Journal of Affective Disorders, 25 (1992) 39-46 0 1992 Elsevier Science Publishers B.V. All rights reserved 01650327/92/$05.00

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JAD 00894

Cerebrospinal fluid neuropeptides in mood disorder and dementia Csaba M. Banki a, Lajos Karma& a, Garth Bissette b and Charles B. Nemeroff c a Regional Neuropsychiatric Institute, Nagykallo, Hungary, ’ Duke University Medical Center, Department of Psychiatry, Durham, North Carolina, USA and c Emory University School of Medicine, Department of Psychiatry, Atlanta, Georgia, USA

(Received 19 November 1991) (Revision received 20 January 1992) (Accepted 27 January 1992)

Summary Cerebrospinal fluid (CSF) concentrations of immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were measured in female psychiatric inpatients with DSM-III-R diagnoses of major depression, mania, generalized anxiety and somatization disorder. In addition, elderly patients with dementia disorders, with or without concomitant major depression, were also investigated. CSF SRIF was not significantly different among these groups; on the other hand, mean CSF CRH concentrations were significantly higher in major depression and in dementia with depression as compared with neurological controls with no psychiatric disorders. CSF CRH levels in mania, simple dementia, or anxiety or somatization disorder were not significantly different from the controls. Background physical or clinical variables did not account for the differences in CRH concentrations. It is concluded that CSF CRH elevation may be present in some patients with major depression independent of age and an underlying dementia disorder.

Key words: Depression; Dementia; Cerebrospinal

Introduction Mood disorders appear to be frequently associated with alterations of neuropeptide function in the central nervous system. One of the principal regulatory peptides of the hypothalamic-pitui-

Address for correspondence: Csaba M. Banki, H-4321 Nagykallo,P.O. Box 37. Hungary. Fax: (36-42163-402.

fluid; Somatostatin;

Corticotropin-releasing

hormone

tary-adrenocortical (HPA) system, corticotropinreleasing hormone (CRH), has been repeatedly found to be elevated in the cerebrospinal fluid (CSF) of patients with major depression (Nemeroff et al., 1984; Bissette et al., 1985; Banki et al., 1987). Elevated CSF CRH levels declined significantly after a course of ECT (Nemeroff et al.. 1991). Central CRH over-production can explain, at least in part, the known HPA overdrive in major depression which is one of the best

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documented biological finding in this disorder (Carroll, 1982; Gold et al., 1984): severs: iines of evidence support the hypothesis that HPA overactivity indeed plays an important part in the pathogenesis of mood disorders (Holsboer, 1988; Amsterdam et al., 1989). Elevated CSF concentration of CRH indicates central CRH overproduction at least in some regions of the brain. However, little is known about the actual origin of CRH found in the lumbar CSF: the demonstration of a crania-caudal gradient of the peptide (Arato et al., 1989) suggests that at least in part it is derived from the brain. CRH is widely, but unevenly, distributed in various brain areas and exerts behavioural effects resembling some typical symptoms of major, or melancholic, depression (Nemeroff, 1988). Much less is known about CSF CRH concentration in other disorders: a limited number of patients with schizophrenia, senile dementia, mania, or anxiety disorders had no major peptide alterations as compared with nonpsychiatric controls (Nemeroff et al., 1984; Banki et al., 1987). Dementia, an organic mental disorder often associated with depression (Lauter and Dame, 1991), has been frequently reported to share features of HPA abnormalities, such as dexamethasone non-suppression, with true melancholia (Carnes et al., 1983; Allen and Pitts, 1984; Jenike and Albert, 1984). CSF CRH was found to be correlated with some cognitive factors in one study of depressed individuals despite the I.ck of an overall elevation (Roy et al., 1987; De Jong and Roy, 1990). Somatostatin, a tetradecapeptide with widespread CNS localization and strong behavioural effects, has also been suggested to be involved in the pathogenesis of mood disorders either directly or through its multiple effects on other neurotransmitter and neuromodulator systems (Rubinow et a!., 1984; Nemeroff et al., 1987). Low CSF somatostatin (SRIF) concentrations were found in various groups of depressed patients (Agren and Lundqvist, 1984; Rubinow et al., 1984; Doran et al., 1986). However, this finding appeared to be nonspecific because SRIF reduction in the CSF was also found in schizophrenia, dementia, and neurological conditions (Sagar et al., 1984; Joynt and McNeil], 1984; Loosen and Banki, 1988; Bissette et al., 1986).

Postmortem studies reported SRIF reduction in the brain in Alzheimer’s disease (Sagar et al., 1984), schizophrenia (Nemeroff et al., 1983), and some other diseases (Bissette and Nemeroff, 1988). In order to examine whether CSF CRH and SRIF alterations are associated specifically with depressive symptoms we investigated the neuropeptide concentrations in the CSF of female psychiatric inpatients with major depression, generalized anxiety disorder, somatization disorder, and elderly patients with dementia with and without major depressive features. Subjects and Methods Recently hospitalized female psychiatric inpatients were asked to participate in the study after an initial evaluation to exclude major confounding factors (such as significant physical, neurological, or endocrinological disease, recent psychotropic or hormone-containing drug use, current substance abuse, pregnancy or lactation). Some clinical and demographic characteristics of the patient group are given in Table 1. Control subjects (N = 36) were inpatients from a neurological unit, receiving treatment for symptoms such as neuralgias, headache, or myalgias; we excluded patients with epilepsy, Parkinson’s disease, or other CNS disorders. None of the control subjects had received psychotropic medication or hormone preparations for at least 2 months before admission and they had no DSMIII-R diagnosable psychiatric disorder at inclusion. Somatization disorder patients (N = 12) were hospitalized in a psychiatric unit and had been free from medication for at least 2 weeks. Subjects with generalized anxiety (N = 11) had a mean history of their disorder slightly above 3 years but had no definite panic attacks or obsessive-compulsive symptoms. Patients with major depression (N = 36) had had at least 2 episodes of clinically verified major depression and were severely ill at the time of the study (their Hamilton Depression Rating Scale score was between 24 and 48, mean: 38). Sixteen of the depressed patients had melancholic features, ten others had psychotic features, and all the remaining subjects had ‘severe’ depression as defined in the DSM-

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III-R. Finally, manic patients (N = 18) were recently admitted and actively psychotic at the time of the study; four were in the first episode and 14 in a repeated episode of their bipolar disorder. None of the manic patients had been maintained on lithium or carbamazepine for at least 3 months before the study. All diagnoses were made using strict DSM-III-R criteria, using a locally adopted semi-structured interview procedure which yields good inter-rater agreement for mood and anxiety disorders (kappa > 0.88) and for dementia disorders (kappa > 0.96). A separate sample of elderly patients with significant dementia, as defined by DSM-III-R terms, were also included (Table 1). They were all female, and had a moderate to severe cognitive decline as shown by an initial score on the Mini-Mental Status examination (MMS) (Cockrell and Folstein, 1988) of 20 or less. Twenty of them had multi-infarct dementia (MID) and 31 suffered from senile dementia of Alzheimer type (SDAT): the two were separated by clinical features such as history, presence of an underlying vascular disease, onset, course, type of the deficit, etc. Dementia was not solely diagnosed by MMS scores. In addition, 22 demented patients had significant major depressive features meeting the DSM-III-R criteria for major depression (except for an underlying organic mental condition) they were labelled as a ‘dementia with depression’ group and separated from the 29 remaining subjects with ‘simple dementia’. This latter group

included patients without significant mood or psychotic symptoms. Informed consent was obtained in writing, according to the Declaration of Helsinki from all participants in the presence of staff members; whenever available, relatives of demented patients were also asked to give verbal consent. During the first 3 to 5 hospital days no psychotropic drugs were given (except for single doses of either 10 mg diazepam or 300-600 mg chlomethiazole to reduce anxiety or agitation or to promote sleep when necessary). Routine physical and neurological examination including ECG, I6-channel EEG, but no computerized tomography, were done in each case. Lumbar punctures were performed, after an overnight fasting and bedrest, in sitting position at the fourth lumbar space: the first 10 ml CSF was collected in a plastic tube and immediately frozen, without preservatives, to - 70°C. No significant postpunction complaints were seen, except for a mild and transient headache in about 20% of tile patients. CSF samples were transported by air, on dry ice, at 3-4 months’ intervals to the United States for peptide analysis. All samples were coded and the code was made available to the laboratory only after all samples had been processed. We found no significant differences among the neuropeptide results received from the subsequent shipments of samples, indicating stability of the assay prccedures. Both CRH and SRIF were measured in the CSF by specific radioimmunoas-

TABLE 1

Demographicand clinical characteristics of the mood disorders (MOOD) and the demented (DEM) patients. Mood includes the control group except where indicated otherwise MOOD(N= Age Weight (kg) Height (cm) G.A.F. score * Years from onset * Weeks of episode * HAMD

MMS

113)

19- 68 (44.0+ 10.3) 41- 92 (66.8+ 13.7) 14%166(156 + 7.2) 14- 56 (28.3 _c8.8) 1- 13 (median: 4) 2- 10 (median: 4) 24- 48 (38.0+ 10.4)

-

DEM(N=51) 56- 88 (75.2+ 8.0) 41- 89 (55.9&11.3) 140-160(151 f 5.4! 5- 40 (22.2+ 9.8) 2- 8 (median: 5) -

o-

20 (10.7+6.1)

* = excluding the controls (N = 36). HAMD = Hamilton Depression Rating Scale (24-item) total score; MMS= Mini-Mental status total score. Values in parentheses are mean *standard deviation following the actual range.

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procedures described in detail earlier (Nemeroff et al., 1984; Bissette et al., 1986); the interassay variances in this study remained below 10% for either peptide. The statistical analysis was done by analysis of variance of the log-transformed data (because of the non-normality and skewed distribution of the peptide data) followed by Scheffe’s post hoc tests. Pearson’s correlation coefficients were calculated between the peptide measures and the background variables and multiple regression analyses were computed to determine the effect of the latter on the CSF neuropeptide concentrations. say

Results CSF CRH was inhomogeneously distributed in the six patient groups (Fig. 1). Although the distribution of the CRH values was dense and approximately normal in controls it was markedly skewed in patients; therefore, log-transformed data were used for statistical calculations.

D 0

.’

Fig. 1. CSF CRH concentrations in six diagnostic Groups of female psychiatric inpatients. Bars represent the mean values. C = controls, A = anxiety and somatization disorders, M = mania, D = major depression, S = simple dementia, X = dementia with depression.

TABLE 2 CSF CRH means + standard deviations (PG/ML) cal groups of female patients Diagnosis

CSF CRH, pg/ml

Neurokcontrols (36) Anxiety/Somatization (23) Mania (18) Major depression (36) Dementia (29) Dementia with depression (22)

47.5 f 56.9f 55.9+ 69.1+ 50.2 f 69.1+

10.1 17.0 14.9 36.3 17.6 26.7

in six clini-

ANOVA with the log-data: Ft5,158)= 4.17, P < 0.002

N shown in parentheses.

The means and standard deviations of CSF CRH concentrations in six groups are given in Table 2. There was no significant difference between the anxiety and the somatization disorder groups (P > 0.881, allowing us to combine the two to form a ‘nonpsychotic-nondemented’ sample. Post hoc tests indicated no statistically significant CSF CRH differences between any of the combined anxiety/somatization, the manic, or the simple demented groups and the control group with no psychiatric symptoms !P > 0.80. P > 0.90, and P > 0.99, respectively). On the other hand, both the major depression group (P < 0.02) and the ‘dementia with major depression’ group (P < 0.04) had significantly higher mean CSF CRH concentrations than the controls. There was no statistically significant difference between the CSF CRH level of the two depressed group. The statistical inhomogeneity of the samples was also verified by a nonparametric Mruskal-Wallis) procedure (H = 19.06, df = 5. P < 0.0021, performed to control for the non-normality of the log-transformed data. In contrast, CSF SRIF concentration proved to be statistically homogeneous across the patient groups (Table 3). While major depressive patients had a mean CSF SRIF concentration at the lower end of’ the range of the means, the dementecl patients with major depression had an opposite tendency. CSF SRIF data were not available for a few subjects in each group, therefore the case numbers in Table 3 do not agree with those in Table 2. Correlation coefficients between clinical an’d neuropeptide variables were computed separately

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TABLE 3 CSF SRIFmeans k standard deviations (PG/ML) cal groups of female patients Diagnosis

CSF SRIF, pg/ml

Neurokcontrols (32) Anxiety/Somatization (22) Mania (14) Major Depression (32) Dementia (23) Dementia with depression (16)

30.7 + 11.4 29.0f 13.6 33.9& 14.8 27.8+ 13.0 33.0 + 15.5 40.3 + 25.4

in six clini-

ANOVA with the log-data: F&133) = 1.67, P > 0.15

N shown in parentheses.

for the mood disorders and the dementia subsamples because the two were markedly different in terms of age, diagnosis, organic symptoms, and cognitive impairment. Only a few of them reached the 5% statistical significance level; therefore, neither CRH nor SRIF concentrations proved to be statistically significantly dependent on the simultaneous effects of age, body weight, body height, current severity of illness (measured by the Global Assessment of Functioning (GAF) score of the DSM-III-R), duration of illness, and number of hospitalizations in either the younger mood disorder samples or the elderly demented patients as demonstrated by the lack of signifi-

TABLE 4 Correlations between clinical and neuropeptide variables in the mood and dementia groups and multiple regression analysis

Age Weight Height G.A.F.score Years from onset No.Hospitalizations MMS R2 for CRH R” for SRIF

MOOD (N=77)

DEMENTIA (N=51)

0.263 - 0.033 - 0.221 -0.183 -0.171 0.003

0.101 0.084 -0.118 0.106 0.130 0.043 0.125

0.092 0.112

0.077 0.093

None of the bivariate Pearson’s correlation coefficients, nor any of the multiple regression coefficients (R’) were statistically significant. MOOD does not include the control group here.

cant results of two separate multiple regression analyses (Table 4). In addition, there were no significant correlations between the 24-item Hamilton Depression Rating Scale scores and either peptide concentrations in depression (CRH: r=0.16; SRIF: r = 0.08); and there were no significant correlations between the level of anxiety (items 9 + 10 on the HAMD) in the depressed and the anxiety subgroups (CRH: r = 0.12; SRIF: r = 0.07). Finally, there was no significant difference between the CSF concentrations of CRH or SRIF of patients receiving (N = 19) or not receiving anxiolytics before the LP (P 0.89 and P 0.76 for CRH and SRIF, respectively). Discussion We found significantly elevated mean CSF CRH concentrations in hospitalized, acutely ill patients with major depression as compared to controls; this is in line with earlier reports on Swedish, American, and Hungarian patients (Nemeroff et al., 1984; Bissette et al., 1985; Banki et al., 1987). The control means in this and in earlier studies were comparable ,nd not markedly different from the one study that failed to demonstrate significant elevation of CSF CRH in depression (Roy et al., 1987); in addition, that report also found a tendency for higher CSF CRH values for depressed patients with dexamethasone non-suppression. In most studies the higher mean CSF CRH levels appeared to be attributable to a subgroup of depressed patients with markedly elevated values (frequently above 100 pg/ml); Roy et al. (1987) also had one such patient. On the other hand, neither clinical features nor dexamethasone suppression seem to be associated with the CSF CRH elevation (Banki et al., 1987); interestingly, the one high-CRH patient of Roy et al. (1987) was also a normal suppressor. We found no significant elevation of CSF CRH in either anxiety disorder, somatization disorder, or acutely and severely ill manic patients. There are very few data for comparison in these conditions. joy et al. (19901 reported normal CSF CRH and SRIF concentrations in subjects with alcohol dependence as compared to healthy controls, but those subjects had been withdrawn from

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alcohol for at least 3 weeks and had therefore no anxiety or mood symptoms. Anxiety disorders may be associated with dexamethasone nonsuppression, indicating HPA overactivity, but this is observed in panic or obsessive-compulsive rather than in generalized anxiety disorders (Arana et al., 1985) and is less frequent than in major depression. The absence of significant elevation in mania argues against the possibility that higher CSF CRH was spuriously produced by agitation (ic:., faster mixing of cranial and lumbar fluid), by p:;ychosis, or simply by ‘stress’. Aging itself, and organic brain disease in particular, has been assumed to increase HPA activity, possibly due to an impaired negative feedback at the hippocampal level (Meaney et al., 1991). Some authors reported decreased brain CRH concentration and increased CRH binding in SDAT (Ferrier and Leake, 1990). The presence of depressive symptoms was, however, not evaluated in those patients in the period before death; if dementia with depression involves increased release of CRH it would be consistent with a decreased tissue concentration of CRH. This process may, however, be limited to cases with marked depressive symptoms, because in our population neither SDAT nor MID patients with severe dementia (MMS scores below 10) showed CRH elevation without depression. The stronger association of HPA overactivity with depression rather than with dementia was also postulated earlier from results with the dexamethasone suppression test (Carnes et al., 1983): non-suppression was more frequent in dementia only in the presence of depression. The association of dementia and depression clearly requires further study (Lauter and Dame, 1991) but the CSF CRH data indicate that HPA overactivity in elderly demented patients may be limited to those having prominent depressive symptomatology. The lack of correlation between neuropeptide measures and various clinical background variables is in accordance with previous findings (Nemeroff et al., 1984; Banki et al., 1987) and confirms the assumption that CRH elevation in the CSF may be a state-dependent correlate of major depression. Future research must investigate why this is observed only in a subgroup of depressed patients who are otherwise clinically

major

indistinguishable from the patients with normal CSF CRH concentrations. In contrast to earlier reports we could not demonstrate decreased CSF SRIF concentrations in either dementia or depression. Both conditions have been reported to be associated with subnormal values (Rubinow et al., 1984; Bissette et al., 1986). Since our control subjects were not healthy volunteers but neurological patients one could postulate that neuralgias, migraine headache, skeletocostal myalgias etc., may also cause SRIF reduction in the lumbar CSF. This is, however, not very likely because of the remarkably normal CRH values in these subjects. Our control SRIF values were somewhat lower that those reported from other laboratories (Rubinow et al., 1984; Roy et al., 1990), perhaps because we did not use acidic preservatives; however, this would not affect intergroup differences. In contrast to other reports the uniformity of mean CSF SRIF concentrations across demented, depressed, manic, and anxious/somatizing patients (Doran et al., 1986) was a remarkable feature of our finding. Whether it was attributable to non-specific hospitalization stress (related to the relatively early lumbar punctures, within the first hospital week) or to some other factor remains to be studied. In conclusion, we found a significant elevation in CSF CRH, but not SRIF, concentration in major depression and in demented patients with major depressive symptoms while neither mania, nor simple dementia or anxiety or somatization disorder was associated with similar changes. These results support the hypothesis that depressive symptoms may, at least in some patients, develop as a consequence of a central CRH overproduction.

References Agren.

H. and Lundqvist,

statin

in human

CSF

choneuroendocrinology Allen,

R.E.

and Pitts, F.N.

C. (1984) marks

Low levels of somato-

depressive

episodes.

Psy-

9, 233-248. (1984)

Dexamethasone

suppres-

sion in depressed elderly or.ttpatients. J. Clin. Psychiat. 45, 397-398. Amsterdam,

J.D.,

Maislin,

G.,

Gold,

P. and Winokur,

(1989) The assessment of abnormalities sponsiveness at multiple

in hormonal

A. re-

levels of the hypothalamicpitu-

45 itary-adrenocortical axis in depressive illness. Psychoneuroendocrinology 14, 43-62. Arana, G.W., Baldessarini, R.J. and Ornsteen, M. (1985) The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch. Gen. Psychiat. 42, 1193-1204. Arato, M., Banki, C.M., Bissette, G. and Nemeroff, C.B. (19891 Elevated CSF CRF in suicide victims. Biol. Psychiat. 25. 355-359. Banki. C.M., Bissette, G.. Arato, M., O’Connor, L. and Nemeroff, C.B. (1987) CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. Am. J. Psychiat. 144, 873-877. Bissette, G.. Spielman, F., Stanley, M., Banki, C.M., Fink, M., Triiskman-Bendz, L., Golden, R.N., Arato, M. and Nemeroff, C.B. (19851 Further studies of corticotropin-releasing factor-like immunoreactivity in CSF of patients with affective disorders. Sot. Neurosci. Abstr. 11, 133. Bissette, G., Widerldv, E., Walleus, H., Karlsson, K., Eklund, A., Forssman, A. and Nemeroff, C.B. (1986) Alterations in CSF concentrations of somatostatin-like immunoreactivity (SRIF-LB in neuropsychiatric disorders. Arch. Gen. Psychiat. 43, 1148-l 154. Bissette, G. and Nemeroff, C.B. (1988) The role of neuropeptides in the pathogenesis and treatment of schizophrenia. In: C.B. Nemeroff (Ed.), Neuropeptides in Psychiatric and Neurological Disorders, John Hopkins University Press, Baltimore, pp. 49-75. Carnes, M., Smith, J.C.. Kalin, N.H. and Bauwens, S.F. (1983) The dexamethasone suppression test in demented outpatients with and without depression. Psychiat. Res. 9, 337344. Carroll, B.J. (19821 The dexamethasone suppression test for melancholia. Brit. J. Psychiat. 140, 292-304. Cockrell, J.R. and Folstein, M.F. (1988) Mini-mental state examination (MMSE). Psychopharm. Bull. 24, 689-692. De Jong, J.A. and Roy, A. (19901 Relationship of cognitive factors to CSF corticotropin-releasing hormone in depression. Am. J. Psychiat. 147, 350-352. Doran, A.R., Rubinow, D.R., Roy, A. and Pickar, D. (1986) CSF somatostatin and abnormal response to dexamethasane administration in schizophrenic and depressed patients. Arch. Gen. Psychiat. 43, 365-369. Ferrier, IN. and Leake, A. (1990) Peptides in the neocortex in Alzheimer’s disease and ageing. Psychoneuroendocrinology 15, 89-95. Gold, P.W., Chrousos, G., Kellner. C., Post, R.M., Roy, A., Augerinos, P., Schulte, H., Oldfield, E. and Loriaux, D.L. (1984) Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am. J. Psychiat. 141, 619-627. Holsboer, R. (1988) Implications of altered limbic-hypothalamic-pituitary-adrenocortical (LHPA) function for neurobiology of depression. Acta Psychiat. Stand. 77 (suppl. 3411, 72- 11 I. Joynt, R.J. and McNeil], T.H. (1984) Neuropeptides in aging and dementia. Peptides 5, 269-274.

Jenike. M.A. and Albert, M.S. (19841 The dexamethasone suppression test in patients with presenile and senile dementia of the Alzheimer’s type. J. Am. Geriat. Sot. 32, 441-444. Lamer, J-J. and Dame, S. (1991) Depressive disorders and dementia: the clinical view. Acta Psychiat. Stand. 83 (suppl. 3661.40-46. Loosen, P-T. and Banki, CM. (1988) The use of nonopiate neuropeptides as diagnostic tools in psychiatric and neurological disorders. In: C.B. Nemeroff (Ed.), Neuropeptides in Psychiatric and Neurological Disorders, John Hopkins University Press, Baltimore, pp. 18-48. Meaney, M.J., Mitchell, J.B., Aitken, D.H., Bhatnagar, S., Bodnoff, S.R., Iny, L.J. and Sarrieau, A. (1991) The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life. Psychoneuroendocrinology 16, 85-103. Nemeroff, C.B.. Youngblood, W.W., Manberg, P.J., Prange, A.J. and Kizer, J.S. (1983) Regional brain concentrations of neuropeptides in Huntington’s chorea and schizophrenia. Science 221, 972-975. Nemeroff, C.B., Widerldv, E., Bissette, G., Walleus, H., Karlsson, I., Eklund, K., Kilts, C.D., Loosen, P.T. and Vale, W. (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226, 1342-1344. Nemeroff, C.B., Walsh, T.J. and Bissette, G. (1987) Somatostatin and behavior: preclinical and clinical studies. In: S. Reichlin (Ed.), Somatostatin, Plenum, New York, pp. l57167. Nemeroff, C.B. (1988) The role of corticotropin-releasing factor in the pathogenesis of major depression. Pharmacopsychiatry 21, 76-82. Nemeroff, C.B., Bissette, G., Akil. H. and Fink, M. (1991) Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy. Br. J. Psychiat. 158. 59-63. Roy, A., Pickar, D., Paul, S., Doran, A., Chrousos, G.P. and Gold, P.W. (1987) CSF corticotropin-releasing hormone in depressed patients and normal control subjects. Am. J. Psychiat. 144, 641-645. Roy, A., De Jong, J., Gold, P., Rubinow, D., Adinoff, B., Ravitz, B., Waxman, R. and Linnoila, M. (1990) Cerebrospinal fluid levels of somatostatin, corticotropin-releasing hormone and corticotropin in alcoholism. Acta PsYchiat. Stand. 82, 44-48. Rubinow, D.R., Gold, P.W., Post, R.M., Ballenger, J.C. and Cowdry, R.W. (1984) Somatostatin in patients with affective illness and in normal volunteers. In: R.M. Post and J.C. Ballenger (Eds.), Neurobiology of Mood Disorders, Williams and Wilkins, Baltimore, pp. 369-387. Sagar, S.M., Beal, M.F., Marshall, P.E., Landis, D.M. and Martin, J.B. (1984) Implications of neuropeptideq in neurological diseases. Peptides, 5 (SUPPI. 11, 255-262.

Cerebrospinal fluid neuropeptides in mood disorder and dementia.

Cerebrospinal fluid (CSF) concentrations of immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were measured in female psych...
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