Pure Major Depression Research Articles

Screening mixed depression and bipolarity in the postpartum period at a primary health care center

IntroductionMixed depression is a clinical condition accompanied by the symptoms of (hypo)mania and is considered to be a predictor for bipolar disorder. Compared to pure major depression, mixed depression is worse in progress. There are limited data on the prevalence of mixed depression since it is a relatively new entity. Therefore, the present study aimed to investigate the prevalence of mixed depression during the postpartum period which is risky for mood disorders. MethodsThe study included 63 postpartum women. The participants were administered Beck Depression Scale, Edinburgh Postnatal Depression Scale (EPDS), Mood Disorders Questionnaire (MDQ), and Modified Hypomania Symptom Checklist-32 (mHCL-32). ResultsThe MDQ scores of the women with expected depression according to the EPDS cut-off scores, were significantly higher than the women with lower EPDS scores (t=−4.968; p<0.001). The modified hypomania scores were significantly higher in the women with higher depression scores compared to the women under EPDS cut-off scores (t=−4.713; p<0.001). According to the EPDS and BDS results, 27 (42.9%) and 14 (22.2%) women needed additional clinical examination for depression, respectively. In addition, 3 (4.8%) women require additional clinical examination for bipolar disorder. The scores for the first item of MDQ were above the cut-off value in 11 (17.5%) women. According to the mHCL-32 results, 50 (79.4%) women had at least 1 symptom, 45 (71.4%) women had at least 3 symptoms, and 43 (68.3%) women had at least 5 symptoms of mixed depression. ConclusionPostpartum mixed depression should be promptly diagnosed by using appropriate diagnostic tools, particularly by primary health care physicians. Patients with mixed depression should be closely monitored to avoid manic switch.

CLASSIFICATION OF ANXIETY DISORDERS COMORBID WITH MAJOR DEPRESSION: COMMON OR DISTINCT INFLUENCES ON RISK?

Anxiety and depression display frequent comorbidity. Individuals with comorbid disorders also often have more extreme symptomatology than those with single disorders. This correlation between comorbidity and severity poses an interesting question: Are comorbid forms of anxiety and depression essentially just more severe versions of the pure disorders? In a large major depression (MD) case-control sample of individuals from the China, Oxford and VCU Experimental Research on Genetic Epidemiology project, we examined the patterns of lifetime anxiety comorbidity (including generalized anxiety disorder--GAD, panic disorder, and five phobia subtypes) among MD cases (N = 5,864) in this population. Binary and multinomial logistic regression was used to estimate associations between risk factors and outcomes including MD as well as latent class membership, which were compared using continuation ratios. We found a five-class solution to fit best, and each resulting class had a distinct pattern of association with the tested risk factors. The use of continuation ratios suggests that a class characterized by high endorsement of GAD is comparable to a more severely affected "pure MD" group. The other three classes (characterized by agoraphobia, various specific phobias, and by high endorsement of all comorbid anxiety disorders, respectively) appear to differ meaningfully from MD alone. Risk for MD resulting from environmental and psychosocial factors may also predispose individuals to GAD, and less consistently, other anxiety disorders. Presentations of MD with certain phobias display distinguishably different patterns of risk, however, and are therefore likely qualitatively distinct.

Polymorphic variation at the serotonin 1-A receptor gene is associated with comorbid depression and generalized anxiety

Serotonin 1-A receptors are key regulators of serotonin activity and their dysregulation might be implicated in the emergence of both major depression (MD) and generalized anxiety disorder (GAD). Previous studies have yielded inconclusive results as to whether the 5-HT1A receptor gene (HTR1A) has a role in the aetiology of MD and no study up to date has analysed this polymorphism on either pure MD or MD comorbid with GAD. In this study, 1059 patients taking part in the PREDICT-Gene study were ascertained for Diagnostic and Statistical Manual of Mental Disorders-IV MD and GAD diagnoses using the Composite International Diagnostic Interview and the Primary Care Evaluation of Mental Disorders questionnaire, respectively. They were also genotyped for the C(-1019)G functional polymorphism at the promoter region of HTR1A gene. Genetic variability at HTR1A was significantly associated with MD [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.14-2.44; P = 0.008], although this effect disappeared after adjusting for GAD (OR = 1.43; 95% CI = 0.96-2.14; P = 0.080). Similarly, a crude association between C(-1019)G polymorphism and GAD was found (OR = 2.54; 95% CI = 1.28-4.86; P = 0.003), but these results became no longer significant after adjusting for MD (OR = 1.97; 95% CI = 0.99-3.91; P = 0.050). However, a main effect of HTR1A G(-1019) allele on comorbid MD-GAD was found (OR = 3.41; 95% CI = 1.44-8.05; P = 0.005) and it remained robust and statistically significant after adjusting by sex, age and family history of psychological problems (OR = 2.82; 95% CI = 1.18-6.77; P = 0.020). In our study, the HTR1A C(-1019)G polymorphism was found to be associated to the frequent clinical presentation of comorbid MD and GAD, suggesting a common genetic background for mixed depression and anxiety states. These findings should be considered as preliminary. Future replications in independent samples would be needed to confirm or discard such association.

Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders

Anxiety disorders are often comorbid with major depression (MD) and alcohol use disorders (AUD). Two common functional polymorphisms in catechol-O-methyltransferase (COMT Val158Met) and brain-derived neurotrophic factor (BDNF Val66Met) genes have been implicated in the neurobiology of anxiety and depression. We hypothesized that attentional response and working memory (auditory P300 event-related potential and Weschler Adult Intelligence Scale, Revised digit symbol scores) as well as genetic vulnerability would differ between pure anxiety disorders and comorbid anxiety. Our study sample comprised 249 community-ascertained men and women with lifetime DSM-III-R diagnoses. We analyzed groups of participants with pure anxiety disorders, pure MD, pure AUD, comorbid anxiety, and no psychiatric disorder. Participants were well at the time of testing; state anxiety and depressed mood measures were at most only mildly elevated. Individuals with pure anxiety disorders had elevated P300 amplitudes (P=0.0004) and higher digit symbol scores (P<0.0001) compared with all the other groups. Individuals with comorbid anxiety had the greatest proportion of COMT Met158 and BDNF Met66 alleles (P=0.009) as well as higher harm avoidance-neuroticism (P<0.0005) than all other groups. Our results suggest that there may be two vulnerability factors for anxiety disorders with differing genetic susceptibility: (a) heightened attention and better working memory with mildly elevated anxiety-neuroticism, a constellation that may be protective against other psychopathology; and (b) poorer attention and working memory with greater anxiety-neuroticism, a constellation that may also increase vulnerability to AUD and MD. This refinement of the anxiety phenotype may have implications for therapeutic interventions.

Psychotropic drug use in Israel: results from the national health survey.

Despite increasing psychotropic drug prescriptions worldwide, little is known about utilization of these medications in the general population in Israel. We examined psychotropic drug use in the general population of Israel and the patterns of use among individuals with different DSM-IV diagnoses of 12-month mental disorders. A representative sample was derived from the National Population Register of noninstitutionalized residents aged 21 and older. Face-to-face interviews were conducted from May 2003 to April 2004. Individuals were asked about any psychotropic drug use in the past 12 months. DSM-IV disorders were assessed using a revised version of the World Health Organization's Composite International Diagnostic Interview. Psychotropic drug utilization was observed in 6.9% of the general population and in 19.6% of individuals with any 12-month psychiatric disorder. The extent of use varied according to sociodemographic variables and the specific DSM-IV diagnostic categories. Among individuals with a 12-month diagnosis of pure major depression, only 13.6% received any antidepressants within the same period; exclusive use of antidepressants was 5.7%, while 3.3% of the individuals used only anxiolytics. Similar to findings in other European countries, our findings suggest that the majority of individuals diagnosed with a common mental disorder are not being treated with psychotropic drugs or are being inappropriately treated.

Anxious and depressive disorders and their comorbidity: Effect on central nervous system noradrenergic function

Although comorbidity of anxiety with depression is common, investigations of physiologic abnormalities related specifically to comorbidity are rare. This study examined relationships of DSM-IV-defined depression, anxiety, and their comorbidity to noradrenergic function measured by blunting of the growth hormone (GH) response to the alpha2 adrenoreceptor agonist (and imidazoline receptor agent) clonidine and by blood pressure and symptom responses. Fifteen subjects with pure social anxiety or panic disorder, 15 with pure major depression, and 18 with both depression and anxiety were compared with healthy control subjects matched for age and gender. Other factors known to affect GH (weight, menstrual status, prior antidepressant, or other drug exposure) were controlled. Anxiety produced GH blunting, but depression was associated with normal GH responses. The comorbid state did not affect results beyond the impact of anxiety. Preclonidine stress-related GH elevations were observed, to the greatest degree in anxious subjects. Relevant symptom, but not blood pressure, changes were significantly associated with blunting. With use of pure depression and anxiety groups and careful control of other factors known to affect GH, these results demonstrate central nervous system noradrenergic dysfunction in anxiety disorders. In contrast to less rigorously controlled studies, noradrenergic function in depression was normal.

Psychotropic drug utilization in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project.

To assess psychotropic drug utilization in the general population of six European countries, and the pattern of use in individuals with different DSM-IV diagnoses of 12-month mental disorders. Data were derived from the European Study of the Epidemiology of Mental Disorders (ESEMeD/MHEDEA 2000), a cross-sectional psychiatric epidemiological study in a representative sample of 21 425 adults aged 18 or older from six European countries (e.g. Belgium, France, Germany, Italy, the Netherlands and Spain). Individuals were asked about any psychotropic drug use in the past 12 months, even if they used the drug(s) just once. A colour booklet containing high-quality pictures of psychotropic drugs commonly used to treat mental disorders was provided to help respondents recall drug use. Psychotropic drug utilization is generally low in individuals with any 12-month mental disorder (32.6%). The extent of psychotropic drug utilization varied according to the specific DSM-IV diagnosis. Among individuals with a 12-month diagnosis of pure major depression, only 21.2% had received any antidepressants within the same period; the exclusive use of antidepressants was even lower (4.6%), while more individuals took only anxiolytics (18.4%). These data question the appropriateness of current pharmacological treatments, particularly for major depression, in which under-treatment is coupled with the high use of non-specific medications, such as anxiolytics.

Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety.

Although substantial evidence suggests that stressful life events predispose to the onset of episodes of depression and anxiety, the essential features of these events that are depressogenic and anxiogenic remain uncertain. High contextual threat stressful life events, assessed in 98 592 person-months from 7322 male and female adult twins ascertained from a population-based registry, were blindly rated on the dimensions of humiliation, entrapment, loss, and danger and their categories. Onsets of pure major depression (MD), pure generalized anxiety syndrome (GAS) (defined as generalized anxiety disorder with a 2-week minimum duration), and mixed MD-GAS episodes were examined using logistic regression. Onsets of pure MD and mixed MD-GAS were predicted by higher ratings of loss and humiliation. Onsets of pure GAS were predicted by higher ratings of loss and danger. High ratings of entrapment predicted only onsets of mixed episodes. The loss categories of death and respondent-initiated separation predicted pure MD but not pure GAS episodes. Events with a combination of humiliation (especially other-initiated separation) and loss were more depressogenic than pure loss events, including death. No sex differences were seen in the prediction of episodes of illness by event categories. In addition to loss, humiliating events that directly devalue an individual in a core role were strongly linked to risk for depressive episodes. Event dimensions and categories that predispose to pure MD vs pure GAS episodes can be distinguished with moderate specificity. The event dimensions that preceded mixed MD-GAS episodes were largely the sum of those that preceded pure MD and pure GAS episodes.

Distinguishing generalized anxiety disorder from major depression: prevalence and impairment from current pure and comorbid disorders in the US and Ontario.

Estimation of comparative disease burden in epidemiological surveys is complicated by the fact that high comorbidities exist among many chronic conditions. The easiest way to take comorbidity into consideration is to distinguish between pure and comorbid conditions and to evaluate the incremental effects of comorbid conditions in prediction equations. This approach is illustrated here in an analysis of the effects of pure and comorbid major depression (MD) and generalized anxiety disorder (GAD) on a number of different measures of role impairment in the US National Comorbidity Survey (NCS) and the Mental Health Supplement to the Ontario (Canada) Health Survey (the Supplement). Pure MD and pure GAD were found to have roughly equal independent associations with role impairments. The incremental effects of having comorbid MD and GAD were found to vary depending on the outcome under investigation. The paper closes with a discussion of the methodological complexities associated with generalizing to comorbidities that involve rare conditions or more than two disorders.

Dr. Kessler and Colleagues Reply

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. Kessler and Colleagues ReplyRONALD C. KESSLER, PH.D., ROBERT DUPONT, M.D., HANS-ULRICH WITTCHEN, PH.D., and PATRICIA A. BERGLUND, M.B.A., RONALD C. KESSLERSearch for more papers by this author, PH.D., ROBERT DUPONTSearch for more papers by this author, M.D., HANS-ULRICH WITTCHENSearch for more papers by this author, PH.D., and PATRICIA A. BERGLUNDSearch for more papers by this author, M.B.A., Boston, Mass.Published Online:1 Dec 2000https://doi.org/10.1176/appi.ajp.157.12.2061AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Dr. Olfson cites the global kappa value from our overview article on the validity of the National Comorbidity Survey diagnoses (Kessler et al., 1998). He apparently did not read our more detailed report on the validity of the National Comorbidity Survey assessment of generalized anxiety disorder (1), in which we showed that the low concordance between a modified version (UM-CIDI) of the Composite International Diagnostic Interview and the SCID was due to a controversial component of DSM-III-R criterion A, that the worries must be excessive or unrealistic. This requirement was revised in DSM-IV. As reported in our 1995 article (1), kappa increases to 0.66 (with a positive predictive value of 0.63) when the excessive/unrealistic requirement is taken out of consideration. This kappa value is as high as the test-retest consistency of the SCID (2).On the basis of this observation, I find it difficult to accept Dr. Olfson’s conclusion that the failure of his small primary care study to replicate the National Comorbidity Survey’s finding of significant impairment in pure generalized anxiety disorder was due to the imprecision of the National Comorbidity Survey’s generalized anxiety disorder assessment. A more plausible explanation, in my view, is the one proposed in our article, but not mentioned in Dr. Olfson’s letter: that Dr. Olfson’s small study contained only four respondents with pure generalized anxiety disorder, making it impossible to assess the impairment of pure generalized anxiety disorder with any precision. Consistent with this interpretation, a much larger primary care study cited in our article, but not mentioned in Dr. Olfson’s letter (3), yielded results consistent with those of the National Comorbidity Survey and inconsistent with Dr. Olfson’s data.Dr. Olfson also commented on the difference between statistical and substantive significance. He is, of course, correct in noting that this is an important difference. However, he is incorrect in saying that the clinical significance of our finding regarding the impairment of pure generalized anxiety disorder is unclear. The fact that 78.2% of community respondents with generalized anxiety disorder reported no work impairment means that 21.8% did report work impairment. This percentage is not meaningfully different from the 24.7% rate of work impairment found among respondents with pure major depression. Both these percentages were dramatically higher than the 5.3% rate of work impairment found among respondents with neither generalized anxiety disorder nor major depression. These effects on work impairment are much larger than those found for the vast majority of other chronic conditions (4) and account for literally millions of dollars in lost productivity in the United States each year.

Suicidal ideation and suicide attempts: comorbidity with depression, anxiety disorders, and substance abuse disorder.

The effect of comorbidity on rates of suicidal ideation and suicide attempts from an adult general population of former West Germany is investigated. The assessment instrument is a modified German version of the Diagnostic Interview Schedule (DIS), a fully standardized interview for the assessment of selected DSM-III lifetime diagnoses as well as suicidal ideation and suicide attempts. Of the general population 4.1% (2.2% male and 4.1% female) made suicide attempts during their lifetime. Only 2 of 18 people who attempted suicide did not meet criteria for a DSM-III-R diagnosis. Cases with pure major depression did not have an odds ratio for suicide attempts significantly higher than subjects with no DSM-III diagnosis. However, cases with both a major depression and a lifetime-anxiety-disorder diagnosis showed significantly elevated odds ratios. Therefore, it is suggested that comorbidity of anxiety and depression, and not depression itself, seems to be a risk factor for suicide attempts.

The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey.

Major depression is a frequent and disabling psychiatric disorder in the United States. This report examines the prevalence and risk factor profile of both pure and comorbid major depression according to data from the National Comorbidity Survey. To estimate the prevalence of psychiatric comorbidity in the United States, a national sample of 8,098 persons 15-54 years of age from the 48 conterminous states was surveyed with a modified version of the Composite International Diagnostic Interview. From the survey data the prevalence of current (30-day) major depression was estimated to be 4.9%, with a relatively higher prevalence in females, young adults, and persons with less than a college education. The prevalence estimate for lifetime major depression was 17.1%, with a similar demographic distribution. Both 30-day and lifetime prevalence estimates were higher than estimates from the earlier Epidemiologic Catchment Area study. When pure major depression was compared with major depression co-occurring with other psychiatric disorders, the risk factor profiles exhibited clear differences. These findings suggest a greater burden of major depression in community-dwelling persons than has been estimated from previous community samples. The risk factor profile showed significant differences between persons with pure and combined major depression.

Social adjustment, coping style, and clinical course among DSM‐III‐R community unipolar depressives

AbstractThe study describes social adjustment and coping style among three DSM‐III‐R unipolar depression diagnostic groups (pure dystbymia, double depression, and pure major depression). The primary goal was to determine if these variables would discriminate between the groups. Also studied were the clinical course features of the unipolar groups. Data from 106 nontreatntent, community‐recruited subjects participating in a DSM‐IV mood disorders field trial at Virginia Commonwealth University were used for this study. Results indicated no differences in social adjustment and coping style among the pure dysthymia, double depression, and major depression groups. One exception was the significantly higher GAF scores among the pure dysthymia group. Clinical course differences were found between the two combined dysthymia groups (pure dysthymics and double depressives) when compared to the major depressive group. Dysthymics reported an earlier age of onset and a higher prevalence of insidious onset. Major depressives were able to pinpoint exacerbating stressors precipitating syndromal episodes. Depression 2:36–42 (1994). © 1994 Wiley‐Liss, Inc.

Differentiating affective and characterologic DSM‐III‐R psychopathology in non‐treatment, community unipolar depressives

AbstractThe present study investigated affective and characterologic psychopathology in a sample of 41 community, non‐treatment unipolar depressed subjects. Based on DSM‐III‐R diagnostic criteria, subjects were placed into one of three groups: pure dysthymia, double depression, or pure major depression. All subjects were then administered the Personality Disorder Examination (PDE) to determine DSM‐III‐R, Axis II comorbidity. State depression and anxiety were also assessed at the Axis II interview. Depressive personality features were assessed as well. The groups with pure dysthymia or double depression exhibited proportionally higher Axis II rates and more depressive personality features than the pure major depression group. However, when Axis II prevalence rates were statistically compared among the three groups no statistically significant differences were found, a result that may be attributable to the small sample size. Overall, 37% of the subjects met criteria for one or more Axis II diagnoses. Results indicate substantial characterologic as well as affective features in unipolar depressives with dysthymia in the course. Depression 2:80–88 (1994). © 1994 Wiley‐Liss, Inc.

DSM-III Personality Disorders among Patients with Major Depression, Anxiety Disorders, and Mixed Conditions

Of 298 mainly nonpsychotic psychiatric outpatients between 19 and 59 years of age, a group of patients having either pure major depression, major depression in combination with anxiety disorders, or pure anxiety disorders was extracted. The anxiety disorders were further differentiated in panic and nonpanic anxiety disorders. The groups were compared as to differences in frequency of personality disorders assessed by means of the Structured Interview for DSM-III Personality Disorders. The mixed major depression/anxiety disorder group appeared to be the most deviant with more severe personality disorders such as paranoid and borderline in addition to avoidant and dependent personality disorder. The differentiation between panic and nonpanic anxiety showed that it was patients with nonpanic anxiety features in addition to major depression who had this higher frequency of personality disorders. These findings imply that it is important to distinguish between major depression cases with and without anxiety disorders both in forthcoming research and in clinical practice.

Basic character inventory personality traits among patients with major depression, anxiety disorders and mixed conditions

Two hundred and seventy-two mainly nonpsychotic psychiatric outpatients between 19 and 59 years of age were divided into various clinical groups according to DSM-III: pure major depression, major depression in combination with various anxiety disorders, pure anxiety disorders and a group with other mental disorders. The groups were compared as to differences in personality traits assessed by means of the Basic Character Inventory. The mixed major depression/non-panic anxiety disorder group appeared to be the most deviant with more oral-neurotic personality traits in addition to obsessive traits, while the pure major depressive disorder and the pure anxiety disorder group were less disturbed. Especially cases with non-panic-anxiety features in addition to major depression were those which manifested a neurotic obsessive personality structure. These findings imply that it is important to distinguish between major depression cases with and without various anxiety disorders.

MCMI Personality Disorders Among Patients With Major Depression With and Without Anxiety Disorders

Two hundred and ninety-eight mainly nonpsychotic psychiatric outpatients between 19 and 59 years of age were divided into various clinical groups according to DSM-III: pure major depression, major depression in combination with various anxiety disorders, pure anxiety disorders, and a remaining group with other mental disorders, somatoform and adjustment disorders, and other affective disorders. The anxiety disorders were further divided into panic and nonpanic disorders. The groups were compared as to differences in frequency of personality disorders assessed by means of the Millon Multiaxial Clinical Inventory. The results show that patients with diagnoses of both major depression and anxiety disorders during their lifetime more often had borderline and passive—aggressive personality disorders. It turned out that the patients with nonpanic anxiety in addition to major depression were more prone to have these disorders. The present study corroborates other family, twin, and clinical studies showing that patients with mixed anxiety/depression are a more severe category of patients.

Parental representation in patients with major depression, anxiety disorder and mixed conditions

Differences in parental bonding between patients with pure major depression, mixed anxiety-depression and pure anxiety disorders were investigated in 272 consecutive outpatients. A low parental care score seemed to be the best discriminating variable between the mixed group and the 3 other groups. This study supports previous family and twin studies as well as clinical studies emphasizing the mixed group as a special disorder group, possibly with a different etiology. The role of the father in child development seems to be particularly important.

Major depression in combination with panic and non-panic anxiety: Childhood memories and precipitating events

A consecutive sample of 298 mainly non-psychotic psychiatric outpatients was classified according to DSM-III. The pathogenetic differences between pure major depression, major depression in combination with panic disorder, non-panic anxiety disorders and pure anxiety disorders were investigated. The patients' reports of childhood relationship to parents and siblings, family atmosphere, their own personality characteristics as children and precipitating events were compared between the various groups. It appears that particularly major depression in combination with non-panic anxiety disorders reported somewhat differently from the other patients's groups. Patients in the first group generally remembered their childhood as being more traumatic with a less satisfactory relationship to their parents. Prior to the onset, they had more often experienced conflicts with their partner, spouse or fiance causing exacerbation of symptoms. These findings support previous studies suggesting that patients with mixed anxiety/depression are different from other patients, and also that various anxiety disorders may have different etiology.

Compounded depression and family functioning during the acute episode and at 6-month follow-up

Thirty-seven inpatients with pure major depression were compared with 41 inpatients with compounded depression (major depression with coexistent axis I, II, and/or III disorders) to assess the impact of the patients' illness on their families. Families of patients with compounded depression had worse family functioning (especially in their ability to solve problems and in maintaining acceptable standards of behavior), both during the acute depressive episode and at 6-month follow-up. A significantly smaller percentage of patients with compounded depression had recovered by 6 months (28%) than those with pure depression (51%).