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IntroductionCorrectional workers (CWs) are frequently exposed to potentially traumatic events in the workplace, leading to an increased prevalence of mental health concerns. Online psychotherapy can address many of the barriers CWs face when seeking adequate mental health care. Despite their benefits, CWs’ experience using digital mental health interventions is relatively unknown. This information could be valuable in developing enhanced care delivery to improve recruitment, retention, satisfaction, and treatment outcomes.MethodsThis study investigated the experiences of a sample of CWs enrolled in a clinical trial evaluating the efficacy of the Online Psychotherapy Tool (OPTT) in this population. Participants were surveyed and interviewed to capture their opinions and feedback on the program. Survey analysis was conducted through Qualtrics statistical analysis software. The interview transcripts and open-ended survey questions were analyzed using thematic analysis methods in NVivo.ResultsParticipants (n=14) were cis-gender, predominantly white, with an average age of 38 years. While most respondents preferred in-person therapy, they also reported the benefits of the online psychotherapy program. Specifically, they expressed positive perceptions of the platform, the quality and interaction of their care provider, and the homework assignments and skills learned. Lack of motivation to complete weekly homework assignments was a frequently cited challenge. Unhelpful aspects of the therapy noted issues with the online format and frustration with certain program elements.DiscussionParticipants expressed a positive outlook on the program, the platform, and treatment outcomes. A preference for in-person therapy was still indicated, demonstrating the need to focus on engagement in digital mental health interventions. In addition, the findings of this study shed light on the factors that can influence help-seeking in this population, including stigma in the work environment, demanding work schedules, workplace perceptions, and previous experiences accessing mental health services.

Abstract Background Post-secondary students frequently experience high rates of mental health challenges. However, they present meagre rates of treatment-seeking behaviours. This elevated prevalence of mental health problems, particularly after the COVID-19 pandemic, can lead to distress, poor academic performance, and lower job prospects following the completion of education. To address the needs of this population, it is important to understand students' perceptions of mental health and the barriers preventing or limiting their access to care. Methods A broad-scoping online survey was publicly distributed to post-secondary students, collecting demographic, sociocultural, economic, and educational information while assessing various components of mental health. Results In total, 448 students across post-secondary institutions in Ontario, Canada, responded to the survey. Over a third (n = 170; 38.6%) of respondents reported a formal mental health diagnosis. Depression and generalized anxiety disorder were the most commonly reported diagnoses. Most respondents felt that post-secondary students did not have good mental health (n = 253; 60.5%) and had inadequate coping strategies (n = 261; 62.4%). The most frequently reported barriers to care were financial (n = 214; 50.5%), long wait times (n = 202; 47.6%), insufficient resources (n = 165; 38.9%), time constraints (n = 148; 34.9%), stigma (n = 133; 31.4%), cultural barriers (n = 108; 25.5%), and past negative experiences with mental health care (n = 86; 20.3%). The majority of students felt their post-secondary institution needed to increase awareness (n = 231; 56.5%) and mental health resources (n = 306; 73.2%). Most viewed in-person therapy and online care with a therapist as more helpful than self-guided online care. However, there was uncertainty about the helpfulness and accessibility of different forms of treatment, including online interventions. The qualitative findings highlighted the need for personal strategies, mental health education and awareness, and institutional support and services. Conclusions Various barriers to care, perceived lack of resources, and low knowledge of available interventions may contribute to compromised mental health in post-secondary students. The survey findings indicate that upstream approaches such as integrating mental health education for students may address the varying needs of this critical population. Therapist-involved online mental health interventions may be a promising solution to address accessibility issues.

BackgroundLockdowns and social distancing resulting from the COVID-19 pandemic have worsened the population’s mental health and made it more difficult for individuals to receive care. Electronic cognitive behavioral therapy (e-CBT) is a cost-effective and evidence-based treatment for anxiety and depression and can be accessed remotely. ObjectiveThe objective of the study was to investigate the efficacy of online psychotherapy tailored to depression and anxiety symptoms during the pandemic. MethodsThe pilot study used a pre-post design to evaluate the efficacy of a 9-week e-CBT program designed for individuals with depression and anxiety affected by the pandemic. Participants were adults (N=59) diagnosed with major depressive disorder and generalized anxiety disorder, whose mental health symptoms initiated or worsened during the COVID-19 pandemic. The online psychotherapy program focused on teaching coping, mindfulness, and problem-solving skills. Symptoms of anxiety and depression, resilience, and quality of life were assessed. ResultsParticipants demonstrated significant improvements in symptoms of anxiety (P=.02) and depression (P=.03) after the intervention. Similar trends were observed in the intention-to-treat analysis. No significant differences were observed in resilience and quality-of-life measures. The sample comprised mostly females, making it challenging to discern the benefits of the intervention in males. Although a pre-post design is less rigorous than a controlled trial, this design was selected to observe changes in scores during a critical period. Conclusionse-CBT for COVID-19 is an effective and accessible treatment option. Improvements in clinical symptoms of anxiety and depression can be observed in individuals whose mental health is affected by the COVID-19 pandemic. Trial RegistrationClinicalTrials.gov NCT04476667; https://clinicaltrials.gov/study/NCT04476667 International Registered Report Identifier (IRRID)RR2-10.2196/24913

IntroductionDepression is a leading cause of disability worldwide, affecting up to 300 million people globally. Despite its high prevalence and debilitating effects, only one-third of patients newly diagnosed with depression initiate treatment. Electronic cognitive behavioural therapy (e-CBT) is an effective treatment for depression and is a feasible solution to make mental health care more accessible. Due to its online format, e-CBT can be combined with variable therapist engagement to address different care needs. Typically, a multi-professional care team determines which combination therapy most benefits the patient. However, this process can add to the costs of these programs. Artificial intelligence (AI) has been proposed to offset these costs.MethodsThis study is a double-blinded randomized controlled trial recruiting individuals experiencing depression. The degree of care intensity a participant will receive will be randomly decided by either: (1) a machine learning algorithm, or (2) an assessment made by a group of healthcare professionals. Subsequently, participants will receive depression-specific e-CBT treatment through the secure online platform. There will be three available intensities of therapist interaction: (1) e-CBT; (2) e-CBT with a 15–20-min phone/video call; and (3) e-CBT with pharmacotherapy. This approach aims to accurately allocate care tailored to each patient’s needs, allowing for more efficient use of resources.DiscussionArtificial intelligence and providing patients with varying intensities of care can increase the efficiency of mental health care services. This study aims to determine a cost-effective method to decrease depressive symptoms and increase treatment adherence to online psychotherapy by allocating the correct intensity of therapist care for individuals diagnosed with depression. This will be done by comparing a decision-making machine learning algorithm to a multi-professional care team. This approach aims to accurately allocate care tailored to each patient’s needs, allowing for more efficient use of resources with the convergence of technologies and healthcare.EthicsThe study received ethics approval and began participant recruitment in December 2022. Participant recruitment has been conducted through targeted advertisements and physician referrals. Complete data collection and analysis are expected to conclude by August 2024.Clinical trial registrationClinicalTrials.Gov, identifier NCT04747873.

BackgroundGeneralized anxiety disorder (GAD) is a debilitating mental health disorder with first-line treatments include cognitive behavioral therapy (CBT) and pharmacotherapy. CBT is costly, time-consuming, and inaccessible. Electronic delivery (e-CBT) is a promising solution to address these barriers. However, due to the novelty of this intervention, more research testing the e-CBT efficacy independently and in conjunction with other treatments is needed.ObjectiveThis study investigated the efficacy of e-CBT compared to and in conjunction with pharmacotherapy for GAD.MethodsThis study employed a quasi-experimental design where patients selected their preferred treatment modality. Patients with GAD were enrolled in either e-CBT, medication, or combination arms. The 12-week e-CBT program was delivered through a digital platform. The medications followed clinical guidelines. The efficacy of each arm was evaluated using questionnaires measuring depression, anxiety, and stress severity, as well as quality of life.ResultsThere were no significant differences between arms (N e-CBT = 41; N Medication = 41; N Combination = 33) in the number of weeks completed or baseline scores. All arms showed improvements in anxiety scores after treatment. The medication and combination arms improved depression scores. The e-CBT and Combination arms improved quality of life, and the combination arm improved stress scores. There were no differences between the groups in depression, anxiety, or stress scores post-treatment. However, the combination arm had a significantly larger improvement in quality of life. Gender and treatment arm were not predictors of dropout, whereas younger age was.ConclusionIncorporating e-CBT on its own or in combination with pharmaceutical interventions is a viable option for treating GAD. Treating GAD with e-CBT or medication appears to offer significant improvements in symptoms, with no meaningful difference between the two. Combining the treatments also offer significant improvements, while not necessarily superior to either independently. The findings suggest that all options are viable. Taking the patient’s preferred treatment route based on their lifestyle, personality, and beliefs into account when deciding on treatment should be a priority for care providers.

BackgroundBipolar disorder (BD) is a highly prevalent psychiatric condition that can significantly impact every aspect of a person’s life if left untreated. A subtype of BD, bipolar disorder type II (BD-II), is characterized by long depressive episodes and residual depression symptoms, with short-lived hypomanic episodes. Medication and psychotherapy, such as cognitive behavioral therapy (CBT), are the main treatment options for BD-II. CBT specific for BD-II involves the recognition of warning signs, potentially triggering stimuli, and the development of coping skills to increase euthymic periods and improve global functioning. However, access to in-person CBT may be limited by several barriers, including low availability, high costs, and geographical limitations. Thus, web-based adaptations of CBT (e-CBT) have become a promising solution to address these treatment barriers. Nevertheless, e-CBT for the treatment of BD-II remains understudied. ObjectiveThe proposed study aims to establish the first e-CBT program specific for the treatment of BD-II with residual depressive symptoms. The primary objective of this study will be to determine the effect of e-CBT in managing BD symptomatology. The secondary objective will be to assess the effects of this e-CBT program on quality of life and resilience. The tertiary objective will involve gathering user feedback using a posttreatment survey to support the continuous improvement and optimization of the proposed program. MethodsAdult participants (N=170) with a confirmed diagnosis of BD-II experiencing residual depressive symptoms will be randomly assigned to either the e-CBT and treatment as usual (TAU; n=85) group or the TAU (n=85) control group. Participants in the control group will be able to participate in the web-based program after the first 13 weeks. The e-CBT program will consist of 13 weekly web-based modules designed following a validated CBT framework. Participants will complete module-related homework and receive asynchronous personalized feedback from a therapist. TAU will consist of standard treatment services conducted outside of this research study. Depression and manic symptoms, quality of life, and resiliency will be assessed using clinically validated symptomatology questionnaires at baseline, week 6, and week 13. ResultsThe study received ethics approval in March 2020, and participant recruitment is expected to begin in February 2023 through targeted advertisements and physician referrals. Data collection and analysis are expected to conclude by December 2024. Linear and binomial regression (continuous and categorical outcomes, respectively) will be conducted along with qualitative interpretive methods. ConclusionsThe findings will be the first on the effectiveness of delivering e-CBT for patients with BD-II with residual depressive symptoms. This approach can provide an innovative method to address barriers to in-person psychotherapy by increasing accessibility and decreasing costs. Trial RegistrationClinicalTrials.gov NCT04664257; https://clinicaltrials.gov/ct2/show/NCT04664257 International Registered Report Identifier (IRRID)PRR1-10.2196/46157

ObjectiveThe increased prevalence of major depressive disorder (MDD) amid the COVID-19 pandemic has resulted in substantial growth in online mental health care delivery. Compared to its in-person counterpart, online cognitive behavioral therapy (e-CBT) is a time-flexible and cost-effective method of improving MDD symptoms. However, how its efficacy compares to in-person CBT is yet to be explored. Therefore, the current study compared the efficacy of a therapist-supported, electronically delivered e-CBT program to in-person therapy in individuals diagnosed with MDD.MethodsParticipants (n = 108) diagnosed with MDD selected either a 12 week in-person CBT or an asynchronous therapist-supported e-CBT program. E-CBT participants (n = 55) completed weekly interactive online modules delivered through a secure cloud-based online platform (Online Psychotherapy Tool; OPTT). These modules were followed by homework in which participants received personalized feedback from a trained therapist. Participants in the in-person CBT group (n = 53) discussed sessions and homework with their therapists during one-hour weekly meetings. Program efficacy was evaluated using clinically validated symptomatology and quality of life questionnaires.ResultsBoth treatments yielded significant improvements in depressive symptoms and quality of life from baseline to post-treatment. Participants who opted for in-person therapy presented significantly higher baseline symptomatology scores than the e-CBT group. However, both treatments demonstrated comparable significant improvements in depressive symptoms and quality of life from baseline to post-treatment. e-CBT seems to afford higher participant compliance as dropouts in the e-CBT group completed more sessions on average than those in the in-person CBT group.ConclusionThe findings support e-CBT with therapist guidance as a suitable option to treat MDD. Future studies should investigate how treatment accessibility is related to program completion rates in the e-CBT vs. in-person group.Clinical Trial RegistrationClinicalTrials.Gov Protocol Registration and Results System (NCT04478058); clinicaltrials.gov/ct2/show/NCT04478058.

Introduction: In the last few years, online psychotherapy programs have burgeoned since they are a more accessible and scalable treatment option compared to in-person therapies. While these online programs are promising, understanding the user experience and perceptions of care is essential for program optimization. Methods: This study investigated the experiences of end-users who had previously received online psychotherapy through a web-based platform. A 35-item multiple-choice survey was developed by the research team and distributed to past users to capture their perceptions of the program. Results: The survey yielded 163 responses, with a 90 % completion rate. Participants were predominantly white and female, with an average age of 42 years. While most participants preferred in-person therapy, they also reported the benefits of the online psychotherapy program. Participants had positive perceptions of the platform, the quality and interaction of their therapist, and the homework assignments and skills covered. Lack of motivation to complete weekly homework assignments was cited as a common struggle. Discussion: The findings support online psychotherapy as a beneficial digital mental health tool and highlight some areas for improvement. Scalability and accessibility are key benefits of the platform. At the same time, improvements in participant engagement, including those from equity-seeking and equity-deserving groups, may enhance the efficacy of the programs offered.

Background Alcohol use disorder (AUD) is characterized by problematic alcohol use accompanied by clinically substantial distress. Patients with AUD frequently experience high relapse rates, and only 1 in 5 remain abstinent 12 months post treatment. Traditional face-to-face relapse prevention therapy (RPT) is a form of cognitive behavioral therapy (CBT) that examines one's situational triggers, maladaptive thought processes, self-efficacy, and motivation. However, access to this treatment is frequently limited due to its high cost, long waitlists, and inaccessibility. A web-based adaptation of RPT (e-RPT) could address these limitations by providing a more cost-effective and accessible delivery method for mental health care in this population. Objective This study protocol aims to establish the first academic e-RPT program to address AUD in the general population. The primary objective of this study is to compare the efficacy of e-RPT to face-to-face RPT in decreasing relapse rates. The secondary objective is to assess the effects of e-RPT on quality of life, self-efficacy, resilience, and depressive symptomatology. The tertiary objective is to evaluate the cost-effectiveness of e-RPT compared to face-to-face RPT. Methods Adult participants (n=60) with a confirmed diagnosis of AUD will be randomly assigned to receive 10 sessions of e-RPT or face-to-face RPT. e-RPT will consist of 10 predesigned modules and homework with asynchronous, personalized feedback from a therapist. Face-to-face RPT will comprise 10 one-hour face-to-face sessions with a therapist. The predesigned modules and the face-to-face sessions will present the same content and structure. Self-efficacy, resilience, depressive symptomatology, and alcohol consumption will be measured through various questionnaires at baseline, amid treatment, and at the end of treatment. Results Participant recruitment is expected to begin in October 2022 through targeted advertisements and physician referrals. Completed data collection and analysis are expected to conclude by October 2023. Outcome data will be assessed using linear and binomial regression (for continuous and categorical outcomes, respectively). Qualitative data will be analyzed using thematic analysis methods. Conclusions This study will be the first to examine the effectiveness of e-RPT compared to face-to-face RPT. It is posited that web-based care can present benefits in terms of accessibility and affordability compared to traditional face-to-face psychotherapy. Trial RegistrationClinicalTrials.gov NCT05579210; https://clinicaltrials.gov/ct2/show/NCT05579210 International Registered Report Identifier (IRRID)PRR1-10.2196/44694

BackgroundInsomnia is one of the most prevalent sleep disorders characterized by an inability to fall or stay asleep. Available treatments include pharmacotherapy and cognitive behavioural therapy for insomnia (CBTi). Although CBTi is the first-line treatment, it has limited availability. Therapist-guided electronic delivery of CBT for insomnia (e-CBTi) offers scalable solutions to enhance access to CBTi. While e-CBTi produces comparable outcomes to in-person CBTi, there is a lack of comparison to active pharmacotherapies. Therefore, direct comparisons between e-CBTi and trazodone, one of the most frequently prescribed medications for insomnia, is essential in establishing the effectiveness of this novel digital therapy in the health care system.ObjectiveThe aim of this study is to compare the effectiveness of a therapist-guided electronically-delivered cognitive behavioural therapy (e-CBTi) program to trazodone in patients with insomnia.MethodsPatients (n = 60) will be randomly assigned to two groups: treatment as usual (TAU) + trazodone and TAU + e-CBTi for seven weeks. Each weekly sleep module will be delivered through the Online Psychotherapy Tool (OPTT), a secure, online mental health care delivery platform. Changes in insomnia symptoms will be evaluated throughout the study using clinically validated symptomatology questionnaires, Fitbits, and other behavioural variables.ResultsParticipant recruitment began in November 2021. To date, 18 participants have been recruited. Data collection is expected to conclude by December 2022 and analyses are expected to be completed by January 2023.ConclusionsThis comparative study will improve our understanding of the efficacy of therapist-guided e-CBTi in managing insomnia. These findings can be used to develop more accessible and effective treatment options and influence clinical practices for insomnia to further expand mental health care capacity in this population.Trial registrationClinicalTrials.gov (NCT05125146).

PurposeCorrectional work is described as a high-stress environment associated with increased prevalence of mental health disorders in employees. Identifying appropriate healthcare services necessitates investigating the mental health challenges and needs of correctional workers (CWs).MethodsIndividual interviews (n = 9; 5 M and 4 W) and a mixed gender focus group (n = 6; 3 M and 3 W) were conducted to gather a general sense of the mental health landscape. Data were analyzed to develop a targeted and comprehensive question guide for gender-specific focus groups (n = 14 unique participants; 6 M and 8 W).ResultsEight themes emerged from the gender-specific focus groups. Themes focusing on work culture described the negative repercussions of job stress and the inability to discuss challenges openly due to confidentiality concerns and feelings of seclusion associated with the CW profession. Men were more likely to be subjected to physical violence and women to emotional and sexual harassment from staff and inmates. Themes related to mental health care described the benefits and limitations of the current services and digital mental healthcare. Stigma and accessibility were notable treatment barriers. Lastly, sector-specific therapy was seen as an important component in enhancing engagement and therapist interaction.ConclusionThe study demonstrates the interconnection between work culture and CW mental health that needs to be acknowledged when addressing mental health care.

Chronic exposure to stressors and potentially psychologically traumatic events contributes to the high prevalence of mental health disorders in correctional workers (CWs) and other public safety personnel (PSP). Digital mental health interventions are an accessible and scalable method of improving and maintaining the mental health of this population. The current review explores the benefits of digital mental health interventions for PSP–with a focus on CWs–and how these innovations can address the limitations in in-person mental health care. A systematic literature search of five databases (Medline, PsycInfo, Embase, CINAHL, Google Scholar) was conducted until March 2022. The search yielded 16 publications that focused on digital mental health interventions or care available to CWs and other PSP. The benefits of digital innovations were summarized into five categories which discussed (1) their ability to enhance accessibility and reduce stigma; (2) the provision of evidence-based and structured psychotherapy programs; (3) variability in the degree of therapist engagement; (4) the integration of proactive interventions; and (5) enhancing engagement by acknowledging unique experiences and interpersonal relationships. Although digital mental health technologies for CWs are still in their infancy, there is strong evidence to support their effectiveness in ameliorating symptoms of mental distress. Future research should consider how ethnicity, gender, culture, sexual orientation, and socioeconomic status can be integrated into these therapies and how the interplay between different stakeholders and organizations can impact the effectiveness of online therapies and programs.

BackgroundThere has been a recent rise in the use of eHealth treatments for a variety of psychological disorders, including eating disorders. ObjectiveThis meta-analysis of randomized controlled trials is the first to evaluate the efficacy of eHealth interventions specifically for the treatment of binge eating disorder (characterized by compulsive overconsumption of food, in a relatively short period, and without compensatory behaviors such as purging or fasting). MethodsA search on the electronic databases PubMed, Web of Science, Embase, MEDLINE, and CINAHL was conducted for randomized controlled trials that compared the efficacy of eHealth treatment interventions with waitlist controls. ResultsFrom the databases searched, 3 studies (298 participants in total) met the inclusion criteria. All interventions were forms of internet-based guided cognitive behavioral therapy. The results of the analysis demonstrated that when compared with waitlist controls, individuals enrolled in eHealth interventions experienced a reduction in objective binge episodes (standardized mean difference [SMD] −0.77, 95% CI −1.38 to −0.16) and eating disorder psychopathology (SMD −0.71, 95% CI −1.20 to −0.22), which included shape (SMD −0.61, 95% CI −1.01 to −0.22) and weight concerns (SMD −0.91, 95% CI −1.33 to −0.48). There was no significant difference in BMI between the eHealth interventions and controls (SMD −0.01, 95% CI −0.40 to 0.39). ConclusionsThese findings provide promising results for the use of internet-based cognitive behavioral therapy for binge eating disorder treatment and support the need for future research to explore the efficacy of these eHealth interventions.

BackgroundPublic safety personnel have regular and often intense exposure to potentially traumatic events at work, especially workplace violence in the case of correctional workers. Subsequently, correctional workers are at higher risk of developing mental health problems such as posttraumatic stress disorder. Public safety personnel are up to 4 times more likely to experience suicidal ideation, suicidal attempts, and death by suicide compared to the general population. Despite this high prevalence, help-seeking behaviors from public safety personnel are low due to stigma and irregular work hours limiting access to care. Innovative treatments are needed to address these challenges. ObjectiveThis study will investigate the efficacy of an electronically delivered cognitive behavioral therapy (e-CBT) program tailored to correctional workers’ mental health problems. MethodsThis study is composed of 4 phases. In phase 1, we will interview correctional workers individually and in focus groups to identify personal, social, and cultural factors affecting their mental health and barriers to care. Phase 2 will use the information gathered from the interviews to develop gender- and diagnosis-specific e-CBT modules. These will be presented to a new group of participants who will provide further feedback on their usability and accessibility. In phase 3, we will randomly assign participants to either an e-CBT or treatment as usual arm. The program will be evaluated with validated symptomatology questionnaires and interviews. Phase 4 will use this additional information to fine-tune the e-CBT modules for a larger-scale randomized controlled trial design comparing the e-CBT program to in-person CBT. All e-CBT modules will be delivered through a secure online platform. ResultsThe study received ethics approval in December 2020, and participant recruitment began in March 2021. Participant recruitment has been conducted through targeted advertisements and physician referrals. To date, there have been 15 participants recruited for Phase 1, and it is expected to conclude in July 2021, with phase 2 beginning in September 2021. Complete data collection and analysis from all phases are expected to conclude by July 2023. Linear and binomial regression (for continuous and categorical outcomes, respectively) will be conducted along with interpretive qualitative methods. ConclusionsIf proven efficacious and feasible, this e-CBT program can provide a high-quality and clinically validated resource to address the mental health problems of correctional workers. Additionally, findings can contribute to the development of innovative treatments for other public safety professions. Trial RegistrationClinicalTrials.gov NCT04666974; https://www.clinicaltrials.gov/ct2/show/NCT04666974 International Registered Report Identifier (IRRID)DERR1-10.2196/30845

BackgroundDietary vitamin D3 (D3) restriction reduces paw grip endurance and motor performance in G93A mice, and increases inflammation and apoptosis in the quadríceps of females. ALS, a neuromuscular disease, causes progressive degeneration of motor neurons in the brain and spinal cord.ObjectiveWe analyzed the spinal cords of G93A mice following dietary D3 restriction at 2.5% the adequate intake (AI) for oxidative damage (4-HNE, 3-NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF-α, IL-6, IL-10), apoptosis (bax/bcl-2 ratio, cleaved/pro-caspase 3 ratio), neurotrophic factor (GDNF) and neuron count (ChAT, SMI-36/SMI-32 ratio).MethodsBeginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI;1 IU D3/g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D3/g feed; 10 M, 9 F) D3. At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P ≤ 0.10, since this was a pilot study.ResultsDEF mice had 16% higher 4-HNE (P = 0.056), 12% higher GPx1 (P = 0.057) and 23% higher Bax/Bcl2 ratio (P = 0.076) vs. AI. DEF females had 29% higher GPx1 (P = 0.001) and 22% higher IL-6 (P = 0.077) vs. AI females. DEF males had 23% higher 4-HNE (P = 0.066) and 18% lower SOD2 (P = 0.034) vs. AI males. DEF males had 27% lower SOD2 (P = 0.004), 17% lower GPx1 (P = 0.070), 29% lower IL-6 (P = 0.023) and 22% lower ChAT (P = 0.082) vs. DEF females.ConclusionD3 deficiency exacerbates disease pathophysiology in the spinal cord of G93A mice, the exact mechanisms are sex-specific. This is in accord with our previous results in the quadriceps, as well as functional and disease outcomes.