perceptions of personal recovery, suggest that PTSD may be an important target for treatment programs for persons recovering from an FEP. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

"I Honestly Would Not Have Known What to Do": An Exploratory Study of Perspectives on Client Suicide Among Vocational Rehabilitation Support Staff.

Despite the high prevalence of suicide both overall and among people with disabilities in particular, little research has explored suicide in the context of the vocational rehabilitation (VR) system or in counseling support staff in general. We analyzed the responses of 14 VR support staff who responded to an open-ended qualitative prompt regarding their experiences with suicide training and competency. Key themes included a perceived lack of and desire for more training regarding suicide, seeking and receiving suicide training outside of VR, and a perceived lack of resources for working with suicidal clients. Responses also underscored the heavy emotional impact of working with these clients, especially when one feels unprepared to do so. These results suggest that it is important to provide VR support staff with resources and training for addressing suicide in their client populations.

Cognitive functioning as a predictor of response to comprehensive cognitive remediation.

Cognitive remediation is aimed at reducing cognitive impairments in severe mental illnesses such as schizophrenia, but little is known about whether severity of cognitive impairment predicts benefit from this intervention. To address this question, this study aggregated data from five randomized controlled trials (N = 300) of a standardized comprehensive, multimodal outpatient cognitive remediation program, the Thinking Skills for Work program, and evaluated whether baseline level of cognitive impairment differentially predicted improvement in cognitive functioning following cognitive remediation vs. usual services. Using standardized scores of neuropsychological functioning to designate "low average," "moderate," and "severe" levels of cognitive impairment, participants with greater cognitive impairment were found to benefit differentially more from cognitive remediation than usual services compared to less cognitively impaired participants. The findings were unaffected by statistically controlling for participant demographic and clinical characteristics. The findings suggest that individuals with the greatest cognitive impairment, for whom cognitive remediation was developed, are also most likely to benefit from this intervention.

Disclosure of mental illness to prospective employers: Clinical, psychosocial, and work correlates in persons receiving supported employment.

Deciding whether to disclose one's psychiatric disorder to a prospective employer is a complex decision for people with severe mental illness seeking to return to work, with potential advantages and disadvantages. The present study examined the rates, patterns, and correlates of disclosure in 51 participants (74.5% schizophrenia or schizoaffective disorder) receiving high fidelity Individual Placement Support (IPS) who obtained competitive work over a two-year study period. Most participants (64.7%) disclosed their psychiatric disorder in their first job, and there was a tendency for those with multiple jobs who did not disclose initially to shift to disclosure in subsequent jobs. Participants who disclosed for their first job had worse baseline cognitive scores on the Positive and Negative Syndrome Scale (PANSS), lower self-esteem, and poorer psychosocial functioning than those who did not disclose. However, participants who disclosed to their first employer were more likely to obtain jobs that matched their interests, and worked significantly longer than those who did not disclose (32.55 vs. 12.50 weeks, respectively). The findings suggest that individuals receiving supported employment who disclose their mental illness to prospective employers may have better work outcomes.

Family burden predicts functional outcome in the early course of schizophrenia beyond psychiatric symptoms and baseline functioning.

The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = -0.321, p = .04, and one-year time point, r = - 0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = -0.390, p = .012, and at the one-year time point, r = -0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome.

Development and validation of the client engagement and service use scale: A pilot study.

Specialized treatment for first episode psychosis offers clients a menu of services coordinated within a specialized treatment team. To enhance the impact of these services, promoting engagement and preventing early treatment drop-out is critical. However, engagement is poorly tracked and typically quantified through proxy variables such as session attendance, medication adherence, or working alliance. The aim of this study is to introduce and pilot a new measure of engagement for first episode psychosis coordinated specialty care, the Client Engagement and Service Use Scale (CENSUS). The CENSUS was evaluated for reliability and validated against the Service Engagement Scale and an appointment count for a small sample (N = 10) of first episode clients. The measure was also evaluated for acceptability by a consumer advocacy group. Clinicians achieved high inter-rater reliability after minimal training. CENSUS items demonstrated medium to large correlations with other measures of engagement. Feedback from the consumer group emphasized that clinicians should ask questions in a way that is nonjudgmental and successfully elicits authentic client feedback about their service preferences. This pilot study yielded preliminary evidence of reliability and validity, suggesting that the CENSUS is a useful and novel tool for tracking and differentiating degrees of client engagement across multiple intervention components and for facilitating structured discussions regarding clients' service utilization and preferences.

What does the Managing Emotions branch of the MSCEIT add to the MATRICS consensus cognitive battery?

The Managing Emotions branch of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT-ME) was included within the MATRICS Consensus Cognitive Battery (MCCB) as the measure of social cognition, although limited research has examined its associations with psychosocial functioning in people with schizophrenia or other severe mental illnesses. This secondary analysis with 107 participants examined what the MSCEIT-ME contributes to our understanding of functioning in this population, and whether it uniquely predicts psychosocial functioning after controlling for performance on the other MCCB tests and negative symptoms. Performance on the MSCEIT-ME was significantly correlated with all three MCCP factors (processing speed, attention/working memory, learning) within schizophrenia-schizoaffective disorder, bipolar disorder, and other mixed diagnoses groups. Better performance on MSCEIT-ME was associated with better psychosocial functioning on the Quality of Life Scale (QLS) in the schizophrenia-schizoaffective disorder group, but not in the bipolar or other mixed diagnoses groups. In addition, in the schizophrenia-schizoaffective disorder group, after controlling for demographic characteristics in stepwise multiple regression analyses, MSCEIT-ME was the only significant predictor of the QLS total score and the QLS interpersonal relations and intrapsychic foundations subscales, with none of the MCCB factors entering any of the regression models. The MSCEIT-ME may reflect a unique aspect of social cognition that is related to impaired psychosocial functioning in schizophrenia and is not tapped by the other cognitive tests on the MCCB. Further research on the MSCEIT-ME could provide unique insights into the social functioning problems in schizophrenia.

Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia.

CONTEXT: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. MAIN OUTCOME MEASURE: ICM volume change scores were adjusted for the change in the HCs. RESULTS: ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). CONCLUSIONS: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.

Cardiorespiratory endurance, muscular flexibility and strength in first-episode schizophrenia patients: use of a standardized fitness assessment.

AIM: This study determined the fitness status and examined potential correlates of fitness in first-episode schizophrenia patients using a standardized fitness test protocol. METHODS: A certified fitness instructor administered the Young Men's Christian Association (YMCA) fitness test to 70 recent-onset schizophrenia participants within 3 months of entry into the study. RESULTS: Percentile ranks of scores on muscular strength and endurance, muscular flexibility and cardiorespiratory fitness in our sample were all below the 50th percentile when compared with national norms in the United States. As expected, patients with a higher body mass index and those who smoked had poorer cardiorespiratory fitness. A non-significant trend indicated that patients with a longer duration of illness had worse cardiorespiratory fitness. Exposure to antipsychotic medication was unrelated to cardiorespiratory fitness. CONCLUSION: Results suggest that physical fitness is impaired and might decline over time in first-episode schizophrenia patients, but this needs to be confirmed in a longitudinal study.

Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory.

CONTEXT: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. MAIN OUTCOME MEASURE: WM volume change scores. RESULTS: WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. CONCLUSIONS: The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.