Gender differences in the symptoms of major depressive disorder

Data from the Canadian Community Health Survey 1.2 were used for a gender analysis of individual symptoms and overall rates of depression in the preceding 12 months. Major depressive disorder was assessed using the Composite International Diagnostic Interview in this national, cross-sectional survey. The female to male ratio of major depressive disorder prevalence was 1.64:1, with n = 1766 having experienced depression (men 668, women 1098). Women reported statistically more depressive symptoms than men (p < 0.001). Depressed women were more likely to report "increased appetite" (15.5% vs. 10.7%), being "often in tears" (82.6% vs. 44.0%), "loss of interest" (86.9% vs. 81.1%), and "thoughts of death" (70.3% vs. 63.4%). No significant gender differences were found for the remaining symptoms. The data are interpreted against women's greater tendency to cry and to restrict food intake when not depressed. The question is raised whether these items preferentially bias assessment of gender differences in depression, particularly in nonclinic samples.     

Clinical predictors of suicide in primary major depressive disorder

OBJECTIVE: Follow-up studies of patients with depressive disorders have identified only a few replicable predictors of suicide and have not explored possible interactions between them. The following analysis takes advantage of a large cohort of depressed patients given detailed, structured interviews 2 decades ago. METHOD: The data set on which this analysis is based was collected between 1976 and 1990. Research personnel administered the Schedule for Affective Disorders and Schizophrenia to 785 adults who had major depressive disorder (Research Diagnostic Criteria) but who lacked other Axis I disorders. The current analysis used the National Death Index to determine mortality status as of 2003. RESULTS: One in 4 of the 134 deaths were by suicide for an overall suicide rate of 4.2%. In comparison to the remaining 752 patients, the 33 who died by suicide were more likely to have been inpatients and to have had a history of suicide attempts at the time of baseline assessment. They had also expressed more hopelessness and had higher ratings of suicidal tendency. The last of these variables was the most robust by far and, when tested with other predictors in regression analyses, was the only one to retain significance (p < .0001). No interactions between predictors emerged. As in an earlier, similar study, the suicidal tendency rating was predictive of suicides that occurred after the first year of follow-up, which suggests that suicidal tendencies comprise a trait that persists across episodes. CONCLUSION: A global rating of suicidality appears to be the single most important predictor of eventual suicide in patients with major depressive disorder.     

重性抑郁障碍的临床特征及其性别差异

目的了解重性抑郁障碍的临床特征及其性别差异。方法采用多阶段分层整群抽样方法随机抽取18周岁及以上的人群10073名,以改编后的一般健康问卷12项（GHQ-12）为筛选工具,以美国精神障碍诊断与统计手册第四版（DSM-IV）轴I障碍定式临床检查患者版（SCID-I/P）为调查的诊断工具。结果重性抑郁障碍的抑郁心境、失眠、疲倦或精力缺乏、兴趣或愉快感缺乏、思考力降低、体重减轻或食欲下降、无价值感、自己死亡的想法、精神运动性激越的出现频率较高;在抑郁发作类型、季节特征、既往发作缓解程度、目前类型、症状严重程度、首次发作年龄及反复发作间歇期的性别比较均无统计学差异。结论重性抑郁障碍各种临床症状的出现频率不同,性别对重性抑郁障碍临床特征的影响有待进一步研究。     

Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder

Objectives. A significant proportion of patients with major depressive disorder (MDD) do not improve following treatment with first-line antidepressants and, currently, there are no objective indicators of predictors of antidepressant response. The aim of this study was to investigate pre-treatment peripheral gene expression differences between future remitters and non-responders to citalopram treatment and identify potential pharmacogenomic predictors of response. Methods. We conducted a gene expression study using Affymetrix HG-U133 Plus2 microarrays in peripheral blood samples from untreated individuals with MDD (N = 77), ascertained at a community outpatient clinic, prior to an 8-week treatment with citalopram. Gene expression differences were assessed between remitters and non-responders to treatment. Technical validation of significant probesets was carried out by qRT-PCR. Results. A total of 434 probesets displayed significant correlation to change in score and 33 probesests were differentially expressed between eventual remitters and non-responders. Probesets for SMAD 7 (SMA- and MAD-related protein 7) and SIGLECP3 (sialic acid-binding immunoglobulin-like lectin, pseudogene 3) were the most significant differentially expressed genes following FDR correction, and both were down-regulated in individuals who responded to treatment. Conclusions. These findings point to SMAD7 and SIGLECP3 as candidate predictive biomarkers of antidepressant response.     

Gender differences in the clinical features of unipolar major depressive disorder

Gender differences in the presence or absence and the severity of forty-seven clinician-rated features of depression were examined, controlling for the sex of the rater. Subjects consisted of 498 moderately to severely depressed patients coming for treatment and diagnosed as suffering from nonpsychotic, unipolar major depressive disorder. Significant differences were found only for increased appetite and weight. No differences were observed in endogenous symptoms, global severity of depression, or impairment in functioning. The results indicate that, although the rate of major depressive disorder is greater in women, its symptomatology is relatively homogeneous with regard to gender.     

Prevalence and predictors of recurrence of major depressive disorder in the adult population

Hardeveld F, Spijker J, De Graaf R, Nolen WA, Beekman ATF. Prevalence and predictors of recurrence of major depressive disorder in the adult population. Objective: Knowledge of the risk of recurrence after recovery of a major depressive disorder (MDD) is of clinical and scientific importance. The purpose of this paper was to provide a systematic review of the prevalence and predictors of recurrence of MDD. Method: Studies were searched in Medline en PsychINFO using the search terms ‘recur*’, ‘relaps*’, ‘depress*’, ‘predict*’ and course. Results: Recurrence of MDD in specialised mental healthcare settings is high (60% after 5 years, 67% after 10 years and 85% after 15 years) and seems lower in the general population (35% after 15 years). Number of previous episodes and subclinical residual symptoms appear to be the most important predictors. Gender, civil status and socioeconomic status seem not related to the recurrence of MDD. Conclusion: Clinical factors seem the most important predictors of recurrence. Data from studies performed in the general population and primary care on the recurrent course of MDD are scarce.     

Potential peripheral biological predictors of suicidal behavior in major depressive disorder

Previous studies have shown that dysfunctions in the serotonin system and hypothalamic-pituitary-adrenal axis (HPA) are associated strongly with suicidal behavior and suicide, especially among individuals with major depressive disorder. Suicidal behavior has been explained using both the stress-diathesis model and the state-trait interaction model. Specifically, diatheses, or trait-dependent risk factors, are associated with dysfunctions in the serotonin system; however, stress responses, or state-dependent factors, are associated with HPA hyperactivity. Decreases in cholesterol and brain-derived neurotrophic factor (BDNF) levels have been associated with impaired brain plasticity among individuals with suicidal behavior. Decreased serotonin functioning has been measured using cerebral spinal fluid (CSF) 5-HIAA, fenfluramine challenge studies, and platelet 5-HT2A receptors. HPA axis dysfunction has been evaluated with the dexamethasone suppression test. Cholesterol and BDNF levels have been measured in blood serum or plasma.Nevertheless, challenges to finding promising and accessible neurobiological predictors of suicide and suicidal behavior remain. As suicide behavior is a complex phenomenon, a combined or multidimensional approach, including each of the aforementioned methods, may be required to predict suicide risk among individuals with major depressive disorder.     

Gender differences in major depressive disorder in a Hungarian community survey

INTRODUCTION: The aim of this study was to investigate the characteristics of Major Depressive Disorder (MDD) in males and females in a sample of the Hungarian adult population. METHOD: 2953 randomly selected subjects between 18 and 64 years old were interviewed using the Hungarian version of the Diagnostic Interview Schedule (DIS), which generated DSM-III-R diagnoses. RESULTS: The lifetime and period prevalences of MDD were more than twice as high in women than in men. The gender difference appeared in early adolescence and continued up until the age of 50. An increased risk for anxiety disorders was found in patients with MDD, irrespective of gender, and in the majority of cases (65%) the anxiety symptoms preceded the onset of MDD. Depressed women tended to have more symptoms and a more marked tendency for recurrence than men. The preponderance of females was twice as high in MDD with comorbid anxiety than in MDD without it, in spite of the fact that the likelihood of the coexistence of MDD and anxiety disorders did not differ by gender. CONCLUSION: The higher MDD prevalence rate in women might be the consequence of a higher rate of pre-existing anxiety disorder(s).     

Prospective study of clinical predictors of suicidal acts after a major depressive episode in patients with major depressive disorder or bipolar disorder

OBJECTIVE: The authors investigated the predictive potential of a stress-diathesis model for suicidal behavior based on correlates of past suicidal acts. In this model, suicidal acts are precipitated by stressors such as life events or a major depressive episode in the setting of a propensity for acting on suicidal urges. This diathesis is expressed as the tendency to develop more pessimism in response to a stressor and/or the presence of aggressive/impulsive traits. The predictive potential of the diathesis was tested by determining whether clinical correlates of past suicidal behavior predict suicidal acts during a 2-year follow-up of patients with a major depressive episode. METHOD: Patients with DSM-III-R major depressive disorder or bipolar disorder (N=308) were assessed at presentation for treatment of a major depressive episode. Potential predictors of suicidal acts in the 2 years after study enrollment were identified on the basis of an association with previous suicidal behavior and were tested by using Cox proportional hazards regression analysis. In addition, pessimism and aggression/impulsivity factors were generated, and their predictive ability was tested by using Cox proportional hazards regression analysis. RESULTS: The three most powerful predictors of future suicidal acts were a history of suicide attempt, subjective rating of the severity of depression, and cigarette smoking, each of which had an additive effect on future risk. The pessimism and aggression/impulsivity factors both predicted suicidal acts, and each factor showed an additive effect. CONCLUSIONS: In addition to obtaining a history of suicidal behavior, clinicians may find it useful to assess patients' current level of pessimism, aggressive/impulsive traits, and comorbidity with substance use disorders, including nicotine-related disorders, to help identify patients at risk for suicidal behavior after major depression. Interventions such as aggressive pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive symptoms may protect such at-risk individuals from future suicidal behavior.     

Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder

OBJECTIVE: To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. METHODS: In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. OUTCOME MEASURES: Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-Index during prophylaxis and time to first recurrence after initiation of lithium treatment. RESULTS: During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p<0.001; 52 d/yr less; 95; CI 31-73 d) and a low Morbidity-Index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n=4) or a lack of efficacy (n=2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. CONCLUSIONS: The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants.     

Gender and the course of major depressive disorder through adolescence in clinically referred youngsters

OBJECTIVES: To determine whether there are gender differences among psychiatrically referred young patients in the presenting features and subsequent course of major depressive disorder (MDD) through adolescence. METHOD: The subjects were 92 participants in a longitudinal follow-up study that included repeated standardized psychiatric evaluations. Gender effects were examined on features of MDD as patients progressed from late childhood (mean age 11 years) to late adolescence (mean age 17 years). RESULTS: Salient features of MDD did not differ for girls versus boys, including age at MDD onset, recovery from the index episode, risk of a new episode, and rates of various comorbid disorders in the index and recurrent episodes. Rates of selected symptoms and severity of the depressive syndrome also were comparable for boys and girls throughout their development. CONCLUSIONS: Gender differences have been documented in epidemiological and community samples with respect to rates and correlates of depressed mood and some features of depressive disorders. However, the study of gender differences among clinically referred depressed youths has only recently gained momentum. The present findings complement existing reports suggesting a lack of compelling gender effects on salient presenting features and adolescent outcomes of MDD in clinically referred youths. Additional work is needed to determine whether gender effects are detectable on other clinical parameters of MDD during adolescence or further along in development.     

Anxiety and somatic symptoms as predictors of treatment-related adverse events in major depressive disorder

The purpose of this study was to examine the relationship between the degree of anxiety or somatic symptoms present before treatment with the subsequent diagnosis of treatment-related adverse events (TRAEs) in patients with major depressive disorder (MDD) enrolled in an 8-week open trial of fluoxetine (20 mg). Baseline symptom questionnaires (SQ) were completed by 170 MDD patients enrolled in the trial. We then tested whether pre-treatment scores for anxiety and somatic symptoms predicted (1) whether patients were subsequently diagnosed with TRAEs; (2) whether they were subsequently diagnosed with moderate or severe TRAEs; or (3) whether a greater number of TRAEs were diagnosed during the trial. We found that depressed patients who presented with prominent somatic symptoms were significantly more likely to report at least one moderate or severe side effect during the course of treatment, but not more likely to report a greater number of side effects. Pre-treatment anxiety was not related to the development of side effects.     

Psychosocial and clinical predictors of symptom persistence vs remission in major depressive disorder.

OBJECTIVE: The present study evaluates the impact of a range of psychosocial factors on the outcome of major depression while controlling for the effect of clinical variables. METHOD: Patients (n = 171) seen in consultation at a mood disorders clinic completed measures of neuroticism, rumination, coping style, sexual abuse history, and parental bonding experiences at Time 1 and completed measures of interpersonal and achievement life events and depression 12 months later. RESULTS: In univariate analyses, neuroticism, rumination, interpersonal and achievement life events, and sexual abuse history were associated with nonremission, whereas avoidance coping was associated with remission at Time 2. Interpersonal and achievement life events and sexual abuse history were associated with nonimprovement, whereas avoidance coping was associated with improvement at Time 2. Significant predictors of both remission and improvement in logistic regression analyses controlling for clinical variables (depression and anxiety severity, duration of illness, and age) included avoidance, interpersonal life events, and the interaction between avoidance and interpersonal life events. CONCLUSIONS: Interpersonal events and responses to depression (that is, coping) play an important role in the outcome of major depression. Further attention to coping style and interactions between psychological factors and life events is warranted in future research on depression persistence.     

C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder

Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug-naïve patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P?< 0.001 and P?< 0.001, respectively). After treatment the CRP levels remained significantly different (P?< 0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6?ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6?ng/ml had 28.2 higher odds of a diagnosis of BD II (P?< 0.001, 95% confidence interval: 10.96–72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state.     

Psychic and somatic anxiety symptoms as predictors of response to fluoxetine in major depressive disorder

The purpose of this study was to examine whether the presence/severity of psychic and somatic anxiety symptoms predicted clinical response following a 12-week, flexible-dose (20-60 mg daily), open-label trial of fluoxetine for major depressive disorder (MDD). The presence and severity of psychic and somatic anxiety symptoms were assessed with the use of select subscales of the Symptom Questionnaire and the Hopkins Symptom Checklist among 518 outpatients with MDD. With the use of separate logistic regressions, we tested for the relationship between clinical response, baseline Hamilton Depression Rating Scale (HAM-D-17) scores, and subscale scores at baseline entered separately as independent variables Overall completion, response and remission rates for the trial were 64.2%, 55.4%, and 48.9%, respectively. All subscale scores selected for this analysis significantly predicted treatment response to fluoxetine. The presence/severity of psychic and somatic anxiety symptoms of MDD at baseline predicted an increased likelihood of non-response to fluoxetine in MDD. Studies examining whether specific treatment strategies are more effective than the selective serotonin reuptake inhibitors for MDD patients with high levels of co-morbid psychic and somatic anxiety symptoms are warranted.     

A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder

Background

Some, although not all, studies report small hippocampal volume in patients with major depressive disorder (MDD) relative to healthy controls. Here, we explore the contribution of key demographic and clinical variables to this difference.

Methods

We used meta-analytic techniques to provide an updated analysis of data from 32 magnetic resonance imaging studies of hippocampal volume in patients with MDD.

Results

Our analysis confirmed the difference in hippocampal volume, but only among patients with MDD whose duration of illness was longer than 2 years or who had more than 1 disease episode. We found no such effect in studies that included patients who did not fit these criteria. The effect was limited to children and middle-aged or older adults. Analyzed collectively, studies including young adult patients showed equivalent hippocampal volumes across MDD patients and controls, a result that may be attributable to a reduced burden of illness in this population. Age at onset of disease, severity of depression at the time of scanning, sex and slice thickness did not contribute to differences in hippocampal volume between patients with MDD and controls.

Limitations

The small size of many of the clinical and demographic subgroups may have limited statistical power to detect between-group differences.

Conclusion

Although all studies were cross-sectional, our results suggest that hippocampal volume reductions generally occur after disease onset in patients with MDD. These findings have implications for the timing of clinical interventions aimed at reducing the impact of MDD on neuronal structure and function.