进食障碍患者血DST及尿MHPG.SO4排出量的测定

对３４例进食障碍（ＥＤ）患者及２１名健康人进行血ＤＳＴ及尿ＭＨＰＧ．ＳＯ４排出量测定。结果表明ＥＤ患者血ＤＳＴ阳性率明显高于对照组。两组间尿ＭＨＰＧ．ＳＯ４的排出量未见明显差异。本文结果未发现ＥＤ患者ＨＰＡ轴脱抑制率与抑郁症状有关，但在抗抑郁治疗后，ＥＤ患者的ＤＳＴ阳性率下降，临床症状得到缓解。本研究结果表明，ＥＤ患者的ＨＰＡ轴功能异常极突出，并提示这种异常可能与异常的进食态度及行为关系密切。     

Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy

Several systematic studies have evaluated serial dexamethasone suppression tests (DST) in patients with major depression who were treated with antidepressant medications. DST changes were noted to parallel clinical improvement in most recovering patients. If serial DSTs are a valid state-related correlate of depressive pathophysiology, all types of effective antidepressant treatment should result in DST 'normalization'. However, no treatment modalities other than antidepressant medications have been studied serially with systematic assessments. To test whether serial DSTs reflect clinical progress in depressives treated solely with electroconvulsive therapy (ECT), we studied weekly DSTs and Hamilton Rating Scales for Depression (HRSD) in 22 drug-free depressed patients. We observed progressive DST 'normalization' in most patients and moderately high correlations between weekly DST and HRSD values throughout treatment. Most patients receiving ECT became DST suppressors. In most patients the DST appeared to reflect the severity of depressive pathophysiology, perhaps providing serial feedback to clinicians monitoring the progress of treatment with ECT.     

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 heterogeneous 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/non-endogenous 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 heterogeneous 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.     

A closer look at treatment resistant depression: is it due to a bipolar diathesis?

BACKGROUND: Treatment resistant depression is a common clinical problem. Studies have shown that a large number of patients with depression do not have a satisfactory clinical outcome in spite of adequate trials of antidepressant drugs. In this study, we investigated demographic and clinical characteristics, diagnostic subtypes, and illness outcome of patients with resistant depression and a history of escape of response to adequate trials of at least two antidepressants for a previous episode. METHOD: Sixty-one patients who were seen consecutively at a mood disorders clinic with the diagnosis of "unipolar" treatment resistant depression, and followed up for at least one year, were interviewed using the Structured Clinical Interview for DSM-IV. Prospectively collected data including the occurrence of episodes of hypomania, and supplemental information from family members on illness course were also used for purposes of diagnostic re-evaluation. RESULTS: At intake, 35% of the patients were diagnosed as having a bipolar disorder. At follow-up, there was a 59% prevalence of bipolar disorder. Of the patients with major depressive disorder, 52% were subsequently classified as having bipolar spectrum disorder. The most important finding was that 80% of patients were found to show evidence of bipolarity. Moreover, the most common change in medication was a switch to mood stabilizers. CGI ratings showed significant improvement in functioning from the time of initial consultation. LIMITATIONS: This was a naturalistic study, and the data were collected in a non-blind fashion. CONCLUSIONS: The findings suggest that the majority of cases of unipolar treatment resistant depression, occurring in the context of loss of antidepressant response, have a bipolar diathesis.     

Study of the diagnostic value of the dexamethasone suppression test in endogenous depression

The diagnostic value of the dexamethasone suppression test (DST) in "endogenous" depression was evaluated in 209 psychiatric inpatients. A high incidence of abnormal DST results was observed in "endogenous" depressives (52%), schizo-affective (69%) and borderline patients (38%). However, 25% of the patients with other psychiatric disease also failed to suppress on the DST. Diagnostic criteria, previous history of alcoholism, psychiatric drug treatment, age and sex did not significantly affect DST performance. The present data do not indicate that the DST represents a highly specific marker of "endogenous" depression.     

The dexamethasone suppression test in schizo-affective depression

The dexamethasone suppression test (DST) was performed on 30 patients fulfilling RDC or Kendell criteria for schizo-affective depression. Symptoms characteristic of depression or schizophrenia were noted, and the severity of psychosis and the severity and endogenicity of depression were assessed. Ratings of severity were repeated at 2-month follow-up. Ten of the 30 subjects were DST non-suppressors, but no clear differences in symptoms, severity of illness or outcome between suppressors and non-suppressors emerged. Thus, although schizo-affective depression is associated with an increased frequency of HPA axis abnormality as assessed by the DST, this test does not clarify the status of schizo-affective depression in the classification of psychiatric illness.     

Who responds to prophylactic lithium?

Response to prophylactic lithium was studied in relation to clinical and psychological characteristics in a large series of patients with recurrent affective disorders. The findings were that bipolar patients with a family history of mania or depression had more favourable responses than those with no family history of affective disorders. Unipolar patients with more endogenous illnesses and those with pure familial depressive disease had more favourable responses than those with less endogenous illnesses and those with sporadic and depression spectrum diseases. Good responders showed generally less personality disturbance on a variety of measures than fair-to-poor responders. Response to lithium over 6 months in unipolar illness and over the first year in bipolar illness was strongly associated with long-term response.     

Life events and the dexamethasone suppression test in affective illness

Forty patients with primary endogenous major depression were followed up during a 12-month period after recovery, on maintenance therapy. Neither the results of the DST, nor the life events reported could predict the occurrence of affective relapses although bereavement life events tended to be observed more frequently in patients relapsing, regardless of the type of antidepressant treatment.     

Immune cell parameters in severely depressed patients: negative findings

Cross-sectional population studies reported decreased mitogen-induced lymphocyte responsiveness in severely depressed patients. This immunologic impairment, indicative of T- and/or B-cell dysfunction, was related to disturbances in the dexamethasone suppression test (DST) and to age effects. Glucocorticoid overdrive, a hallmark for severe depression, exerts immunosuppressive effects through the impact on neutrophils, lymphocytes, and monocytes and natural killer cells (NKC). This paper has analyzed the relation of peripheral blood immune parameters to severe depression, DST results and age. The population consisted of 37 inpatients categorized according to DSM-III as minor depression (300.40, 309.00), simple major depression (296.X2) or major depression with melancholia and/or with psychotic features (296.X3, 296.X4). The number of leukocytes, neutrophils, lymphocytes and monocytes was counted. T-cell (total T-cell, T-helper, T-suppressor, HLA-DR), B-cell (LN1 and immunoglobulin (Ig) receptors), monocytes (M1 and M3 membrane antigens) and NKC activity were identified by phenotype using monoclonal antibodies. No differences were detected between the depressive subgroups for any of the parameters examined. There were no relationships between these immune variables and the severity of illness, DST results or age.     

The dexamethasone suppression test as a predictor of suicidal behavior in unipolar depression

BACKGROUND: Non-suppression on the dexamethasone suppression test (DST) in unipolar depression has been found to be associated with completed suicide, with less consistent data for attempted suicide and hospitalizations for suicidality. The purpose of this study was to examine DST non-suppression as a predictor of these three aspects of suicidal behavior. METHODS: Records were reviewed for 101 patients who met criteria for major depressive disorder and/or dysthymic disorder and had a DST performed. All patients were treated naturalistically and were followed for an average of 2 years. DST suppressors and non-suppressors were compared with respect to three outcomes: (1) completed suicide; (2) attempted suicide; and (3) hospitalizations for suicidality. RESULTS: DST non-suppressors were significantly more likely to have completed suicide or be hospitalized for suicidality than DST suppressors, with a non-significant trend for attempts. Total suicidal events were also significantly more frequent in the non-suppressor group. LIMITATIONS: Axis II diagnoses and severity of illness were not assessed. Knowledge of DST results may have influenced the decision to hospitalize patients. CONCLUSIONS: DST non-suppression identifies unipolar depressed patients with a higher risk for future suicide completion or hospitalization for suicidality. Performance of DST upon initiation of treatment may be a useful adjunct in identifying suicidal risk.     

Hypothalamic-pituitary-adrenal axis function in patients with chronic depression

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis function in patients with chronic depression has previously been shown to be normal when measured using the dexamethasone suppression test (DST). We examined patients with chronic depression using the sensitive dexamethasone/corticotropin releasing hormone (dex/CRH) test and the dexamethasone suppression test (DST) to establish whether HPA axis abnormalities are present in this group. We also compared the sensitivity of the two tests and compared the results with previous studies in depression that have not specifically selected chronic patients. METHOD: Twenty-nine patients with the chronic subtype of major depressive disorder and 28 matched controls underwent examination of HPA axis function. RESULTS: Neither the cortisol response to the DST or the dex/CRH test differed significantly between the patient and control groups. There was a trend in favour of more patients than controls having an abnormal response to the dex/CRH test (P = 0.052). Neither the patients with an abnormally enhanced response, nor the magnitude of response could be predicted by any illness or demographic variable. CONCLUSION: The HPA axis is not overtly abnormal in chronic depression. This contrasts with previous findings in acute depression and bipolar disorder and may suggest that the HPA axis abnormalities present in acute depression resolve, but are not accompanied by symptom resolution. Alternatively, a subgroup of depressives with less HPA dysfunction may progress to chronicity. This has implications for treatment and prognosis. The dex/CRH is a more sensitive test of HPA axis function than the DST in patients with chronic depression.     

Is DST status associated with depression characteristics?

Depressed inpatients have a DST non-suppression rate that is several times greater than that of depressed outpatients. To explore what clinical features of depression might explain this difference, 25 depressed inpatients who were DST non-suppressors were compared with 16 DST suppressors, using 70 clinical variables. Those variables that were different between these two groups of inpatients were then used to compare depressed inpatients and outpatients. Three variables that were significantly associated with DST status in depressed inpatients were also found to differentiate between depressed inpatients and depressed outpatients. DST suppression was associated with a family history of alcoholism, with the symptom hypersomnia, and with a younger age at index interview.     

Separation of subtypes of depression using discriminant analysis. Separation of bipolar endogenous depression from nonendogenous ("Neurotic") depression

We derived a discriminant function separating patients with bipolar endogenous depression ("melancholia") from patients with nonendogenous ("neurotic") depression, and showed that the difference between the groups was not one of overall severity of illness alone. The discriminant function (DF) included 5 clinical items. We reduced the DF to a discriminant index (DI) with integral item weights, and trichotomized the DI scores into two definite classifications and an intermediate, uncertain classification. We cross-validated this DI in a separate group of patients, and found no decrease in the accuracy of classification on cross-validation. Thirty-three of 41 (80%) of the patients in the cross-validation group were classified by the DI; 26 of 33 (79%) correctly. We also validated the DI classification against an external, biological marker, the dexamethasone suppression test (DST). The DI predicted the DST result with the same accuracy as the clinical diagnoses did, supporting the validity of the DI.     

Validity of an operational definition for neurotic unipolar major depression

After we reviewed the literature to identify the clinical and phenomenologic correlates of neurotic depression, we constructed a 6-item operational definition to distinguish neurotic unipolar major depressive disorder from non-neurotic major depression. The neurotic depressives were characterized by a low rate of abnormal dexamethasone suppression test (DST) results and a strong family history of alcoholism. Neurotic depressives improved less than non-neurotic depressives during the index hospitalization, and were more frequently rehospitalized during a 6-month prospective follow-up. Neurotic subtyping was significantly negatively associated with DSM-III melancholia. Neurotic classification remained significantly associated with the above validating variables after melancholic status was held constant, whereas melancholic subtyping did not predict DST results, familial alcoholism rates, or outcome when neurotic status was controlled.     

Correlation between plasma cortisol and CSF catecholamines in endogenous depressed dexamethasone nonsuppressors

Nineteen endogenous depressive in-patients (13 with major depression and 6 with bipolar disorder-depressed) and 10 other patients with dysthymic disorder serving as the control group were given the dexamethasone suppression test (DST, 1 mg/subject). The results showed that the DST sensitivity in endogenous depressives was 73.7% and the specificity was 90%. After the patients were treated daily for 6 weeks with 150–200 mg imipramine, 88.9% of those endogenous depressive patients who previously had a positive DST response exhibited a negative response. Moreover, a significantly negative correlation was found between the CSF norepinephrine level and the pre-dexamethasone 4 p.m. plasma cortisol level in those endogeous depressed patients who had a positive DST response. Pre-treatment data also showed that the 4 p.m. plasma cortisol had a significant negative correlation with CSF dopamine. These findings suggest that endogenous depression with positive DST could be related not only to a lower norepinephrine level, but also to a lower dopamine level.     

Neuroendocrine investigation in children and adolescents with dysthymic disorders: the DST, TRH and clonidine tests

A neuroendocrine study was conducted in eight children and adolescents with dysthymic disorders (three females and five males) and in eight age- and sex-matched psychologically normal controls. The dexamethasone suppression test (DST), TSH and GH responses to TRH stimulation and GH response to clonidine stimulation were studied in parallel in each patient. Depressive symptomatology was monitored with the Poznanski Rating Scale. The DST, TRH and clonidine tests revealed normal responses in each patient. TRH induced abnormal GH rises in five of the eight patients. There were no correlations between neuroendocrine parameters and degree of depression, age, sex or weight of the patients, age of onset, duration and family history of the disease.     

Sipatrigine could have therapeutic potential for major depression and bipolar depression through antagonism of the two-pore-domain K+ channel TREK-1

Major depressive disorder (MDD) is a chronic, recurring and potentially life-threatening mental illness. Current treatments are inadequate - many depression medications, although safe and effective, generally have a slow onset of clinical benefit and around half of the MDD patients do not show full remission with optimized treatment. Therefore, there is still a need for the development of faster-acting and more effective medication for MDD. Recent studies have demonstrated that the TREK-1 protein, one of the 17 members of the two-pore domain K+ (K2P) potassium channel family, is inhibited by the antidepressant fluoxetine. Deletion of TREK-1 in mice caused a substantially reduced elevation of corticosterone levels under stress, and produced behaviour similar to that of naive animals treated with fluoxetine in various behavioural tests. These findings suggested that the blocker of the TREK-1 channel might potentially be a new type of antidepressant. Sipatrigine (BW619C89), a neuroprotective agent, has been found to be a potent antagonist of TREK-1. Its related compound, lamotrigine, has been approved for the treatment of bipolar depression and is used to supplement antidepressant medication in patients with treatment-resistant depression. Furthermore, in addition to its antagonistic effect on TREK-1, sipatrigine is also a glutamate release inhibitor. Excessive glutamatergic neurotransmission is associated with depressive-like behaviours and inhibiting glutamate neurotransmission may be implicated in antidepressant therapeutic mechanisms. From the above findings of the effects of sipatrigine on TREK-1 and glutamate neurotransmission, it is hypothesised that sipatrigine could have potential therapeutic effects for MDD or bipolar depression. Further evaluation of its antidepressant therapeutic and toxic effects in animal models is needed before clinical application.     

Clinical and functional outcomes of depression treatment in patients with and without chronic medical illness

BACKGROUND: In patients with chronic medical conditions, depression can be viewed as an expected reaction to illness or an independent condition requiring active treatment. We examine how clinical and functional outcomes of depression treatment compare in primary-care patients with and without chronic medical illness. METHOD: Health plan administrative data were used to identify primary-care patients initiating antidepressant treatment, including a general sample (n=204) and cohorts with ischemic heart disease (n=68), diabetes (n=93), or obstructive lung disease (n=74). Telephone interviews at baseline, 2 months, and 6 months assessed depression (Structured Clinical Interview for DSM-IV, Hopkins Symptom Checklist depression scale), functional status (SF-36) and days of disability because of to illness. RESULTS: At baseline, depression severity in patients with diabetes and obstructive lung disease was similar to those without medical co-morbidity, but significantly lower in those with ischemic heart disease. Social and emotional functioning were similar across all groups, but those with chronic medical illness reported greater physical impairment. All groups showed significant improvement in depression over six months, but the rate of improvement was significantly slower in those with heart disease. All groups showed significant and similar improvement in social and emotional functioning, but physical functioning showed little change. Days of disability and restricted activity improved significantly in all groups. Improvement in depression during treatment was strongly related to change in disability. CONCLUSIONS: Patients with chronic medical illness and co-morbid depression show significant improvements in mood, social and emotional functioning, and disability following initiation of depression treatment. Depression may be a stronger determinant of disability than is stable chronic medical illness.     

Evidence of an early information processing speed deficit in unipolar major depression

BACKGROUND: Slowing of the speed of information processing has been reported in geriatric depression, but it is not clear if the impairment is present in younger patients, if motor retardation is responsible, or if antidepressant medications play a role. METHOD: Twenty unmedicated unipolar depressed inpatients were compared with 19 medicated depressed in-patients and 20 age-, sex- and verbal IQ-matched controls on inspection time (IT), a measure of speed of information processing that does not require a speeded motor response. We also examined the relationship between IT and current mood and length of depressive illness. RESULTS: Unmedicated depressed patients showed slowing of information processing speed when compared to both medicated depressed patients and controls. The latter two groups were not significantly different from each other. Slowing of IT was not associated with current mood, but was negatively correlated with length of illness since first episode. No differences in IT were found between patients receiving medication with anticholinergic effects and patients receiving medication with no anticholinergic effects. CONCLUSIONS: The findings indicate that unipolar depression is associated with a slowing of speed of information processing in younger patients who have not received antidepressant medication. This does not appear to be a result of motor slowing.     

Acute tryptophan depletion in healthy young women with a family history of major affective disorder

BACKGROUND: Acute tryptophan depletion (ATD), a means of reducing brain serotonin synthesis, lowers mood in normal males with a multi-generational family history of major affective disorder (MAD) and in normal women devoid of any family history of psychiatric illness. As both a family history of MAD and female sex are factors predisposing to depression, the hypothesis that a mood lowering response to ATD may reflect a susceptibility to depression was further investigated in young women with an extensive, multi-generational family history of MAD. In addition, the temporal stability of mood change following repeated trials of ATD was also assessed in this study. METHODS: To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested on two separate occasions. The control treatment, administered on a third occasion, was a nutritionally balanced amino acid mixture containing tryptophan. RESULTS: A marked lowering of plasma tryptophan (85-90 %) was achieved by both depletions. In comparison to the balanced condition, family history positive (FH +) women showed no lowering of mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood change between the two ATD trials (N = 13) exhibited poor temporal stability. CONCLUSIONS: These results may indicate that serotonin responsiveness is not an important characteristic of vulnerability to depression in these women. Alternately, these negative results may be due to the exclusion of a large number of FH + women who had already experienced an episode of depression, resulting in the selection of a biased FH + sample who are resistant to the mood lowering effects of ATD.