For several years, psychobiologists have sought to identify biological markers which might characterize patients with endogenous depression major depressive disorder with melancholia). Recently, advances in neuroendocrine research have been applied to the study of depression. The cluster of symptoms which define endogenous depression (mood, sleep, appetite, and circadian rhythm disturbances) appear to be regulated by the limbic-hypothalamic system. Hypothalamic nuclei regulate these functions as well as pituitary hormone function which, in turn, regulates peripheral endocrine organs such as the adrenal and thyroid glands. During acute depressive episodes, it is likely that the adaptability of neuroendocrine compensatory mechanisms become impaired and yield measurable dysfunction. Exogenous hormone administration challenges this compensatory system and can elicit subtle evidence of neuroendocrine dysregulation. A variety of neuroendocrine deficits have been described in acutely depressed patients in contrast to other groups of psychiatric patients. The dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation test, in particular, have shown considerable clinical value when used as adjuncts in the assessment of patients with psychiatric disorder. Several reports have noted escape from dexamethasone suppression in 40% to 50%, and blunted thyrotropin (TSH) responses to TRH injection in 25% to 35% of endogenously depressed patients in contrast to few nondepressed patients, schizophrenics, or normal volunteers.1"16
In the past few years, we have endeavored to ascertain the replicability of previously reported findings for neuroendocrine dysfunction in a heterogenous sample of psychiatric patients newly admitted to our private psychiatric hospital. Our clinical investigations have confirmed these earlier reports.9 The combined use of the DST and TRH tests increases the sensitivity for identification of endogenous depression without toss of specificity.8'9 In addition, we have noted that these neuroendocrine challenge studies may have broader possibilities for clinical and therapeutic applications in psychiatry. Table 1 lists ten areas of clinical application which might be considered, although the validity of each approach has not yet been entirely established.
The clinical application of neuroendocrine challenge studies requires that they be used within the context of a comprehensive psychiatric evaluation. We utilize a structured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia- Lifetime Version, in addition to numerous clinical rating scales.17 The neuroendocrine challenge studies are a component of the overall assessment process which still requires the clinical assessment and judgment of the examining physician. The neuroendocrine tests are conducted within the first week of hospitalization prior to the initiation of pharmacotherapy in most cases. The TRH test is conducted in the morning following an overnight fast. An intravenous line is started from which a baseline collection of TSH is obtained. Subsequently, 500 µg of TRH are infused over 30 seconds followed by serial TSH collections at 15, 30, and 45 minutes. TRH stimulates the pituitary gland to release TSH reserves, which in most patients is 10 to 20 µ?/ ml greater than the baseline TS H measurements (denoted as ? max TSH). The criteria for an abnormal TSH response to TRH varies between centers. In our setting, a threshold criteria of Δ max TSH < 7 µ?/rnl has been effective in discriminating endogenously depressed patients from other psychiatric groups, similar to the studies of Gold et al.8'9'1 We administer the DST similar to the methodology of Carroll and his associates.3 One mg of dexamethasone is given at 11:30 PM followed by a 4 PM and i 1:30 PM postdexamethasone serum Cortisol collection on the following day. Post-dexamethasone Cortisol values > 5 µg/dl are considered evidence for a failure OfSUpPrCSSiOn.''9
POTENTIAL CLINICAL APPLICATIONS OF NEUROENDOCRINE CHALLENGE STUDIES
NEUROENDOCRINE CHALLENGE STUDIES IN SUBGROUPS OF PSYCHIATRIC PATIENTS
The Identification of Major Depressive Disorder
Table 1 summarizes the data collected on 153 newly admitted psychiatric patients who received both the TR H stimulation test and DST as part of a comprehensive evaluation. Neuroendocrine dysregulation (either an abnormal DST or TRH test) was found in 76 patients, most of whom met DSM-III criteria for a major depressive disorder. An abnormal DST was noted in 43% of patients with Major Depressive Disorder, in contrast to 7% of schizophrenic patients (p < .05) and 8% of nondepressed patients (p < .025). A blunted TSH response to TRH was found in 32% of patients with Major Depressive Disorder in contrast to 7% of schizophrenics and no nondepressed patients (p < .01). Overall, neuroendocrine dysregulation was noted in 59 of the 94 patients with Major Depressive Disorder (63%) in contrast to 14% of schizophrenics (p < .025) and 8% of non-depressed patients (p < .005). There were no significant differences between subgroups of Major Depressive Disorder using bipolar/ unipolar dichotomy or between bipolar manic and bipolar depressed patients. Only 12% of the patients with Major Depressive Disorder revealed dysregulation on both the DST and TRH tests. This finding was not statistically significant and suggests that HPA and HPT axis function are independent of each other. Our findings are consistent with those of other studies and confirm the validity of these neuroendocrine challenge studies in a private hospital setting.
Discriminating Mania from Schizophrenia
The neuroendocrine challenge studies provide some distinction between schizophrenic and affective psychoses such that they might be useful in discriminating these syndromes in acutely psychotic patients. Such patients may present with symptoms of hyperactivity, grandiosity, delusions and paranoia which make precise diagnoses during the acute psychotic state difficult. Extein et al reported that manic patients could be discriminated from schizophrenic patients utilizing the TRH test.18 We found blunted TSH responses to TRH in 60% of acutely manic bipolar patients in contrast to 7% of schizophrenic patients (p < .01). Further, seven of ten manic patients (70%) in contrast to two of 14 (14%) schizophrenic patients revealed neuroendocrine dysregulation on either the DST or TRH test (p < .005). Thus, our findings replicate those of Extein et al.18
Neuroendocrine Dysfunction in Schizophreniform Disorder
The possibility that neuroendocrine dysregulation might be identifying an underlyingendogenousdepressive diathesis is of particular relevance to the schizophreniform disorder group. Patients who present with a first break acute psychosis of less than six months (schizophreniform according to the DSM-IlI criteria) can later be reclassified as schizophrenic or Major Depressive Disorder. The early identification of Major Depressive Disorder would facilitate pharmacotherapy and clarify treatment planning. In the past, variable like premorbid history, sudden onset of illness, and family history of affective disorder have been described in so-called "good prognosis" schizophrenic patients.19'20 Some authors, however, have suggested that these patients are indistinguishable from bipolar patients.21 To date, clinical and historical variables alone have not been sufficient in determining which acutely psychotic (schizophreniform) patients will recover, which patients will require maintenance medications, and which patients might do well with no medication at all. Kane et al noted relapse in seven of 1 7 schizophreniform patients (4 1 %) who received placebo for one year in contrast to no relapse in 1 1 patients treated with fluphenazine.22 On the other hand, Hirshowitz et al found that lithium carbonate was effective in a schizophreniform patient group.2"'
NEUROENDOCRINE DYSREG ULATION IN SUBGROUPS OF PSYCHIATRIC PATIENTS
As noted in Table 2, abnormal DSTs were noted in 24% of our schizophreniform disorder patients and abnormal TRH tests in 29% of these patients. We were able to follow 17 of these patients for six months at which time reclassification of their schizophreniform diagnosis was made.24 Seven patients were reclassified as subchronic schizophrenia according to DSM-HI criteria because they never regained their premorbid level of functioning and continued to show evidence of thought disorder. Ten patients were reclassified as probable affective disorder because they did regain their premorbid level of functioning, had lucid intervals, and responded to either lithium carbonate or antidepressant medications. A reexamination of the index neuroendocrine function obtained at the time of initial psychosis revealed that none of the seven subchronic schizophrenic patients had had blunted TSH responses to TRH in contrast to five of the ten probable affective disorder patients (p < .05). Overall, abnormal DSTs or TRH tests at the time of index psychosis predicted the ultimate clinical reclassification of these patients at six months with a 70% sensitivity, 86% specificity, and 84% predictive value.24
Endogenous Depression and Alcoholism
Hypercortisolemia, escape from DST and blunted TSH responses to TRH have all been described in alcolohic patients.25 Many alcoholic patients are considered to be depressed, and antidepressant medications are frequently prescribed during the treatment of alcoholism.26 However the identification of endogenous depression within an alcoholic population is often difficult to establish and the use of neuroendocrine challenge studies might be useful in making this assessment.
Alcohol can have direct effects upon limbichypothalamic function which can dysinhibit the neuroendocrine feedback system and result in false positive neuroendocrine tests. '25'27 Despite this limitation most studies have found normal DSTs and TRH tests in nondepressed alcoholic patients. 2?,?1'? Kroll et al noted abnormal DSTs in seven of 29 withdrawing alcoholic patients, three of whom met research criteria for Major Depressive Disorder.27 Loosen and Prange noted blunted TSH response to TRH injection in six of 12 withdrawing alcoholics.2
We have examined 31 alcoholic patients utilizing both the TRH test and the DST. Sixteen patients met DSM-III criteria for Major Depressive Disorder as well as alcohol dependence. All patients were withdrawing from alcohol at the time of the investigation, and studies were conducted within 28 days of their last drink. Nine of 16 alcoholics with depression (56%) revealed escape from DST in contrast to none of 1 5 non-depressed alcoholics (p < .01). On the other hand, the TRH test did not distinguish between depressed and non-depressed alcoholic patients. Using the threshold of ? max TSH < 7 µU/ ml, three non-depressed alcoholics (20%) in contrast to seven depressed alcoholics (44%) revealed blunted TSH responses to TRH injection. We suspect that the TRH test findings reflect the toxic effect of alcohol on the HPT axis. Thus, the DST but not the TRH test may be a useful biological marker to discriminate underlying endogenous depression within an alcoholic population. The use of antidepressant medications in these patients may be warranted.
Neuroendocrine Dysfunction in Children and Adolescents
Endogenous depression may be present in pre-pubertal and adolescent patients, although the depressive symptoms may not always be the same as those in adults. PuigAntich has described pre-pubertal children who meet diagnostic criteria for endogenous depression and have neuroendocrine disturbances as well.29 Poznanski and associates have recently demonstrated abnormal DSTs in five of eight pre-pubertal children meeting research criteria for endogenous depression (63%) in contrast to one of nine non-depressed pre-pubertal children ( 1 l%).30 We studied 19 non-depressed pre-pubertal children meeting DSM-III criteria for conduct disorder and found escape from suppression in two patients (1 1%) similar to the findings of Poznanski.31 It would appear that the DST may have clinical utility as a diagnostic aid in the identification of depressed children.
The DST has also been studied in adolescent patients. Robbins and associates found abnormal DSTs in one of seven adolescent patients meeting research criteria for Major Depressive Disorder and none of 13 adolescents who were not depressed.32 We studied 120 adolescent patients and found escape from suppression in 25 patients (21 %).33 Seventeen adolescent patients met DSM-III criteria for Major Depressive Disorder. Seven of these 17 patients (41%) revealed abnormal DSTs, similar to the percentage found in adult populations. However, we also found abnormal DSTs in seven of 38 patients with dysthymic disorder (18%), seven of 47 patients with conduct disorder (15%), and four of 15 patients with schizophreniform disorder (27%). While the sensitivity of Major Depressive Disorder was similar to that of an adult population, the predictive value and specificity of the DST in an adolescent population was weak. It is possible that the adolescent patients who had abnormal DSTs will eventually develop affective symptoms consistent with a Major Depressive Disorder. A trial of antidepressant medications may be warranted in these patients, although definitive studies have yet to be conducted.
Studies of Suicidal Patients
Some investigators have noted abnormal DSTs in depressed patients who later committed suicide.34'35 We studied 49 primary unipolar depressives oí which 17 were acutely suicidal at the time of hospitalization and administered DST to all.35 Fourteen of the 17 acutely suicidal patients revealed abnormal DSTs (82%) in contrast to nine of 32 non-suicidal depressed patients (28%). Five of the 1 7 patients who had been suicidal at the time of admission made subsequent suicide attempts within six months in contrast to none of the other 32 patients (p < .05). All five of these patients had had abnormal DSTs on admission. It would appear that the abnormal DST had identified a high risk group for suicide attempts within the larger group of unipolar depressives who were hospitalized.
GENETIC SUBTYPES OF MAJOR DEPRESSIVE DISORDER
Neuroendocrine dysregulation has been noted in some but not all patients with depressive disorder. The findings of false negatives is likely due to the indirect relationship which neuroendocrine studies have with endogenous depression, the imprecision of the tests themselves, and the heterogeneity of disorders which are phenotypically presented as depression. There have been numerous strategies for the delineation of genetic subtypes of depressive disorder which have sought to establish more homogeneous entities. The family history typology method of Winokur divides unipolar depressed patients into familial pure depressive disease (patients with a first degree family history of depressive disorder), depressive spectrum disease (patients with a first degree family history of alcoholism, sociopathy, with or without depression), and sporadic depressive disease (no first degree family history of alcoholism, depression or sociopathy).3 Schlesser et al reported abnormal DSTs in 76% of patients characterized as familial pure depressive disease in contrast to 7% of those with depressive spectrum disease.15 Similarly, we reported abnormal DSTs in 68% of patients with FPDD in contrast to 1 3% of DSD patients (p < .02). " Other investigators, however, have not replicated this finding.38'39 Further, a distinction of this kind has not been demonstrated for the TRH test.40'41 While not definitive of a specific genetic subgroup, the presence of an abnormal DST may provide a more homogeneous subgrouping of depressed patients within the larger group meeting DSM-III criteria for depression.
The DST appears to be state-related in that dysregulation is correlated with acute depression and generally normalizes when the patient recovers. Consequently, the DST could not be considered a trait marker for vulnerability to depression and would not lend itself to family studies. Similarly, the TRH test has been studied primarily in acutely depressed patients and normalization of dysfunction is expected to occur when the patient recovers. Several studies have noted a persistence of a blunted TSH response in many depressed patients despite recovery which may relate to a trait marker for high vulnerability to depression. Loosen and Prange have suggested that a blunted TSH response to TRH may be a trait marker in some patients and a state marker in others.2 A demonstration that blunted TSH responses occur in ill relatives would be necessary to demonstrate a genetic relationship of the blunted response todepression. Brambilla et al found blunting in two of six well relatives of an affected proband.6 However, this finding may indicate that the blunted response exacerbates an underlying predisposition to depressive illness but is not necessarily etiologically related to it. Further studies are needed with patients who reveal persistently blunted TSH responses. In the meantime, it would appear that the presence of a blunted response in the relative of a depressed patient may be a marker for high risk in that individual.
PHARMACOTHERAPY AND NEUROENDOCRINE DYSREGULATION
Some studies have shown that endogenous depressives who reveal abnormal DSTs have a better clinical response to antidepressant medications than similar patients who reveal normal DST responses.42"44 Brown et al found that 82% of endogenous depressives wit h abnormal DSTs had good responses compared to only 30% of depressives with normal DSTs.43 Greden et al and Carman et al found similar results.42'44 Brown et al went on to suggest that an abnormal DST might assist in the selection of the type of antidepressant medication to use.4* They suggested that abnormal DSTs might reflect a noradrenaline deficient syndrome which would respond to desipramine or Imipramine treatment. They also suggest that amitriptyline would be more effective in patients with normal DSTs who might be serotonin deficient. Greden et al, however, found no difference between Imipramine and amitriptyline in a group of 26 depressed patients who had revealed abnormal DSTs prior to treatment.42 Our clinical experience has not demonstrated a preferential response to antidepressants based upon neuroendocrine dysfunction. We have found that patients treated with Imipramine, amitriptyline, dibenzoxazepine, or monoamine oxidase inhibitors reveal the same pattern of clinical response independent of DST or TRH test results. Further, as will be described below, the relapse rate appears to be independent of the type of drug selected or the length of its use.
Goodwin et al recently reported that the addition of thyroid hormone (L-triiodothyronine, T3) to imipramine or amitriptyline treatment in refractory depressives revealed dramatic improvements within three days.45 Their findings confirmed the suggestions of Prange and associates who have long recommended the adjunctive use of L-triiodothyronine for depressed patients.46 In our clinical practice, we have noted that the adjunctive use of L-triiodothyronine is particularly suitable for depressed patients who reveal augmented TSH responses to TRH. We have found Δ max TSH responses > 23 µ?/ml but< 35 µU/ml in 15% of our depressed patients, primarily women.47 This response may be considered evidence for a subclinical hypothyroidism inpatients who are otherwise euthyroid. The addition of T3 in these patients, therefore, makes good clinical sense.
CLINICAL OUTCOME AND NEUROENDOCRINE DYSREGULATION
SERIAL MONITORING OF THE NEUROENDOCRINE CHALLENGE STUDIES
The state-related function of the neuroendocrine challenge studies suggests that serial monitoring will reflect biological recovery when patients are symptomatically improved. Most studies have revealed a normalization of abnormal DSTs in depressed patients when they recover.3'10'13 On the other hand, fewer than half of the blunted TSH responses to TRH normalize when patients are symptomatically recovered.1,2,7,11,12,14
We repeat neuroendocrine studies in most patients who have revealed neuroendocrine dysregulation at the time of admission. We have followed many of these patients for a minimum of six months to assess their early clinical outcome and to correlate these findings with the persistence or normalization of neuroendocrine dysfunction. As noted Table 3, 27 of 32 patients (84%) who had initially revealed abnormal DSTs eventually normalized the DST. In contrast, only eight of 19 recovered depressive patients (42%) who had revealed blunted TR H tests ever normalized this response. These findings are consistent with the reports of other investigators in the literature. The close temporal relationship between normalization of the DST and symptomatic improvement suggests an etiological relationship between HPA axis dysfunction and endogenous depression. On the other hand, the lesser association between normalization of a blunted TRH test and symptomatic improvement suggests that additional mechanisms are implicated in the relationship between HPT axis dysfunction and depression. As noted above, the possibility that some patients who reveal persistently blunted TSH responses to TRH have a trait, rather than state-related dysfunction requires further investigation.
The identification of neuroendocrine dysregulation during acute depression appears to provide a specific marker for the assessment of biological recovery in these patients. The serial administration of these tests can demonstrate stabilization or persistent dysregulation of the underlying neuroendocrine fault and can therefore provide useful clinical information for the management of the disorder. A recurrence of dysregulation may indicate an imminent relapse in a remitted patient. We have also found that the failure to normalize predicts early relapse in many patients.
In our studies, four of the five patients who revealed persistent escape from DST (80%) relapsed within six months in contrast to five of 23 patients (22%) who had normalized their dysfunction. Further, two of the five patients who had normalized revealed a recurrence of dysregulation at the time of their relapse.
The TRH test was also useful in the prediction of clinical course. As noted above, only eight of 19 patients who revealed blunted TSH responses at the time of acute depression normalized their response subsequent to symptomatic recovery. All of these eight patients had sustained their improvements at the six-month interval: On the other hand, seven of the 1 1 patients (64%) who had revealed persistently blunted TSH responses relapsed within six months.
Thus, failure to normalize either the DST or the blunted TSH response to TRH was correlated with early relapse in 11 of 16 patients (67%). Relapse was not related to the type of treatment given, specific antidepressant drugs, time interval between initiation of treatment or symptomatic improvement, or the severity of clinical depression at the time of admission. In our studies, 85% of patients who relapsed were still receiving antidepressant medications at the time of their relapse. These findings are consistent with the reports of Kirkegaard who noted that continued antidepressant medication did not avert relapse in patients who had persistently blunted TSH responses to TRH.48 It is conceivable, however, that the intensity of the depressive relapse in these patients was attenuated by the continuation of antidepressant medications. The decision to continue or discontinue medication must still depend upon the clinical judgment of the clinician.
NEUROENDOCRINE CHALLENGE STUDIES IN TREATMENT
The neuroendocrine studies can be useful adjuncts in the therapeutic approach to depressed patients. The finding of an abnormal DST or blunted TRH test can strengthen the diagnosis of endogenous depression and provide greater confidence in the selection of psychopharmacologic agents. The persistence of neuroendocrine dysregulation despite symptomatic improvement suggests incomplete resolution of the depressive state and requires careful monitoring. Finally, a recurrence of neuroendocrine dysregulation suggests imminent relapse in a patient who may have symptomatic improvement.
The finding of neuroendocrine dysregulation is not equivalent to a diagnosis of endogenous depression despite the close association demonstrated in many studies. Neuroendocrine dysregulation reflects limbichypothalamic dysfunction which may be associated with depression but may also be related to other limbic dysfunctions. Somatization, anxiety, insomnia, or anorexia may all be aspects of depression, but may also be characteristic of limbic-hypothalamic disturbance. Dysregulation demonstrated in any of these conditions suggests an underlying endogenous factor. The use of antidepressant medication may be warranted in these cases even if the patient does not appear clinically depressed. We treated a 31 -year- old attorney who had complained of anxiety with sleep disorder and no depression with antidepressants following the demonstration of an abnormal DST. Her clinical improvement on antidepressants correlated with the normalization of the DST. Her diagnosis remained generalized anxiety disorder although it appeared that an underlying endogenous factor related to limbic-hypothalamic dysfunction had contributed to the overt manifestation of her psychiatric difficulties.
As described earlier, the neuroendocrine challenge studies can be applied in the discrimination of mania from schizophrenia, and can be particularly useful in the first break patient or acutely psychotic patient in whom a history cannot be ascertained. The demonstration of an abnormal DST or TRH test may be viewed as consistent with a probable affective diathesis as opposed to schizophrenia. A trial of lithium carbonate or anti-depressant medications may be warranted in these cases and it may be possible to avert long-term maintenance antipsychotic medications in some of these individuals. The combination of clinical examination, assessment of premorbid and family history, and neuroendocrine challenge studies can facilitate the evaluation of psychiatric disorder and maximize therapeutic planning.
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2. Loosen PT. Prange AJ Jr: Serum thyrotropin response to thyrotropin releasing hormone in psychiatric patients: A review. AmJ Psychiatry 1982; 139:405-416.
3. Carroll BJ. Fein berg M. Greden J F. el al: A specific laboratory lest for the diagnosis of melancholia. Arch Gen Psychiatry 1981; 38:15-22.
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7. Maeda K, Kato Y. Ohgo S, et al: Growth hormone and prolactin release after injection of thyrotropin releasing hormone in patients with depression. J Clin Endocrinol Metab 1975; 40:501-505.
8. Extein I. Pottash ALC. Gold MS: Relationship of thyrotropin releasing hormone test and dexamethasone suppression test abnormalities in unipolar depression. Psychiatric Res 1981;4:49-53.
9. Targum SD, Sullivan AC, Byrnes SM: Neuroendocrine inter-relationships in major depressive disorder. Am J Psychiatry 1982; 139:282-286.
10. Greden JF, Albala AA, Haskett R F, et al: Normalization of dexamethasone suppression test: A laboratory index of recovery from endogenous depression. Biol Psychiatry 1980; 15:449-458.
11. Asnis GM, Sachar EJ. Halbreich U. et al: Endocrine responses to thyrotropin releasing hormone in major depressive disorders. Psychiatric Res 1981;5:205-215.
12. Papakostas Y, Fink M, Lee J, et al: Neuroendocrine measures in psychiatric patients: Course and outcome with ECT. Psychiatric Res 1981; 4:55-64.
13. Albala AA, Greden JF, Tarika J, et al: Changes in serial dexamethasone suppression tests among unipolar depressives receiving electroconvulsive treatment. Bio! Psychiatry 1981; 16:551-560.
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17. Sphzer RL. Endicott J: Schedule for Affective Disorders and Schizophrenia-Lifetime Version. New York, Biometrics Research, New York State Psychiatric Institute, 1975.
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19. Vaillant GE: A ten year follow-up of remitting schizophrenics. Schizophr Bull 1978;4:78-85.
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22. Kane JM, Rifkin A, Quitkin F, et al: Fluphenazine versus placebo in patients with remitted, acute first episode schizophrenia. Arch Gen Psychiatry 1982; 39:70-73.
23. Hrrschowtz J, Casper R, Garvcr DL, el al: Lilhium response in good prognosis schizophrenia. Am J Psychiatry 1980; 137:916-920.
24. Targum SD: Schizophreniform disorder: Neuroendocrine function and clinical reassessment. Proceedings of the Society of Biological Psychiatry 1982, Abstract No. 47.
25. Cicero TJ: Neuroendocrinological effects of alcohol. Annals Review Medicine 1981; 32:123-142.
26. Hamm JE. Major LF. Brown GL: The quantitative measurement of depression and anxiety in male alcoholics. AmJ Psychiatry 1979; 136:580-582.
27. Kroll P, Ritchie J. Palmer C, et al: Dexamethasone suppression lest in alcoholics. Proceedings of the Society of Biological Psychiatry 1982, Abstract No. 9.
28. Targum SD, Wheadon DE, Chastek CT, et al: Dysregulaiion of hypothalamic-pituitary-adrenal axis function in depressed alcoholic patients. J Affective Disord. 1982; F.347-353.
29. Puig-Antich J: Affective disorder in childhood: A review and perspective. Psychiatric Clinics of North America 1980; 3:403-424.
30. Poznanski EO, Carroll BJ, Banegas MC, et al: The dexamethasone suppression test in pre-pubertal depressed children. Am J Psychiatry 1982; 139:322-324.
31. Targum SD, Chastek CT, Sullivan AC: Dexamethasone suppression test in prepubertal conduct disorder. Psychiatric Res 1981; 5:107-108,
32. Robbins DR, Alessi NE, Colfer MV, et al: The dexamethasone suppression test in adolescent depression. Presented at the 134th Meeting of the American Psychiatric Association, New Orleans, 1981, Abstract NR 26.
33. Targum SD, Capodanno AE: Dexamethasone suppression test in adolescent psychiatric in-patients. Proceedings of the I35th Meeting of the American Psychiatric Association. Toronto, Canada, 1982.
34. Coryell W, Schlesser MA: Suicide and the dexamethasone suppression test in unipolar depression. Am J Psychiatry 1981; 138:1120-1121.
35. Targum SD, Rosen L, Capodanno AE: The dexamethasone suppression test in suicidal unipolar depressives. Am J Psychiatry, to be published.
36. Winokur G: Unipolar depression- is it divisible into autonomous subtypes? Arch Gen Psychiatry 1979; 36:47-52.
37. Targum SD, Byrnes SM, Sullivan AC: Subtypes of unipolar depression distinguished by the dexamethasone suppression test. J Affective Disord 1982;4:21-27.
38. Rush AJ. Giles DE, Roffwarg HP, et a): Sleep EEG and dexamethasone suppression test findings in outpatients with unipolar major depressive disorders. Biol Psychiatry 1982; 17:327-341.
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40. Coppen A, Rao VAR, Bishop M. et al: Neuroendocrine studies in affective disorders, II. Plasma thyroid stimulating hormone response to thyrotropin releasing hormone in affective disorders. J Affective Disord 1 980; 2:3 1 7-320.
41. Targum SD, Byrnes SM. Sullivan AC: The TRH stimulation test in subtypes of unipolar depression. J Affective Disord 1982; 4:29-34.
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44. Carman JS, Hall K. Wyatt ES: Dexamethasone non-suppression-predictor of thymoScptic response in catatonic and schizoaffective patients. Proceedings of the Society of Biological Psychiatry 1980, Abstract No. 36.
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47. Targum SD, Sullivan AC. Byrnes SM: Compensatory pituitary-thyroid mechanisms in major depressive disorder. Psychiatric Res 1982; 6:85-96.
48. Kirkegaard C. Carroll BJ: Dissociation of TSH and adrenoconico disturbances in endogenous depression. Psychiatric Res 1980; 3:253-264.
POTENTIAL CLINICAL APPLICATIONS OF NEUROENDOCRINE CHALLENGE STUDIES
NEUROENDOCRINE DYSREG ULATION IN SUBGROUPS OF PSYCHIATRIC PATIENTS
CLINICAL OUTCOME AND NEUROENDOCRINE DYSREGULATION