517 results on '"Maria A. Oquendo"'
Search Results
2. In vivo serotonin transporter and 1A receptor binding potential and ecological momentary assessment (EMA) of stress in major depression and suicidal behavior
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Elizabeth A. Bartlett, Francesca Zanderigo, Barbara Stanley, Tse-Hwei Choo, Hanga C. Galfalvy, Spiro P. Pantazatos, M. Elizabeth Sublette, Jeffrey M. Miller, Maria A. Oquendo, and J. John Mann
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Pharmacology ,Psychiatry and Mental health ,Neurology ,Pharmacology (medical) ,Neurology (clinical) ,Biological Psychiatry - Published
- 2023
3. Suicide
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Leo Sher and Maria A. Oquendo
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General Medicine - Published
- 2023
4. Examination of the Factor Structure of Psychopathology in a Mozambican Sample
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Ali Giusto, Adrienne Romer, Kathryn Lovero, Palmira Fortunado dos Santos, Claire Greene, Lidia Gouveia, Antonio Suleman, Paulino Feliciano, Maria A. Oquendo, Jennifer Mootz, and Milton L. Wainberg
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Clinical Psychology ,Article - Abstract
Factor-analytic studies are needed in global samples to advance understanding of psychopathology. Here, we examined the structure of psychopathology and a general psychopathology (p) factor using data from a cross-sectional study of 971 adults (63% women) from Maputo City, Mozambique. We used confirmatory factor analyses of symptoms from 15 psychiatric disorders to test common models of the structure of psychopathology. Models that included Internalizing, Substance Use, and Thought Disorder factors as well as a general p factor fit the data well. Measurement invariance testing revealed that factor loadings on p differed by gender. Higher levels of p, Internalizing, and Thought Disorder factors were associated with greater suicide risk, psychiatric comorbidity, chronic medical illnesses, and poorer functioning. A general p factor and Internalizing, Substance Use Disorder, and Thought Disorder factors were identifiable in this Mozambican sample. Understanding psychopathology dimensions is a step toward building more scalable mental health service approaches globally.
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- 2022
5. A Multi-Site Study of Mental Disorders in the Mozambican Health Care System
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Lidia Gouveia, Kathryn Lovero, Wilza Fumo, Afonso Mazine Tiago Fumo, Palmira Dos Santos, Ana Olga Mocumbi, Maria A. Oquendo, Jair J. Mari, Milton Wainberg, and Cristiane Duarte
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Psychiatry and Mental health ,Health Policy ,Public Health, Environmental and Occupational Health ,Pshychiatric Mental Health - Abstract
BackgroundIn Mozambique, human and financial resources for public mental health services are extremely limited. Understanding the mental health needs of those seeking healthcare can inform efficient targeting of mental health services. We examined if the frequency of mental disorders in a health facility varied based on the level of specialization of such facility, from primary care without mental health specialists (PrCMH-), to those with mental health specialists (PrCMH+) and tertiary care (TerC), where both inpatient and outpatient mental health services are available.MethodsParticipants were adults seeking health or mental health services at six facilities (2 PrCMH+, 3 PrCMH-, and 1 TerC) in the cities of Maputo and Nampula in Mozambique. Mental disorders were assessed by the MINI International Neuropsychiatric Interview (MINI) 4.0.0. We compared the sociodemographic characteristics and MINI diagnoses across the three types of health facilities. Multiple logistic regression models determined the likelihood that a person seeking services at each type of facility would have any mental disorder, common mental disorders (CMD), severe mental disorders (SMD), substance use disorders (SUD), and moderate-to-high suicide risk, adjusting for sociodemographic factors. ResultsOf the 612 total participants, 52.6% (n=322) were positive for at least one mental disorder: 37.1% were positive for CMD, 28.9% for SMD, 13.2% for SUD, and 10.5% had suicide risk. Presence of any mental disorder was highest in TerC (62.5%) and lowest in PrCMH- (48.4%). Adjusting for sociodemographic covariates, participants in PrCMH+ were significantly more likely to have SMD (OR: 1.85, 95%CI: 1.10-3.11) and SUD (OR: 2.79, 95%CI: 1.31-5.94) than participants in PrCMH-; participants in TerC were more likely to have CMD (OR: 1.70, 95%CI: 1.01-2.87) and SUD (OR: 2.57, 95%CI: 1.14-5.79) than in PrCMH-. Suicide risk was the only condition that did not differ across facility types.ConclusionsAs anticipated, people with mental disorders were more likely to be cared for at facilities with mental health specialists. However, our study suggests there is a remarkably high frequency of mental disorders across different types of facilities within the Mozambican healthcare system. These results suggest a need to increase mental health services at the primary care level.
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- 2022
6. Does It Matter What Screener We Use? A Comparison of Ultra-brief PHQ-4 and E-mwTool-3 Screeners for Anxiety and Depression Among People With and Without HIV
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Cale N. Basaraba, Melissa A. Stockton, Annika Sweetland, Andrew Medina-Marino, Kathryn L. Lovero, Maria A. Oquendo, M. Claire Greene, Ana Olga Mocumbi, Lidia Gouveia, Milena Mello, Palmira dos Santos, Antonio Suleman, Dirceu Mabunda, Flávio Mandlate, Amalio Xavier, Wilza Fumo, Luciana Massinga, Saida Khan, Paulino Feliciano, Bianca Kann, Andre Fiks Salem, Charl Bezuidenhout, Jennifer J. Mootz, Cristiane S. Duarte, Francine Cournos, Melanie M. Wall, and Milton L. Wainberg
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Infectious Diseases ,Social Psychology ,Public Health, Environmental and Occupational Health ,Article - Abstract
The burden of depression and anxiety disorders is high in sub-Saharan Africa, especially for people with HIV (PWH). The Patient Health Questionnaire-4 (PHQ-4) and Electronic Mental Wellness Tool-3 (E-mwTool-3) are ultra-brief screening tools for these disorders. We compared the performance of PHQ-4 and E-mwTool-3 for screening MINI-International Neuropsychiatric Interview diagnoses of depression and anxiety among a sample of individuals with and without HIV in two primary care clinics and one general hospital in Maputo City, Mozambique. Areas-under-the-curve (AUC) were calculated along with sensitivities and specificities at a range of cutoffs. For PWH, at a sum score cutoff of ≥ 1, sensitivities were strong: PHQ-4:Depression = 0.843; PHQ-4:Anxiety = 0.786; E-mwTool-3:Depression = 0.843; E-mwTool-3:Anxiety = 0.929. E-mwTool-3 performance was comparable to PHQ-4 among people with and without HIV.
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- 2022
7. Emotional contagion behavior in a group of young girls in a secondary school in Maputo, Mozambique
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Lίdia Gouveia, Flávio Mandlate, Carolina Ziebold, Wilza Fumo, Dirceu Mabunda, Kathryn L Lovero, Afonso Mazine Tiago Fumo, Palmira dos Santos, António Pacheco Palha, Ana Olga Mocumbi, Maria A Oquendo, Milton L Wainberg, Cristiane S Duarte, and Jair J Mari
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Psychiatry and Mental health - Abstract
Background: Emotional Contagion Behavior (ECB), the synchronized expression of emotional symptoms among members of a group, has been observed globally. In Mozambique, there have been numerous reports of ECB in recent years. Since 2010 several girls from a secondary school in Maputo City, Mozambique exhibited ECB which involved repeated fainting spells, sometimes including verbal aggression and threats to colleagues and teachers. We conducted a study to analyze sociodemographic and clinical characteristics associated with ECB. Methods: This cross-sectional study included 154 females aged from 16 to 24 years old. We considered emotional contagion behavior as repeated fainting spells, sometimes including verbal aggression and threats to others (colleagues and teachers). Participants responded to a sociodemographic questionnaire, the Beck Anxiety Scale, and the revised Eysenck Personality Questionnaire (EPQ-R). Bivariate and multivariate logistic regression models analyzed sociodemographic and clinical characteristics associated with EBC. Results: Among study participants, 57 presented ECB and 97 did not. The likelihood of ECB was higher among those with previous history of ECB (OR = 8.28, 95% CI [2.51, 27.30]; p ⩽ .001) and extroverted personality profile (OR = 1.15, 95% CI [1.01, 1.30]; p = .038). Having a romantic relationship was related to lower likelihood of having ECB (OR = 0.04, 95% CI [0.01, 0.19]; p = .001). Conclusions: These results suggest that ECB may repeat over time and be related to challenges pertaining to personality development, the presence of sexual life, and close relationships with peers faced by adolescent girls.
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- 2022
8. Association between mental disorders and adherence to antiretroviral treatment in health facilities in two Mozambican provinces in 2018: a cross-sectional study
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Flavio M. Mandlate, M. Claire Greene, Luis F. Pereira, Maria Lidia Gouveia, Jair Jesus Mari, Francine Cournos, Cristiane S. Duarte, Maria A. Oquendo, Marcelo Feijó Mello, and Milton L. Wainberg
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Psychiatry and Mental health - Abstract
Introduction Lower adherence to antiretroviral treatment (ART) has been found among people with HIV (PWH) who have comorbid mental disorders like depression and alcohol use in Sub-Saharan African. However, there has been less exploration with regards to other mental disorders. Methods This study assessed the association of multiple mental disorders and adherence to ART based on the data from primary/tertiary health care facilities in Maputo and Nampula, Mozambique. We administered a sociodemographic questionnaire, Mini International Neuropsychiatric Interview (MINI) Plus 4.0.0 adapted for use in Mozambique to assess mental conditions, and a 3-item self-report to measure ART adherence. Results 395 HIV-positive (self-report) participants on ART, with an average age of 36.7 years (SD = 9.8), and 30.4% were male. The most common mental disorders were major depressive disorder (27.34%) followed by psychosis (22.03%), suicidal ideation/behavior (15.44%), and alcohol-use disorder (8.35%). Higher odds of missing at least one dose in the last 30 days (OR = 1.45, 95% CI: 1.01, 2.10) were found in participants with any mental disorder compared to those without a mental disorder. The highest levels of non-adherence were observed among those with drug use disorders and panic disorder. Conclusions In Mozambique, PWH with any co-occurring mental conditions had a lower probability of ART adherence. Integrating comprehensive mental health assessment and treatment and ART adherence interventions tailored to PWH with co-occurring mental disorders is necessary to attain optimal ART adherence and reach the UNAIDS ART target.
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- 2023
9. Twenty-six years of psychosocial interventions to reduce suicide risk in adolescents: Systematic review and meta-analysis
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Liat, Itzhaky, Sara, Davaasambuu, Steven P, Ellis, Sebastian, Cisneros-Trujillo, Katrina, Hannett, Kelly, Scolaro, Barbara H, Stanley, J John, Mann, Milton L, Wainberg, Maria A, Oquendo, and M Elizabeth, Sublette
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Risk ,Suicide Prevention ,Psychiatry and Mental health ,Clinical Psychology ,Treatment Outcome ,Adolescent ,Humans ,Suicide, Attempted ,Child ,Psychosocial Intervention ,Self-Injurious Behavior ,Suicidal Ideation - Abstract
During adolescence, suicide risk increases; effective treatments are needed to reduce risk.Databases were searched (1995-2020) for randomized controlled trials (RCTs) concerning psychosocial treatments for suicide prevention in adolescents (10-18 yrs). Data were extracted from the timepoint closest to 6 months. Cohen's ds were estimated for reducing suicidal ideation (SI), self-harming behaviors (SHB) excluding strictly non-suicidal self-injury, and suicide attempts (SA) and analyzed using generalized least square regression. Meta-analytic innovations included within-person correlations to reflect trait suicidality; annualization to control for exposure; estimated lifetime risk based on ages; and modeling inclusion/exclusion criteria. Alternate approaches included relative risk and comparison of intervention and control treatments to baseline.Of 30 RCTs, 6 assessing SHB (4 measuring SA), and 7 assessing SI demonstrated treatment effectiveness. Overall, interventions decreased SI (n = 25) with low effect size (d = 0.08, p = 0.01), non-significant after controlling for publication bias (d = 0.05, p = 0.1); interventions were non-significant for SHB (n = 25, d = 0.001, p = 0.97) or SA (n = 18, d = 0.03, p = 0.52). To prevent one SHB, the number needed to treat (NNT) was 45[26,156]; for SA, NNT=42[24,149]. Non-superiority may relate to effectiveness of control treatments. Thus, experimental and control treatments also were compared to baseline: both reduced SI (p 0.0001), and effectiveness improved for SHB (NNT=12) and SA (NNT=11).Study heterogeneity and inconsistent statistical reporting limited meta-analysis.Psychosocial interventions for suicide risk in adolescents showed little effectiveness compared with control treatments; suicide outcomes improved in both groups compared to baseline. Different approaches may be needed, including precision medicine methodologies and standardized statistical reporting criteria.
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- 2022
10. Women's mental health in Mozambique: is maternity a protective factor?
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Saida Khan, Pamela Scorza, Kathryn L. Lovero, Palmira dos Santos, Wilza Fumo, Barbara Camara, Maria A. Oquendo, Milton L. Wainberg, Marcelo Fejo, and Cristiane S. Duarte
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General Earth and Planetary Sciences ,General Environmental Science - Abstract
BackgroudGlobally, women have been shown to have high rates of common mental disorders (CMDs). In low and middle-income countries (LMICs), women face significant challenges related to maternity. However, no study has compared mental health problems among pregnant/post-partum women, childless women of childbearing age, and women with children in a low-income country. We sought to compare the frequency of CMD and suicide risk in a sample of women presenting or accompanying patients in primary care in two Mozambican semi-urban settings.MethodsWe administered the MINI International Neuropsychiatric Interview to 853 women, of whom 220 (25.8%) were pregnant/post-partum, 177 (20.8%) were non-pregnant and childless, and 456 (53.5%) were non-pregnant and with children more than 1-year-old. Logistic regression models compared the likelihood of a psychiatric disorder across groups, adjusting for sociodemographic and chronic-illness covariates.ResultsWe found a high frequency of CMD and suicide risk among all women in this low-income context sample. In adjusted models, no differences in rates of depression, anxiety, or panic disorder were observed among groups. However, suicide risk was higher in women without children than pregnant/post-partum women.ConclusionThe frequency of CMD among women of childbearing age in our study was higher than documented rates in high-income countries and other LMIC. Additionally, we found that motherhood was not protective and that pregnancy and the postpartum period were not stages of increased risk for most disorders. This highlights the need to expand mental health services not only for perinatal women but all women of childbearing age in this and possibly similar settings.
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- 2022
11. Suicidal behavior across a broad range of psychiatric disorders
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Yingcheng E. Xu, Daniel A. Barron, Katherin Sudol, Sidney Zisook, and Maria A. Oquendo
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Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Molecular Biology - Published
- 2023
12. Assessment and Management of Suicidal Risk
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Glenn A. Melvin, Maria A. Oquendo, Barbara Stanley, and Kelly Posner
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- 2023
13. In vivo serotonin 1A receptor hippocampal binding potential in depression and reported childhood adversity
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Elizabeth A. Bartlett, Ashley A. Yttredahl, Maura Boldrini, Andrea E. Tyrer, Kathryn R. Hill, Mala R. Ananth, Matthew S. Milak, Maria A. Oquendo, J. John Mann, Christine DeLorenzo, and Ramin V. Parsey
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Psychiatry and Mental health - Abstract
Background Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [11C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT1AR, and thus, a history of CA may explain the disparate findings. Methods Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n = 16, unipolar n = 12) and 19 non-depressed healthy volunteers (HVs) underwent [11C]CUMI-101 imaging to quantify 5-HT1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT1AR with severe CA compared with mild/moderate CA and HVs. Results There was a group-by-region effect (p = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p-values > 0.05). Conclusions With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.
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- 2023
14. Suicide: An Overview for Clinicians
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Leo, Sher and Maria A, Oquendo
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Suicide Prevention ,Suicide ,Mood Disorders ,Risk Factors ,Humans ,Suicide, Attempted ,Suicidal Ideation - Abstract
Most suicides have a diagnosable psychiatric disorder, most frequently, a mood disorder. Psychosocial issues and neurobiological abnormalities such as dysregulation in stress response systems contribute to suicidal behavior. All psychiatric patients need to be screened for the presence of suicidal ideation. Clinicians are expected to gather information about patient's clinical features and to formulate decisions about patient's dangerousness to self and the treatment plan. As psychiatric disorders are a major risk factor for suicide their pharmacologic and psychological treatment is of utmost importance to prevent suicide. Restriction of access to lethal means is important for suicide prevention.
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- 2022
15. Risk factors for pre-adolescent onset suicidal behavior in a high-risk sample of youth
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Giovanna Porta, Jamie Zelazny, J. John Mann, Maria A. Oquendo, Nadine M. Melhem, Boris Birmaher, David A. Brent, and Barbara Stanley
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Adult ,Adolescent ,Offspring ,Suicide, Attempted ,Article ,Suicidal Ideation ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,Suicidal ideation ,Multinomial logistic regression ,First episode ,Mood Disorders ,business.industry ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Exact test ,Mood disorders ,Adolescent Behavior ,Suicidal behavior ,Female ,Analysis of variance ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
OBJECTIVE: To identify risk factors for preadolescent onset suicidal behavior compared with adolescent/young adult onset suicidal behavior in a longitudinal sample of youth with parental history of mood disorders. METHODS: The sample includes 545 youth who were age 21 years or less at the time of their baseline assessment. Participants underwent baseline and yearly study assessments. Observations were censored at the time point closest to the first episode of suicidal behavior for youth with suicidal behavior and at the time of last observation for youth without suicidal behavior. Youth were categorized into 3 groups: first onset of suicidal behavior before the age of 13 (n=32), first onset of suicidal behavior between the ages of 13–21 (n=51) and those without suicide related behaviors (n=462). ANOVA, Chi-square, Fisher’s exact test and multinomial regression were used to test the hypotheses. RESULTS: Significant predictors of preadolescent onset suicidal behavior were diagnosis of depressive disorder (RRR=11.41, p
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- 2021
16. Partnerships in Research to Implement and Disseminate Sustainable and Scalable Evidence-Based Practices (PRIDE) in Mozambique
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Jair de Jesus Mari, Jean-Marie Alves-Bradford, Jennifer J. Mootz, Melanie M. Wall, Andre Fiks Salem, Kathryn L. Lovero, Lidia Gouveia, Phuti Ngwepe, Francine Cournos, Dirceu Mabunda, Maria A. Oquendo, Andrew Medina-Marino, Andrea H. Marques, Marcelo Feijó de Mello, Milena Mello, Wilza Fumo, Milton L. Wainberg, Cristiane S. Duarte, Paulino Feliciano, Ana Olga Mocumbi, Myrna M. Weissman, Palmira Fortunato Dos Santos, Antonio Suleman, Zuleyha Cidav, and Charl Bezuidenhout
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Mental Health Services ,Pride ,Evidence-based practice ,media_common.quotation_subject ,Primary health care ,Article ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Stepped care ,030212 general & internal medicine ,Dissemination ,Mozambique ,Randomized Controlled Trials as Topic ,media_common ,Community Health Workers ,business.industry ,Mental Disorders ,Closing (real estate) ,Public relations ,Mental health ,030227 psychiatry ,Psychiatry and Mental health ,Evidence-Based Practice ,Task shifting ,business - Abstract
BACKGROUND: Mental health conditions impose a major burden worldwide, especially in low- and middle-income countries (LMICs), where health specialists are scarce. A challenge to closing LMICs’ mental health treatment gap is determining the most cost-effective task-shifting pathway for delivering mental health services using evidence-based interventions (EBIs). This article discusses the protocol for the first study implementing comprehensive mental health services in LMICs. METHODS: In partnership with the Mozambican Ministry of Health, this cluster-randomized, hybrid implementation effectiveness type-2 trial will evaluate implementation, patient, and service outcomes of three task-shifting delivery pathways in 20 Mozambican districts (population 4.7 million). In pathway 1 (usual care), community health workers (CHWs) and primary care providers (PCPs) refer patients to district-level mental health clinics. In pathway 2 (screen, refer, and treat), CHWs screen and refer patients to PCPs for behavioral and pharmacological EBIs in community clinics. In pathway 3 (community mental health stepped care), CHWs screen patients and deliver behavioral EBIs in the community and refer medication management cases to PCPs in clinics. Mixed-methods process evaluation will be used to examine factors affecting pathway implementation, adoption, and sustainability. Clinical activities will occur without research team support. Ministry of Health personnel will coordinate training and supervision. RESULTS: The most cost-effective pathway will be scaled up in all districts for 12 months. NEXT STEPS: This novel study integrating comprehensive mental health services into primary care will inform a toolkit to help the Mozambican Ministry of Health scale up the most cost-effective pathway for mental health services and can be a template for other LMICs.
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- 2021
17. Mental disorders and adherence to antiretroviral treatment in health facilities in Mozambique
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Flavio M. Mandlate, M. Claire Greene, Luis F. Pereira, Maria Lidia Gouveia, Jair Jesus Mari, Francine Cournos, Cristiane S. Duarte, Maria A. Oquendo, Marcelo Feijó Mello, and Milton L. Wainberg
- Abstract
IntroductionLess adherence to antiretroviral treatment (ART) has been found among people suffering from HIV (PWH) with comorbid mental disorders like depression and alcohol use in Mozambique, a Sub-Saharan African country. However, less is explored with regards to other mental disorders.MethodsThis study assessed the association of multiple mental disorders and adherence to ART based on the data from primary/tertiary health care facilities in Maputo and Nampula, Mozambique. We administered a sociodemographic questionnaire, Mini International Neuropsychiatric Interview (MINI) Plus 4.0.0 adapted for use in Mozambique to assess mental conditions, and a 3-item self-report to measure ART adherence.ResultsOut of 1469 participants, 409 were HIV positive (self-report), with an average age of 36.7 years (SD=9.8), and 30.4% were male. The most common mental disorders were major depressive disorder (27.34%) followed by psychosis (22.03%), suicidal ideation/behavior (15.44%), and alcohol-use disorder (8.35%). Higher levels of non-adherence to ART [(Mean Difference=1.19, 95% CI: 1.04, 1.37)] and the likelihood of missing at least one dose in the last 30 days (OR=3.06, 95% CI: 2.00, 4.67) were found in participants with any mental disorder compared to those without a mental disorder. The highest levels of non-adherence were observed among those with drug use disorders and panic disorder.ConclusionsIn Mozambique, PWH with any co-occurring mental conditions had a lower probability of ART adherence. Integrating comprehensive mental health assessment and treatment and ART adherence interventions tailored to PWH with co-occurring mental disorders is necessary to attain optimal ART adherence and reach the UNAIDS ART target.
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- 2022
18. Prevalence and correlates of suicidal behavior in primary care settings in Mozambique
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Vasco F. J. Cumbe, Maria Nélia Manaca, Dana L. Atkins, Alberto Muanido, Leecreesha Hicks, Maria A. Oquendo, Jair de Jesus Mari, and Bradley H. Wagenaar
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Adult ,Primary Health Care ,Suicide, Attempted ,Suicidal Ideation ,Psychiatry and Mental health ,Risk Factors ,Suicidal behavior ,Prevalence ,Suicide attempt ,Humans ,Female ,Suicidal plan ,Mozambique ,Primary health care - Abstract
Background This study assessed the prevalence of suicidal behavior and associated risk factors in public primary health care in Mozambique. Methods The Mini International Neuropsychiatric Interview was used to evaluate suicidal behavior among 502 adults attending three Primary Health Care (PHC) settings. Results In the past month, 13% (n = 63) of PHC attendees expressed suicidal ideation, 8% (n = 40) had made a suicide plan, 4% (n = 20) had made a suicide attempt, and 5% (n = 25) reported a lifetime suicide attempt. Females had 2.8-fold increased odds of suicide plan (95% CI: 1.5, 5.5) and 3.3-fold increased odds of suicide attempt in the past month (95% CI: 1.2, 9.1). Each 10-year increase in age was associated with 0.61-fold the odds of suicide plan (95% CI: 0.38, 0.98) and 0.09-fold the odds of suicide attempt (95% CI: 0.01, 0.69) in the past month. People living with HIV (PLWHA) had 2.2-fold increased adjusted odds of past month suicide attempt (CI: 1.1, 4.1). Conclusion Suicidal behaviors are common among adults attending PHC clinics in Mozambique. Screening and linkage to effective preventive interventions are urgently needed in PHC settings. Females, younger individuals, and PLWHA are at elevated risk for suicidal behavior in PHC.
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- 2022
19. Structural brain measures linked to clinical phenotypes in major depression replicate across clinical centres
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Maria A. Oquendo, Christos Davatzikos, Darsol Seok, Kristin A. Linn, Myrna M. Weissman, Nicholas C. Cullen, Yvette I. Sheline, Meichen Yu, Romain Duprat, Desmond J. Oathes, Irem Aselcioglu, Philip A. Cook, Tyler M. Moore, and Russell T. Shinohara
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0301 basic medicine ,Cingulate cortex ,business.industry ,Precuneus ,Anhedonia ,medicine.disease ,Neuroticism ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Frontal lobe ,Sexual abuse ,medicine ,Major depressive disorder ,medicine.symptom ,Big Five personality traits ,business ,Molecular Biology ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Abnormalities in brain structural measures, such as cortical thickness and subcortical volumes, are observed in patients with major depressive disorder (MDD) who also often show heterogeneous clinical features. This study seeks to identify the multivariate associations between structural phenotypes and specific clinical symptoms, a novel area of investigation. T1-weighted magnetic resonance imaging measures were obtained using 3 T scanners for 178 unmedicated depressed patients at four academic medical centres. Cortical thickness and subcortical volumes were determined for the depressed patients and patients' clinical presentation was characterized by 213 item-level clinical measures, which were grouped into several large, homogeneous categories by K-means clustering. The multivariate correlations between structural and cluster-level clinical-feature measures were examined using canonical correlation analysis (CCA) and confirmed with both 5-fold and leave-one-site-out cross-validation. Four broad types of clinical measures were detected based on clustering: an anxious misery composite (composed of item-level depression, anxiety, anhedonia, neuroticism and suicidality scores); positive personality traits (extraversion, openness, agreeableness and conscientiousness); reported history of physical/emotional trauma; and a reported history of sexual abuse. Responses on the item-level anxious misery measures were negatively associated with cortical thickness/subcortical volumes in the limbic system and frontal lobe; reported childhood history of physical/emotional trauma and sexual abuse measures were negatively correlated with entorhinal thickness and left hippocampal volume, respectively. In contrast, the positive traits measures were positively associated with hippocampal and amygdala volumes and cortical thickness of the highly-connected precuneus and cingulate cortex. Our findings suggest that structural brain measures may reflect neurobiological mechanisms underlying MDD features.
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- 2021
20. Examining the relationship between gray matter volume and a continuous measure of bipolarity in unmedicated unipolar and bipolar depression
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Harry Rubin-Falcone, Reuben Heyman-Kantor, Ainsley K. Burke, Jeffrey M. Miller, J. John Mann, Mina M. Rizk, Yashar Yousefzadeh Fard, Maria A. Oquendo, Francesca Zanderigo, Matthew S. Milak, M. Elizabeth Sublette, and Gregory M. Sullivan
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medicine.medical_specialty ,Bipolar Disorder ,Brain Structure and Function ,Audiology ,computer.software_genre ,behavioral disciplines and activities ,Gray (unit) ,03 medical and health sciences ,0302 clinical medicine ,Voxel ,mental disorders ,Humans ,Medicine ,Bipolar disorder ,Gray Matter ,Major depressive episode ,Depression (differential diagnoses) ,Cerebral Cortex ,Depressive Disorder, Major ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Major depressive disorder ,medicine.symptom ,business ,computer ,030217 neurology & neurosurgery - Abstract
It has been argued that unipolar major depressive disorder (MDD) and bipolar disorder (BD) exist on a continuous spectrum, given their overlapping symptomatology and genetic diatheses. The Bipolarity Index (BI) is a scale that considers bipolarity as a continuous construct and was developed to assess confidence in bipolar diagnosis. Here we investigated whether BI scores correlate with gray matter volume (GMV) in a sample of unmedicated unipolar and bipolar depressed individuals.158 subjects (139 with MDD, 19 with BD) in a major depressive episode at time of scan were assigned BI scores. T1-weighted Magnetic Resonance Imaging scans were obtained and processed with Voxel-Based Morphometry using SPM12 (CAT12 toolbox) to assess GMV. Regression was performed at the voxel level to identify clusters of voxels whose GMV was associated with BI score, (p0.001, family-wise error-corrected cluster-level p0.05), with age, sex and total intracranial volume as covariates.GMV was inversely correlated with BI score in four clusters located in left lateral occipital cortex, bilateral angular gyri and right frontal pole. Clusters were no longer significant after controlling for diagnosis. GMV was not correlated with BI score within the MDD cohort alone.Incomplete clinical data required use of a modified BI scale.BI scores were inversely correlated with GMV in unmedicated subjects with MDD and BD, but these correlations appeared driven by categorical diagnosis. Future work will examine other imaging modalities and focus on elements of the BI scale most likely to be related to brain structure and function.
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- 2021
21. Relationships between inflammatory markers and suicide risk status in major depression
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M. Elizabeth Sublette, Maria Luísa Figueira, Licínia Ganança, J. John Mann, Xinguo Ren, Maria A. Oquendo, Zahra Basseda, Hanga Galfalvy, Thomas B. Cooper, Sebastian Cisneros-Trujillo, and Repositório da Universidade de Lisboa
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medicine.medical_specialty ,Suicide, Attempted ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Biological Psychiatry ,Depression (differential diagnoses) ,Inflammation ,chemistry.chemical_classification ,Depressive Disorder, Major ,Suicide attempt ,Depression ,business.industry ,medicine.disease ,Eicosapentaenoic acid ,030227 psychiatry ,Suicide ,Psychiatry and Mental health ,Omega-3 polyunsaturated fatty acids (PUFA) ,chemistry ,Docosahexaenoic acid ,Cytokines ,Major depressive disorder ,Analysis of variance ,business ,Biomarkers ,030217 neurology & neurosurgery ,Polyunsaturated fatty acid - Abstract
© 2020 Elsevier Ltd. All rights reserved., Pro-inflammatory status has been implicated in depression and suicidal behaviors. Polyunsaturated fatty acids (PUFAs) and cytokines, two types of inflammatory biomarkers, have been associated with suicide, independent of depression severity. How these biomarkers relate to each other is less clear. We measured plasma phospholipid levels of arachidonic acid (AA%), docosahexaenoic acid (DHA%), and eicosapentaenoic acid (EPA%) as a percentage of total phospholipids, as well as serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), in 80 patients with major depressive disorder (MDD) and 24 healthy controls (HC). Individual PUFA and cytokine species were compared using ANOVA across four suicide risk-stratified groups: 1) highest-risk, recent (within 5 years) suicide attempters (n = 20); 2) high-risk, severe current suicidal ideators (having intent or plan) with no recent attempt history (n = 22); 3) low-risk, current non-ideators who were also lifetime non-attempters (n = 38); and 4) HC (n = 24). None of the participants were enrolled following an acute suicide attempt. Of biomarkers studied, only DHA% (p = 0.012) and IL-1β (p = 0.002) differed between groups. In post-hoc testing, DHA% was lower in attempters than ideators (p = 0.018) or MDD non-ideators (trend level, p = 0.073). IL-1β was lowest in attempters, differentiating them from ideators (p = 0.009) and HC (p = 0.004). Recent suicide attempt, one of the most powerful predictors of suicide risk, was also most closely tied to inflammatory indices in this study. Low DHA% as an indicator of suicide risk is consistent with previous reports; however, lower IL-1β was unexpected and may relate to acuity/chronicity of inflammation. There is a need for prospective studies of immune status with respect to suicidal behaviors., This work was supported by the American Foundation for Suicide Prevention (AFSP) [(PI: Sublette) 10/1/13 – 9/30/15], the Association for Research and Development of the School of Medicine, University of Lisbon (Ganança), and by the National Institutes of Health [5 R01 MH48514-20 (PI: Oquendo) 12/01/08-11/30/14] and [1 P50 MH090964-01A1 (PI: Mann) 7/19/13 – 6/30/18].
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- 2021
22. PAULA J. CLAYTON, MD
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Jane L. Pearson, Maria A. Oquendo, Kathy Shear, Myrna M. Weissman, Steve Zalcman, Chip Reynolds, Ray DePaulo, Katie A. Busch, Matt Rudorfer, Christine Moutier, Bob Hirschfield, John F. Greden, Sid Zisook, Murray B. Stein, John E. Rush, Jan Fawcett, Jill M. Harkavy-Friedman, Barry D. Lebowitz, Maria Kovacs, and Naomi M. Simon
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Psychiatry and Mental health ,Clinical Psychology - Published
- 2021
23. Racial Disparities in Mental Health Outcomes Among Women With Early Pregnancy Loss
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Sarita Sonalkar, Jade M. Shorter, Mary D. Sammel, Courtney A. Schreiber, Nathanael Koelper, and Maria A Oquendo
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Adult ,medicine.medical_specialty ,Early Pregnancy Loss ,Black People ,law.invention ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Adverse Childhood Experiences ,Pregnancy ,law ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Healthcare Disparities ,Original Research ,Depressive Disorder, Major ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,General Medicine ,Odds ratio ,medicine.disease ,Abortion, Spontaneous ,Clinical trial ,Mental Health ,Cohort ,Gestation ,Contents ,Female ,business ,Stress, Psychological - Abstract
The risk for major depression is common 30 days after treatment for early pregnancy loss, especially among Black women., OBJECTIVE: To explore the relationship between race and depression symptoms among participants in an early pregnancy loss clinical trial. METHODS: We performed a planned secondary analysis of a randomized trial by comparing treatments for medical management of early pregnancy loss. We hypothesized that Black participants would have higher odds of risk for major depression (measured with the CES-D [Center for Epidemiological Studies-Depression] scale) 30 days after early pregnancy loss treatment when compared with non-Black participants. We analyzed the data as a cohort, with the primary exposure being race and secondary exposure being high adverse childhood experience scores (measured with the Adverse Childhood Experience scale). Our primary outcome was risk for major depression (score of 21 or higher on the CES-D scale) 30 days after early pregnancy loss treatment. RESULTS: Three hundred participants diagnosed with a nonviable intrauterine pregnancy from 5 to 12 weeks of gestation were randomized as part of the original trial from May 2014 to April 2017. Of 275 respondents included in this analysis, 120 [44%] self-identified as Black and 155 [56%] self-identified as non-Black. After early pregnancy loss treatment, 65 [24%] participants were at risk for major depression. Black participants had an increased risk for major depression (57%) after early pregnancy loss treatment compared with non-Black participants (43%; odds ratio [OR] 2.02; 95% CI 1.15–3.55). After adjustment for risk for baseline depression, adverse childhood experience score, and parity, the odds of risk for major depression 30 days after pregnancy loss treatment remained higher for Black participants when compared with non-Black participants (OR 2.02; 95% CI 1.15–3.55; adjusted OR 2.48; 95% CI 1.28–4.81). CONCLUSION: Overall, approximately one quarter of women who experience an early pregnancy loss are at an increased risk for major depression 30 days after treatment. This risk is about twice as high for Black women compared with non-Black women. There is a need for appropriate mental health resources for women undergoing early pregnancy loss care. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02012491.
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- 2020
24. Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial
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Maria A. Oquendo, Daniel M. Alschuler, Myrna M. Weissman, Ramin V. Parsey, Christian A. Webb, Gerard E. Bruder, Patrick J. McGrath, Thomas J. Carmody, Pia Pechtel, Madhukar H. Trivedi, John G. Keilp, Melvin G. McInnis, Cristina Cusin, Crystal Cooper, Maurizio Fava, Diego A. Pizzagalli, Patricia J. Deldin, Ashleigh Rutherford, and Yuen-Siang Ang
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Bupropion ,Sertraline ,medicine.medical_specialty ,business.industry ,Serotonin reuptake inhibitor ,medicine.disease ,Placebo ,Article ,030227 psychiatry ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,Internal medicine ,medicine ,Major depressive disorder ,Verbal fluency test ,Antidepressant ,business ,Neurocognitive ,030217 neurology & neurosurgery ,Applied Psychology ,medicine.drug - Abstract
BackgroundTreatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.MethodsIn the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.ResultsGreater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.ConclusionThese exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
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- 2020
25. Technology and implementation science to forge the future of evidence-based psychotherapies: the PRIDE scale-up study
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Myrna M. Weissman, Palmira Fortunato Dos Santos, Cristiane S. Duarte, Marcelo Feijó de Mello, Bianca Kann, Terriann Nicholson, Maria A. Oquendo, Melissa Stockton, Milena Mello, Antonio Suleman, Milton L. Wainberg, Anibal Anube, Paulino Feliciano, Francine Cournos, Ana Olga Mocumbi, Rogerio Mulumba, M. Claire Greene, Phuti Ngwepe, David S. Mandell, Jair de Jesus Mari, Jean-Marie Alves-Bradford, Jennifer J. Mootz, Andre Fiks Salem, Kathryn L. Lovero, Dirceu Mabunda, Charl Bezuidenhout, Simone H Schriger, Wilza Fumo, Maria Lídia Gouveia, and Flavio Mandlate
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Mental Health Services ,Technology ,Medical education ,Evidence-based practice ,Mental Disorders ,Attendance ,Qualitative property ,Certification ,Mental health ,Focus group ,Article ,Psychotherapy ,Psychiatry and Mental health ,Interim ,Workforce ,Humans ,Psychology ,Implementation Science - Abstract
ObjectiveTo report the interim results from the training of providers inevidence-based psychotherapies (EBPs) and use of mobile applications.Design and SettingThe Partnerships in Research to Implement and Disseminate Sustainable and Scalable Evidence (PRIDE) study is a cluster-randomised hybrid effectiveness-implementation trial comparing three delivery pathways for integrating comprehensive mental healthcare into primary care in Mozambique. Innovations include the use of EBPs and scaling-up of task-shifted mental health services using mobile applications.Main outcome measuresWe examined EBP training attendance, certification, knowledge and intentions to deliver each component. We collected qualitative data through rapid ethnography and focus groups. We tracked the use of the mobile applications to investigate early reach of a valid screening tool (Electronic Mental Wellness Tool) and the roll out of the EBPsParticipantsPsychiatric technicians and primary care providers trained in the EBPs.ResultsPRIDE has trained 110 EBP providers, supervisors and trainers and will train 279 community health workers in upcoming months. The trainings improved knowledge about the EBPs and trainees indicated strong intentions to deliver the EBP core components. Trained providers began using the mobile applications and appear to identify cases and provide appropriate treatment.ConclusionsThe future of EBPs requires implementation within existing systems of care with fidelity to their core evidence-based components. To sustainably address the vast mental health treatment gap globally, EBP implementation demands: expanding the mental health workforce by training existing human resources; sequential use of EBPs to comprehensively treat mental disorders and their comorbid presentations and leveraging digital screening and treatment applications.
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- 2020
26. Lay HIV counselors' knowledge and attitudes toward depression: A mixed-methods cross-sectional study at primary healthcare centers in Mozambique
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Flavio Mandlate, M. Claire Greene, Luis F. Pereira, Annika C. Sweetland, Donald Kokonya, Cristiane S. Duarte, Francine Cournos, Maria A. Oquendo, Milton L. Wainberg, Mohsin Sidat, Esperança Sevene, and Marcelo F. Mello
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Adult ,Male ,Counselors ,Cross-Sectional Studies ,Attitude ,Primary Health Care ,Depression ,Public Health, Environmental and Occupational Health ,Benzoquinones ,Humans ,Female ,HIV Infections ,Mozambique - Abstract
IntroductionDepression is the most common mental disorder among people living with HIV/AIDS and has a negative impact on HIV treatment outcomes. Training lay HIV counselors to identify and manage depression may contribute to improved patient access and adherence to treatment, and reduce stigma and discrimination among lay health workers toward both HIV and depression. The purpose of this study was to assess the current knowledge and attitudes of lay HIV counselors toward managing depression in primary care in Mozambique.MethodsWe conducted a mixed-methods cross-sectional study to assess depression-related knowledge and attitudes among lay HIV counselors in 13 primary healthcare facilities in Mozambique. We used the quantitative Depression Attitude Questionnaire (DAQ) scale, followed by open-ended questions to further explore three key DAQ domains: the nature of depression, treatment preferences, and professional attitudes or reactions.ResultsThe sample included 107 participants (77.6% female, mean age: 32.3 years, sd = 7.4). Most (82.2%) had less than a high/technical school education. Findings suggested that some HIV counselors had knowledge of depression and described it as a cluster of psychological symptoms (e.g., deep sadness, anguish, apathy, isolation, and low self-esteem) sometimes leading to suicidal thoughts, or as a consequence of life stressors such as loss of a loved one, abuse, unemployment or physical illness, including being diagnosed with HIV infection. HIV counselors identified talking to trusted people about their problems, including family and/or counseling with a psychotherapist, as the best way for patients to deal with depression. While acknowledging challenges, counselors found working with patients with depression to be rewarding.ConclusionLay health counselors identified HIV and psychosocial issues as key risk factors for depression. They believed that the treatment approach should focus on social support and psychotherapy.
- Published
- 2022
27. Smaller left hippocampal subfield CA1 volume is associated with reported childhood physical and/or sexual abuse in major depression: A pilot study
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Harry Rubin-Falcone, M. Elizabeth Sublette, R. Todd Ogden, Xuejing Lin, Ainsley K. Burke, Minlan Yuan, J. John Mann, Maria A. Oquendo, Mina M. Rizk, and Jeffrey M. Miller
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Adult ,Hippocampus ,Pilot Projects ,Hippocampal formation ,Amygdala ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Child ,Depression (differential diagnoses) ,Retrospective Studies ,Depressive Disorder, Major ,Depression ,business.industry ,Sex Offenses ,Organ Size ,medicine.disease ,Magnetic Resonance Imaging ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,medicine.anatomical_structure ,nervous system ,Sexual abuse ,Major depressive disorder ,Sex offense ,business ,030217 neurology & neurosurgery ,Clinical psychology ,Psychopathology - Abstract
Background Smaller hippocampal volumes are reported in adults with major depressive disorder (MDD) and in reported childhood abuse. The hippocampus is a complex structure with distinct functional subfields. We sought to examine the effect of MDD diagnosis and childhood abuse on hippocampal subfields. Methods Forty-one MDD participants (17 reported abuse and 24 did not) and 46 healthy volunteers (HV) (2 reported abuse) underwent T1- weighted structural magnetic resonance imaging (MRI) and clinical characterization in a retrospective design. A subfield segmentation program was used to measure the whole and subfield hippocampal volumes. Linear mixed-effects models were fitted for group comparisons. Results No main effect of diagnosis interaction effect between diagnosis and subfield region was observed. However, a comparison of abused MDD vs. HVs showed a group by region interaction. A significant interaction between childhood abuse and region was observed. Effects were confined to the left side of the brain, and post hoc, exploratory region-specific tests indicated smaller left CA1 volume in abused MDD compared with non-abused MDD. In addition, smaller amygdala volume was found in all MDD compared with HVs. Limitations We did not have a sample of healthy volunteers with reported childhood abuse. Conclusions The diagnosis of pure MDD may not be sufficient to exert effects on hippocampal volumes, indicating the importance of taking into account childhood trauma in studies on psychopathological mechanisms. Left CA1 might be the hippocampal subfield most relevant to reported childhood abuse. Smaller amygdala volume may be related to MDD diagnosis independent of childhood abuse.
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- 2020
28. Detecting suicidal thoughts: The power of ecological momentary assessment
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Liat Itzhaky, Maria A. Oquendo, J. John Mann, Tse-Hwei Choo, Barbara Stanley, Ilana Gratch, Hanga Galfalvy, and John G. Keilp
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Adult ,Ecological Momentary Assessment ,Poison control ,Suicide prevention ,Occupational safety and health ,Suicidal Ideation ,03 medical and health sciences ,0302 clinical medicine ,Injury prevention ,Humans ,Medicine ,Suicidal ideation ,Retrospective Studies ,Depressive Disorder, Major ,Ecology ,business.industry ,Human factors and ergonomics ,Ideation ,medicine.disease ,humanities ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Major depressive disorder ,Smartphone ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
BACKGROUND Researchers and clinicians have typically relied on retrospective reports to monitor suicidal thoughts and behaviors. Smartphone technology has made real-time monitoring of suicidal thoughts possible via mobile ecological momentary assessment (EMA). However, little is known about how information gleaned from EMA compares with that obtained by retrospective reports. The authors sought to compare suicidal ideation (SI) assessed over 1 week using EMA with a retrospective gold-standard interviewer-administered measure covering the same period. METHODS Fifty-one adults with major depressive disorder completed 1 week of EMA (6×/day) assessing SI. Following completion of EMA, participants completed an interviewer-administered Scale for Suicide Ideation (SSI) retrospectively assessing the same week. RESULTS SI severity assessed through EMA was positively correlated with scores on the retrospective SSI. However, 58% of participants reporting ideation with EMA denied any past-week ideation on the SSI. Participants who endorsed SI during EMA but not on the SSI were no less likely to have a history of suicidal behavior than those who reported SI in both formats. CONCLUSION EMA captures instances of suicidal thinking that go undetected through retrospective report and thereby may help us to identify an at-risk subgroup otherwise missed.
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- 2020
29. Large-scale network dynamics in neural response to emotionally negative stimuli linked to serotonin 1A binding in major depressive disorder
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Francesca Zanderigo, M. Elizabeth Sublette, Maria A. Oquendo, Jeffrey M. Miller, J. John Mann, Kevin N. Ochsner, Paul Sajda, Ainsley K. Burke, Harry Rubin Falcone, Noam Schneck, Barbara Stanley, and Tao Tu
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0301 basic medicine ,Serotonin ,Hippocampus ,Inferior frontal gyrus ,Hippocampal formation ,Serotonergic ,behavioral disciplines and activities ,Amygdala ,Article ,Midbrain Raphe Nuclei ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine ,Humans ,Molecular Biology ,Depressive Disorder, Major ,medicine.diagnostic_test ,Raphe ,business.industry ,Brain ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Positron-Emission Tomography ,Receptor, Serotonin, 5-HT1A ,business ,Functional magnetic resonance imaging ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Serotonergic dysfunction is implicated in major depressive disorder (MDD), but the mechanisms of this relationship remain elusive. Serotonin 1A (5-HT1A) autoreceptors regulate brain-wide serotonin neuron firing and are positioned to assert large-scale effects on negative emotion. Here we investigated the relationship between raphe 5-HT1A binding and brain-wide network dynamics of negative emotion. 22 healthy-volunteers (HV) and 27 medication-free participants with MDD underwent positron emission tomography (PET) using [11C]CUMI-101 (CUMI) to quantify 5-HT1A binding in midbrain raphe nuclei and functional magnetic resonance imaging (fMRI) scanning during emotionally negative picture viewing. Causal connectivity across regions responsive to negative emotion was estimated in the fMRI data using a multivariate dynamical systems model. During negative picture viewing, MDD subjects demonstrated significant hippocampal inhibition of amygdala, basal-ganglia, thalamus, orbital frontal cortex, inferior frontal gyrus and dorsomedial prefrontal cortex (IFG, dmPFC). MDD-related connectivity was not associated with raphe 5-HT1A binding. However, greater hippocampal inhibition of amygdala, thalamus, IFG and dmPFC correlated with hippocampal 5-HT1A binding. Correlation between hippocampal 5-HT1A binding and the hippocampal inhibition network was specific to MDD but not HV. MDD and HV groups also differed with respect to the correlation between raphe and hippocampal 5-HT1A binding which was more pronounced in HV. These findings suggest that increased hippocampal network inhibition in MDD is linked to hippocampal serotonergic dysfunction which may in turn arise from disrupted linkage in raphe to hippocampus serotonergic circuitry.
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- 2020
30. Sleep complaints are associated with increased suicide risk independently of psychiatric disorders: results from a national 3-year prospective study
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Maria A. Oquendo, Philippe Courtet, Nicolas Hoertel, Michel Lejoyeux, Carlos Blanco, Pierre A. Geoffroy, Frédéric Limosin, Mark Olfson, and Hugo Peyre
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0301 basic medicine ,medicine.medical_specialty ,Suicide attempt ,business.industry ,Prevalence ,Sleep in non-human animals ,Structural equation modeling ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,Increased risk ,medicine ,Suicide Risk ,Prospective cohort study ,Psychiatry ,business ,Molecular Biology ,030217 neurology & neurosurgery ,Psychopathology - Abstract
Prior research suggests that sleep disturbances are associated with increased risk of suicide. However, sleep disturbances are associated with a wide range of psychiatric disorders, and it is unknown whether this association is independent of psychopathology. In a large nationally representative prospective survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we used structural equation modeling to examine the shared and specific effects of three sleep complaints (i.e., trouble falling asleep, early morning awakening, and hypersomnia) on the 3-year occurrence of attempting suicide. Because psychiatric disorders increase the risk of suicide attempt almost exclusively through a general psychopathology factor representing their shared effect, covariates included that factor, prior history of suicide attempt, and a wide range of sociodemographic and clinical characteristics. The 3-year prevalence rate of suicide attempt was 0.6% (n = 241). Compared with participants who did not attempt suicide between the two waves, those who did reported significantly more frequently having trouble falling asleep (44.6% vs. 16.6%), early morning awakening (38.9% vs. 12.7%), and hypersomnia (35.0% vs. 10.7%). Following adjustments, effects of sleep complaints on this risk were significant and exerted almost exclusively through a general sleep complaints factor representing the shared effect across all sleep complaints. There were no residual associations of any individual sleep complaint with attempting suicide above that association. Sleep complaints are associated with an increased risk of attempting suicide independently of psychopathology, and should be included in suicide risk assessments as these symptoms may provide targets for reducing the risks of suicidal behaviors.
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- 2020
31. Suicide Risk Assessment and Prevention: Challenges and Opportunities
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Maria A. Oquendo and Eileen P Ryan
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medicine.medical_specialty ,business.industry ,Reviews ,Suicide prevention ,Psychological evaluation ,Mood ,Intervention (counseling) ,Medicine ,Anxiety ,Mental health care ,medicine.symptom ,Substance use ,business ,Psychiatry ,Suicide Risk - Abstract
Despite increased access to mental health care for the previously uninsured and expanding evidence-based treatments for mood, anxiety, psychotic, and substance use disorders, suicide is on the rise in the United States. Since 1999, the age-adjusted suicide rate in the United States has increased 33%, from 10.5 per 100,000 standard population to 14.0. As of yet, there are no clinically available biomarkers, laboratory tests, or imaging to assist in diagnosis or the identification of the suicidal individual. Suicide risk assessment remains a high-stakes component of the psychiatric evaluation and can lead to overly restrictive management in the name of prevention or to inadequate intervention because of poor appreciation of the severity of risk. This article focuses primarily on suicide risk assessment and management as a critical first step to prevention, given the fact that more research is needed to identify precision treatments and effective suicide prevention strategies. Suicide risk assessment provides the clinical psychiatrist with an opportunity for therapeutic engagement with the ultimate goals of relieving suffering and preventing suicide.
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- 2020
32. Deficits of white matter axial diffusivity in bipolar disorder relative to major depressive disorder: No relationship to cerebral perfusion or body mass index
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Harry Rubin-Falcone, Jonathan W. Stewart, J. John Mann, Maria A. Oquendo, Patrick J. McGrath, David J. Hellerstein, Francesca Zanderigo, M. Elizabeth Sublette, and Martin J. Lan
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Adult ,Male ,medicine.medical_specialty ,Bipolar Disorder ,Internal capsule ,behavioral disciplines and activities ,Body Mass Index ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Internal Capsule ,Internal medicine ,mental disorders ,medicine ,Humans ,Inferior longitudinal fasciculus ,Cerebral perfusion pressure ,Major depressive episode ,Biological Psychiatry ,Depressive Disorder, Major ,business.industry ,Superior longitudinal fasciculus ,Middle Aged ,medicine.disease ,White Matter ,030227 psychiatry ,Psychiatry and Mental health ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Cerebral blood flow ,Cerebrovascular Circulation ,Cardiology ,Major depressive disorder ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Objective To compare white matter integrity (WMI) in bipolar disorder (BD) relative to healthy volunteers (HVs) and major depressive disorder (MDD). To determine the relationship of bipolar-specific differences in WMI to cerebral perfusion, body mass index (BMI), and blood pressure as indices of cardiovascular function. Methods Thirty-two participants with BD, 44 with MDD, and 41 HV were recruited. All BD and MDD participants were in a major depressive episode, and all but 12 BD participants were medication-free. 64-direction diffusion tensor imaging (DTI) and arterial spin labeling (ASL) sequences were obtained. Tract-based spatial statistics (TBSS) on four DTI indices were employed to distinguish patterns of DTI in BD relative to HV and MDD groups. BMI, blood pressure, and medical histories were also obtained for the BD participants. Results A cluster of lower axial diffusivity (AD) was found in BD participants in comparison to the HVs in the left posterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and internal capsule. Mean AD in the significant cluster was not associated with cerebral blood flow (CBF) in the region as measured by ASL, and was not associated with BMI or blood pressure. A cluster of lower AD was also found in the BD group when compared to MDD that had spatial overlap with the HV comparison. Conclusions The results indicate a deficit of AD in BD when compared to MDD and HV groups. No association between AD values and either cerebral perfusion, BMI, or blood pressure was found in BD.
- Published
- 2019
33. Dynamic Resting-State Network Biomarkers of Antidepressant Treatment Response
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Roselinde H. Kaiser, Henry W. Chase, Mary L. Phillips, Thilo Deckersbach, Ramin V. Parsey, Maurizio Fava, Patrick J. McGrath, Myrna Weissman, Maria A. Oquendo, Melvin G. McInnis, Thomas Carmody, Crystal M. Cooper, Madhukar H. Trivedi, and Diego A. Pizzagalli
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Adult ,Depressive Disorder, Major ,Sertraline ,Brain ,Humans ,Magnetic Resonance Imaging ,Biological Psychiatry ,Antidepressive Agents ,Biomarkers - Abstract
Delivery of effective antidepressant treatment has been hampered by a lack of objective tools for predicting or monitoring treatment response. This study aimed to address this gap by testing novel dynamic resting-state functional network markers of antidepressant response.The Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study randomized adults with major depressive disorder to 8 weeks of either sertraline or placebo, and depression severity was evaluated longitudinally. Participants completed resting-state neuroimaging pretreatment and again after 1 week of treatment (n = 259 eligible for analyses). Coactivation pattern analyses identified recurrent whole-brain states of spatial coactivation, and computed time spent in each state for each participant was the main dynamic measure. Multilevel modeling estimated the associations between pretreatment network dynamics and sertraline response and between early (pretreatment to 1 week) changes in network dynamics and sertraline response.Dynamic network markers of early sertraline response included increased time in network states consistent with canonical default and salience networks, together with decreased time in network states characterized by coactivation of cingulate and ventral limbic or temporal regions. The effect of sertraline on depression recovery was mediated by these dynamic network changes. In contrast, early changes in dynamic functioning of corticolimbic and frontoinsular-default networks were related to patterns of symptom recovery common across treatment groups.Dynamic resting-state markers of early antidepressant response or general recovery may assist development of clinical tools for monitoring and predicting effective intervention.
- Published
- 2021
34. Community Health Workers’ Knowledge, Attitudes, and Practices towards Epilepsy in Sofala, Central Mozambique
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Vasco Francisco Japissane Cumbe, Claire Greene, Afonso Mazine Tiago Fumo, Hélder Fumo, Dirceu Mabunda, Lídia Chaúque Gouveia, Maria A. Oquendo, Cristiane S. Duarte, Mohsin Sidat, and Jair de Jesus Mari
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Community Health Workers ,Health Knowledge, Attitudes, Practice ,Epilepsy ,Seizures ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Humans ,Reproducibility of Results ,epilepsy ,community health workers ,knowledge ,attitudes ,practices ,primary health care ,Mozambique - Abstract
Background: Epilepsy is the most common neurological disease in the world, affecting 50 million people, with the majority living in low- and middle-income countries (LMICs). A major focus of epilepsy treatment in LMICs has been task-sharing the identification and care for epilepsy by community health workers (CHWs). The present study aimed to assess the knowledge, attitudes, and practices (KAPs) of CHWs towards epilepsy in Mozambique. Methods: One hundred and thirty-five CHWs completed a questionnaire that included socio-demographic characteristics and 44-items divided into six subscales pertaining to KAPs towards epilepsy (QKAP-EPI) across nine districts of Sofala, Mozambique. The internal consistency was examined to evaluate the reliability of the instrument (QKAP-EPI). The association between sociodemographic variables and QKAP-EPI subscales was examined using linear regression models. Results: The internal consistency was moderate for two subscales (causes of epilepsy, α = 0.65; medical treatment, α = 0.694), acceptable for cultural treatment (α = 0.797) and excellent for 2 subscales (safety and risks, α = 0.926; negative attitudes, α = 0.904). Overall, CHWs demonstrated accurate epilepsy knowledge (medical treatment: mean = 1.63, SD = 0.28; safety/risks: mean = 1.62, SD = 0.59). However, CHWs reported inaccurate epilepsy knowledge of the causes, negative attitudes, as well as culturally specific treatments for epilepsy, such as: “if a person with epilepsy burns when set on fire they cannot be treated”. Knowledge about how to manage epileptic seizures varied across the different emergency care practices, from the accurate belief that it is not advisable to place objects in the individual’s mouth during an epileptic seizure, to the wrong perception of the need to hold the person in seizures to control seizures. Heterogeneity in the level of epilepsy knowledge was observed among CHWs, when considering epilepsy according to the local names as treatable (“Dzumba”) and other forms as untreatable (“Nzwiti”). Conclusion: CHWs knowledge of medical treatment and epilepsy safety/risks were adequate. However, information on the causes of epilepsy, stigmatizing attitudes, cultural treatment, and some knowledge of epileptic seizure management were low. These areas of poor knowledge should be the focus of educating CHWs in increasing their ability to provide quality care for patients with epilepsy in Mozambique.
- Published
- 2022
35. Plasma testosterone levels and subsequent suicide attempts in males with bipolar disorder
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Michael F. Grunebaum, J. John Mann, Leo Sher, Maria A. Oquendo, and M. Elizabeth Sublette
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Male ,medicine.medical_specialty ,Bipolar Disorder ,business.industry ,Testosterone (patch) ,Suicide, Attempted ,medicine.disease ,Psychiatry and Mental health ,Endocrinology ,Risk Factors ,Internal medicine ,Medicine ,Humans ,Testosterone ,Bipolar disorder ,business - Published
- 2021
36. Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography
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Ashley Yttredahl, Maria A. Oquendo, Ansel T. Hillmer, Jeffrey M. Miller, Richard E. Carson, J. John Mann, and Kelly Smart
- Subjects
Adult ,medicine.medical_specialty ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Molecular neuroscience ,κ-opioid receptor ,behavioral disciplines and activities ,Gyrus Cinguli ,Article ,Cellular and Molecular Neuroscience ,Rating scale ,Internal medicine ,medicine ,Humans ,Biological Psychiatry ,Depression (differential diagnoses) ,Depressive Disorder, Major ,medicine.diagnostic_test ,business.industry ,Depression ,Putamen ,Receptors, Opioid, kappa ,Brain ,medicine.disease ,Frontal Lobe ,Psychiatry and Mental health ,Frontal lobe ,Positron emission tomography ,Case-Control Studies ,Positron-Emission Tomography ,Cardiology ,Major depressive disorder ,Female ,business ,Insula ,RC321-571 - Abstract
Preclinical studies have implicated kappa opioid receptors (KORs) in stress responses and depression-related behaviors, but evidence from human studies is limited. Here we present results of a secondary analysis of data acquired using positron emission tomography (PET) with the KOR radiotracer [11C]GR103545 in 10 unmedicated, currently depressed individuals with major depressive disorder (MDD; 32.6 ± 6.5 years, 5 women) and 13 healthy volunteers (34.8 ± 10 years, 6 women). Independent component analysis was performed to identify spatial patterns of coherent variance in KOR binding (tracer volume of distribution, VT) across all subjects. Expression of each component was compared between groups and relationships to symptoms were explored using the 17-item Hamilton Depression Rating Scale (HDRS). Three components of variation in KOR availability across ROIs were identified, spatially characterized by [11C]GR103545 VT in (1) bilateral frontal lobe; (2) occipital and parietal cortices, right hippocampus, and putamen; and (3) right anterior cingulate, right superior frontal gyrus and insula, coupled to negative loading in left middle cingulate. In MDD patients, component 3 was negatively associated with symptom severity on the HDRS (r = −0.85, p = 0.0021). There were no group-wise differences in expression of any component between patients and controls. These preliminary findings suggest that KOR signaling in cortical regions relevant to depression, particularly right anterior cingulate, could reflect MDD pathophysiology.
- Published
- 2021
37. Serotonin Transporter Binding in Major Depressive Disorder: Impact of Serotonin System Anatomy
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Elizabeth A. Bartlett, Francesca Zanderigo, Denise Shieh, Jeffrey Miller, Patrick Hurley, Harry Rubin-Falcone, Maria A. Oquendo, M. Elizabeth Sublette, R. Todd Ogden, and J. John Mann
- Subjects
Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,mental disorders ,Molecular Biology - Abstract
Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic axons; and (2) using the Copenhagen University Hospital Neurobiology Research Unit (NRU) 5-HT Atlas, based on brain-wide binding patterns of multiple serotonin receptor types. [11C]DASB 5-HTT PET scans were obtained in 59 unmedicated participants with MDD in a current depressive episode and 32 healthy volunteers (HVs). Binding potential (BPP) was quantified with empirical Bayesian estimation in graphical analysis (EBEGA). Within the [11C]DASB tract, MDD showed significantly lower BPP compared with HVs (p=0.02). The BPP diagnosis difference varied by tract location at a trend-level (p=0.08), with MDD binding deficit strongest most proximal to brainstem raphe nuclei. NRU 5-HT Atlas ROIs showed trend-level lower BPPin MDD relative to HVs (p=0.06) and BPP diagnosis difference that varied by region (p=0.001). BPP was lower in MDD in 4/10 regions (p-values
- Published
- 2021
38. COBALT: Supporting the mental well-being of the health care workforce with technology-facilitated care during Covid-19 and beyond
- Author
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Cecilia Livesey, Kelley Kugler, Jack J. Huang, Eleanor Burton, Avanti Rangnekar, Grace Vojta, Maria A. Oquendo, Lisa Bellini, and David A. Asch
- Subjects
Technology ,Mental Health ,SARS-CoV-2 ,Health Policy ,Health Personnel ,Workforce ,COVID-19 ,Humans ,Cobalt ,Delivery of Health Care ,Pandemics - Abstract
Two-thirds of health professionals facing the clinical demands of responding to the Covid-19 pandemic experience psychiatric symptoms, including post-traumatic stress, anxiety, substance use, depression, insomnia, and suicide.
- Published
- 2021
39. Neural predictors and effects of cognitive behavioral therapy for depression: the role of emotional reactivity and regulation - CORRIGENDUM
- Author
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Harry Rubin-Falcone, Jochen Weber, Ronit Kishon, Kevin Ochsner, Lauren Delaparte, Bruce Doré, Sudha Raman, Bryan T. Denny, Maria A. Oquendo, J. John Mann, and Jeffrey M. Miller
- Subjects
Psychiatry and Mental health ,Cognitive Behavioral Therapy ,Depression ,Emotions ,Humans ,Applied Psychology - Published
- 2021
40. Primary familial basal ganglia calcification presented with depression and obsessive–compulsive symptoms: A case report
- Author
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Maria Lídia Gouveia, Mohsin Sidat, Dirceu Mabunda, Vasco Cumbe, Maria A. Oquendo, and Jair de Jesus Mari
- Subjects
Psychiatry and Mental health ,medicine.medical_specialty ,Neurology ,business.industry ,General Neuroscience ,Medicine ,Basal ganglia calcification ,Neurology (clinical) ,General Medicine ,business ,Obsessive compulsive symptoms ,Dermatology ,Depression (differential diagnoses) - Published
- 2020
41. Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response
- Author
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Maria A. Oquendo, Crystal Cooper, Andrew LaBella, Melvin G. McInnis, Maurizio Fava, Madhukar H. Trivedi, Diego A. Pizzagalli, Benji T. Kurian, Myrna M. Weissman, Mengru Zhang, Chuan Huang, Rajapillai L. I. Pillai, Ramin V. Parsey, Patrick J. McGrath, Jie Yang, and Christine DeLorenzo
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Placebo ,Hippocampus ,behavioral disciplines and activities ,Amygdala ,Article ,03 medical and health sciences ,0302 clinical medicine ,Sertraline ,Internal medicine ,mental disorders ,Fractional anisotropy ,medicine ,Humans ,Depressive Disorder, Major ,Raphe ,business.industry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Antidepressive Agents ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,medicine.anatomical_structure ,Anisotropy ,Raphe Nuclei ,Major depressive disorder ,Antidepressant ,Female ,business ,Raphe nuclei ,Selective Serotonin Reuptake Inhibitors ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. Methods 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. Results Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. Conclusions We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.
- Published
- 2019
42. Discovery and replication of cerebral blood flow differences in major depressive disorder
- Author
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Benji T. Kurian, Peiying Liu, Ramin V. Parsey, Patrick J. McGrath, Maurizio Fava, Thomas J. Carmody, Mary L. Phillips, Bruce D. Grannemann, Crystal Cooper, Jorge R. C. Almeida, Hanzhang Lu, Maria A. Oquendo, Thilo Deckersbach, Cherise Chin Fatt, Myrna M. Weissman, Elizabeth Bartlett, Madhukar H. Trivedi, Ashley Malchow, and Melvin G. McInnis
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Thalamus ,behavioral disciplines and activities ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Neuroimaging ,Internal medicine ,mental disorders ,medicine ,Molecular Biology ,Brain function ,business.industry ,Inferior parietal lobule ,medicine.disease ,Psychiatry and Mental health ,030104 developmental biology ,nervous system ,Cerebral blood flow ,Cardiology ,Major depressive disorder ,business ,Insula ,Perfusion ,030217 neurology & neurosurgery - Abstract
Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
- Published
- 2019
43. Prevalence of depression among patients with presumptive pulmonary tuberculosis in Rio de Janeiro, Brazil
- Author
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Pedro da Silva Martins, Annika C. Sweetland, José Ricardo de Almeida França, Karina M de Castro-Silva, Anna Cristina Calçada Carvalho, Maria A. Oquendo, Afrânio Lineu Kritski, and Maria Tavares Cavalcanti
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,Tuberculosis ,lcsh:RC435-571 ,Cross-sectional study ,prevalence ,macromolecular substances ,environment and public health ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pulmonary tuberculosis ,lcsh:Psychiatry ,Surveys and Questionnaires ,Internal medicine ,Prevalence ,Humans ,Medicine ,Major depressive episode ,Tuberculosis, Pulmonary ,Depression (differential diagnoses) ,Mini-international neuropsychiatric interview ,Depressive Disorder, Major ,Primary Health Care ,integumentary system ,Depression ,business.industry ,Middle Aged ,medicine.disease ,3. Good health ,030227 psychiatry ,Patient Health Questionnaire ,Psychiatry and Mental health ,Cross-Sectional Studies ,tuberculosis ,Socioeconomic Factors ,Female ,medicine.symptom ,business ,Brazil ,030217 neurology & neurosurgery - Abstract
Objective: To estimate the prevalence of major depressive episode (MDE) in patients with presumptive pulmonary tuberculosis (pre-PTB, defined by cough lasting ≥ 3 weeks) and compare it between patients with pulmonary tuberculosis (PTB) and without PTB. Methods: Patients with pre-PTB (n=260) were screened for depression using the Patient Health Questionnaire (PHQ-9). Those individuals with scores ≥ 10 were subsequently assessed with the depression module of the Mini International Neuropsychiatric Interview (MINI-Plus) to confirm diagnosis. Associations of categorical variables with PTB and MDE were calculated using the chi-square test and OR. Results: PTB was confirmed in 98 patients (37.7%). A high proportion of both groups (active PTB and no PTB) screened positive for depression (60.2 vs. 62.1%, respectively). Among 159 patients who screened positive for depression, a subset of 97 (61.0%) were further evaluated with the MINI-Plus; current MDE was confirmed in 54.6% (53/97). On univariate and multivariate analysis, female sex was the only factor associated with the diagnosis of current MDE (p = 0.04). Conclusion: The prevalence of MDE was high among individuals with prolonged respiratory symptoms, independent of PTB diagnosis. This is consistent with other studies of depression in primary care in Brazil.
- Published
- 2019
44. Pretreatment Rostral Anterior Cingulate Cortex Connectivity With Salience Network Predicts Depression Recovery: Findings From the EMBARC Randomized Clinical Trial
- Author
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Phil Adams, Ashleigh Rutherford, Melvin G. McInnis, Patrick J. McGrath, Alexis E. Whitton, Crystal Cooper, Christian A. Webb, Daniel G. Dillon, Maurizio Fava, Franziska Goer, Maria A. Oquendo, Myrna M. Weissman, Joseph M. Trombello, Gerard E. Bruder, Thomas J. Carmody, Madhukar H. Trivedi, Diego A. Pizzagalli, Patricia J. Deldin, Jürgen Kayser, and Ramin V. Parsey
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Placebo ,Gyrus Cinguli ,Article ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Sertraline ,Neural Pathways ,medicine ,Humans ,Theta Rhythm ,Biological Psychiatry ,Default mode network ,Anterior cingulate cortex ,Depressive Disorder, Major ,business.industry ,Hamilton Rating Scale for Depression ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Posterior cingulate ,Major depressive disorder ,Female ,business ,Insula ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Baseline rostral anterior cingulate cortex (rACC) activity is a well-replicated nonspecific predictor of depression improvement. The rACC is a key hub of the default mode network, which prior studies indicate is hyperactive in major depressive disorder. Because default mode network downregulation is reliant on input from the salience network and frontoparietal network, an important question is whether rACC connectivity with these systems contributes to depression improvement. Methods Our study evaluated this hypothesis in outpatients (N = 238; 151 female) enrolled in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) 8-week randomized clinical trial of sertraline versus placebo for major depressive disorder. Depression severity was measured using the Hamilton Rating Scale for Depression, and electroencephalography was recorded at baseline and week 1. Exact low-resolution electromagnetic tomography was used to compute activity from the rACC, and key regions within the default mode network (posterior cingulate cortex), frontoparietal network (left dorsolateral prefrontal cortex), and salience network (right anterior insula [rAI]). Connectivity in the theta band (4.5–7 Hz) and beta band (12.5–21 Hz) was computed using lagged phase synchronization. Results Stronger baseline theta-band rACC–rAI (salience network hub) connectivity predicted greater depression improvement across 8 weeks of treatment for both treatment arms (B = −0.57, 95% confidence interval = −1.07, −0.08, p = .03). Early increases in theta-band rACC–rAI connectivity predicted greater likelihood of achieving remission at week 8 (odds ratio = 2.90, p = .03). Conclusions Among patients undergoing treatment, theta-band rACC–rAI connectivity is a prognostic, albeit treatment-nonspecific, indicator of depression improvement, and early connectivity changes may predict clinically meaningful outcomes.
- Published
- 2019
45. Cortisol Stress Response and in Vivo PET Imaging of Human Brain Serotonin 1A Receptor Binding
- Author
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J. John Mann, Maria A. Oquendo, Barbara Stanley, Louisa J. Steinberg, Hanga Galfalvy, Harry Rubin-Falcone, Eli Min, John G. Keilp, Jeffrey M. Miller, M. Elizabeth Sublette, Thomas B. Cooper, R. Todd Ogden, and Joshua A. Kaufman
- Subjects
Male ,Hydrocortisone ,Pyridines ,PET imaging ,Pain, Procedural ,Regular Research Articles ,Piperazines ,stress ,0302 clinical medicine ,Trier social stress test ,Pharmacology (medical) ,Carbon Radioisotopes ,Brain Mapping ,Catheter insertion ,Brain ,Middle Aged ,serotonin ,Psychiatry and Mental health ,Receptor, Serotonin, 5-HT1A ,Major depressive disorder ,5-HT1A receptor ,Female ,Psychological stressor ,Adult ,Cortisol secretion ,medicine.medical_specialty ,Adolescent ,Rest ,cortisol ,Serotonergic ,Catheterization ,Young Adult ,03 medical and health sciences ,Stress, Physiological ,Internal medicine ,medicine ,Humans ,Aged ,Pharmacology ,Depressive Disorder, Major ,business.industry ,medicine.disease ,030227 psychiatry ,Endocrinology ,Positron-Emission Tomography ,Serotonin ,Radiopharmaceuticals ,business ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
Background Abnormalities in the hypothalamic-pituitary-adrenal axis, serotonergic system, and stress response have been linked to the pathogenesis of major depressive disorder. State-dependent hyper-reactivity of the hypothalamic-pituitary-adrenal axis is seen in major depressive disorder, and higher binding to the serotonin 1A receptor is observed as a trait in both currently depressed and remitted untreated major depressive disorder. Here, we sought to examine whether a relationship exists between cortisol secretion in response to a stressor and serotonin 1A receptor binding throughout the brain, both in healthy controls and participants with major depressive disorder. Methods Research participants included 42 medication-free, depressed subjects and 31 healthy volunteers. Participants were exposed to either an acute, physical stressor (radial artery catheter insertion) or a psychological stressor (Trier Social Stress Test). Levels of serotonin 1A receptor binding on positron emission tomography with [11C]WAY-100635 were also obtained from all participants. The relationship between [11C]WAY-100635 binding and cortisol was examined using mixed linear effects models with group (major depressive disorder vs control), cortisol, brain region, and their interactions as fixed effects and subject as a random effect. Results We found a positive correlation between post-stress cortisol measures and serotonin 1A receptor ligand binding levels across multiple cortical and subcortical regions, independent of diagnosis and with both types of stress. The relationship between [11C]WAY-100635 binding and cortisol was homogenous across all a priori brain regions. In contrast, resting cortisol levels were negatively correlated with serotonin 1A receptor ligand binding levels independently of diagnosis, except in the RN. There was no significant difference in cortisol between major depressive disorder participants and healthy volunteers with either stressor. Similarly, there was no correlation between cortisol and depression severity in either stressor group. Conclusions This study suggests that there may be a common underlying mechanism that links abnormalities in the serotonin system and hypothalamic-pituitary-adrenal axis hyper-reactivity to stress. Future studies need to determine how hypothalamic-pituitary-adrenal axis dysfunction affects mood to increase the risk of suicide in major depression.
- Published
- 2019
46. Neurocognitive functioning in community youth with suicidal ideation: gender and pubertal effects
- Author
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Maria A. Oquendo, Tami D. Benton, Monica E. Calkins, Raquel E. Gur, Ran Barzilay, Ruben C. Gur, Jason D. Jones, Rhonda C. Boyd, and Tyler M. Moore
- Subjects
Male ,Adolescent ,Article ,Suicidal Ideation ,Cohort Studies ,Thinking ,Executive Function ,Young Adult ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,Rating scale ,medicine ,Humans ,Cognitive Dysfunction ,Effects of sleep deprivation on cognitive performance ,Child ,Suicidal ideation ,Philadelphia ,Psychiatric Status Rating Scales ,Psychopathology ,Cognition ,Adolescent Development ,030227 psychiatry ,Psychiatry and Mental health ,Logistic Models ,Female ,medicine.symptom ,Psychology ,Neurocognitive ,030217 neurology & neurosurgery ,Social cognitive theory ,Developmental psychopathology ,Clinical psychology - Abstract
BackgroundAlthough there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.AimsTo characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.MethodParticipants (N = 6151, age 11–21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.ResultsYouth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.ConclusionsSuicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.Declaration of interestR.B. serves on the scientific board and reports stock ownership in ‘Taliaz Health’, with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.
- Published
- 2019
47. Resting‐state amplitude of low‐frequency fluctuation is associated with suicidal ideation
- Author
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Mina M. Rizk, M. Elizabeth Sublette, John G. Keilp, Harry Rubin-Falcone, Maria A. Oquendo, Martin J. Lan, Spiro P. Pantazatos, J. John Mann, and Jeffrey M. Miller
- Subjects
Adult ,Male ,medicine.medical_specialty ,Brain activity and meditation ,Hippocampus ,Audiology ,Article ,Suicidal Ideation ,03 medical and health sciences ,0302 clinical medicine ,Thalamus ,Post-hoc analysis ,medicine ,Humans ,Major depressive episode ,Suicidal ideation ,Brain Mapping ,Depressive Disorder, Major ,Resting state fMRI ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Magnetic Resonance Imaging ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Major depressive disorder ,Female ,Caudate Nucleus ,medicine.symptom ,business ,Functional magnetic resonance imaging ,human activities ,030217 neurology & neurosurgery - Abstract
Background Identifying brain activity patterns that are associated with suicidal ideation (SI) may help to elucidate its pathogenesis and etiology. Suicide poses a significant public health problem, and SI is a risk factor for suicidal behavior. Methods Forty-one unmedicated adult participants in a major depressive episode (MDE), 26 with SI on the Beck Scale for Suicidal Ideation and 15 without SI, underwent resting-state functional magnetic resonance imaging scanning. Twenty-one healthy volunteers (HVs) were scanned for secondary analyses. Whole brain analysis of both amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF was performed in MDE subjects to identify regions where activity was associated with SI. Results Subjects with SI had greater ALFF than those without SI in two clusters: one in the right hippocampus and one in the thalamus and caudate, bilaterally. Multi-voxel pattern analysis distinguished between those with and without SI. Post hoc analysis of the mean ALFF in the hippocampus cluster found it to be associated with a delayed recall on the Buschke memory task. Mean ALFF from the significant clusters was not associated with depression severity and did not differ between MDE and HV groups. Discussion These results indicate that SI is associated with altered resting-state brain activity. The pattern of elevated activity in the hippocampus may be related to how memories are processed.
- Published
- 2019
48. Neural predictors and effects of cognitive behavioral therapy for depression: the role of emotional reactivity and regulation
- Author
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Maria A. Oquendo, Bruce P. Doré, J. John Mann, Harry Rubin-Falcone, Lauren Delaparte, Bryan T. Denny, Sudha Raman, Ronit Kishon, Jochen Weber, Kevin N. Ochsner, and Jeffrey M. Miller
- Subjects
Adult ,Male ,Adolescent ,medicine.medical_treatment ,Emotions ,Precuneus ,Hippocampus ,behavioral disciplines and activities ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Neural Pathways ,medicine ,Humans ,Reactivity (psychology) ,Applied Psychology ,Depressive Disorder, Major ,Neural correlates of consciousness ,Cognitive Behavioral Therapy ,medicine.diagnostic_test ,Autobiographical memory ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,030227 psychiatry ,Oxygen ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Treatment Outcome ,medicine.anatomical_structure ,Major depressive disorder ,Female ,Psychology ,Functional magnetic resonance imaging ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
BackgroundCognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.MethodsWe now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.ResultsPre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.ConclusionsCBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.
- Published
- 2019
49. Gray and white matter differences in adolescents and young adults with prior suicide attempts across bipolar and major depressive disorders
- Author
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Maria A. Oquendo, Jennifer A.Y. Johnston, Siyan Fan, Linda Spencer, Anjali Sankar, Amanda Wallace, Brian Pittman, Fei Wang, Elizabeth Lippard, and Hilary P. Blumberg
- Subjects
Adult ,Male ,Bipolar Disorder ,Adolescent ,Prefrontal Cortex ,Uncinate fasciculus ,Suicide, Attempted ,Hippocampus ,behavioral disciplines and activities ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,Fractional anisotropy ,medicine ,Humans ,Bipolar disorder ,Gray Matter ,Young adult ,Prefrontal cortex ,Depressive Disorder, Major ,Suicide attempt ,business.industry ,Brain ,Organ Size ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Diffusion Magnetic Resonance Imaging ,Mood disorders ,Case-Control Studies ,Anisotropy ,Major depressive disorder ,Female ,business ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Background Findings regarding brain circuitry abnormalities in suicide attempters (SAs) converge across bipolar disorder (BD) and major depressive disorder (MDD), the most common disorders observed in suicides. These abnormalities appear to be present during adolescence/young adulthood when suicide rates increase steeply, and suicide is a leading cause of death in this age group. Identification of brain circuitry common to adolescent/young adult SAs with BD and MDD is important for generating widely effective early prevention strategies. We examined brain circuitry in SAs in adolescents/young adults across these two disorders. Methods Eighty-three participants (ages 14–25 years), 46 with BD (21 SAs) and 37 with MDD (19 SAs), underwent structural and diffusion-weighted magnetic resonance scanning. Whole-brain analyses compared gray matter (GM) volume and white matter (WM) fractional anisotropy (FA) between SAs and non-suicide attempters (NSAs) across and within BD and MDD (p Results Across and within BD and MDD, SAs showed differences compared to NSAs in ventral prefrontal cortex (PFC) GM volume and fronto-limbic (including uncinate fasciculus (UF)) WM FA. Exploratory analyses showed additional within-disorder differences for BD SAs in dorsolateral PFC (dlPFC) and hippocampus GM volume and UF FA, and for MDD SAs dorsomedial and dlPFC GM and dorsal frontal WM. However, there was no significant interaction between suicide attempt status and diagnosis. Limitations Modest sample size. Conclusions Common fronto-limbic gray and white matter alterations in adolescent/young adult SAs are potential targets for suicide prevention strategies across mood disorders. Preliminary findings of disorder-specific regional findings could suggest diagnostic-specific optimal targets may exist.
- Published
- 2019
50. Preliminary examination of gray and white matter structure and longitudinal structural changes in frontal systems associated with future suicide attempts in adolescents and young adults with mood disorders
- Author
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Judah Weathers, Siyan Fan, Maria A. Oquendo, Susan Quatrano, Linda Spencer, Anjali Sankar, Elizabeth Lippard, Brian Pittman, Hilary P. Blumberg, and Jennifer A.Y. Johnston
- Subjects
Male ,Bipolar Disorder ,Internal capsule ,Adolescent ,Prefrontal Cortex ,Suicide, Attempted ,Gyrus Cinguli ,Article ,Suicidal Ideation ,White matter ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal Capsule ,Fractional anisotropy ,medicine ,Humans ,Gray Matter ,Young adult ,Depressive Disorder, Major ,Mood Disorders ,business.industry ,Targeted interventions ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Frontal Lobe ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Cross-Sectional Studies ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Mood disorders ,Anisotropy ,Female ,business ,Gray (horse) ,030217 neurology & neurosurgery ,Clinical psychology ,Diffusion MRI - Abstract
BACKGROUND: Mood disorders are major risk factors for suicidal behavior. While cross-sectional studies implicate frontal systems, data to aid prediction of suicide-related behavior in mood disorders are limited. Longitudinal research on neuroanatomical mechanisms underlying suicide risk may assist in developing targeted interventions. Therefore, we conducted a preliminary study investigating baseline gray and white matter structure and longitudinal structural changes associated with future suicide attempts. METHODS: High-resolution structural magnetic resonance imaging, diffusion tensor imaging, and suicide-related behavioral assessment data for 46 adolescents and young adults with mood disorders [baseline age(mean)=18 years; 61% female] were collected at baseline and at follow-up (interval(mean)=3 years). Differences in baseline and longitudinal changes in gray matter volume and white matter fractional anisotropy in frontal systems that distinguished the participants who made future attempts from those who did not were investigated. RESULTS: Seventeen (37%) of participants attempted suicide within the follow-up period. Future attempters (those attempting suicide between their baseline and follow-up assessment), compared to those who did not, showed lower baseline ventral and rostral prefrontal gray matter volume and dorsomedial frontal, anterior limb of the internal capsule, and dorsal cingulum fractional anisotropy, as well as greater decreases over time in ventral and dorsal frontal fractional anisotropy (p
- Published
- 2019
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