Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study.

BACKGROUND: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. METHODS: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2. RESULTS: After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups. CONCLUSIONS: rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052122).

Computational modeling and minimization of unintended neuronal excitation in a LIFU stimulation.

The neuromodulation effect of low-intensity focused ultrasound (LIFU) is highly target-specific. Unintended off-target neuronal excitation can be elicited when the beam focusing accuracy and resolution are limited, whereas the resulted side effect has not been evaluated quantitatively. There is also a lack of methods addressing the minimization of such side effects. Therefore, this work introduces a computational model of unintended neuronal excitation during LIFU neuromodulation, which evaluates the off-target activation area (OTAA) by integrating an ultrasound field model with the neuronal spiking model. In addition, a phased array beam focusing scheme called constrained optimal resolution beamforming (CORB) is proposed to minimize the off-target neuronal excitation area while ensuring effective stimulation in the target brain region. A lower bound of the OTAA is analytically approximated in a simplified homogeneous medium, which could guide the selection of transducer parameters such as aperture size and operating frequency. Simulations in a human head model using three transducer setups show that CORB markedly reduces the OTAA compared with two benchmark beam focusing methods. The high neuromodulation resolution demonstrates the capability of LIFU to effectively limit the side effects during neuromodulation, allowing future clinical applications such as treatment of neuropsychiatric disorders.

Digital Medicine System in Veterans With Severe Mental Illness: Feasibility and Acceptability Study.

BACKGROUND: Suboptimal medication adherence is a significant problem for patients with serious mental illness. Measuring medication adherence through subjective and objective measures can be challenging, time-consuming, and inaccurate. OBJECTIVE: The primary purpose of this feasibility and acceptability study was to evaluate the impact of a digital medicine system (DMS) among Veterans (patients) with serious mental illness as compared with treatment as usual (TAU) on medication adherence. METHODS: This open-label, 2-site, provider-randomized trial assessed aripiprazole refill adherence in Veterans with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. We randomized 26 providers such that their patients either received TAU or DMS for a period of 90 days. Semistructured interviews with patients and providers were used to examine the feasibility and acceptability of using the DMS. RESULTS: We enrolled 46 patients across 2 Veterans Health Administration sites: 21 (46%) in DMS and 25 (54%) in TAU. There was no difference in the proportion of days covered by medication refill over 3 and 6 months (0.82, SD 0.24 and 0.75, SD 0.26 in DMS vs 0.86, SD 0.19 and 0.82, SD 0.21 in TAU, respectively). The DMS arm had 0.85 (SD 0.20) proportion of days covered during the period they were engaged with the DMS (mean 144, SD 100 days). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient findings described the positive impact of the DMS on medication adherence, challenges with the DMS patch connectivity and skin irritation, and challenges with the DMS app that affected overall use. Providers described an overall interest in using a DMS as an objective measure to support medication adherence in their patients. However, providers described challenges with the DMS dashboard and integrating DMS data into their workflow, which decreased the usability of the DMS for providers. CONCLUSIONS: There was no observed difference in refill rates. Among those who engaged in the DMS arm, the proportion of days covered by refills were relatively high (mean 0.85, SD 0.20). The qualitative analyses highlighted areas for further refinement of the DMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03881449; https://clinicaltrials.gov/ct2/show/NCT03881449.

Personalizing repetitive transcranial magnetic stimulation for precision depression treatment based on functional brain network controllability and optimal control analysis.

Brain neuromodulation effectively treats neurological diseases and psychiatric disorders such as Depression. However, due to patient heterogeneity, neuromodulation treatment outcomes are often highly variable, requiring patient-specific stimulation protocols throughout the recovery stages to optimize treatment outcomes. Therefore, it is critical to personalize neuromodulation protocol to optimize the patient-specific stimulation targets and parameters by accommodating inherent interpatient variability and intersession alteration during treatments. The study aims to develop a personalized repetitive transcranial magnetic stimulation (rTMS) protocol and evaluate its feasibility in optimizing the treatment efficiency using an existing dataset from an antidepressant experimental imaging study in depression. The personalization of the rTMS treatment protocol was achieved by personalizing both stimulation targets and parameters via a novel approach integrating the functional brain network controllability analysis and optimal control analysis. First, the functional brain network controllability analysis was performed to identify the optimal rTMS stimulation target from the effective connectivity network constructed from patient-specific resting-state functional magnetic resonance imaging data. The optimal control algorithm was then applied to optimize the rTMS stimulation parameters based on the optimized target. The performance of the proposed personalized rTMS technique was evaluated using datasets collected from a longitudinal antidepressant experimental imaging study in depression (n = 20). Simulation models demonstrated that the proposed personalized rTMS protocol outperformed the standard rTMS treatment by efficiently steering a depressive resting brain state to a healthy resting brain state, indicated by the significantly less control energy needed and higher model fitting accuracy achieved. The node with the maximum average controllability of each patient was designated as the optimal target region for the personalized rTMS protocol. Our results also demonstrated the theoretical feasibility of achieving comparable neuromodulation efficacy by stimulating a single node compared to stimulating multiple driver nodes. The findings support the feasibility of developing personalized neuromodulation protocols to more efficiently treat depression and other neurological diseases.

Effects of escitalopram therapy on functional brain controllability in major depressive disorder.

Antidepressant drugs are the mainstay of treatment for patients with major depressive disorders (MDD). Given the critical role of the underlying neural control mechanism in the physiopathology of depression, this study aims to investigate the effects of escitalopram, a type of antidepressant drug, on the changes of functional brain controllability throughout the escitalopram treatment for MDD. We collected resting-state functional magnetic resonance imaging data from 20 unmedicated major depressive patients at baseline (visit 1, pre-treatment), one week (visit 2, 1-week after the onset of the treatment) and six weeks (visit 3, after the 6-week escitalopram treatment). Our results revealed that the global average and modal controllability of MDD patients were significantly larger and smaller, respectively, compared to healthy subjects (P < 0.01). Furthermore, the modal controllability rank of the frontoparietal network in depression patients was also significantly smaller than the healthy subjects (P < 0.01). However, throughout the escitalopram treatment, the global average and modal controllability, and the controllability of the default mode network and frontoparietal network of MDD patients were consistently changed to the healthy subjects' level. Our results also showed that the changes of global average and modal controllability measures can predict the improvements of clinical scores of the MDD patients as the escitalopram treatment advanced (P < 0.05). In conclusion, this study reveals promising brain controllability-based biomarkers to mechanistically understand and predict the effects of the escitalopram treatment for depression and maybe extended to predict and understand the effects of other interventions for other neurological and psychiatric diseases.

Determinants of High Psychiatric Utilization at a Large Urban Safety-Net Hospital.

Research indicates that high utilizers of the health care system are more likely to have mental illness, to be from socially disadvantaged groups, and to have limited access to community-based services. In this retrospective study, three definitions of high utilization were examined: (1) across time: non-high utilization versus high-utilization, (2) single year versus multi-year, and (3) year-to-year. Univariate logistic regression models were fit to a set of 20 theory-selected predictors of high utilization. An optimal multiple predictor model was then derived via penalized multiple logistic regression (via elastic net, a machine learning algorithm). Three factors were identified in the optimized model as increasing the likelihood of high utilization: having a diagnosis of schizophrenia, having a co-occurring personality disorder diagnosis, and having less than a high school education. Given the complex needs of psychiatric high utilizers, innovative approaches should be considered to improve patient outcomes and reduce costly psychiatric hospitalizations.

Cognitive Deficits and Clinical Symptoms with Hippocampal Subfields in First-Episode and Never-Treated Patients with Schizophrenia.

Memory dysfunction and associated hippocampal disturbances play crucial roles in cognitive impairment of schizophrenia. To examine the relationships between cognitive function and the hippocampal subfields (HSs) in first-episode never-treated (FENT) schizophrenia patients, the HSs were segmented in 39 FENT patients and 30 healthy controls using a state-of the-art automated algorithm. We found no significant differences in any HSs between the patients and controls. However, multivariate regression analysis showed that the left cornu ammonis 1 (CA1), left hippocampal tail, left presubiculum, and right molecular layer contributed 40% to the variance of the PANSS negative symptom score. After adjusting for sex, age, education, and intracranial volume, the partial correlation analysis showed that the volumes of left CA1, CA3, CA4, molecular layer, granule cell layer and both left and right subiculum were negatively correlated with the MATRICS consensus cognitive battery (MCCB) Hopkins Verbal Learning Test (HVLT). Multiple regression analysis showed that the left CA1 and CA3 hippocampal abnormalities contributed 66% to the variance of the HVLT. Our results suggest no detectable HS deficits were found in FENT schizophrenia patients. However, the HSs may be involved in the symptoms and cognitive deficits of schizophrenia patients in the early phase of their illness.

Author Correction: Predicting individual responses to the electroconvulsive therapy with hippocampal subfield volumes in major depression disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A low affinity cis-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons.

Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulate diverse target genes across subsets of Drosophila efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across many neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here we examine the cis-regulatory mechanisms restricting BMP-induced FMRFa neuropeptide expression to Tv4-neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the FMRFa enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4-neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.

Deep transcranial magnetic stimulation for obsessive compulsive disorder.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that can be chronic and debilitating if not properly treated. Current first-line treatments for OCD include cognitive-behavioral therapy with exposure and response prevention and serotonin uptake inhibitor medications; however, these therapies are not effective for all individuals. AREAS COVERED: Deep transcranial magnetic stimulation (dTMS) has been hypothesized to be an effective alternative for individuals with treatment-resistant OCD. dTMS has thought to be favorable due to its low side effect profile and its minimally invasive nature. EXPERT OPINION: This review evaluates the current research on effectiveness of dTMS therapy for individuals with treatment-resistant OCD. This review also investigates shortcomings in current dTMS research and the hypothesized future of dTMS therapy.

Intact Auditory Cortical Cross-Frequency Coupling in Early and Chronic Schizophrenia.

BACKGROUND: Previous work has identified a hierarchical organization of neural oscillations that supports performance of complex cognitive and perceptual tasks, and can be indexed with phase-amplitude coupling (PAC) between low- and high-frequency oscillations. Our aim was to employ enhanced source localization afforded by magnetoencephalography (MEG) to expand on earlier reports of intact auditory cortical PAC in schizophrenia and to investigate how PAC may evolve over the early and chronic phases of the illness. METHODS: Individuals with early schizophrenia (n=12) (≤5 years of illness duration), chronic schizophrenia (n=16) (>5 years of illness duration) and healthy comparators (n = 17) performed the auditory steady state response (ASSR) to 40, 30, and 20 Hz stimuli during MEG recordings. We estimated amplitude and PAC on the MEG ASSR source localized to the auditory cortices. RESULTS: Gamma amplitude during 40-Hz ASSR exhibited a significant group by hemisphere interaction, with both patient groups showing reduced right hemisphere amplitude and no overall lateralization in contrast to the right hemisphere lateralization demonstrated in controls. We found significant PAC in the right auditory cortex during the 40-Hz entrainment condition relative to baseline, however, PAC did not differ significantly between groups. CONCLUSIONS: In the current study, we demonstrated an apparent sparing of ASSR-related PAC across phases of the illness, in contrast with impaired cortical gamma oscillation amplitudes. The distinction between our PAC and evoked ASSR findings supports the notion of separate but interacting circuits for the generation and maintenance of sensory gamma oscillations. The apparent sparing of PAC in both early and chronic schizophrenia patients could imply that the neuropathology of schizophrenia differentially affects these mechanisms across different stages of the disease. Future studies should investigate the distinction between PAC during passive tasks and more cognitively demanding task such as working memory so that we can begin to understand the influence of schizophrenia neuropathology on the larger framework for modulating neurocomputational capacity.

Is It Possible to Improve Working Memory With Prefrontal tDCS? Bridging Currents to Working Memory Models.

A great deal of research has been performed with the promise of improving such critical cognitive functions as working memory (WM), with transcranial direct current stimulation (tDCS), a well-tolerated, inexpensive, easy-to-use intervention. Under the assumption that by delivering currents through electrodes placed in suitable locations on the scalp, it is possible to increase prefrontal cortex excitability and therefore improve WM. A growing number of studies have led to mixed results, leading to the realization that such oversimplified assumptions need revision. Models spanning currents to behavior have been advocated in order to reconcile and inform neurostimulation investigations. We articulate such multilevel exploration to tDCS/WM by briefly reviewing critical aspects at each level of analysis but focusing on the circuit level and how available biophysical WM models could inform tDCS. Indeed, such models should replace vague reference to cortical excitability changes with relevant tDCS net effects affecting neural computation and behavior in a more predictable manner. We will refer to emerging WM models and explore to what extent the general concept of excitation-inhibition (E/I) balance is a meaningful intermediate level of analysis, its relationship with gamma oscillatory activity, and the extent to which it can index tDCS effects. We will highlight some predictions that appear consistent with empirical evidence - such as non-linearities and trait dependency of effects and possibly a preferential effect on WM control functions - as well as limitations that appear related to the dynamical aspects of coding by persistent activity.

Microdosing and standard-dosing take-home buprenorphine from the emergency department: A feasibility study.

OBJECTIVE: Emergency department (ED)-initiated buprenorphine may prevent overdose. Microdosing is a novel approach that does not require withdrawal, which can be a barrier to standard inductions. We aimed to evaluate the feasibility of an ED-initiated buprenorphine/naloxone program providing standard-dosing and microdosing take-home packages and of randomizing patients to either intervention. METHODS: We broadly screened patients ≥18 years old for opioid use disorder at a large, urban ED. In a first phase, we provided consecutive patients with 3-day standard-dosing packages, and then we provided a subsequent group with 6-day microdosing packages. In a second phase, we randomized patients to standard dosing or microdosing. We attempted 7-day telephone follow-ups and 30-day in-person community follow-ups. The primary feasibility outcome was number of patients enrolled and accepting randomization. Secondary outcomes were numbers screened, follow-up rates, and 30-day opioid agonist therapy retention. RESULTS: We screened 3954 ED patients and identified 94 with opioid use disorders. Of the patients, 26 (27.7%) declined participation: 10 identified a negative prior experience with buprenorphine/naloxone as the reason, 5 specifically cited precipitated withdrawal, and none cited randomization. We enrolled 68 patients. A total of 14 left the ED against medical advice, 8 were excluded post-enrollment, 21 received standard dosing, and 25 received microdosing. The 7-day and 30-day follow-up rates were 9/46 (19.6%) and 15/46 (32.6%), respectively. At least 5/21 (23.8%) provided standard dosing and 8/25 (32.0%) provided microdosing remained on opioid agonist therapy at 30 days. CONCLUSIONS: ED-initiated take-home standard-dosing and microdosing buprenorphine/naloxone programs are feasible, and a randomized controlled trial would be acceptable to our target population.

Renpenning syndrome in a female.

Renpenning syndrome (OMIM: 309500) is a rare X-linked disorder that causes intellectual disability, microcephaly, short stature, a variety of eye anomalies, and characteristic craniofacial features. This condition results from pathogenic variation of PQBP1, a polyglutamine-binding protein involved in transcription and pre-mRNA splicing. Renpenning syndrome has only been reported in affected males. Carrier females do not usually have clinical features, and in reported families with Renpenning syndrome, most female carriers exhibit favorable skewing of X-chromosome inactivation. We describe a female with syndromic features typical of Renpenning syndrome. She was identified by exome sequencing to have a de novo heterozygous c.459_462delAGAG mutation in PQBP1 (Xp11.23), affecting the AG hexamer in exon 4, which is the most common causative mutation in this syndrome. Streaky hypopigmentation of the skin was observed, supporting a hypothesized presence of an actively expressed, PQBP1 mutation-bearing X-chromosome in some cells. X-inactivation studies on peripheral blood cells demonstrated complete skewing in both the proband and her mother with preferential inactivation of the maternal X chromosome in the child. We demonstrated expression of the PQBP1 mutant transcript in leukocytes of the affected girl. Therefore, it is highly likely that the PQBP1 mutation arose from the paternal X chromosome.

Treatment response prediction and individualized identification of first-episode drug-naïve schizophrenia using brain functional connectivity.

Identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics would be of great value, but there has been limited progress. In this study, by using machine learning algorithms and the functional connections of the superior temporal cortex, we successfully identified the first-episode drug-naive (FEDN) schizophrenia patients (accuracy 78.6%) and predict their responses to antipsychotic treatment (accuracy 82.5%) at an individual level. The functional connections (FC) were derived using the mutual information and the correlations, between the blood-oxygen-level dependent signals of the superior temporal cortex and other cortical regions acquired with the resting-state functional magnetic resonance imaging. We also found that the mutual information and correlation FC was informative in identifying individual FEDN schizophrenia and prediction of treatment response, respectively. The methods and findings in this paper could provide a critical step toward individualized identification and treatment response prediction in first-episode drug-naive schizophrenia, which could complement other biomarkers in the development of precision medicine approaches for this severe mental disorder.

Interaction of BDNF and cytokines in executive dysfunction in patients with chronic schizophrenia.

Multiple lines of evidence indicate that patients with chronic schizophrenia (SCZ) display executive dysfunction across the illness course. However, the potential molecular pathophysiologic mechanisms remain poorly elucidated. Neurodevelopmental changes caused by alterations of inflammatory mediators and neurotrophins have been shown to occur in the earliest stages of SCZ, and be associated with executive dysfunction (ED) in SCZ. Therefore, the current study was to investigate whether the interplay between BDNF and inflammatory mediators was involved in the disruption of executive function of long-term hospitalized patients with chronic SCZ. Serum cytokines and BDNF levels were measured in 112 long-term hospitalized patients with chronic SCZ and 44 healthy normal controls. Executive functions were assessed by verbal fluency tests (VFT), the Stroop word-color test (Stroop), and the Wisconsin card sorting tests (WCST).The results showed that the patients had higher IL-2, IL-6, IL-8, but lower TNF-α and BDNF compared to control subjects. In the patient group, BDNF was positively associated with IL-2 and IL-8 levels, while lower BDNF levels were correlated with ED measured by VFT and WCST tests. Multiple stepwise regression analyses confirmed that BDNF × IL-8 and BDNF × TNF-α were factors influencing the total score of VFT, while BDNF × IL-8 and BDNF × TNF-α were recognized as influencing factors for WCST scores. Our results suggest complex interactions between BDNF and cytokines were involved in the pathophysiology of executive function impairments in patients with SCZ.

Home-based self-administered transcranial direct current stimulation in older adults with knee osteoarthritis pain: An open-label study.

Clinic-based transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to improve pain. However, no published studies have reported using home-based self-administered tDCS in older adults with knee osteoarthritis (OA). The present study aimed to evaluate the preliminary efficacy and feasibility of home-based self-administered tDCS with real-time remote supervision on clinical pain, anxiety, depression, and sleep disturbances in older adults with knee OA. Twenty 50- to 85-year-old community-dwelling participants with knee OA received 10 daily home-based sessions of 2 mA tDCS for 20 min with real-time remote supervision. We measured clinical pain severity via the Visual Analog Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Short-Form McGill Pain Questionnaire. We assessed anxiety, depression, and sleep disturbances using the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety-short form, depression-short form, and sleep disturbance-short form, respectively. All 20 participants completed all 10 home-based tDCS sessions without serious adverse effects. Both clinical pain severity and sleep disturbances were improved after completion of the 10 tDCS sessions. Anxiety and depression scores were not significantly improved. We demonstrated that home-based self-administered tDCS with real-time remote supervision was feasible and beneficial in alleviating clinical pain in older adults with knee OA. These findings support future studies with larger samples and longer-term follow-up evaluations.

Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG.

BACKGROUND: Dysregulation of the inositol cycle is implicated in a wide variety of human diseases, including developmental defects and neurological diseases. A homozygous frameshift mutation in IMPA1, coding for the enzyme inositol monophosphatase 1 (IMPase), has recently been associated with severe intellectual disability (ID) in a geographically isolated consanguineous family in Northeastern Brazil (Figueredo et al., 2016). However, the neurophysiologic mechanisms that mediate the IMPA1 mutation and associated ID phenotype have not been characterized. To this end, resting EEG (eyes-open and eyes-closed) was collected from the Figueredo et al. pedigree. Quantitative EEG measures, including mean power, dominant frequency and dominant frequency variability, were investigated for allelic associations using multivariate family-based association test using generalized estimating equations. RESULTS: We found that the IMPA1 mutation was associated with relative decreases in frontal theta band power as well as altered alpha-band variability with no regional specificity during the eyes-open condition. For the eyes-closed condition, there was altered dominant theta frequency variability in the central and parietal regions. CONCLUSIONS: These findings represent the first human in vivo phenotypic assessment of brain function disturbances associated with a loss-of-function IMPA1 mutation, and thus an important first step towards an understanding the pathophysiologic mechanisms of intellectual disability associated with the mutation that affects this critical metabolic pathway.

Treatment Retention Among Patients Participating in Coordinated Specialty Care for First-Episode Psychosis: a Mixed-Methods Analysis.

Young adults experiencing first-episode psychosis have historically been difficult to retain in mental health treatment. Communities across the United States are implementing Coordinated Specialty Care to improve outcomes for individuals experiencing first-episode psychosis. This mixed-methods research study examined the relationship between program services and treatment retention, operationalized as the likelihood of remaining in the program for 9 months or more. In the adjusted analysis, male gender and participation in home-based cognitive behavioral therapy were associated with an increased likelihood of remaining in treatment. The key informant interview findings suggest the shared decision-making process and the breadth, flexibility, and focus on functional recovery of the home-based cognitive behavioral therapy intervention may have positively influenced treatment retention. These findings suggest the use of shared decision-making and improved access to home-based cognitive behavioral therapy for first-episode psychosis patients may improve outcomes for this vulnerable population.