Single Major Depressive Episode Research Articles

Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers.

Major depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder's symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive. The aim of this study was to investigate the genetic characterization of MDD heterogeneity. Using Swedish patient register data on 1.5 million individuals, the authors identified 46,255 individuals with specialist-diagnosed MDD. Eighteen subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis. A sibling-based design and classic quantitative genetic models were applied to estimate heritability of MDD subgroups and genetic correlations between subgroups. Estimates of heritability ranged from 30.5% to 58.3% across subgroups. The disabled and youth-onset subgroups showed significantly higher heritability (55.1%-58.3%) than the overall MDD sample (45.3%, 95% CI=43.0-47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity showed significantly lower estimates (30.5%-34.4%). Estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90. Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data. The findings of differential heritability and partially distinct genetic components in subgroups provide important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.

Do-not-resuscitate (DNR) status and major depressive disorder (MDD): Clinical association and hospitalization outcomes.

To understand (1) the association of Major Depressive Disorder (MDD) and do-not-resuscitate (DNR) status among hospitalized patients and (2) the association of MDD and hospitalization outcomes among DNR patients. This was a cross-sectional analysis of United States Healthcare Cost and Utilization Project, Nationwide Inpatient Sample data from 2009 to 2013 for patients >18 years. To address the first objective, we used multivariable logistic regression among all hospitalized patients to compute the adjusted odds ratio (aOR) of having DNR status if patients have active MDD of varying severities after controlling for age, sex, race, suicidal ideation, and Elixhauser Comorbidity Index. To address the second objective, we used multivariable regression among patients with DNR status to compute aOR of having hospitalization outcomes such as increased length of stay, higher total charges, leaving against medical advice, and mortality if patients have MDD. Among all hospitalizations, 2.3% had DNR status. There was an inverse association between severity of MDD and having DNR status. Relative to those without MDD, patients with moderate recurrent MDD episode (aOR 0.74 (95% confidence interval (CI): 0.65-0.85) and severe recurrent MDD episode (aOR of 0.42 (95% CI: 0.37-0.48)) were significantly less likely to have DNR status. Among DNR patients, those with all severities of MDD except mild single episode MDD were >40% less likely to die during hospitalization. Among DNR patients, patients with MDD had 0.7 day longer length of stay, and >$4,500 higher total charges. Patients are less likely to have DNR status if they have active MDD. Among patients with DNR status, those with MDD are less likely to die during hospitalization than those without MDD. With current practice, depression is not associated with increased likelihood of death due to foregoing resuscitation prematurely, though the exact mechanisms of these findings need further investigation.

Depressive symptoms and neuroticism-related traits are the main factors associated with wellbeing independent of the history of lifetime depression in the UK Biobank.

Wellbeing has a fundamental role in determining life expectancy and major depressive disorder (MDD) is one of the main modulating factors of wellbeing. This study evaluated the modulators of wellbeing in individuals with lifetime recurrent MDD (RMDD), single-episode MDD (SMDD) and no MDD in the UK Biobank. Scores of happiness, meaningful life and satisfaction about functioning were condensed in a functioning-wellbeing score (FWS). We evaluated depression and anxiety characteristics, neuroticism-related traits, physical diseases, lifestyle and polygenic risk scores (PRSs) of psychiatric disorders. Other than individual predictors, we estimated the cumulative contribution to FWS of each group of predictors. We tested the indirect role of neuroticism on FWS through the modulation of depression manifestations using a mediation analysis. We identified 47 966, 21 117 and 207 423 individuals with lifetime RMDD, SMDD and no MDD, respectively. Depression symptoms and personality showed the largest impact on FWS (variance explained ~20%), particularly self-harm, worthlessness feelings during the worst depression, chronic depression, loneliness and neuroticism. Personality played a stronger role in SMDD. Anxiety characteristics showed a higher effect in SMDD and no MDD groups. Neuroticism played indirect effects through specific depressive symptoms that modulated FWS. Physical diseases and lifestyle explained only 4-5% of FWS variance. The PRS of MDD showed the largest effect on FWS compared to other PRSs. This was the first study to comprehensively evaluate the predictors of wellbeing in relation to the history of MDD. The identified variables are important to identify individuals at risk and promote wellbeing.

Separating Clinical and Subclinical Depression by Big Data Informed Structural Vulnerability Index and Its impact on Cognition: ENIGMA Dot Product.

Big Data neuroimaging collaborations including Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) integrated worldwide data to identify regional brain deficits in major depressive disorder (MDD). We evaluated the sensitivity of translating ENIGMA-defined MDD deficit patterns to the individual level. We treated ENIGMA MDD deficit patterns as a vector to gauge the similarity between individual and MDD patterns by calculating ENIGMA dot product (EDP). We analyzed the sensitivity and specificity of EDP in separating subjects with (1) subclinical depressive symptoms without a diagnosis of MDD, (2) single episode MDD, (3) recurrent MDD, and (4) controls free of neuropsychiatric disorders. We compared EDP to the Quantile Regression Index (QRI; a linear alternative to the brain age metric) and the global gray matter thickness and subcortical volumes and fractional anisotropy (FA) of water diffusion. We performed this analysis in a large epidemiological sample of UK Biobank (UKBB) participants (N=17,053/19,265 M/F). Group-average increases in depressive symptoms from controls to recurrent MDD was mirrored by EDP (r2=0.85), followed by FA (r2=0.81) and QRI (r2=0.56). Subjects with MDD showed worse performance on cognitive tests than controls with deficits observed for 3 out of 9 cognitive tests administered by the UKBB. We calculated correlations of EDP and other brain indices with measures of cognitive performance in controls. The correlation pattern between EDP and cognition in controls was similar (r2=0.75) to the pattern of cognitive differences in MDD. This suggests that the elevation in EDP, even in controls, is associated with cognitive performance - specifically in the MDD-affected domains. That specificity was missing for QRI, FA or other brain imaging indices. In summary, translating anatomically informed meta-analytic indices of similarity using a linear vector approach led to better sensitivity to depressive symptoms and cognitive patterns than whole-brain imaging measurements or an index of accelerated aging.

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001). Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

Selective Serotonin Reuptake Inhibitor Use Among Army Aviators.

INTRODUCTION: Mental health is an important aspect of Army aviation medicine given that it significantly impacts career longevity, readiness, and healthcare usage. One of the most commonly used classes of medications to treat mental health disorders is the selective serotonin reuptake inhibitor (SSRI). Here we present a descriptive epidemiological review of SSRI use in Army aviators over a 10-yr period.METHODS: An archival dataset retrieved from the U.S. Army Aeromedical Electronic Resource Office covering the years 2005 to 2015 was queried for cases of SSRI use. Frequencies were generated by primary diagnoses and aeromedical disposition for the SSRI subset of data.RESULTS: A total of 114 unique cases of SSRI use were identified (122 total aeromedical outcomes). These cases included 41 waiver recommendations, 59 suspension recommendations, and 22 cases of waiver continuations. The top five most common primary diagnoses were depressive disorder (N 32), anxiety state (N 21), posttraumatic stress disorder (N 16), single major depressive episode (N 13), and adjustment disorder with depressed mood (N 12).DISCUSSION: Understanding of the etiology, pathophysiology, and treatment of mental health disorders particularly within the safety-focused and unforgiving aviation environment has continued to evolve. With the application of evidence-based policy, deliberate aeromedical decision-making, and methodical risk mitigation, SSRI use does have a place within aviation. Aviators suffering in silence with deleterious impact to performance and safety or aircrew seeking services on the outside without knowledge or oversight of certification authorities must remain in the past.Kelley AM, Bernhardt K, McPherson M, Persson JL, Gaydos SJ. Selective serotonin reuptake inhibitor use among Army aviators. Aerosp Med Hum Perform. 2020; 91(11):897900.

The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

BackgroundMood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. MethodsTo clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). ResultsSeventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment—the relationship is positive in bipolar disorder but negative in major depressive disorder. ConclusionsThe mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

Resting-state mapping of neural signatures of vulnerability to depression relapse

BackgroundPatients with major depressive disorder (MDD) can frequently develop new depressive episodes after remission. However, the neural mechanisms underlying the increased risk for depressive relapse remain unclear. Herein, we aimed to explore whether the specific changes to regional and inter-regional spontaneous brain activities within DMN are associated with the course of episodes in pooled MDD patients. MethodsResting-state functional magnetic resonance imaging was performed on patients with single-episode MDD (SEMDD, n = 30) and multiple-episode MDD (MEMDD, n = 54), and 71 age-, gender-, and educational level-matched healthy controls (HCs). We then accessed the differences in both the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity by using the right precuneus as the seed among different groups. ResultsCompared to the MEMDD and HC groups, the SEMDD group exhibited increased fALFF values in the right subgenual anterior cingulate cortex and right middle temporal gyrus. Decreased fALFF values in the right thalamus in the MEMDD group were also identified relative to the SEMDD and HC group. The peak values of fALFF in the right precuneus showed a negative correlation with the number of depressive episodes across the entire pool of MDD patients. No correlation was identified between functional connectivity using the right precuneus as the seed and the number of depressive episodes for the pooled MDD patients. LimitationsMedication, a relatively small sample size, and hypothesis driven study. ConclusionsOur neuroimaging results identified depression relapse-associated neural signatures and also indicated the role of reduced emotional appraisals in the thalamus. It is now possible to believe that the regional activity not inter-regional connectivity within the DMN may be involved in the pathology of depression relapse.

Risk factors for suicide attempts in people with depressive disorders treated in secondary health care

Depression is the most common psychiatric disorder in people with suicidal behavior. The knowledge of its risk factors should help to design preventive strategies. To describe suicidal behavior and risk factors for attempted suicide in people with major depressive disorders (MDD). A 12-month follow-up study was conducted in 112 outpatients at three psychiatric care centers of Ñuble, Chile, with baseline and quarterly assessments. Demographic, psychosocial and clinical factors as potential risk factors of suicide attempts, were assessed. A clinical interview with DSM-IV diagnostic criteria checklist, Hamilton Depression Scale and the List of Threatening Experiences and Multidimensional Scale of Perceived Social Support were applied. Sixty seven percent of participants had suicidal ideation and 43.8% had attempted suicide. Suicide risk was significantly higher in participants with a single major depressive episode (odds ratio [OR] = 3.98; 95% confidence intervals [CI] = 1,29-12,32 p = 0.02) and those with previous suicide attempts (OR = 13.15; 95% CI = 3,87-44.7 p < 0.01). Young age, not having a partner, being unemployed, having a severe major depressive episode, having psychotic symptoms, having a personality disorder and being devoid of medical illness increased the risk of suicide attempts, but they did not reach statistical significance. Significant risk factors should be specially considered when designing suicide preventive strategies in patients with MDD.

Phenotypic and genetic analysis of cognitive performance in Major Depressive Disorder in the Generation Scotland: Scottish Family Health Study

Lower performances in cognitive ability in individuals with Major Depressive Disorder (MDD) have been observed on multiple occasions. Understanding cognitive performance in MDD could provide a wider insight in the aetiology of MDD as a whole. Using a large, well characterised cohort (N = 7012), we tested for: differences in cognitive performance by MDD status and a gene (single SNP or polygenic score) by MDD interaction effect on cognitive performance. Linear regression was used to assess the association between cognitive performance and MDD status in a case-control, single-episode–recurrent MDD and control-recurrent MDD study design. Test scores on verbal declarative memory, executive functioning, vocabulary, and processing speed were examined. Cognitive performance measures showing a significant difference between groups were subsequently analysed for genetic associations. Those with recurrent MDD have lower processing speed versus controls and single-episode MDD (β = −2.44, p = 3.6 × 10−04; β = -2.86, p = 1.8 × 10−03, respectively). There were significantly higher vocabulary scores in MDD cases versus controls (β = 0.79, p = 2.0 × 10−06), and for recurrent MDD versus controls (β = 0.95, p = 5.8 × 10−05). Observed differences could not be linked to significant single-locus associations. Polygenic scores created from a processing speed meta-analysis GWAS explained 1% of variation in processing speed performance in the single-episode versus recurrent MDD study (p = 1.7 × 10−03) and 0.5% of variation in the control versus recurrent MDD study (p = 1.6 × 10−10). Individuals with recurrent MDD showed lower processing speed and executive function while showing higher vocabulary performance. Within MDD, persons with recurrent episodes show lower processing speed and executive function scores relative to individuals experiencing a single episode.

The association between the hypothalamic pituitary adrenal axis and tryptophan metabolism in persons with recurrent major depressive disorder and healthy controls

ObjectivesPersistent changes in serotonergic and hypothalamic pituitary adrenal (HPA) axis functioning are implicated in recurrent types of major depressive disorder (MDD). Systemic tryptophan levels, which influence the rate of serotonin synthesis, are regulated by glucocorticoids produced along the HPA axis. We investigated tryptophan metabolism and its association with HPA axis functioning in single episode MDD, recurrent MDD and non-depressed individuals. MethodsWe included depressed individuals (n = 1320) and controls (n = 406) from the Netherlands Study of Depression and Anxiety (NESDA). The kynurenine to tryptophan ratio (kyn/trp ratio) was established using serum kynurenine and tryptophan levels. Several HPA axis parameters were calculated using salivary cortisol samples. We adjusted the regression analyses for a wide range of potential confounders and differentiated between single episode MDD, recurrent MDD and control. ResultsTryptophan, kynurenine and the kyn/trp ratio did not differ between controls and depressed individuals. Increased evening cortisol levels were associated with a decreased kyn/trp ratio in the total sample (Crude: β = −.102, p < .001; Adjusted: β = −.083, p < .001). This association was found to be restricted to recurrently depressed individuals (Crude: β = −.196, p < .001; Adjusted: β = −.145, p = .001). Antidepressant treatment did not affect this association. ConclusionsOur results suggest that an imbalance between HPA axis function and tryptophan metabolism could be involved in recurrent depression.

Prevalence and correlates of DSM-5 major depressive and related disorders in the community

Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category.

M28 - Polygenic Risk For BIP, MDD, And SCZ In Andalusian Multiplex Families

Background Recent large-scale genome-wide association studies (GWAS) have successfully identified common genetic variations contributing to the risk for psychiatric disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). It has been suggested that familial cases of psychiatric disorders are not only driven by rare variants but also by an accumulation of common genetic risk variants. In the Andalusian Bipolar Family Study (ABiFStudy), 100 multiplex families with bipolar I disorder, bipolar II disorder, recurrent MDD, and single episode MDD cases have been recruited. The objectives of the current study were to assess the patterns of common polygenic variation for BIP, MDD, and SCZ and their association with neuropsychological measures in the affected and unaffected members of the families. Methods Genome-wide genotyping was carried out in 395 members of 33 families including 244 affected individuals using the Illumina Infinium PsychArray BeadChip (PsychChip). Genotype data was imputed using the 1000 Genomes Phase 3 reference panel. The polygenic risk score (PRS) for SCZ was calculated using the 2014 PGC SCZ2 data set. The PRS for MDD was calculated based on the latest freeze of the PGC MDD working group. PRS for BD will be calculated using the latest freeze of the PGC BD working group, after exclusion of family members included in the PGC data and results will be presented at the conference. Analyses were conducted via linear mixed polygenic models taking family structure into account, using the R package GenABEL. Covariates in the analyses were gender, age at the interview, and assessment batch. Results Preliminary analyses revealed no significant associations between BD or MDD diagnosis and either MDD or SCZ PRS. Stratification into disease subgroups affected the results but simultaneously decreased power. The age at onset was nominally associated with the SCZ PRS in MDD cases. Accordingly, inclusion of the age at onset had a significant effect on the models. Discussion We found no evidence for an accumulation of common risk variants for MDD or SCZ in members affected with either MDD or BD in comparison to healthy family members. This could either indicate that disease in these families is caused by rare variants or that all family members carry a high load of risk variants. Ongoing sequencing studies in the families will complement these results. Moreover, comparisons with healthy, unrelated Spanish controls will be used to examine whether healthy family members show an increased genetic risk for psychiatric diseases.

Patterns of depressive disorders across 13 years and their determinants among midlife women: SWAN mental health study

BackgroundLittle is known about the course of depression in midlife women. This study aims to identify factors that distinguish risk factors for persistent or recurrent depression from those of a milder course across 13-years of follow-up. Methods297 Black and White premenopausal women aged 42–52 were enrolled at the Study of Women's Health Across the Nation Pittsburgh site. Psychiatric interviews obtained information on lifetime psychiatric diagnoses at baseline and occurrences of depression annually. We identified four depression patterns: 91(31%) had Persistent/recurrent major depressive disorder (MDD), 27(9%) Single Episode MDD, 35(12%) Minor Depression (minD) only, 144(48%) No Depression. We compared baseline risk factors for the Persistent/recurrent MDD group with each of the other three. ResultsA lifetime history of major or minor depression (p-values =.001–.08) and 2+ very upsetting life events in the previous year (p-values=.003–.04) were more likely to be reported by women in the Persistent/recurrent group than in the other three. The Persistent/recurrent group was more likely to report a family history of depression (p=.03) than the MinD group, and to report current sleep problems (p=.002) at baseline than the Single Episode MDD group. LimitationsSmall numbers of women with minD or a Single Episode MDD. Childhood maltreatment and family depression history were retrospectively reported. ConclusionsA Persistent/recurrent depression course is common during midlife. In addition to personal and family histories of depression, providers of midlife health care should recognize that current sleep problems and recent very upsetting events are strong risk factors for a pernicious depression course.

Functional versus syndromal recovery in patients with major depressive disorder and bipolar disorder.

Many patients with major depressive disorder (MDD) or bipolar disorder (BD) experience impairments in daily life. We investigated whether patients with single-episode MDD (MDD-s), recurrent MDD (MDD-r), and BD differ in functional impairments, whether time since last episode (syndromal state, in 4 categories) contributes to impairment, whether this association is moderated by diagnosis, and the role of depressive symptoms. Data were derived from 1,664 participants in the Netherlands Study of Depression and Anxiety (MDD-s, n = 483; MDD-r, n = 1,063; BD, n = 118), from 2006 into 2009. In additional analyses, 530 healthy controls were included. DSM-IV-TR diagnosis and information about syndromal state were based on the Composite International Diagnostic Interview. Psychosocial impairment was assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Adjusted associations between diagnosis, syndromal state, impairment, and depression severity were investigated. Syndromal state not being taken into account, patients with BD experienced more functional impairment than patients with MDD-s or with MDD-r, and in all diagnostic groups, impairments decreased with increasing time since last episode. However, impact of syndromal state on functioning showed a different course between diagnostic groups (mean [SD] WHODAS score: current: MDD-s 30.8 [2.8], MDD-r 32.7 [0.9], BD 37.7 [2.1], P = .07; recently remitted: MDD-s 21.7 [3.5], MDD-r 24.0 [1.2], BD 22.1[3.2], P = .7; remitted: MDD-s 10.6 [3.7], MDD-r 21.6 [1.4], BD 19.2 [4.4], P = .02; remitted > 1 year: MDD-s 13.3 [0.6], MDD-r 14.7 [0.5], BD 17.1 [2.2], P = .8). Depression severity accounted for these differences. Moreover, functioning in all remitted patients remained impaired when compared to that in healthy controls. Functional recovery may take up to 1 year after syndromal remission in recurrent depressive and bipolar disorder, mainly due to residual depressive symptoms, emphasizing the need for prolonged continuation treatment.

The prospective association between obesity and major depression in the general population: does single or recurrent episode matter?

BackgroundObesity and major depressive disorder (MDD) are important public health problems. MDD is a heterogeneous disorder and the direction of its association with obesity remains unclear. Evidence grows that recurrent MDD (MDD-R) differs in etiology and prognosis from single episode MDD (MDD-S), which could affect associations with obesity. However, evidence on this differential effect is lacking. The aim of this study was to examine the direction of the association between obesity and MDD, single or recurrent episode.MethodsA longitudinal study was performed in a cohort of 1094 participants of the PREVEND study, on whom data were collected at baseline and at an average 2-year follow-up. MDD-S and MDD-R were assessed by the Composite International Diagnostic Interview (CIDI 2.1). Obesity was defined as Body Mass Index ≥ 30 kg/m2. Binary logistic regression analyses were conducted to examine whether obesity predicts MDD-S/MDD-R or vice versa, adjusted for potential confounders.ResultsProspective analyses showed that BMI at baseline was associated with the onset of MDD-R (Odds ratio, OR = 1.32; 95% confidence interval, 95%CI: 1.11; 1.57) during 2-year follow-up, but not with the onset of MDD-S (OR = 0.98; 95%CI: 0.89; 1.07). Obesity at baseline was not associated with the onset of MDD-S during follow-up (OR = 0.75; 95%CI: 0.25; 2.30), but associated with the onset of MDD-R during follow-up (OR = 11.63; 95%CI: 1.05; 128.60). Neither MDD-S nor MDD-R were associated with the development of obesity during 2-year follow-up (OR = 1.67, 95%CI: 0.64; 4.29 and OR = 2.32, 95%CI: 0.82; 6.58, respectively).ConclusionsOur findings add to the available evidence that obesity might specifically be associated with the onset of multiple episodes of major depression (MDD-R). Although the reverse association was not found, MDD-R tends to be also associated with subsequent development of obesity, but larger studies are needed to fully assess this issue. The heterogeneity of MDD should be considered when examining the effect of obesity on MDD.

Predictive validation of single‐episode uncomplicated depression as a benign subtype of unipolar major depression

To evaluate the predictive validity of a proposed benign major depressive disorder (MDD) subtype, single-episode 'uncomplicated MDD', defined as MDD that remits within 6 months and lacks severe impairment, psychotic ideation, suicidal ideation, psychomotor retardation, and feeling worthless. Using two-wave National Epidemiologic Survey on Alcohol and Related Conditions data, four groups differing in wave 1 lifetime MDD history (no history [n = 27 609]; single-episode uncomplicated [n = 418]; other single-episode [n = 1943]; multiple episode [n = 2473]) were evaluated for 3-year follow-up rates of major depressive episode (MDE), generalized anxiety disorder (GAD), and suicide attempt. Follow-up rates for no-MDD-history, single-episode uncomplicated MDD, other single-episode MDD, and multiple-episode MDD, respectively, were depressive episode 6.1%, 6.9%, 19.5%, 27.1%; GAD 2.7%, 4.3%, 7.8%, 11.2%; and suicide attempt 0.3%, 0.1%, 0.8%, 1.7%. For all validators, 3-year rates for single-episode uncomplicated cases were not significantly different from no-MDD-history rates, but significantly lower than both single- and multiple-episode other-MDD rates. Mild MDD, defined by having only five or six symptoms, did not yield similarly benign results; logistic regression showed 'uncomplicated' provides incremental validity over 'mild' in explaining validator rates. Validator differences were not explainable by treatment-rate differences. Single-episode uncomplicated MDD is a benign subtype lacking typical MDD negative sequelae. The planned DSM-5.1 revision should reinstitute an extended bereavement exclusion applied to all stressors.

Mental Disorders in Mexican Patients With Multiple Sclerosis

Mental Disorders in Mexican Patients With Multiple Sclerosis

Pramipexole, Ropinirole, and Mania in Parkinson’s Disease

Back to table of contents Previous article Next article Letter to the EditorFull AccessPramipexole, Ropinirole, and Mania in Parkinson’s DiseaseABHAY SINGH, M.B.B.S., ROBERT ALTHOFF, M.D., Ph.D., R. JARED MARTINEAU, M.D., and JAMES JACOBSON, M.D., ABHAY SINGHSearch for more papers by this author, M.B.B.S., ROBERT ALTHOFFSearch for more papers by this author, M.D., Ph.D., R. JARED MARTINEAUSearch for more papers by this author, M.D., and JAMES JACOBSONSearch for more papers by this author, M.D., Burlington, Vt.Published Online:1 Apr 2005https://doi.org/10.1176/appi.ajp.162.4.814-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Dopamine receptor agonists, such as pramipexole and ropinirole, are a safe and effective initial therapy for mild to moderate Parkinson’s disease. There are at least three lines of evidence to suggest that this class of drugs may also be related to mood symptoms. First, at the clinical level, besides ameliorating motor symptoms, pramipexole has shown antidepressant effects in Parkinson’s disease, in major depression, and in treatment-resistant unipolar and bipolar depression. Next, at the basic science level, pramipexole and ropinirole are novel dopamine receptor agonists with a high affinity for all dopamine D2 subfamily receptors and show highest affinity for the D3 receptor subtype (1). The antidepressant effect of pramipexole and ropinirole may be related to a resensitization or potentiation of the D2/D3 receptors in the mesolimbic system, a region relevant to mood regulation (2). Finally, in a recent clinical trial by Goldberg and colleagues (3), one case of mania was reported in a patient with a personal history of bipolar depression while being treated with pramipexole. Here, we describe a case of mania in a patient with Parkinson’s disease given pramipexole and ropinirole who had no personal or family history of bipolar disorder.Ms. A was a 37-year-old white woman with a 4-year history of Parkinson’s disease. Her family history revealed a paternal grandmother with a single major depressive episode and a sibling with anorexia nervosa. Her Parkinson’s disease symptoms had been treated with levodopa and selegiline with moderate response. Because of episodic rigidity and dyskinesia, pramipexole was added to her treatment regimen and increased to 1.5 mg b.i.d., with improvement of motor symptoms. However, in the first week after its addition, she developed symptoms of elevated mood, increased sex drive, energy, psychomotor activity, and decreased need for sleep. After 6 months on this regimen, she developed irritability, paranoia, and delusions of jealousy. Selegiline and pramipexole were discontinued, and she began taking quetiapine, titrated to 50 mg, at bedtime. Her psychotic symptoms resolved in 1 month. Quetiapine was discontinued without symptom recurrence. Two months later, her levodopa dose was decreased because of tremors and dyskinesias, and ropinirole was added and titrated to 0.75 mg t.i.d. She rapidly developed insomnia, increased energy, and agitation. Consequently, ropinirole was discontinued, which led to symptom resolution. She remained stable taking levodopa alone for several months. Ropinirole was reinstituted but led to reemergence of manic symptoms, necessitating discontinuation, which resulted in amelioration of mania.The long-term studies of dopamine receptor agonists support their use instead of levodopa earlier in the treatment of Parkinson’s disease in order to delay levodopa-related motor complications. We provide evidence here that dopamine receptor agonists may induce mood symptoms and that there is potential for the novel agents of this class, pramipexole and ropinirole, to induce manic symptoms necessitating close monitoring and further study.

Lifetime depression history and sexual function in women at midlife.

We examined the association between lifetime depression history and sexual function in a community-based sample of midlife women. Specifically, 914 women aged 42-52 who were participants in the Study of Women's Health Across the Nation completed a self-report assessment of their sexual behaviors, sexual desire, sexual arousal, and sexual satisfaction over the past 6 months. On the basis of the Structured Clinical Interview for the DSM-IV , participants were categorized into 1 of 3 lifetime major depressive disorder (MDD) history groups: no MDD history, single episode MDD, and recurrent MDD. In line with previous reports, women with a history of recurrent MDD reported experiencing less frequent sexual arousal, less physical pleasure, and less emotional satisfaction within their current sexual relationships. Although the groups did not differ in their reported frequency of sexual desire or partnered sexual behaviors, lifetime depression history was associated with increased rates of self-stimulation (masturbation). Associations between lifetime depression history and lower levels of physical pleasure within partnered sexual relationships and higher rates of masturbation remained significant following control for current depressive symptoms, study site, marital status, psychotropic medication use, and lifetime history of anxiety or substance abuse/dependence disorder. Future research is needed to characterize the temporal and etiologic relationships among lifetime depressive disorder, current mood state, and sexual function in women across the lifespan.