Accurate structure prediction of biomolecular interactions with AlphaFold 3.

The introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.

Functional connectivity analysis on electroencephalography signals reveals potential biomarkers for treatment response in major depression.

BACKGROUND: The treatment efficacy varies across individual patients with major depressive disorder (MDD). It lacks robust electroencephalography (EEG) markers for an antidepressant-responsive phenotype. METHOD: This is an observational study enrolling 28 patients with MDD and 33 healthy controls (mean age of 40.7 years, and 71.4% were women). Patients underwent EEG exams at baseline (week0) and week1, while controls' EEG recordings were acquired only at week0. A resting eye-closing EEG segment was analyzed for functional connectivity (FC). Four parameters were used in FC analysis: (1) node strength (NS), (2) global efficiency (GE), (3) clustering coefficient (CC), and (4) betweenness centrality (BC). RESULTS: We found that controls had higher values in delta wave in the indices of NS, GE, BC, and CC than MDD patients at baseline. After treatment with antidepressants, patients' FC indices improved significantly, including GE, mean CC, and mean NS in the delta wave. The FC in the alpha and beta bands of the responders were higher than those of the non-responders. CONCLUSIONS: The FC of the MDD patients at baseline without treatment was worse than that of controls. After treatment, the FC improved and was close to the values of controls. Responders showed better FC in the high-frequency bands than non-responders, and this feature exists in both pre-treatment and post-treatment EEG.

Change of home visit frequency by public health nurses predicts emergency escorts for psychiatric patients living in the community: A retrospective medical record review.

Background: Improper or insufficient treatment of mental health illness harms individuals, families, and society. When psychiatric treatment shifts from a hospital-based to a community-based health care system, risk management is essential to the provision of effective care. Objective: We examine whether an upgrade in home visit frequency of psychiatric patients as identified by public health nurses can predict the subsequent need for emergency escort services for medical treatment. Design: A 2-year retrospective medical record review. Settings: A district of New Taipei City in Taiwan. Participants: A total of 425 patients with a diagnosed mental health illness cared for through home visits by public health nurses from January 2018 to December 2019. Methods: We accessed the Ministry of Health and Welfare's psychiatric care management information system to identify a set of medical records, and analyzed these records using chi-square and regression analyses. Results: The analyses indicated that the groups experiencing the greatest need for emergency escort services were: male, 35-49 years old, with a senior high school level of education, without a disability identification card, with a schizophrenia diagnosis, and had been reported by the nurse as having progressed to a serious level. Nurses' increased frequency of home visits (an indicator that the patient's overall condition was worsening) and nurses' reports of increased severity of problems were significant predictors of the need for emergency escort services. Conclusions: The nurses' adjustment of visit frequency based on the results of the visit assessment predicts the need for emergency escort services for mental patients. The findings support not only the professional roles and functions of public health nurses, but also the importance of strengthening psychiatric health community support services.

Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study.

BACKGROUND/PURPOSE: Predictors for out-of-hospital cardiac arrest (OHCA) in COVID-19 patients remain unclear. We identified the predictors for OHCA and in-hospital mortality among such patients in community isolation centers. METHODS: From May 15 to June 20, 2021, this cohort study recruited 2555 laboratory-confirmed COVID-19 patients admitted to isolation centers in Taiwan. All patients were followed up until death, discharge from the isolation center or hospital, or July 16, 2021. OHCA was defined as cardiac arrest confirmed by the absence of circulation signs and occurring outside the hospital. Multinomial logistic regressions were used to determine factors associated with OHCA and in-hospital mortality. RESULTS: Of the 37 deceased patients, 7 (18.9%) had OHCA and 30 (81.1%) showed in-hospital mortality. The mean (SD) time to OHCA was 6.6 (3.3) days from the symptom onset. After adjusting for demographics and comorbidities, independent predictors for OHCA included age ≥65 years (adjusted odds ratio [AOR]: 13.24, 95% confidence interval [CI]: 1.85-94.82), fever on admission to the isolation center (AOR: 12.53, 95% CI: 1.68-93.34), and hypoxemia (an oxygen saturation level below 95% on room air) (AOR: 26.54, 95% CI: 3.18-221.73). Predictors for in-hospital mortality included age ≥65 years (AOR: 10.28, 95% CI: 2.95-35.90), fever on admission to the isolation centers (AOR: 7.27, 95% CI: 1.90-27.83), and hypoxemia (AOR: 29.87, 95% CI: 10.17-87.76). CONCLUSIONS: Time to OHCA occurrence is rapid in COVID-19 patients. Close monitoring of patients' vital signs and disease severity during isolation is important, particularly for those with older age, fever, and hypoxemia.

Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein.

AIMS: To study effects on cellular innate immune responses to ORF8, ORF10, and Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, in combination with cannabidiol (CBD). MAIN METHODS: HEK293 cells transfected with plasmids expressing control vector, ORF8, ORF10, or M protein were assayed for cell number and markers of apoptosis at 24 h, and interferon and interferon-stimulated gene expression at 14 h, with or without CBD. Cells transfected with polyinosinic:polycytidylic acid (Poly (I:C)) were also studied as a general model of RNA-type viral infection. KEY FINDINGS: Reduced cell number and increased early and late apoptosis were found when expression of viral genes was combined with 1-2 µM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. In cells expressing viral genes, CBD augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2'-5'-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL. CBD also augmented expression of these genes in control cells not expressing viral genes, but without enhancing apoptosis. CBD similarly enhanced the cellular anti-viral response to Poly (I:C). SIGNIFICANCE: Our results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but an augmented innate anti-viral response to these genes in the presence of CBD. Thus, CBD may prime components of the innate immune system, increasing readiness to respond to RNA-type viral infection without activating apoptosis, and could be studied for potential in prophylaxis.

Clinical and behavior characteristics of individuals who used ketamine.

This study aims to depict and compare clinical characteristics and risk behavior among groups of individuals using ketamine, polydrugs or smoking cigarette. A total of 185 drug-using participants and 49 smokers participated in this study. A cross-sectional interview was used to collect information on demographics, drug- and sex-related behaviors, HIV serostatus, lower urinary tract symptoms (LUTS), behavioral dispositions. N-back memory test was used to measure short-term memory. Result shows that 10 participants (5.41%) were HIV positive and 14 (7.57%) having LUTS. Individuals with ketamine and polydrugs use have significantly worse drug-related problem than cigarette smokers. Compared to cigarette smokers and ketamine users, individuals with polydrug users scored significantly higher on impulsivity measures. Cigarette smokers performed significantly better than the other two groups on the memory tests. A few patients had been infected with HIV and diagnosed with LUTS. Findings support that memory on short term recalls of patients with ketamine use might be impaired. Study findings warrants the necessarily of further study on influences of using ketamine.

COVID-19 stigma associates with burnout among healthcare providers: Evidence from Taiwanese physicians and nurses.

BACKGROUND/PURPOSE: During pandemics like SARS-CoV-2, healthcare providers' well-being and morale are in particular at stake. Burnout may substantially hinder the well-being and morale of healthcare providers, challenging our efforts at disease containment. This study investigated the relationship between perceived COVID-19 stigma and burnout symptoms among physicians and nurses. We further aimed to identify potential factors that may moderate this relationship, including profession, clinical contact with COVID-19 patients, and prior experience with 2003 SARS-CoV-1. METHODS: We used a web-based, structured survey from March 12th to 29th, 2020 to collect cross-sectional, self-reported data. Participants were provided with a link to the survey which took them on average 5-8 minutes. Survey consisted of demographic characteristics, clinical experiences, perceived COVID-19 related stigma, and burnout symptoms. Linear regression with bootstrapping techniques was adopted to test the relations between stigma and burnout, as well as other potential moderators, while adjusting for demographic and clinical factors. RESULTS: Of the 1421 consented respondents, 357 identified as physicians while 1064 identified as nurses. Participants reported some levels of stigma, and noticeable burnout symptoms. Burnout symptoms were positively correlated with COVID-19 stigma, profession, and currently care for confirmed/suspected COVID-19 patients. The interaction between stigma and profession (Stigma × Nurses) but no other interaction terms reached the significance level, suggesting that the slope for nurses was flatter than the slope for physicians. CONCLUSION: The study results suggest that COVID-19 stigma may contribute to burnout among physicians and nurses, and this relation may not vary across clinical roles and experiences but profession.

Mental health crisis in healthcare providers in the COVID-19 pandemic: a cross-sectional facility-based survey.

OBJECTIVES: During a pandemic, healthcare providers experience increased mental and physical burden. Burnout can lead to treatment errors, patient mortality, increased suicidal ideation and substance abuse as well as medical malpractice suits among medical staff. This study aimed to investigate the occurrence of burnout, acute stress disorder, anxiety disorder and depressive disorder among healthcare providers at the third month of the COVID-19 pandemic. DESIGN: A cross-sectional facility-based survey. SETTING: Hospitals around the country with different levels of care. PARTICIPANTS: A total of 1795 respondents, including 360 men and 1435 women who participated in the survey. PRIMARY OUTCOME MEASURES: Burnout was assessed using the Physician Work Life Study. A score of ≥3 implied burnout. RESULTS: Of the 1795 respondents, 723 (40.3%) reported burnout, and 669 (37.3%) cared for patients with COVID-19. Anxiety levels were mild in 185 (10.3%) respondents, moderate in 209 (11.6%) and severe in 1401 (78.1%). The mean Center for Epidemiologic Studies Depression Scale-10 score was 9.5±6.3, and 817 (45.5%) respondents were classified as having depression. Factors associated with burnout were working in acute and critical care (ACC) divisions (adjusted OR (aOR)=1.84, 95% CI 1.20 to 3.39, p=0.019), caring for patients with COVID-19 (aOR=3.90, 95% CI 1.14 to 13.37, p=0.031) and having depressive disorder (aOR=9.44, 95% CI 7.44 to 11.97, p<0.001). CONCLUSIONS: Physicians and nurses are vulnerable to burnout during a pandemic, especially those working in ACC divisions. Anxiety disorder, depressive disorder and care of patients with COVID-19 may be factors that influence the occurrence of burnout among healthcare providers.

Olfactory disorder in patients infected with SARS-CoV-2.

Three (60%) of five patients with coronavirus disease 2019 (COVID-19) had olfactory disorder. Two exhibited anosmia at the onset of COVID-19, while one had hyposmia 4 days after the onset of COVID-19. All patients with olfactory disorder were completely recovered with a mean recovery length of 11.3 days.

Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity.

Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

Anxiety symptoms and preventive measures during the COVID-19 outbreak in Taiwan.

BACKGROUND: It is hypothesized that anxiety and behavioral responses are intense at the beginning of an epidemic. The objective of this study was to investigate anxiety symptoms and use of preventive measures against COVID-19. The study also compared the association between preventive measures and anxiety symptoms during the week immediately preceding the study and those symptoms and measures at the beginning of the outbreak. METHODS: A cross-sectional population survey using an online questionnaire commenced on 14 February 2020. The study participants were residents of Taiwan ages 20 to 70 years. The 6-item state version of the State-Trait Anxiety Inventory (STAI-6) was used to assess anxiety symptoms. The questions about preventive measures asked participants about their personal protection, cough etiquette, contact precautions, voluntary quarantine, and prompt reporting. Multivariable logistic regression was used to determine the factors influencing an increase in the preventive measures scores. RESULTS: Of a total of 3555 completed responses, a total of 52.1% (95% confidence interval [CI] 50.4-53.7) of the respondents reported moderate to severe levels of anxiety symptoms in the past week, whereas 48.8% (95%CI 47.2-50.5) reported moderate to severe anxiety symptoms at the beginning of the outbreak. With a higher score indicating greater anxiety, the median scores for anxiety symptoms in the past week and at the beginning of the outbreak were 46.7 (IQR [interquartile range] 36.7-53.3) and 43.3 (IQR 36.7-53.3), respectively. The median scores for the preventive measures taken in the past week and at the beginning of the outbreak were 26.0 (IQR 21.0-30.0) and 24.0 (IQR 19.0-28.0), respectively, out of a maximum score of 36. In the multivariable analysis, an increased anxiety symptom score from the beginning of the outbreak to the past week (adjusted OR = 7.38, 95%CI 6.28-8.66) was a strongly significant determinant of an increased preventive measures score in the past week compared with the score at the beginning of the outbreak. CONCLUSIONS: Anxiety and preventive measures scores were high and increased with the epidemic rate. Higher anxiety was associated with an increased use of preventive measures against COVID-19.

Adherence among HIV-positive injection drug users undergoing methadone treatment in Taiwan.

AIMS: The study aims were to investigate adherence to methadone maintenance treatment (MMT) and to identify associated clinical factors in patients who inject drugs diagnosed with human immunodeficiency virus (HIV) infection in Taiwan. METHODS: Data were from the National Health Surveillance System on HIV and the National Drug Treatment System on MMT. HIV-positive people who inject drugs (HIVPWID) were defined as the study population. Information obtained included age, sex, education, marital status, employment, methadone dose, and date of diagnosis of HIV infection. Adherence was defined as taking methadone for the past 90, 180 and 365 days, then categorized as high (> 90%), moderate (51 to 90%), or low (<=50%) adherent respectively. RESULTS: Of 1641 HIVPWID registered in the datasets from 2007 to 2012, 961 (58.56%) had received MMT. For HIVPWID evaluated at 90 days (n = 951), 271 (28.5%), 382 (40.2%), and 298 (31.3%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 180 days (n = 936), 190 (20.3%), 349 (37.3%), and 397 (42.4%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 365 days (n = 919), 133 (14.5%), 271 (29.5%), and 515 (56.0%) were classified as high, moderate, and low adherent respectively. After controlling for sociodemographics, results showed that methadone dose, location of MMT clinic, and date of HIV diagnosis were significantly associated with MMT adherence. CONCLUSIONS: Study findings underscore the importance to MMT adherence of methadone dosage, early diagnosis of patient's HIV infection, and area of patient residence.

Transdiagnostic and Illness-Specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.

BACKGROUND: Mental disorders are typically defined as distinct diagnostic entities, but similar patterns of clinical and cognitive impairments are frequently found across diagnostic groups. We investigated whether these transdiagnostic deficits result from common neural substrates across disorders or various illness-specific mechanisms, or a combination of both. METHODS: Functional magnetic resonance imaging data were collected from clinically stable patients with major depressive disorder (n = 53), bipolar disorder (n = 78), or schizophrenia (n = 100) and matched healthy control subjects (n = 109) using a single scanner. Group comparisons were conducted to identify transdiagnostic and illness-specific features, and possible confounding effects of medication were considered. A multivariate approach with cross-validation was used to associate dysconnectivity features with shared cognitive deficits. RESULTS: Transdiagnostic dysconnectivities were identified within somatomotor (Cohen's d = 0.50-0.58) and salience (Cohen's d = 0.52-0.58) networks and between subcortical-limbic (Cohen's d = 0.55-0.69) and subcortical-dorsal attention (Cohen's d = 0.56-0.61) networks. The executive control network was found to be illness-specifically disconnected from the prefrontal-limbic-pallidal circuit in major depressive disorder (Cohen's d = 0.57-0.58), prefronto-striato-parietal circuit in bipolar disorder (Cohen's d = 0.48-0.53), and default mode network in schizophrenia (Cohen's d = 0.47-0.56). Working memory deficits were associated with a linear combination of 11 transdiagnostic and 5 illness-specific dysconnectivities (r = .322, p= 9.7 × 10-4, n = 340). The associations of the identified dysconnectivities with medication dosage were nonsignificant. CONCLUSIONS: Disconnectivity in the somatomotor network was a common transdiagnostic profile, while there were illness-specific patterns in different parts of the prefrontal cortex for different disorders. These findings suggest that prominent psychiatric disorders share common impairments, possibly linked to perception and motor output, as well as unique dysconnectivity profiles that hypothetically mediate the more distinctive features of the disorder-specific psychopathology.

Striatal functional connectivity in chronic ketamine users: a pilot study.

Background: The striatum supports motivated behavior and impulse control. Altered striatal activation and connectivity has been observed in link with impulse control dysfunction in individuals with drug addiction.Objectives: We examined how resting state functional connectivity (rsFC) of the striatum is altered as a result of chronic ketamine misuse.Methods: Thirty-six ketamine users (10 women) and 20 healthy controls (9 women) completed an assessment with the Barratt Impulsiveness Scale (BIS-11) and magnetic resonance imaging. In SPM we examined voxel-wise connectivities of the caudate, pallidum, putamen, and ventral striatum in ketamine users (versus healthy controls) and in association with BIS-11 score and duration of use, all at a corrected threshold.Results: Compared to controls, ketamine users showed higher connectivity between caudate and dorsal anterior cingulate cortex and between pallidum and bilateral cerebellum. In ketamine users, putamen showed higher connectivity with the left orbitofrontal cortex (OFC) in association with both BIS-11 score and months of ketamine use. Mediation analyses suggest that the connectivity z score mediated the relationship between impulsivity and duration of use.Conclusions: These preliminary findings highlighted altered striatal connectivity in chronic ketamine users, and the potential role of putamen OFC connectivity in supporting the correlation between impulsivity and duration of ketamine use. If replicated in a larger sample, these findings may represent neural markers of ketamine misuse.

Optimizing agent behavior over long time scales by transporting value.

Humans prolifically engage in mental time travel. We dwell on past actions and experience satisfaction or regret. More than storytelling, these recollections change how we act in the future and endow us with a computationally important ability to link actions and consequences across spans of time, which helps address the problem of long-term credit assignment: the question of how to evaluate the utility of actions within a long-duration behavioral sequence. Existing approaches to credit assignment in AI cannot solve tasks with long delays between actions and consequences. Here, we introduce a paradigm where agents use recall of specific memories to credit past actions, allowing them to solve problems that are intractable for existing algorithms. This paradigm broadens the scope of problems that can be investigated in AI and offers a mechanistic account of behaviors that may inspire models in neuroscience, psychology, and behavioral economics.

Effectiveness of a brief information, motivation and behavioral skills program on stage transitions and lapse for individuals who use ketamine.

OBJECTIVE: Chronic ketamine use is a significant public health and social problem in East and South East Asia and may lead to impairments in health and cognitive functioning. The study evaluated effects of an information, motivation and behavior skills (IMB) program on changes in motivational stage and ketamine use. METHODS: Ketamine using individuals residing in the City of Taipei were recruited (N = 395): 279 selected an IMB program consisting of a 1-day workshop of six 50-minute interactive sessions provided in small groups. The remaining 116 participants selected an education-as-usual (EAU) program consisting of a 1-day workshop of six 50-minute didactic lectures provided in a large group format. Motivational stage of change and ketamine knowledge were assessed before and after the interventions. Participants were followed one year later to assess their ketamine use status. RESULTS: No significant difference in knowledge increase between the IMB and EAU groups (p = .59). The proportion of participants who transitioned from the contemplation to preparation motivational stages was greater in the IMB group than in the EAU group (p < .01). A significant difference in the rates of ketamine lapse during a one-year post intervention follow up was observed between the IMB (50%) and EAU (75%) groups (p < .01). CONCLUSIONS: Interventions based on IMB principles may be more effective in supporting motivational stage transition and in prevention of lapses to ketamine use as compared to currently offered standard drug education programs. Policy makers should consider including IMB interventions in their rehabilitation programs addressing ketamine use problems.

Controlled randomized trial of walking exercise with positive education on cardiovascular fitness and happiness in retired older adults.

AIM: Regular walking exercise (RWE) is associated with increased cardiovascular fitness and might elevate subjective psychological well-being. Positive education links positive psychology concepts with self-efficacy through the curriculum, which helps foster well-being. This study examines if regular walking exercise with positive education has better effects on cardiovascular fitness and happiness than RWE alone in retired older adults. METHODS: Three arms of experimental design were used: pedometer walking exercise training (PWET); positive education and pedometer walking exercise training (PEPWET); and pedometer walking exercise (PWE). Trained walking exercise was provided to the PWET and PEPWET groups by a walking exercise coach three times per week, for 45 min per session for 12 weeks. Positive education was designed and led by a licensed PhD psychologist every other week. Of 150 participants, 60, 60 and 30 were randomly assigned to PWET, PEPWET and PWE, respectively. Demographic information, Chinese Happiness Inventory, RWE, and 6-min walking distance were assessed before and after the intervention. RESULTS: The percentage of participants who practiced RWE after 12 weeks was significantly higher in the PEPWET group (96.7%), followed by the PWET (75%) and PWE groups (40%). Cardiovascular fitness in the PWET and PEPWET groups was significantly better than in the PWE group. Chinese Happiness Inventory scores in the PWET and PEPWET groups were significantly higher than in the PWE group, and the PEPWET group also showed significantly higher Chinese Happiness Inventory scores than the PWET group. CONCLUSIONS: In addition to RWE, the study findings show that positive education can be beneficial to promote older adults' RWE, cardiovascular fitness and happiness. Geriatr Gerontol Int 2019; 19: 879-884.

Depression in chronic ketamine users: Sex differences and neural bases.

Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users.