Pure Major Depressive Disorder Research Articles

The Dark and Gloomy Brain: Grey Matter Volume Alterations in Major Depressive Disorder–Fine-Grained Meta-Analyses

Background. While the brain correlates of major depressive disorder (MDD) have been extensively studied, there is no consensus conclusion so far. Various meta-analyses tried to determine the most consistent findings, but the results are often discordant for grey matter volume (GMV) atrophy and hypertrophy. Applying rigorous and stringent inclusion criteria and controlling for confounding factors, such as the presence of anxiety comorbidity, we carried out two novel meta-analyses on the existing literature to unveil MDD signatures. Methods. A systematic literature search was performed up to January 2023. Seventy-three studies on MDD patients reporting GMV abnormalities were included in the first meta-analysis, for a total of 6167 patients and 6237 healthy controls (HC). To test the effects of anxiety comorbidity, we conducted a second meta-analysis, by adding to the original pure MDD sample a new cohort of MDD patients with comorbid anxiety disorders (308 patients and 342 HC). An activation likelihood estimation (ALE) analysis and a coordinate-based mapping approach separate for atrophy and hypertrophy were used to identify common brain structural alterations among patients. Results. The pure MDD sample exhibited atrophy in the left insula, as well as hypertrophy in the bilateral amygdala and parahippocampal gyri. When we added patients with comorbid anxiety to the original sample, bilateral insula atrophy emerged, whereas the hypertrophy results were not replicated. Conclusions. Our findings revealed important structural alterations in pure MDD patients, particularly in the insula and amygdala, which play key roles in sensory input integration and in emotional processing, respectively. Additionally, the amygdala and parahippocampal gyrus hypertrophy may be related to MDD functional overactivation to emotional stimuli, rumination, and overactive self-referential thinking. Conversely, the presence of anxiety comorbidity revealed separate effects which were not seen in the pure MDD sample, underscoring the importance of strict inclusion criteria for investigations of disorder-specific effects.

Major depressive disorder subtypes and depression symptoms in multiple sclerosis: What is different compared to the general population?

ObjectiveTo compare and characterize major depressive disorder (MDD) subtypes (i.e., pure atypical, pure melancholic and mixed atypical-melancholic) and depression symptoms in persons with multiple sclerosis (PwMS) with persons without MS (Pw/oMS) fulfilling the DSM-5 criteria for a past 12-month MDD. MethodsMDD in PwMS (n = 92) from the Swiss Multiple Sclerosis Registry was compared with Pw/oMS (n = 277) from a Swiss community-based study. Epidemiological MDD diagnoses were based on the Mini-SPIKE (shortened form of the Structured Psychopathological Interview and Rating of the Social Consequences for Epidemiology). Logistic and multinomial regression analyses (adjusted for sex, age, civil status, depression and severity) were computed for comparisons and characterization. Latent class analysis (LCA) was conducted to empirically identify depression subtypes in PwMS. ResultsPwMS had a higher risk for the mixed atypical-melancholic MDD subtype (OR = 2.22, 95% CI = 1.03–4.80) compared to Pw/oMS. MDD in PwMS was specifically characterized by a higher risk of the two somatic atypical depression symptoms ‘weight gain’ (OR = 6.91, 95% CI = 2.20–21.70) and ‘leaden paralysis’ (OR = 3.03, 95% CI = 1.35–6.82) and the symptom ‘irritable/angry’ (OR = 3.18, 95% CI = 1.08–9.39). ConclusionsMDD in PwMS was characterized by a higher risk for specific somatic atypical depression symptoms and the mixed atypical-melancholic MDD subtype. The pure atypical MDD subtype, however, did not differentiate between PwMS and Pw/oMS. Given the high phenomenological overlap with MS symptoms, the mixed atypical-melancholic MDD subtype represents a particular diagnostic challenge.

Smaller left hippocampal subfield CA1 volume is associated with reported childhood physical and/or sexual abuse in major depression: A pilot study

BackgroundSmaller 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. MethodsForty-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. ResultsNo 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. LimitationsWe did not have a sample of healthy volunteers with reported childhood abuse. ConclusionsThe 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.

A Case of Major Depressive Disorder With Mixed Features: Diagnostic and Treatment Issues.

A Case of Major Depressive Disorder With Mixed Features: Diagnostic and Treatment Issues.

Different Patterns of Heart Rate Variability During Acute Withdrawal in Alcohol Dependent Patients With and Without Comorbid Anxiety and/or Depression

Abstract. The aim of the present study was to examine cardiac autonomic function during acute alcohol withdrawal (AW) in two clinical subgroups with alcohol dependence. To this end we compared 24 patients with pure alcohol dependence (Pure ALC) with 24 alcohol-dependent patients who had comorbid symptoms of anxiety and/or depression (ANX/DEP ALC) on their mean heart rate and several (spectral) measures of heart rate variability (HRV) obtained from the patients when they were withdrawn from alcohol. To elucidate the contribution of anxiety and depression to the cardiac measures we moreover compared these groups to 120 non-comorbid patients with major depressive disorder (MDD), 24 patients with anxiety disorders and 120 matched controls. The Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A) were employed for the clinical symptom ratings. The cardiac measures were found to significantly discriminate among the groups (Hotelling-Lawley F = 3.18, p < .001). Post hoc testing revealed that total HRV (variance in interbeat intervals) was reduced in Pure ALC (p = .033, Cohen’s d = −0.51), ANX/DEP ALC (p < .001, Cohen’s d = −1.33), MDD (p < .001, Cohen’s d = −0.66), and anxiety disorders (p = .002, Cohen’s d = −0.69), relative to controls. When these comparisons were adjusted for smoking history in pack-years, the results were unchanged. The ANX/DEP ALC patients showed significantly greater reduction in total HRV and high frequency (HF)-HRV compared with the Pure ALC patients. Both anxiety and depression moderated the influence of alcohol use and withdrawal on resting HRV. Our results suggest that compared to Pure ALC, ANX/DEP ALC presents a subtype of alcohol dependence with higher vulnerability to reduced HRV during acute AW. Implications for cardiovascular risk are discussed.

The patterns of fractional amplitude of low-frequency fluctuations in depression patients: The dissociation between temporal regions and fronto-parietal regions

This study surveyed the characteristics of the indicator for the fluctuations of default brain activity, fractional amplitude of low-frequency fluctuations (fALFF), in patients with pure major depressive disorder (MDD). Forty-four patients with MDD and 27 normal controls were enrolled in our study. All the participants received the resting-state functional magnetic resonance imaging (rs-fMRI) scans, which were pre-processed by the REST toolbox (resting-state functional MRI data analysis toolbox). The group-related differences of the fALFF between patients and controls were explored by performing comparisons of the fALFF values obtained from rs-fMRI data. The fALFF outputs of patients and controls were compared with global brain volume, age and gender as covariates. In addition, the correlations between the clinical variables (such as depression severity, anxiety severity, illness duration) and fALFF values were also estimated in each group and across both groups. The patients with MDD had significantly higher fALFF values than the controls, for the left temporal subgyral region. In the contrary, the patients had lower values of fALFF than controls, for the right frontal subcallosal gyrus and right parietal postcentral gyrus. In addition, the fALFF values were negatively correlated with the depression severity in the left temporal subgyral region. MDD patients had dissociable alterations in the fALFF values of the fronto-parietal and temporal regions. The pattern of fALFF alterations might be unique for depression patients with later onset-age of young adult phase.

Comparative cost analysis of generalized anxiety disorder and major depressive disorder patients in secondary care from a national hospital registry in Finland

Background: Major depressive disorder (MDD) has shown to cause high costs to society. Earlier research indicates that generalized anxiety disorder (GAD) also causes high costs, but only limited data is available in varying settings. Aims: To analyse the secondary care costs of GAD compared with those of MDD. Methods: Retrospective database analysis from Finnish Hospital Discharge Registers (FHDR). All GAD and MDD patients diagnosed between 1 January 2007 and 31 December 2007 in FHDR were recorded and individual-level secondary care costs during a 48-month follow-up period were measured. Results: The total mean cost of GAD with history of MDD or some other anxiety disorder was significantly higher than that of MDD with history of GAD or some other anxiety disorder during the 48-month follow-up period. The costs of pure GAD were comparable with those of pure MDD, but after adjusting for age and sex, the costs of pure MDD were higher than those of pure GAD. Conclusions: The economic burden of individual GAD patients is comparable with that of MDD patients in secondary care.

Why does the lifetime prevalence of major depressive disorder in the elderly appear to be lower than in younger adults? Results from a national representative sample

BackgroundThe explanation of the lower lifetime prevalence rate of major depressive disorder (MDD) in older adults compared to younger people in community surveys is debated. This study examines the hypothesis that the decrease of the lifetime prevalence of MDD in older adults may be due to an age-related difference in the lifetime prevalence of subthreshold hypomania and, to a lesser extent, to the increased rate of medical induced-depression. MethodsData were derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined lifetime prevalence rates of pure MDD and MDD plus subthreshold hypomania (D(m)) by age, assuming that the lifetime prevalence of pure MDD in older adults would be similar to that in the youngest cohort, consequent to an inverse age-D(m) relationship. We further considered non-hierarchical MDD (i.e., general medical condition depressive disorders were not ruled out) with the same method. ResultsThe lifetime prevalence of D(m) among depressed adults aged 65 years and over was substantially lower compared to the youngest group. When considering non-hierarchical MDD, the odds ratio of the lifetime prevalence estimates of non-hierarchical pure MDD in older adults compared to the youngest group appeared not significantly different from 1. ConclusionsFindings indicate that the decrease of lifetime prevalence of MDD in older adults may be due to an age-related difference in the lifetime prevalence of subthreshold hypomania and, to a lesser extent, to the increased rate of medical induced-depression.

Prevalence of Subthreshold Hypomania and Impact on Internal Validity of RCTs for Major Depressive Disorder: Results from a National Epidemiological Sample

BackgroundGrowing evidence supports the validity of distinguishing major depressive disorder (MDD) plus a lifetime history of subthreshold hypomania (D(m)) from pure MDD in psychiatric classifications. The present study sought to estimate the proportion of individuals with D(m) that would have been included in RCTs for MDD using typical eligibility criteria, and examine the potential impact of including these participants on internal validity.MethodsData were derived from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined the proportion of participants with a current diagnosis of pure MDD and D(m) that would have been eligible in clinical trials for MDD with a traditional set of eligibility criteria, and compared it with that of participants with bipolar 2 disorder if the same set of eligibility criteria was applied. We considered 4 models including different definitions of subthreshold hypomania.ResultsWe found that more than 7 out of ten participants with pure MDD and with D(m) would have been excluded by at least one classical eligibility criterion. Prevalence rate of individuals with D(m) in RCTs for MDD with traditional eligibility criteria would have ranged from 7.98% to 22.59%. Overall exclusion rate of individuals with MDD plus at least 4 lifetime concomitant hypomanic probes significantly differ from those with pure MDD, whereas it was not significantly different in those with at least 2 lifetime concomitant hypomanic probes compared to those with bipolar 2 disorder.ConclusionsThe current design of clinical trials for MDD may suffer from impaired external validity and potential impaired internal validity, due to the inclusion of a substantial proportion of individuals with subthreshold hypomania presenting with similar pattern of exclusion rates to those with bipolar 2 disorder, possibly resulting in a selection bias.

Subthreshold bipolar disorder in a U.S. national representative sample: Prevalence, correlates and perspectives for psychiatric nosography

ObjectiveThere is growing clinical and epidemiological evidence that undiagnosed bipolar features are source of clinical heterogeneity in major depressive disorder (MDD). This study examined and compared the prevalence and correlates of lifetime major depressive episode plus subthreshold hypomania D(m) with pure MDD, bipolar II disorder, and bipolar I disorder. MethodData were drawn from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large cross-sectional survey (n=43,093) representative of the U.S. population. ResultsThe lifetime prevalences were 2.53% for D(m), 1.12% for bipolar II disorder, 2.19% for bipolar I disorder and 10.70% for pure MDD. All bipolar disorders (i.e., D(m), BP-II, and BP-I) were half as frequent as MDD.Lifetime and 12-month psychiatric comorbidity, course and clinical characteristics, symptoms, health status and treatment-seeking rates were significantly different in participants with lifetime D(m) when compared to participants with pure MDD, but not when compared to participants with bipolar II disorder. LimitationsSubthreshold hypomania diagnostic was based on the lifetime presence of at least one of the three screening questions for criterion A for hypomania, without a lifetime history of manic or hypomanic episode. This narrow definition, both in terms of the choice of hypomanic symptoms and their duration, could have led to an underestimation of the proportion of participants with a lifetime history of D(m). In addition, the cross-sectional nature of this study does not allow causal associations to be drawn. ConclusionsOur data confirm and extend evidence of the clinical significance and validity of a subthreshold bipolarity-specifier applied to individuals with DSM-IV MDD. Major depression with subthreshold hypomania could be more accurately incorporated into the bipolar II disorder diagnosis.

Antidepressants for Major Depressive Disorder and Dysthymic Disorder in Patients With Comorbid Alcohol Use Disorders

Mood and alcohol use disorders are often co-occurring, each condition complicating the course and outcome of the other. The aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders. MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or dysthymic disorder in patients with or without alcohol use disorders. The search term placebo was cross-referenced with each of the antidepressants approved by the US, Canadian, or European Union drug regulatory agencies for the treatment of MDD and/or dysthymic disorder. 195 articles were found eligible for inclusion in our analysis, 11 of which focused on the treatment of MDD/dysthymic disorder in patients with comorbid alcohol use disorders. The search was limited to articles published between January 1, 1980, and March 15, 2009 (inclusive). We found that antidepressant therapy was more effective than placebo in patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021). However, this was not the case when selective serotonin reuptake inhibitor (SSRI) antidepressants were examined alone (P > .05). There was no significant difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/dysthymic disorder patients with or without alcohol use disorders (P = .973). Meta-regression analyses yielded no significant differences in the risk ratio of responding to antidepressants versus placebo in trials with comorbid alcohol use disorders, whether antidepressants were used alone or adjunctively to psychotherapy, whether they were used in patients actively drinking or recently sober, or whether they were used in pure MDD or in combined MDD and dysthymic disorder populations. These results support the utility of certain antidepressants (tricyclics, nefazodone) in treating depression in patients with comorbid alcohol use disorders. More data on the use of newer antidepressants, including the SSRIs, for this select patient population are needed.

Depressive and anxiety disorders and the association with obesity, physical, and social activities

There is evidence of more obesity among persons with depressive and depressive and anxiety disorders. However, the nature and the underlying mechanisms of the association are still unclear. This study examines the association between depressive and anxiety disorders and obesity, physical activity, and social activity, and examines whether social and physical activity are potential influencing factors in the association between depressive and anxiety disorders and obesity. Cross-sectional data were used from the Netherlands Study of Depression and Anxiety. A total of 1,854 women and 955 men aged 18-65 years were recruited from the community, general practices, and specialized mental health care. Depressive and anxiety disorders were determined with the Composite International Diagnostic Interview. Body mass index (BMI<30 kg/m(2) ) was used to determine obesity. Physical and social activities were measured by self-report. The odds of obesity adjusted for covariates was significantly higher among those with a current pure Major Depressive Disorder (MDD;odds ratio [OR] OR:1.43; 95% CI:1.07-1.92) compared to controls. Physical activity and social activities were lower among persons with depressive and anxiety disorders compared to controls. The association between MDD and obesity was influenced by social and physical activities. This study confirmed a link between depressive disorders and obesity that was influenced by lower social and physical activities among the depressed.

Major Depressive Disorder With Subthreshold Bipolarity in the National Comorbidity Survey Replication

There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R). The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview. Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder. These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice.

State Effects of Major Depression on the Assessment of Personality and Personality Disorder

The authors sought to determine whether personality disorders diagnosed during a depressive episode have long-term outcomes more typical of those of other patients with personality disorders or those of patients with noncomorbid major depression. The authors used 6-year outcome data collected from the multisite Collaborative Longitudinal Personality Disorders Study (CLPS). Diagnoses and personality measures gathered from the study cohort at the index assessment using interview and self-report methods were associated with symptomatic, functional, and personality measures at 6-year follow-up. Of 668 patients initially recruited to the CLPS, 522 were followed for 6 years. All participants had either a DSM-IV diagnosis of one of four personality disorders (borderline, schizotypal, obsessive-compulsive, or avoidant) or a DSM-IV diagnosis of major depressive disorder with no accompanying personality disorder. Six-year outcomes for patients with comorbid personality disorder and major depressive disorder at the index evaluation were similar to those of patients with pure personality disorder and significantly worse than those of patients with pure major depressive disorder. Stability estimates of personality traits were similar for personality disorder patients with and without major depressive disorder at the index evaluation. These results suggest that personality disorder diagnoses established during depressive episodes are a valid reflection of personality pathology rather than an artifact of depressive mood.

P01-82 - Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity

ContextThere is growing evidence that major depressive disorder (MDD) might be overdiagnosed at the expense of bipolar disorders (BPD).AimTo identify a subgroup of subthreshold BPD among DSM-IV MDD, which is distinct from pure MDD regarding validators of bipolarity.MethodData come from the ten-year prospective-longitudinal EDSP-Study, a community survey from Munich, and were assessed with the DSM-IV/M-CIDI. Subthreshold BPD was defined as fulfilling criteria for MDD plus presence of manic symptoms, but never having met criteria for hypomania.ResultsAmong 488 respondents with MDD, about 60% had pure MDD and 40% subthreshold BPD. Compared to pure MDD, the subthreshold BPD group was found to have(a)an increased family history of mania,(b)considerably higher rates of nicotine dependence and alcohol use disorders,(c)twice as high rates of panic disorder, and(d)a tendency towards higher rates of criminal acts.(e)In prospective analyses, subthreshold BPD converted more often into BPD during follow-up with the criterion D (symptoms are observable by others) being of critical predictive relevance.ConclusionData suggest that MDD is a heterogeneous concept including a large group of subthreshold BPD, which is clinically significant and shares similarities with BPD. Findings might support the need for a broader concept and a more comprehensive screening of bipolarity.

Heterogeneity of DSM-IV Major Depressive Disorder as a Consequence of Subthreshold Bipolarity

There is growing evidence that major depressive disorder (MDD) might be overdiagnosed at the expense of bipolar disorder (BPD). To identify a subgroup of subthreshold BPD among DSM-IV MDD, which is distinct from pure MDD regarding a range of validators of bipolarity, and to examine the pattern of these validators among different groups with affective disorders. Ten-year prospective longitudinal and family study including 3 follow-up waves. Data were assessed with the DSM-IV Munich Composite International Diagnostic Interview. Community sample in Munich, Germany. A total of 2210 subjects (aged 14-24 years at baseline) who completed the third follow-up. Cumulative incidence of pure MDD, BPD, and subthreshold BPD (defined as fulfilling criteria for MDD plus having manic symptoms but never having met criteria for [hypo]mania). Among 488 respondents with MDD, 286 (58.6%) had pure MDD and 202 (41.4%) had subthreshold BPD (cumulative incidence, 9.3%). Compared with respondents who had pure MDD, respondents with subthreshold BPD were found to have a significantly increased family history of mania, considerably higher rates of nicotine dependence and alcohol use disorders, rates of panic disorder that were twice as high, and a tendency toward higher rates of criminal acts. Prospective analyses showed that subthreshold BPD converted more often into BPD during follow-up, with DSM-IV criterion D (symptoms observable by others) being of critical predictive relevance. With increasing severity of the manic component, rates for diverse validators accordingly increased (eg, alcohol use disorders, parental mania) or decreased (harm avoidance). Data suggest that MDD is a heterogeneous concept including a large group with subthreshold BPD, which is clinically significant and shares similarities with BPD. Findings might support the need for a broader concept and a more comprehensive screening of bipolarity, which could be substantial for future research and adequate treatment of patients with bipolarity.

Relationships of neuroticism and extraversion with axis I and II comorbidity among patients with DSM-IV major depressive disorder

Background High comorbidity with axis I and II disorders among major depressive disorder (MDD) patients may in part be due to the predisposing personality dimensions of neuroticism and extraversion. However, a comprehensive view of this relationship is lacking. Methods MDD patients ( n = 193) in the Vantaa Depression Study were interviewed at baseline and at 6 and 18 months with the SCAN and SCID-II, and a general population comparison group ( n = 388) surveyed by mail. Neuroticism and extraversion were measured with the Eysenck Personality Inventory. A dose–exposure relationship between standardized levels of neuroticism and extraversion and type and number of comorbid axis I and II disorders among patients with MDD was hypothesized. Results Prevalence and number of comorbid axis I and II disorders increased significantly with increasing level of neuroticism. In contrast, as the level of extraversion increased, the prevalences of social phobia and cluster C personality disorders decreased. Patients with pure MDD or with any comorbid axis I or II disorder had z-scores of neuroticism of + 0.46, + 0.90 and + 1.30 and of extraversion of − 0.34, − 0.47 and − 0.84, respectively. Limitations Patients' personality scores were not pre-morbid. Conclusion Among MDD patients, a positive dose–exposure relationship appears to exist between neuroticism and prevalence and number of comorbid axis I and II disorders. A negative relationship exists between level of extraversion and prevalence of social phobia and cluster C personality disorders. These findings are consistent with the hypothesis that high neuroticism and low extraversion predispose to comorbid axis I and II disorders among patients with MDD.

Rumination and Worry: Factor Analysis of Self-Report Measures in Depressed Participants

Rumination has featured in psychological models of depression whereas worry is considered to be an important feature of anxiety disorders, particularly generalized anxiety disorder. Similarities between these two types of processes have led researchers to compare them and investigate the relationships between rumination, worry, depression, and anxiety. However, most studies have recruited non-clinical samples. This study aimed to examine the relationship between rumination and worry through joint exploratory factor analysis of measures of rumination (the Ruminative Response Scale) and worry (the Penn State Worry Questionnaire) in a sample of 216 participants (183 women and 33 men) who met DSM-IV criteria for depression on the Inventory to Diagnose Depression. The results suggested that rumination and worry can be distinguished in individuals with depression, as items from the two measures loaded on separate factors. This is consistent with Wells and Matthews’ (1994, Attention and emotion : A clinical perspective. Hove, East Sussex: Erlbaum) suggestion that different forms of perseverative negative thinking are associated with different forms of psychopathology. The study is limited by reliance on a self-report measure of depression and by lack of assurance that the sample consisted of participants with pure major depressive disorder, which future studies need to address.

Generalized anxiety disorder and depression: childhood risk factors in a birth cohort followed to age 32

The close association between generalized anxiety disorder (GAD) and major depressive disorder (MDD) prompts questions about how to characterize them in future diagnostic systems. We tested whether risk factors for MDD and GAD are similar or different. The representative 1972-73 Dunedin birth cohort of 1037 males and females was followed to age 32 with 96% retention. Adult GAD and MDD were diagnosed at ages 18, 21, 26, and 32 years, and juvenile anxiety/depression were also taken into account. Thirteen prospective risk measures indexed domains of family history, adverse family environment, childhood behavior, and adolescent self-esteem and personality traits. Co-morbid MDD+GAD was antedated by highly elevated risk factors broadly across all domains. MDD+GAD was further characterized by the earliest onset, most recurrence, and greatest use of mental health services and medication. Pure GAD had levels of risk factors similar to the elevated levels for co-morbid MDD+GAD; generally, pure MDD did not. Pure GAD had risks during childhood not shared by pure MDD, in domains of adverse family environment (low SES, somewhat more maltreatment) and childhood behavior (internalizing problems, conduct problems, somewhat more inhibited temperament). Pure MDD had risks not shared by pure GAD, in domains of family history (of depression) and personality (low positive emotionality). Specific antecedent risk factors for pure adult MDD versus GAD may suggest partly different etiological pathways. That GAD and co-morbid MDD+GAD share many risk markers suggests that the presence of GAD may signal a pathway toward relatively more severe internalizing disorder.

Effect of comorbid anxiety disorders on the Hypothalamic-Pituitary-Adrenal axis response to a social stressor in major depression

Background Major depressive disorder (MDD) is often complicated by anxiety symptoms, and anxiety disorders occur in approximately 30% of mood cases. This study examined the influence of anxiety comorbidity on the hypothalamic–pituitary–adrenal (HPA) axis response to stress in patients with MDD. Methods Untreated subjects with pure MDD ( n = 15), MDD with comorbid anxiety disorders ( n = 18), and pure anxiety disorders ( n = 15) were recruited by advertising. Age- and gender-matched control subjects were recruited for each subject with a psychiatric diagnosis ( n = 48). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for adrenocorticotropic hormone (ACTH) and cortisol assay. Results When all depressed patients ( n = 33) were compared with their matched control subjects ( n = 33), they showed a significantly greater ACTH response to the stressor; however, this exaggerated ACTH response was exclusively due to the depressed group with comorbid anxiety disorders. A similar but nonsignificant effect was observed in the cortisol response. Subjects with pure mood or pure anxiety disorders showed normal ACTH and cortisol responses to the TSST. All patient groups showed similar levels of TSST-induced anxiety. Conclusions Comorbid anxiety disorders might play a role in the increased activation of the HPA axis observed in patients with major depression.