Endogenous Major Depressive Disorder Research Articles

EPA-1112 - Can eye movements be used as a marker for major depression?

No externally validated tests are available for routine use to confirm clinical diagnosis of major psychiatric disorders. Eye movement abnormalities that distinguish schizophrenia and bipolar disorder have only recently been described. Evidence of oculomotor dysfunction specific to endogenous major depressive disorder (MDD) would represent discovery of a significant endophenotypic interface between psychotic and affective disorders. Out-patients meeting DSM criteria for MDD (n=68, F:M=40:28, median age=49 (IQR 38-57) years) participated in a series of tasks while eye movements were recorded using an EyeLink 1000 infra-red video tracker. Patients' characteristics at time of assessment included median illness duration of 13 years (IQR= 7-23; n=53 available cases), HADS anxiety=11 (IQR 7-15) and depression=9 (IQR 4-11), BDI=27 (IQR 16-33), BPRS= 25 (IQR 20-29) and estimated IQ= 106 (IQR 96-118; n=42). Performance measures from smooth pursuit, picture viewing, and steady fixation were analysed alongside data from controls, schizophrenia, and bipolar disorder cases. A neural network was able to delineate the clinical and control groups with sensitivity=90.4% and specificity=97.1%. Multivariate tests of group differences post hoc revealed that MDD cases were on average poorest in maintaining steady gaze during the fixation task, mirroring the neuropsychological evidence for dysregulation of executive function in prefrontal brain regions. Bipolar and unipolar affective cases performed similarly on smooth pursuit and picture viewing tests, but were systematically different from schizophrenia and control groups. If differences are replicated in further cases, the MDD eye movement marker could be an important tool for psychiatric research, allowing for easier delineation of the major disorders.

Do psychotic, minor and intermittent depressive disorders exist on a continuum?

The following paper uses information from a family study and 10-year follow-up of probands with unipolar depression to describe relationships between psychotic and non-psychotic major depressive disorder (MDD) and, in turn, between psychotic MDD and minor or intermittent depressive disorders. Probands began follow-up as they sought treatment for MDD at any of five participating academic centers. Follow-up evaluations then occurred at 6-month intervals for 5 years and then annually for an additional 5 years. Two-thirds of the probands also entered a family study in which raters attempted direct interviews of all available adult first-degree relatives. Findings that individual symptoms comprising the endogenous MDD subtype had higher severity ratings, that the full MDD syndrome was present for a greater number of weeks in each year of follow-up, and that time to new episodes of MDD were shorter, all indicated that patients with psychotic features had a severe variant of MDD. An increased familial risk for psychotic MDD per se, and a sustained tendency for psychotic features to recur, indicated an important discontinuity, however. The increase in morbidity over time which characterized psychotic patients manifested in the full MDD syndrome, but not in mild MDD, minor or intermittent depressive syndromes. These milder syndromes tended to be more prominent over time among patients who began with non-psychotic MDD. This fails to support a continuum spanning both psychotic MDD and the mild, subsyndromal forms of unipolar depression.

Rapid Eye Movement Density Among Adolescents With Major Depressive Disorder Revisited

In the context of a follow-up study investigating the clinical continuity of major depressive disorder (MDD) and biological markers from prepuberty and adolescence to young adulthood, we are performing new analyses on polysomnographic data previously reported by Goetz et al¹in theArchives. During this process, we noted a finding that we did not originally report; this finding replicates some recent articles regarding rapid eye movement (REM) density during the first REM period. Goetz et al¹described the sleep of 49 adolescents, mostly outpatients (86%), in whom MDD (ie, 25 adolescents with endogenous MDD [MDD-E] and 24 adolescents with nonendogenous MDD [MDD-NE]) was diagnosed and 40 adolescents without a history of a psychiatric disorder. Findings included increased sleep latency, increased awake time, and decreased sleep efficiency among adolescents with depression vs adolescent controls. No unconfounded REM sleep differences between the adolescents with depression and adolescent controls were reported.

Effect of clomipramine and lithium on fenlfuramine-induced hormone release in major depression

Prolactin (PRL) and cortisol responses to oral administration of d-1 fenfluramine hydrochloride (60 mg) and placebo were examined in patients with endogenous major depressive disorder on three separate occasions: prior to treatment with clomipramine (CMI), after 4 weeks of CMI administration (175–250) mg/day), and 3 weeks after addition of lithium (Li) carbonate (serum level 0.5–0.9 mmol) to the treatment regimen. CMI significantly increased baseline PRL levels which were further elevated following Li supplementation. PRL response to fenfluramine (minus elevated baseline PRL levels) but not to placebo, was significantly increased by CMI administration, reflected over the 6-hr time course examined and in peak minus baseline values. Following addition of Li, the degree of enhancement was diminished although the peak minus baseline value remained significant relative to the pretreatment response. Cortisol levels were not increased by fenfluramine and were not altered by CMI or CMI + Li administration. The effect of CMI extends previous observations regarding the action of antidepressant treatment on serotenergically mediated hormone release. Methodological considerations relevant to the effect of CMI + Li are discussed.

Growth hormone secretion in prepubertal children with major depression. II. Sleep-related plasma concentrations during a depressive episode.

Plasma growth hormone (GH) concentrations were determined every 20 minutes during sleep in 71 prepubertal children: 22 had endogenous major depressive disorder, 20 had nonendogenous major depressive disorder, 21 had nondepressed neurotic disorders, and eight were normal. Both depressive groups secreted significantly more GH during sleep than did controls. Measures included maximal GH plasma peak and area under the curve (AUC) during the total sleep period, during the first three hours after sleep onset, and during the first five hours after sleep onset. An AUC cutoff of 2,000 ng X min/mL identified positively half the prepubertal children with major depression; with a specificity of 78% (v neurotics) and 100% (v normal children). Increased GH secretion during sleep may be a marker of illness, a past episode, or trait for prepubertal major depression regardless of endogenicity.

Growth hormone secretion in prepubertal children with major depression. III. Response to insulin-induced hypoglycemia after recovery from a depressive episode and in a drug-free state.

Insulin tolerance tests (ITTs) were performed after at least four months of sustained recovery from an episode of a major depressive disorder in 18 drug-free prepubertal children. Eleven had a definite endogenous subtype; seven did not. Sixteen children with nondepressed neurotic disorders made up a control group. The children with past endogenous depression continued to have significant hyposecretion of growth hormone (GH) in this test when compared with the other groups. Illness-recovery correlations were highly significant for the major depressive group as a whole. Paired comparisons of both depressive groups were not significantly different from illness to recovery. We conclude that prepubertal children with endogenous major depression continue to have hyposecretion of GH in response to ITTs in a recovered state and that this neuroendocrine marker is state independent. A GH hyporesponse to ITT may be a true marker of a past episode or of trait for endogenous major depressive disorder in prepuberty.

Growth hormone secretion in prepubertal children with major depression. I. Final report on response to insulin-induced hypoglycemia during a depressive episode.

Insulin tolerance tests (ITTs) were carried out on 46 drug-free prepubertal children with severe emotional disorders. Thirteen met unmodified Research Diagnostic Criteria for major depressive disorder, definite endogenous subtype, 17 met the criteria for nonendogenous major depressive disorder, and 16 fit DSM-III criteria for nondepressed neurotic disorders. The group with endogenous depression had significant hyposecretion of growth hormone (GH) in this test when compared with the other groups. Since GH hyposecretion in response to ITT has been found in most studies to be associated with endogenous major depression in adults, the data support the validity of the diagnosis of prepubertal endogenous major depressive disorder and the hypothesis of similarity or identity of prepubertal and adult major depressive disorders.

Psychodynamic and Characterological Heterogeneity among Adolescents with Major Depressive Disorders

This examination of six adolescents who were hospitalized for an Endogenous Major Depressive Disorder suggests wide heterogeneity in several personality dimensions. These personality dimensions may be critical in the determination of prognosis of the major affective disorder allows no simple generalizations about the need for treatment of other personality disturbances. Further study of these factors should enhance both our clinical interventions with children and adolescents and our understanding of the processes involved in personality and affective development.

HLA antigens in schizophrenia, major depressive disorder, and schizoaffective disorder.

We carried out a study with 150 patients suffering from endogenous psychosis in order to confirm earlier findings of an association between HLA and various psychiatric syndromes. Our sample consisted of 107 schizophrenics, 25 patients with recurrent endogenous major depressive disorder, and 18 schizoaffectives. A significant excess of HLA B27 was found among schizophrenics with a family history of endogenous psychosis. This association is consistent with reported earlier studies. The preliminary data on the schizoaffective sample suggest a positive association with HLA B7. The data on patients with endogenous major depressive disorder failed to identify an association with HLA.

Depression in Anorexia Nervosa

The case histories of 84 patients with a diagnosis of anorexia nervosa were evaluated on the basis of Research Diagnostic Criteria (RDC) for Major Depressive Disorder and Endogenous Major Depressive Disorder. Fifty-six percent met RDC criteria for a major depressive disorder and 35% met RDC criteria for an endogenous depression. MMPI data revealed a mean depression (D) score of 68 with the mean profile showing elevation of scales 2(D), 7(PT) and 8(SC). This study suggests that depression is a more common accompaniment in patients with anorexia nervosa than is usually appreciated. The evidence suggests that anorexia nervosa and major depressive disorder may co-exist and the significance of this is discussed.

Diagnosis of endogenous depression: Comparison of clinical, research and neuroendocrine criteria

Eighty-nine depressed outpatients were studied by clinical criteria, Research Diagnostic Criteria (RDC), and the dexamethasone suppression test (DST) of neuroendocrine regulation. A simple outpatient version of the DST, requiring only one blood sample, correctly identified 40% of patients diagnosed clinically as endogenous depression (ED), with a specificity of 98% and a diagnostic confidence of 95%. Differences in age, sex, or severity of symptoms between endogenous and non-endogenous depressives did not account for these results. By comparison, the diagnostic performance of the DST was weaker for the RDC categories Major Depressive Disorder (MDD) and primary MDD. These were less selective and more heterogenous than the clinical category ED. The clinical diagnoses of ED were supported in 98% of cases by the RDC, but 22% of RDC endogenous MDD diagnoses were not supported by the clinical diagnoses. Abnormal DST results were found only in patients with both the clinical diagnosis of ED and the RDC diagnosis of endogenous MDD. Patients with definite endogenous MDD had a significantly higher frequency of abnormal DST results (42%) than those with probable endogenous MDD (14%), or those with other RDC diagnoses (3%). A significant association was found between positive DST results and a positive family history of depression. These results support other evidence for use of a positive DST result as an external validating criterion for ED. The category MDD contained all cases diagnosed clinically as ED, but was diluted by cases diagnosed clinically as non-endogenous depression who had no neuroendocrine disturbance. The results also confirmed that the endogenous/nonendogenous and primary/secondary classifications of depression are not identical. We conclude: (1) that the DST can be used in the differential diagnosis of depressed outpatients as well as inpatients; (2) that the RDC category primary MDD and the Washington University category primary depression are more heterogenous and probably less valid than the clinical category ED; (3) that the RDC for endogenous MDD have only moderate validity; (4) that RDC diagnoses cannot substitute for careful clinical diagnoses in research studies, (5) that the best use of the RDC is to support clinical diagnoses, but not to generate diagnoses independently as a free-standing system; (6) that the concept of endogenous or endogenomorphic depression has validity and should be retained in research studies of depression.

Use of the Research Diagnostic Criteria and the Schedule for Affective Disorders and Schizophrenia to study affective disorders.

In a pilot study of 150 manic or depressive patients, the authors used the Research Diagnostic Criteria (RDC) and the Schedule for Affective Disorders and schizophrenia (SADS) to perform preliminary analysis of symptom pictures of the index episode of different diagnostic groups, joint diagnostic classification of the different subtypes of major depressive disorder, and differential outcome by diagnostic groups. The results suggest that schizophrenic symptoms in affective disorders do have diagnostic and prognostic significance, that the term "psychotic depression" should be limited to impaired reality testing without reference to degree of incapacitation, that situational-nonsituational and endogenous-nonendogenous classifications are separate depressive subtypes, and that it may not be true that patients with endogenous major depressive disorder have a better prognosis than patients with nonendogenous depression.