Severe melancholic depression is more vulnerable than non-melancholic depression to minor precipitating life events

BACKGROUND: The present study examines the moderating role of global depression severity on the relation of melancholic versus non-melancholic depression to severe and non-severe levels of stress. METHOD: A community sample of 50 women with unipolar major depressive disorder, of which 54% met Research Diagnostic Criteria for melancholic depression, were interviewed regarding stressful life events experienced prior to onset. Events were coded as severe or non-severe based on the rigorous Bedford College contextual rating system. RESULTS: Greater severity of depression was related to a higher likelihood of a severely stressful event prior to onset only for women with non-melancholic major depression. By contrast, greater severity of depression was related to a higher likelihood of a non-severe, more minor, stressful event prior to onset only for women with melancholic major depression. LIMITATIONS: The present study was limited by its use of a female volunteer sample, which might not be entirely representative of the population of individuals with major depression. In addition, the study employed a cross-sectional design, which limits conclusions relating to the causal relation of stress to melancholic versus non-melancholic depression. CONCLUSIONS: Far from being autonomous of stress, individuals with severe melancholic depression may be especially sensitive to stress, such that their episodes are influenced by more minor stressors than those of individuals with non-melancholic depression.     

Is interpersonal sensitivity specific to non-melancholic depressions?

Background: We investigated whether melancholic and non-melancholic Japanese depressive patients differed in regard to a personality feature, interpersonal sensitivity, as measured by the Interpersonal Sensitivity Measure (IPSM). Methods: In addition to 154 normal controls, 66 remitted melancholic patients and 55 remitted non-melancholic patients filled out the IPSM and two widely-used comprehensive personality inventories, the Temperament and Character Inventory (TCI) and the Munich Personality Test (MPT). The subdivision of patients was made according to three major symptom-based criteria for melancholia (those of RDC, DSM-III, DSM-IV). Results: Multivariate and post-hoc univariate analyses of variance revealed significant differences among the three groups in several personality dimensions after Bonferroni's adjustments of P values. While reported scores of both melancholic and non-melancholic patients deviated from normative scores on several personality dimensions, non-melancholic patients reported significantly higher scores on the total IPSM and the 'fragile inner-self' (a subscore of the IPSM) than did normal controls or melancholic depressives. The principal component analysis isolated two factors related to depressive disorders: one factor corresponding to the five IPSM scores; and the other corresponding to harm avoidance, neuroticism and frustration tolerance. The scores on the former factor differentiated non-melancholic depressives from melancholic depressives and normal controls. The scores on the latter factor differentiated both melancholic and non-melancholic depressives from normal controls. Limitations: Prospective studies in which depressive subjects are subdivided into melancholic and non-melancholic subjects will be required to see whether the personality deviations here related to depressive disorders strongly reflect the premorbid personality function. Conclusions: These results indicate that the IPSM scales (particularly, the fragile inner-self scale and the total IPSM scale) are relatively independent of all dimensions included in the two comprehensive personality inventories, and have a capability to describe personality differences between non-melancholic depression and melancholia.     

Stroop performance in depressive patients: a preliminary report

BACKGROUND: The Stroop interference test requires executive control functions, in particular inhibition of a learned routine (in this case word reading). Depressive patients show deficits on tests of executive function. However, the impact of confounding variables like type of depression and anxiety level is not yet elucidated for depressive patients. This is of clinical importance, since executive functions seem to play an important role in predicting treatment response and functional outcome. METHODS: 23 depressive patients and 27 healthy subjects performed a computerized mixed trial Stroop task. Depressive patients were divided according to DSM-IV diagnosis into melancholic and non-melancholic subgroups. Furthermore the level of anxiety was assessed in all subjects. RESULTS: When depressed patients were analyzed as a whole group, they showed only a trend towards higher Stroop interference effect at the beginning of the task. When analysis was performed using according to DSM-IV defined melancholic and non-melancholic subgroups, only non-melancholic patients were impaired in the Stroop task compared to melancholic patients and healthy subjects. LIMITATIONS: The sample size was small resulting in low statistical power. Furthermore, the patients were medicated. CONCLUSIONS: The unexpected result that melancholic patients perform better than non-melancholic ones may be due to their more pronounced rigidity, which makes them more resistant against distraction. Hence, more detailed psychopathological assessment is desirable for future investigations in executive functions of melancholic patients.     

The influence of anxiety as a risk to early onset major depression.

OBJECTIVE: we seek to identify and quantify any risk provided by several expressions of "anxiety" to major depression overall, and to separate melancholic and non-melancholic sub-types. METHOD: a sample of 269 patients with a current major depressive episode was assessed for rates of separate formalised anxiety disorders, both for lifetime and prior to the initial depressive episode. We also sought for evidence of familial anxiety and, early childhood expression of anxiety forerunners, measured both state and trait anxiety levels as well as anxiety at a "personality" level, and assessed use of anxiolytic medications. Depressive sub-typing was undertaken using DSM-IV criteria, while "early onset" (EO) depression was defined as an initial onset at 25 years or less, and subsequently re-examined with a cut-off age of 20 years or less. RESULTS: overall. 42% of our sample were assigned as having EO depression, with there being a higher representation of non-melancholic than melancholic EO subjects (i.e., 51% vs. 29%), arguing for sub-type status being respected in the analyses. For both melancholic and non-melancholic subjects two trait anxiety items ("tense"; "keyed up/on edge") were over-represented, suggesting that such a tense anxiety style may provide an antecedent risk to depression (of either sub-type) or be a consequence of depression. Specificity was most evident in the non-melancholic sub-sample, where EO depression was associated with a family history of anxiety, early childhood expressions of anxiety and with two lifetime anxiety disorders (social phobia and obsessive-compulsive disorder). Broadly similar results were returned when "EO" definition was reduced to 20 years or less. CONCLUSIONS: our study is consistent with previous research in identifying anxiety in the form of social inhibition or social avoidance as being particularly likely to precede and perhaps be a conduit to early onset non-melancholic major depression. This conclusion both sharpens risk factor research and indicates an important fulcrum that could be used to assist primary prevention of the depressive disorders.     

Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?

BACKGROUND: Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. METHODS: Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. RESULTS: The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.     

The development of major depressive episodes during the course of dysthymic and episodic major depressive disorders: a retrospective examination of life events

BACKGROUND: The present study examined whether stressful life events are associated with the development of major depressive episodes (MDEs) in a longitudinal, retrospective study of dysthymic and episodic major depressive disorders. METHODS: Sixty-seven outpatients with DSM-III-R dysthymia and 38 outpatients with non-chronic major depression were followed up 30-60 months after entry into the study. Follow-up assessments included a modified version of Paykel's (1997) Interview for Recent Life Events (IRLE) and Keller et al.'s (1987) Longitudinal Interval Follow-up Evaluation. Life events were assessed retrospectively in the 6 months before the most recent MDE or in the 6 months before follow-up for patients without a MDE. RESULTS: In dysthymic patients, MDEs were significantly associated with a new life event in the context of an ongoing chronic stressor. In episodic major depressive patients, relapses were associated with new life events regardless of an ongoing chronic stressor. LIMITATIONS: This was a retrospective study. It was also a conservative test of the association between life events and MDEs as the follow-up period over which life events were assessed was long, increasing the possibility of forgetting; events occurring less than 1 month before relapse were excluded to avoid confounding the event with the MDE; life events were assessed for a more distant time period for patients who experienced MDEs than those who did not; and an abbreviated version of the IRLE was used which may have failed to identify less severe events. CONCLUSIONS: This study suggests that life events may play a role in the onset of MDEs in persons with dysthymic disorder and those with major depressive disorder. Thus, clinicians should monitor dysthymic patients after a stressful life event, particularly if it occurs in the context of a chronic, ongoing stressor.     

The validity of diagnosis of melancholic depression according to different diagnostic systems.

BACKGROUND: Melancholic versus nonmelancholic depression dichotomy is perhaps the most widely accepted distinction in categorization of depression. This research aims to compare RDC, DSM-III, DSM-III-R, DSM-IV and ICD-10 melancholic/endogenous/somatic and nomelancholic/nonendogenous/nonsomatic depressive patients with regards to biological variables thyroid stimulating hormone (TSH), basal and post dexamethasone cortisol levels, age, age of onset of depression, psychosocial stressors, and severity of depression. METHODS: Sixty-five patients who had been diagnosed as having major depression according to DSM III-R, using SCID were included in this study. Patients were divided into melancholic and nonmelancholic subtypes using RDC, DSM-III, DSM III-R, DSM-IV and ICD-10 criteria and groups were compared on the basis of biological variables, as well as age, psychosocial stressors and the severity of depression. RESULTS: RDC endogenous depressives were older, more severely depressed and had higher cortisol levels then RDC nonendogenous depressives. DSM III-R melancholics were older, more severely depressed, reported fewer numbers of psychosocial stressors and had lower levels of TSH than nonmelancholics. DSM-IV melancholics were more severely depressed, had higher basal and post dexamethasone cortisol levels and lower TSH levels. The ICD 10 somatic depression group contained more severe, older depressives with lower TSH levels. CONCLUSION: The results of this research show that different criteria may identify different groups of patients as having melancholic depression. They also partly support the hypothesis that endogenous or melancholic depression have a biological basis. LIMITATIONS OF STUDY: The study involved a relatively small sample size from a single centre and the results are based on this relatively small sample.     

Stressful life events and depressive problems in early adolescent boys and girls: the influence of parental depression, temperament and family environment

BACKGROUND: Stressful life events increase the probability of depressive problems in early adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these events. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment. METHODS: Data were collected as part of a longitudinal cohort study of (pre)adolescents (n = 2127). During the first assessment wave at approximately age 11, we assessed parental depression, family functioning, perceived parenting behaviours, and temperamental frustration and fearfulness. At the second wave, about two and a half years later, stressful life events between the first and second assessment were assessed. Depressive problems were measured at both waves. RESULTS: Adolescents with parents who had a (lifetime) depressive episode were more sensitive to the depressogenic effect of stressful events than adolescents without depressed parents. Furthermore, girls are more sensitive to these effects than boys. The modifying effect of parental depression was not mediated by temperament, family functioning and perceived parenting. LIMITATIONS: Life events were assessed without consideration of contextual information. Depressive problems were measured by questionnaires that did not directly represent DSM-IV criteria. The measure of parental depression was unspecific regarding severity and timing of depressive episodes. CONCLUSION: The results suggest that gender and parental depression are associated with increased sensitivity to depression after experiencing stressful life events during adolescence.     

Reconfirming the role of life events for the timing of depressive episodes. A two-year prospective follow-up study

BACKGROUND: Since the 1960s the association of stressful life events and depression seemed to be firmly established. However, a few recent studies did not confirm those earlier findings. One of the reasons discussed for the inconsistencies was the sampling of milder depressed neurotic out-patients in the earlier studies vs. more severely ill endogenous type in-patients in recent studies. METHODS: This investigation was carried out with 50 consecutively admitted in-patients with endogenous depression according to ICD 9 and unipolar major depression according to DSM-III-R as ascertained by SCID. The control sample consisted of 26 healthy volunteers. Life events and chronic distressing life conditions were recorded with the Munich Interview for the Assessment of Life Events and Conditions (MEL) every 3 months over a period of 2 years along with psychopathological symptoms and recurrencies. Hence the design was prospective in the sense that life events were recorded for one 3-month cross-section, the depressive reaction for the subsequent one. BDI scores taken at the respective cross section were used to control for depressive bias of the subjective part of the patient's life event evaluation. RESULTS: Three months prior to the index hospitalization patients were more often affected by life events and conditions than controls. The number of stressful conditions prior to the index hospitalization indicated the time to relapse after discharge. Controls showed more desirable positive conditions than patients. Relapse patients suffered more often stressful life events and conditions than non-relapsers 3 months prior to their relapse. Multivariate analysis indicates that the cumulative number of life events within the 2-year course is the best predictor of the BDI score at the end of the follow-up period. Limitations: Since the subjective component of life event assessment by MEL displayed a higher impact on the course of depression than the objective part of the assessment, confounding of subjective ratings, attributional styles, and depressive symptoms may be a problem although controlled for in this study. CONCLUSION: The results support the importance of stressful life events and chronic distressing conditions for the 2-year course and outcome of major depression in an in-patient sample. Since the overall consistency of significant results was more pronounced in the subjective than in the objective part of the MEL the results fit best a circular pathogenetic model of interactions between life events, their individual evaluation by the patient, and depressive symptoms.     

Anxious-retarded depression: relation to two-year outcome of major depressive disorder

BACKGROUND: Anxious-retarded depression is a two-dimensionally defined subcategory of depression derived from DSM-IV melancholia. It is related to increased plasma vasopressin, correlative plasma vasopressin and cortisol levels, and a positive family history. We now explored its relation with outcome. METHODS: Seventy depressed patients were included to follow-up for two years. Outcome was defined by time until full-remission. Cox regression analyses were used to compare anxious-retarded and non-anxious-retarded patients, as well as melancholic and non-melancholic patients. RESULTS: Anxious-retarded depression had poor outcome. LIMITATIONS: The number of patients was relatively small. CONCLUSION: The poor outcome of anxious-retarded depression further supports its validity.     

Ocular motor differences between melancholic and non-melancholic depression

BACKGROUND: Major depressive disorder may be a heterogeneous disorder, yet melancholic depression is the most consistently described subtype, regarded as qualitatively different to non-melancholic depression in terms of cognitive and motor impairments. Eye movement studies in depression are infrequent and findings are inconclusive. METHODS: This study employed a battery of saccadic eye movement tasks to explore reflexive saccades, as well as higher order cognitive aspects of saccades including inhibitory control and spatial working memory. Nineteen patients with major depressive disorder (9 melancholic; 10 non-melancholic) and 15 healthy controls participated. RESULTS: Differences were revealed between melancholic and non-melancholic patients. Melancholia was associated with longer latencies, difficulty increasing peak velocities as target amplitudes increased, and hypometric primary saccades during the predictable protocol. In contrast, the non-melancholic depression group performed similarly to controls on most tasks, but saccadic peak velocity was increased for reflexive saccades at larger amplitudes. LIMITATIONS: Most patients were taking antidepressant medication. CONCLUSIONS: The latency increases, reduced peak velocity and primary saccade hypometria with more severe melancholia may be explained by functional changes in the fronto-striatal-collicular networks, related to dopamine dysfunction. In contrast, the serotonergic system plays a greater role in non-melancholic symptoms and this may underpin the observed increases in saccadic peak velocity. These findings provide neurophysiological support for functional differences between depression subgroups that are consistent with previous motor and cognitive findings.     

Stress, personality and depressive symptoms in a 6.5 year follow-up of subjects at familial risk for affective disorders and controls

BACKGROUND: The aim of the study was to identify risk factors in subjects at risk for depressive disorders and controls. METHODS: In a 6.5 year follow-up study we examined the effects of personality (neuroticism, frustration intolerance, rigidity, melancholic type), adverse life events and chronic difficulties on depressive symptoms in 89 high-risk subjects (HRS, siblings and children of patients suffering from an affective disorder), without any mental illness at wave 1 (T1), and 49 controls without any personal and family history of psychiatric disorder at T1. To this end, regression analysis and path analysis using a structural equation model (only for HRS) were performed. RESULTS: Risk factors for depressive symptoms at wave 2 (T2) in HRS comprised acute adverse life events, frustration intolerance (T1) and depressive symptoms (T1). Risk factors for depressive symptoms in controls included chronic difficulties, neuroticism and rigidity. HRS had less stressful life events and the same risk for chronic difficulties, but perceived adverse events as more stressful. LIMITATION: The sample size of the control group is too small for identifying slight effects. CONCLUSION: Our results indicate that the impact on the emergence of depressive symptoms of various risk factors is different in high-risk subjects and controls. High-risk subjects are more sensitive to the depressogenic effects of acute stress and thus avoid potential stressful changes in their life to a higher extent. On the other hand, the influence of persistent factors such as personality traits (neuroticism, rigidity) and chronic difficulties on subsequent depressive symptoms was less pronounced in HRS as compared to controls.     

Parental representations of melancholic and non-melancholic depressives: examining for specificity to depressive type and for evidence of additive effects.

Several studies have suggested that 'anomalous parenting', as measured by the Parental Bonding Instrument (PBI), may be a differential risk factor to subsequent depression in adulthood--being irrelevant to melancholia but over-represented in non-melancholic depressive disorders. Such a 'specificity' effect is confirmed in our current sample of 65 melancholic and 84 non-melancholic depressed patients. Secondly, we examine the risk to depression effected by exposure to one parent with an anomalous parental style, and the extent to which that risk is modified by characteristics of the other parent. We find clear evidence of additive effects with the risk to non-melancholic depression being raised by exposure to 'anomalous parenting' from two parents. Of the varying parental styles measured by the PBI, low parental care from both parents provided the highest risk to non-melancholic depression (being 4-7 time higher in one sample and 13-27 times higher in the other).     

Self-paced and reprogrammed saccades: differences between melancholic and non-melancholic depression

Motor disturbances in major depressive disorder (MDD) are increasingly recognized and may differentiate melancholic, from non-melancholic depression. Motor impairments in melancholic depression have been likened to Parkinson's disease and proposed to have a frontostriatal basis. This study investigated self-pacing and reprogramming skills, thought to rely on frontostriatal functioning, in groups of healthy individuals (n=15), non-melancholic depression patients (n=10) and melancholic depression patients (n=9) using ocular motor tasks. Self-paced saccades were requested to be performed at a rhythm of 1 Hz between two continuously illuminated targets, before and after external cueing. Saccade reprogramming, for direction and amplitude, was explored using a saccadic "oddball" task. Results indicated no group differences for accuracy, intersaccadic intervals (during the self-paced task), latency or peak velocity. However, the melancholic group showed greater intrasubject variability of latencies than the control group, lower peak saccade velocities compared to the non-melancholic group, and reduced accuracy of the primary saccade when compared to the control and the non-melancholic groups. These findings provide further support for distinct motor impairments associated with melancholia that may reflect frontostriatal abnormalities.     

Sad benefit in face working memory: an emotional bias of melancholic depression

Emotion biases feature prominently in cognitive theories of depression and are a focus of psychological interventions. However, there is presently no stable neurocognitive marker of altered emotion-cognition interactions in depression. One reason may be the heterogeneity of major depressive disorder. Our aim in the present study was to find an emotional bias that differentiates patients with melancholic depression from controls, and patients with melancholic from those with non-melancholic depression. We used a working memory paradigm for emotional faces, where two faces with angry, happy, neutral, sad or fearful expression had to be retained over one second. Twenty patients with melancholic depression, 20 age-, education- and gender-matched control participants and 20 patients with non-melancholic depression participated in the study. We analysed performance on the working memory task using signal detection measures. We found an interaction between group and emotion on working memory performance that was driven by the higher performance for sad faces compared to other categories in the melancholic group. We computed a measure of "sad benefit", which distinguished melancholic and non-melancholic patients with good sensitivity and specificity. However, replication studies and formal discriminant analysis will be needed in order to assess whether emotion bias in working memory may become a useful diagnostic tool to distinguish these two syndromes.     

Serum lipid profiles in major depression with clinical subtypes, suicide attempts and episodes

BACKGROUND: We tried to report the data between serum lipid profiles and major depression with different clinical subtypes, with or without suicide attempts, and with single episode or recurrent episodes. METHOD: During a 2-year period, a total of 168 participants (109 patients with major depression and 59 subjects in a healthy control group) were recruited in this study. Blood samples for serum lipid profiles in all participants were collected. Data analysis was performed by using an analysis of covariance (ANCOVA) with body mass index (BMI) adjustment. RESULTS: The data showed that there were no significant differences of any kind in serum lipid profiles between depressive patients with melancholic feature or atypical feature, with or without suicide attempts nor between depressive patients with single episode or recurrent episodes. CONCLUSION: The results suggested there were no serum lipid profiles used as biological markers to distinguish the clinical subtypes, suicide attempts and episodes in patients with major depression.     

S-100B is increased in melancholic but not in non-melancholic major depression

BACKGROUND: Recent evidence suggests that neurodegeneration may be involved in the pathophysiology of major depression. The astroglial peptide S-100B was shown to be increased in many diseases causing neuronal cell damage or degeneration. METHOD: S-100B plasma levels were determined in 28 patients with major depression and 28 matched healthy controls using an immunofluorometric sandwich assay. RESULTS: Patients suffering from melancholic depression showed significantly increased S-100B levels compared to healthy controls while non-melancholic patients demonstrated normal levels. LIMITATIONS: Medication of patients varied. The differentiation between melancholic and non-melancholic patients was performed clinically without using a standardized instrument. CONCLUSIONS: Neurodegeneration or axonal remodeling may be involved in the pathogenesis of melancholic depression.     

Seasonal depression: the dual vulnerability hypothesis revisited

OBJECTIVE: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, other groups with "winter depression" have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy. METHOD: 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (N=192) were treated with an open, 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores. RESULTS: The rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (N=32, 78%), intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47, 51%). LIMITATIONS: This was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined. CONCLUSIONS: There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.