{"paper_id":"8e272365-9aff-418c-9007-40fa2ef39355","body_text":"CI confidence interval CM clinical modification ICD International Classification of Diseases\nconfidence interval\nclinical modification\nInternational Classification of Diseases\nEndometriosis is a common chronic gynecological condition, affecting approximately\n10% of women of reproductive age ( 1 ,\n 2 ). Although some patients are\nasymptomatic, common clinical manifestations of endometriosis may include chronic\npelvic pain, dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility ( 3 ,  4 ).\nIn part because of the range of symptoms, diagnosis of endometriosis is often\ndelayed ( 5 ), resulting in delayed treatment,\nwhich negatively affects patients’ quality of life ( 6 ).\nMajor depressive disorder and anxiety affect 10% to 20% of US adults\n( 7 ,  8 ), with women at double the risk of men ( 7 ). Furthermore, depression and anxiety disorders are risk\nfactors for suicidal ideation and suicide attempts ( 9 ,  10 ). The increased risk of\ndepression and anxiety among endometriosis patients has been reported in several\nstudies. ( 11–13 )\nEndometriosis may be associated with mental health disorders through shared biologic\npathways such as chronic inflammation or through mediation by chronic pain symptoms\n( 14 ,  15 ). The prevalence of anxiety and depression is high in patients who\nsuffer from other forms of chronic pain, such as chronic pelvic pain ( 16 ), low back pain ( 17 ), and migraines ( 18 ), and in a recent meta-analysis, authors suggested the association\nbetween endometriosis and depressive symptoms is mediated largely through chronic\npain ( 19 ). However, the majority of\nexisting studies looking at prevalence and incidence of mental health disorders\namong patients with endometriosis have several limitations, including\ncross-sectional design, small sample size (<50 patients), and data not being\nrepresentative of the overall patient population, such as youth or inclusion of\nregional clinical data only ( 16 ). In\naddition, little is known about the risk of self-directed violence and heterogeneity\nof these associations among select subgroups of patients.\nIdentifying women at high-risk for mental health conditions may improve\npatient-centered disease management and inform the selection of treatment approaches\nin this population. Thus, the objective of our study was to use data representative\nof the care provided to US patients with endometriosis to evaluate incidence of\ndepression, anxiety, and suicide attempts after the diagnosis of endometriosis in a\nlarge sample of patients. We also identified risk factors for these mental health\nconditions among women with endometriosis.\n\nWe conducted a retrospective cohort study using administrative health claims from\nthe Clinformatics Data Mart database (Optum, Inc., Eden Prairie, Minnesota) from\nMay 1, 2000, through March 31, 2019. This database contains adjudicated,\nadjusted, and deidentified medical and outpatient pharmacy claims for\napproximately 87.4 million beneficiaries of United Healthcare, a large\ncommercial insurance provider in the United States. All study data were accessed\nusing techniques compliant with the Health Insurance Portability and\nAccountability Act of 1996. This study was exempt from institutional review\nboard review because it was a retrospective analysis of deidentified\nadministrative health care claims data.\nFor the primary exposure, women diagnosed with endometriosis were identified by\neither 1) ≥2 medical claims with  International Classification of\nDiseases Ninth Revision , Clinical Modification (ICD-9-CM) diagnosis\ncodes 617.x or  Tenth Revision  (ICD-10-CM) diagnosis codes N80.x\nin any position (principal or secondary) on an inpatient or outpatient claim; or\n2) 1 endometriosis-related inpatient or outpatient medical claim with a\nlaparoscopic procedure code within the previous 30 days (i.e.,\n“laparoscopically confirmed” endometriosis). These criteria for\nendometriosis were used to minimize the potential for coding errors or rule-out\ndiagnoses. The cohort entry date (index) for women with endometriosis was the\ndate of the second claim or the date of the endometriosis claim after the\nlaparoscopic procedure, whichever came first. In general, the distribution of\nthe baseline characteristics between women defined using ≥2 claims of\nendometriosis and the laparoscopically confirmed endometriosis was not\nappreciably different; therefore, the primary analysis included women meeting\neither definition (Web Table 1) (available at  https://doi.org/10.1093/aje/kwaa249 ).\nFor each woman with endometriosis, we sampled up to 2 reference patients of the\nsame age (±1 year) without a prior diagnosis of endometriosis but who had\na claim for a general medical or annual gynecological examination on the same\ncohort entry date as the matched exposed patient, using a risk-set sampling\napproach. Variable matching up to 2 reference patients can yield higher\nprecision than 1:1 matching and retains more exposed subjects than a fixed\nratio. Matching on age controlled for confounding. The reference cohort was\ndrawn from general and gynecologic examinations because women’s health\nmay be managed by obstetrician–gynecologists or other health provider\ntypes such as internal or family medicine practitioners. Patients in the\nreference group had to meet the same enrollment, inclusion, and exclusion\ncriteria. A requirement for a medical visit was used to minimize the possibility\nof detection bias that arises due to the increase in the number of clinical\nencounters associated with a new diagnosis of endometriosis, which then may lead\nto the discovery of other morbidities, including a mood disorder ( 20 ).\nWomen in both the exposed and unexposed groups were required to be health plan\nenrollees at least 183 days before and on the cohort entry date with a 45-day\ngap allowed in continuous enrollment. Patients were not eligible if, on the\ncohort entry date, they were younger than < 18 years or older than\n50 years. Women were also excluded if they had a claim prior to any time from\nthe start of follow-up until the date of cohort entry for depression, anxiety,\nself-directed violence, cancer, or hysterectomy; or a prescription claim for a\nfilled antidepressant or antianxiety medication.\nThere were 3 primary outcomes of interest: incident depression, anxiety, and\nself-directed violence. Depression and anxiety were defined using ICD-9-CM and\nICD-10-CM diagnosis codes (Web Table 2) from the medical claim ( 21–25 ).\nSelf-directed violence was defined using ICD-9-CM and ICD-10-CM codes for\nsuicide, suicide attempt, and intentional self-inflicted injury or self-harm\nfrom the medical claim (Web Table 2) ( 26 ,  27 ).\nInformation on participants’ race/ethnicity (White, non-Hispanic; Black,\nnon-Hispanic; Hispanic; Asian, non-Hispanic) and region of residence (West,\nMidwest, South, and Northeast) were provided in the deidentified database. The\nICD-9-CM and ICD-10-CM diagnosis and procedure codes in any position were used\nto detect the presence or absence of comorbid conditions on or any time before\nthe cohort entry date (i.e., the baseline period). National Drug Code\ninformation was used to detect filled medication prescriptions, which served as\na proxy for medication use during the baseline period (Web Table 2).\nBaseline characteristics of women with and without endometriosis were assessed on\nthe start of all available claims data before and including the date of cohort\nentry. A difference was calculated between the exposure and reference value.\nConfidence intervals around the difference were generated using the Wald method\n( 28 ) and a 2-sample comparison of\nmeans using the  t  distribution for continuous variables.\nOutcomes were assessed in the follow-up period beginning 1 day after cohort\nentry to the occurrence of the event, database disenrollment, death,\nhysterectomy, or March 31, 2019, whichever occurred first. Cox proportional\nhazards regression was used to generate hazard ratios and 95% confidence\nintervals for each outcome.\nVariables known or hypothesized to be associated with endometriosis and mental\nhealth conditions were selected as potential confounders ( 2 ,  29–32 ). Factors not associated with the exposure (i.e., had\nan absolute difference <5) or on the causal pathway between\nendometriosis and mental health conditions (e.g., endometriosis-associated pain)\nwere not included in the models. Estimates were adjusted for race/ethnicity,\nregion of residence, uterine fibroids, chronic headaches or migraine headaches,\nchronic low back pain, fibromyalgia, asthma, type 2 diabetes mellitus, fatigue,\nhypertension, hypothyroidism, vitamin D deficiency, and use of opioid\nanalgesics, antihypertensives, and corticosteroids. Additional adjustment for\nother variables in  Table 1  did not\nfurther modify the hazard ratio (data not shown). Except for race/ethnicity (4\ncategories) and region of residence (4 categories), all other variables were\ndefined as ever vs. never. We conducted stratified analyses by age group\n(<35 and ≥35 years) and used the Wald test to detect a\npotential interaction with endometriosis status.\nBaseline Characteristics of Women With and Without Endometriosis\n( n  = 219,918), Optum Clinformatics DataMart,\n2000–2019 a , b\nAbbreviations: CI, confidence interval; GnRH, gonadotropin-releasing\nhormone agonist.\na  Patients were excluded if they had a prior diagnosis of\ndepression, anxiety, or self-directed violence; prior filled\nprescription of an antianxiety or antidepressant medication; prior\ndiagnosis of cancer; or prior hysterectomy.\nb  Data contain 4 mutually exclusive categories based on a\ncombination of self-reported race/ethnicity and imputed\nrace/ethnicity at the census-tract level.\nc  Values are expressed as mean (standard deviation).\nd  Includes dysmenorrhea, dyspareunia, and pelvic pain.\ne  Includes infertility diagnosis, procedures, medications,\nmedical encounters, and use of GnRH antagonists.\nWe restricted the sample to women with endometriosis to assess the association\nbetween baseline factors and the rate of mood disorders. We developed 3 separate\nCox proportional hazards regression models, with anxiety, depression, and\nself-directed harm as the dependent variable. The independent variables included\nin the models were mutually adjusted.\nWe performed several additional sensitivity analyses. First, we restricted the\nexposed population to women with an endometrioses diagnosis code that occurred\nwithin 30 days of a laparoscopic procedure (i.e., surgically confirmed\nendometriosis) because this would be the strictest method to define and confirm\nthe disease. Notably, empiric treatment regimens often are prescribed before\nvisualization of lesions ( 1 ,  33 ). Second, models with alternative\ndefinitions for depression and anxiety were used. In these analyses, depression\nwas defined as 1) an ICD diagnosis code for depression or a prescription claim\nfor a filled antidepressant medication, and 2) an ICD diagnosis code for\ndepression and a prescription claim for a filled antidepressant medication.\nSimilar criteria were applied to define anxiety using ICD diagnosis codes for\nanxiety and/or a prescription claim for a filled antianxiety medication.\nFinally, an adjusted model was generated that excluded uterine fibroids, chronic\nheadaches or migraine headaches, chronic low back pain, fibromyalgia, asthma,\ntype 2 diabetes, fatigue, and hypertension, because these may be downstream\nconsequences of endometriosis. All analyses were performed using Aetion Evidence\nPlatform, version 3.7 (New York, New York), which has been validated ( 34 ). All  P  values were 2\nsided.\n\nAfter applying inclusion and exclusion criteria, 72,677 women diagnosed with\nendometriosis were matched to 147,251 women never diagnosed with endometriosis (Web\nFigure 1). The median age was 34 years (interquartile range, 29, 40). The overall\nmedian follow-up time was 529 (interquartile range, 195, 1,164) days. Those with\nendometriosis were more likely to be White, non-Hispanic, and from the South. Women\nwith endometriosis were more likely to have dysmenorrhea, dyspareunia, pelvic pain,\ninfertility, and use nonopioid analgesics and opioids ( Table 1 ). Other pain-related comorbidities were more\nfrequently documented among women with endometriosis, including chronic headaches or\nmigraine headaches and chronic low back pain. Immunological and chronic conditions\nsuch as allergies, asthma, fatigue, hypertension, hypothyroidism, and thyroid\ndisease occurred more frequently in women with endometriosis (Web Table 3).\nOverall, women with endometriosis had a higher rate of clinically recognized anxiety\n(57.1 vs. 39.8, respectively, per 1,000 person-years), depression (47.7 vs. 31.5,\nrespectively, per 1,000 person-years), and self-directed violence (0.9 vs. 0.4,\nrespectively, per 1,000 person-years) than those without endometriosis ( Table 2 ). After multivariable adjustment\n(model 1), women with endometriosis were 1.38 (95% confidence interval (CI):\n1.34, 1.42) times as likely to develop clinically recognized anxiety, 1.48\n(95% CI, 1.44, 1.53) times as likely to have clinically recognized\ndepression, and 2.03 (95% CI, 1.60, 2.58) times as likely to have clinically\nrecognized self-directed violence ( Table 2 ).\nIn models stratified by age group, the hazard ratios for all outcomes were stronger\nin women younger than 35 years than women ≥35 years of age ( Table 2 ), although statistically significant\nheterogeneity was only met for depression ( P  for heterogeneity\n<0.01 for depression, 0.41 for anxiety, and 0.60 for self-directed violence).\nWhen potential downstream consequences of endometriosis were removed from the model,\nthe results were not appreciably altered (model 2) ( Table 2 ).\nAssociation Between Endometriosis and Anxiety, Depression, and Self-Directed\nViolence, Overall and Stratified by Age Group ( n  =\n219,918), Optum Clinformatics DataMart, 2000–2019 a\nAbbreviations: CI, confidence interval; HR, hazard ratio; PY,\nperson-years.\na  Patients began follow-up 1 day after cohort entry and were\ncensored on occurrence of the outcome, hysterectomy, death,\ndisenrollment, or end of data.\nb  Multivariable model 1 was adjusted for race/ethnicity,\nregion of residence, uterine fibroids, chronic headaches (including\nmigraine), chronic lower back pain, fibromyalgia, asthma, type 2\ndiabetes mellitus, fatigue, hypertension, hypothyroidism, vitamin D\ndeficiency, and use of opioid analgesics, antihypertensives, and\ncorticosteroids.\nc  Multivariable model 2 was adjusted for race/ethnicity,\nregion of residence, hypothyroidism, vitamin D deficiency, and use of\nopioid analgesics, antihypertensives, and corticosteroids.\nThe association between endometriosis and clinically recognized anxiety, depression,\nand self-directed violence was consistent across various sensitivity analyses. When\ndepression and anxiety were defined using 1) diagnosis claims or medication use or\n2) diagnosis claims and medication use, the hazard ratios did not meaningfully\nchange (Web Tables 4–5). Furthermore, results were not appreciably different\nwhen analyses were restricted to women with laparoscopically confirmed endometriosis\n(Web Tables 6–7).\nIn the analysis restricted to women with endometriosis, characteristics associated\nwith significantly greater rate of depression, anxiety, and self-directed harm were\nidentified through multivariable models ( Table\n3 ). Endometriosis-associated pain (i.e., dysmenorrhea, dyspareunia, and\npelvic pain) was associated with higher rates of anxiety, depression, and\nself-directed harm. Other risk factors associated with incident depression and\nincident anxiety included pain-related comorbidities, prior use of opioid\nanalgesics, fatigue, and asthma. Prior use of gonadotropin-releasing hormone\nagonists and oral contraceptives was associated with elevated rates of depression,\nand interstitial cystitis, allergic rhinitis, and allergies were associated with\nelevated rates of anxiety. Factors associated with higher rates of self-directed\nharm included prior use of opioids, migraine headaches, and asthma.\nFactors Associated With Anxiety, Depression, and Self-Directed Violence Among\nWomen With Endometriosis ( n  = 219,918), Optum\nClinformatics DataMart, 2000–2019\nAbbreviations: CI, confidence interval; GnRH, gonadotropin-releasing hormone\nagonist; HR, hazard ratio.\na  Variable not included in the adjusted model. Models were\nalso adjusted for race/ethnicity and region. Reference category\ncomprises those without the condition, unless otherwise specified.\nSeveral factors were associated with significantly lower rates of depression and\nanxiety among women with endometriosis. Women who had a prior pregnancy, uterine\nfibroids, and hyperlipidemia had lower rates of depression and anxiety. Vitamin D\ndeficiency was associated with lower risk of depression; use of oral contraceptives\nand history of infertility were associated with lower risk of anxiety.\n\nRates of clinically recognized anxiety were 1.4 times higher, rates of depression\nwere 1.5 times higher, and rates of self-directed violence were 2 times higher among\nwomen diagnosed with endometriosis compared with women never diagnosed with\nendometriosis, after adjusting for many potential confounders. The results were\nrobust to several sensitivity analyses, including alternative definitions of the\nexposure, outcomes, and study population. Endometriosis-associated pain and\nprevalence of other chronic comorbidities were risk factors for incident depression,\nanxiety, and self-directed violence among women with endometriosis.\nThe positive association between endometriosis and mental health conditions is\nconsistent with findings of 2 prior cohort studies. Within the Taiwan National\nHealth Insurance Research Database, women with endometriosis had a greater risk of\nany depressive disorder (hazard ratio = 1.44, 95% CI,\n1.25, 1.65), and anxiety disorder (hazard ratio = 1.44,\n95% CI, 1.22, 1.70) compared with women without endometriosis ( 35 ). The strongest associations were among\nwomen younger than 40 years of age, similar to our findings ( 35 ). In a previous study that incorporated\nOptum claims data, the association between endometriosis and depression and/or\nanxiety was somewhat weaker (hazard ratio = 1.2, 95% CI,\n1.2, 1.3) than the association we found in the present study, although\nmisclassification of endometriosis and mental health outcomes in this earlier study\nmay have driven results toward the null ( 36 ).\nData on the association between endometriosis and self-directed violence are limited.\nCommon chronic conditions, such as diabetes, epilepsy, and asthma, have been\nassociated with a greater risk of both self-harm and suicide ( 37 ). Researchers conducting a population-based cohort study\nin Finland found that the mortality rate due to suicide and sequelae of intentional\nself-harm was not different in women with surgically verified endometriosis compared\nto those without endometriosis ( 38 ). In\ncontrast, our findings suggest that rates of self-directed violence, which included\nnonfatal and fatal events, were nearly 2–3 times higher for women with\nendometriosis in the United States. It is also possible that the difference in the\nobserved association is due to different patient characteristics and factors related\nto women’s lifestyle and/or increased medical attention and care\nreceived.\nAmong women with endometriosis, we identified several potential risk factors for\nmental health conditions. Endometriosis-associated pain symptoms and other\npain-related comorbidities were associated with greater risk of mental health\nconditions, Consistent with prior studies, our findings suggest that chronic\nendometriosis-associated pain ( 39 ,  40 ) and chronic pain comorbidities ( 16–18 ) may be a\nsignificant factor for the development of depression and anxiety among women with\nendometriosis. In a recent meta-analysis on endometriosis and depressive symptoms,\nwomen with endometriosis were found to be more likely to have depressive symptoms\nrelative to women without endometriosis and, among women with endometriosis, those\nwith pelvic pain reported higher levels of depression compared with those without\npain. Depressive symptoms were not different between patients with endometriosis and\npelvic pain compared with women with pelvic pain due to other conditions ( 19 ) The results of the present study expand\non the findings on endometriosis and depressive symptoms by examining incident\ndiagnosis of depression, as well as anxiety and self-directed harm.\nEndometriosis may affect the development of depression and anxiety through several\npathways. Chronic pain can lead to social isolation and can negatively affect\nemotional well-being ( 41 ,  42 ). Chronic pain may be related to\ndepression through common neuroplasticity mechanism changes, including effects on\nmonoamine neurotransmitters, brain-derived neurotrophic factor, and glutamate and\nits receptor subtypes ( 14 ). From animal\nstudies, researchers found that endometriosis alters brain gene expression and\nelectrophysiology that lead to an increase in pain sensitization, anxiety, and\ndepression ( 43 ). Finally, the chronic\ninflammation of endometriosis may impair the brain–blood barrier and disturb\ncertain areas of the brain, leading to mood or behavioral disturbances ( 14 ,  15 ,  44–49 ). Studies have shown treatment with proinflammatory agents,\nsuch as interferon-α, were associated with more symptoms of depression,\n( 50 ) whereas the use of nonsteroidal\nanti-inflammatory drugs decreased depressive symptoms ( 51 ). In contrast, co-existing fibroids, prior pregnancy, and\ninfertility were associated with lower risk of depression and anxiety. Although\nwomen undergoing infertility treatment may have increased anxiety, ( 52 ) the impact of infertility on depression\nand anxiety may be modified by treatment success ( 53–55 ).\nThere are several clinical implications for the knowledge gained in this study.\nFirst, consistent and active screening for mood disorders in this population of\nwomen would assist with diagnosis and also address potential underlying\npsychological disease processes that affect quality of life. Second, incorporating\nthe conversation regarding psychological well-being into daily care for those with\nendometriosis provides a platform from which to influence the chronic pain cycle and\nworsening of psychological disease that often occurs due to pain perception ( 56 ). Third, treatment options can be offered\nfor both emotion regulation difficulties and physical symptoms, including offering\ncoping strategies from behavioral, cognitive, and emotional standpoints that may\nimprove ultimate adherence to the continued management of these long-term medical\nconditions ( 57 ,  58 ). The significant presence of anxiety, depression, and\nself-directed harm in women with endometriosis as compared with women never\ndiagnosed with endometriosis modifies our practice to identify and continue to\ndestigmatize mental health issues in a population that is otherwise often considered\nhealthy.\nStrengths of this study include the use of a database with a large, contemporary\ncohort of commercially insured individuals with broad geographic coverage, the\nability to adjust for many potential confounders, and the implementation of multiple\nsensitivity analyses that increase the confidence in the observed results.\nFurthermore, because of the prospective nature of this study, the temporal sequence\nbetween the endometriosis diagnosis and the mood disorders is more clearly indicated\nbecause women who had a received a mental health diagnosis before the first\ndiagnosis of endometriosis were excluded. This is critical for establishing\npotential cause-and-effect directionality and for diminishing the risk of diagnostic\nbias.\nSeveral limitations also should be noted, however. First, endometriosis and mood\ndisorders are chronic conditions; therefore, we were unable to assess the timing of\nthe onset of endometriosis or mental health conditions. Rather, we were able to\nassess the temporal relationship of receiving a clinically recognized diagnosis of\nmood disorders among women with previously clinically recognized endometriosis. This\nwas further complicated by delays in diagnosis and limited observed follow-up time\nin this administrative database. Additional research on the long-term risk of mental\nhealth conditions in women with endometriosis and on the impact of diagnostic delays\non mental health in databases with longer follow-up is needed. Second, we used data\nrepresenting commercially insured, continuously enrolled adult women, so findings\nmay not be generalizable to uninsured populations or young women. More effort is\nneeded to examine the risk of mental health outcomes in women of different ethnic\nand cultural background and younger women with endometriosis ( 59 ). Furthermore, women with mild symptoms or who respond\nwell to treatment may have only 1 medical claim for endometriosis and would not meet\nthe study definition for endometriosis; thus, results may not be generalizable to\nall women with endometriosis.\nOther known limitations common to administrative claims data include lack of clinical\ndocumentation, misdiagnosis, and miscoding ( 60 ). For instance, misclassification of endometriosis is possible in\nclaims data because a diagnosis code may not be used in women with suspected\nendometriosis or nonsurgically diagnosed endometriosis. Therefore, a proportion of\nour matched unexposed group included patients with asymptomatic or symptomatic but\nundiagnosed endometriosis, biasing the association toward the null. However, we\nexpect this misclassification to be minimal because the likely community prevalence\nof severe or symptomatic endometriosis is <2% ( 61 ), and the characteristics of this small proportion of\nundiagnosed, exposed women will be diluted among the hundreds of true\nendometriosis-free unexposed women. In addition, the presence of a diagnosis code\nfor endometriosis may have identified women whose symptoms progressed to have\ngreater impact on quality of life, whose treatment included more advanced\ninterventions, or whose disease advanced to a higher, revised American Society for\nReproductive Medicine disease stage. Notably, data to quantify the revised American\nSociety for Reproductive Medicine stage of disease were unavailable in these data\nbecause, unfortunately, they are not routinely or uniformly documented in claims or\nelectronic medical records ( 62 ,  63 ). However, because the revised American\nSociety for Reproductive Medicine disease stage is poorly correlated with severity\nof symptoms, their life impact, or response to treatment, it is unlikely to be an\nimportant confounder ( 64 ). In addition,\n<50% of women with endometriosis in this study had dysmenorrhea, a\ncommon symptom of endometriosis, so pain symptoms may not have been fully captured\nby ICD codes, because there is no standardization for documentation ( 65 ). Compared to administrative data for\nreimbursement, electronic health record databases capture a far richer source of\nclinical data and health behavior information, potentially providing useful insights\ninto the clinical characteristics, symptom duration, and psychiatric symptoms of\nendometriosis patients ( 66 ).\nFinally, as with other studies conducted using administrative claims data, filled\nprescriptions were used as a proxy for medication use. Although there is uncertainty\nwhether a dispensed prescription is consumed by the patient, pharmacy dispensing\nclaims data reliably predict medication exposure to prescription medications,\nespecially for chronically used medications ( 67 ,  68 ).\nWomen diagnosed with endometriosis are at higher risk for clinically recognized\ndepression, anxiety, and self-directed violence relative to women without\nendometriosis. Furthermore, among women with endometriosis, pain is an important\nrisk factor for subsequent mood disorders. A multidisciplinary approach that\nidentifies women with endometriosis who are at risk for development of depression\nand anxiety may improve patient-centered management and affect treatment strategies\nfor preventing and managing mood disorders.\n\nClick here for additional data file.","source_license":"CC0","license_restricted":false}