A study on the correlation of hormonal status with depression-anxiety in menopausal women

Poster session IV

BIOL. PSYCHIATRY 1997;42:1S-2975

had been stopped. In the present study, in an effort to define the reasons, the effect of the washing procedure was studied In platelets pretreated with 5-HT uptake Inhibitors. Blood samples were donated by six adult male volunteers. First, a comparison was made by measuring parameters for s-HT uptake In the platelet rich plasma (PRP) and that In the washed PRP In vitro. No significant changes were observed In Vrnax or Km. Thereafter, the effect of the washing procedure was examined in platelets treated with different 5-HT uptake Inhibitors in vitro. The minimum effect was seen In platelets treated by paroxetine or 6-nitro qUipazine, while amoxapine, desipramine, trazodone, or zimelidine-treated platelets showed susceptibility to the procedure. Therefore, long-lasting binding seems to be proportionally related to the affinity for the 5-HT uptake site. This appaars to be the reason why the residual effect in 5-HT uptake inhibition in the previous study.

@O-99]

Involvement of the frontal cortex In effect of low dose sulplrlde

s. Kaneno. Health Service Center, Tokyo Medical and Dental UnIversity. TokyO. Japan

2538

postulated that tricyclic antidepressant treatment increases the glucocorticoid receptor (GR) In the brain and such a GR up-regulation normalizes the hyperactivity of HPA systems. The GR is associated with heat shock proteins (HSPs) containing HSP90, HSP70 and HSP56 as a functional complex. In this study, we have examined effects of chronic variable stress (CVS) on the assocciation of GR with HSPOO in rat brain using an Immunoblolling procedure. CVS for 14 days increased both cytosolic GR and HSP90 in the hippocampus. The gel filtration chromatography of hippocampal cytosol after CVS demonstrated an Increase in a monomeric GR (-90Kd) but not a GR complex (-300Kd), indicating CVS prevented a formation of GR·HSPs complex. It is suggested that the uncoupling of GR-HSPs complex might contribute to the HPA dysregulation in major depression. It is also proposed that the CVS could be an appropriate animal model for a disturibance in negative feedback control of HPA systems.

190-1 021

Antibodies to neurotransmitters serotonin and dopamine In experimental depressive syndrome

LA. Vertrile, N.A. Kruplna, LA Basharova. Institute 01 General Pathology and Pathophysiology. Academy 01 medical sciences. Moscow, Russia

sulpiride (SLP) is a selective D2 receptor blocker. II is interesting to reveal the mode and action site of low dose SLP, because clinical studies have Indicated that low dose SLP has antidepressant and anxiolytic effects. The aim of this animal study is to indicate behaviorally the implication of the trontaJ cortex In the action of low dose SLP. Method: Unilateral ablation of frontal cortex produced mild contralateral methamphetamine (MAP)-lnduced rotation In rats 10 days after surgery. SLP (15 or 100 mglkg) or haloperidol (HAL, 0.05 mglkg) was treated 30 min before MAP (2.5 mglkg) administration in these rats, and effects of these drugs on MAP·lnduced rotation were examined and compared. ResultS: Low dose SLP reversed the direction of this MAP-Induced rotation. On the other hand, high dose SLP or autoreceptor dose HAL prevented the MAP-induced rotation. The effect of low doses of SLP or HAL has been, 60 far, recognized as the result of the prominent blocking effect on presynaptic dopamine autoreceptor. But, in the present behavioral experimenal model, effect of low dose SLP was different from that of low dose HAL These results suggest that low dose SLP has preferential blocking effect on D2 receptors In the frontal cortex. This effect of SLP may be Involved In Its clinical antidepressant or anxiolytic effect.

Induction of antibodies (AB) to serotonin and dopamine in blood serum was demonstrated in a new rat model of experimental depres• sion-like syndrome, Induced by intraperitoneal injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mglkg daily for 12 days). MPTP administration caused the decrease of the locomotor and Investigatory activity, decrease of daily liquid consumption and lowering of preferenca for the saccharose solution over water. Prolongation of immobi• lization time in forced swimming test was observed as well. AB to serotonin were detected in 84% of MPTP-treated animals (mean level of AB was 1,7 conventional units). AB to dopamine were found In 58% of animals (1,5 conventional units). In blood serum of salina-treated animals AB to serotonin and dopamine were found In 20% and 22% of animals accordingly, the level of AB was significantly lower (1,3 conventional units). The level and fre• quency detection of AB to serotonin did not differ 2 and 3 weeks after MPTP withdrawal. In contrast the level and frequency detection of AB to dopamine were significantly reduced 3 weeks after the withdrawal. It is supposed that AB to serotonin and dopamine play an essential role in the mechanisms of depressive state development.

~O-1 OQ]

190-1031

Immunoblological study of affective disorders

S A. Ivanov&, K.G. Yazykov, E.D. Schastny, V.Ya. Semke. Mental Health Research Institute, Tomsk, Russia The aim of the paper is to study the Immune system activity and serotonin exchange in patients with depressive symptoms during fluoxetin therapy. Methods: The 15 patients with affective disorders ot psychogenic and endogenic character were examined. We determined 25 Immune system parameters (CD2+, CD~, CD16'", CDn<, anlV HLA-Dr+-Iymphocytes), hu• moral immunity parameters, factors of nonspecific resistance and platelet and plasma serotonin content. Results: The depression of cell mediated Immunity and activation of humoral Immunity In patients with depressive symptoms were found. That as shOwn by the decrease of the number of T·, B-Iymphocytes leucocytes ;hagoeyliC activity, increase immunoglobulin G, M. The mean platelet sero• tonin content did not differ from that in the controls, but It an decreased in a half of the patients (about 500 ng/1OS cell) and increased in another half (about 1500 ng/1OS cell). The disbalanca between lymphocyte subpopula• tions resulting from suppressors Increase was seem against the background of hi h serotonin content. The 10th day of ftuoxetin therapy showed a dra• mati~ drop of cellular serotonin content (by 7.3 times). After 3 weeks clinical symptoms reduced, most parameters of ceU-mediated Immunity became

normal·

[!O-1 0]

Dissociation of glucocorticoid receptor with heat shock proteins after chronic variable stress In rat brain

T. MatsUShita, Y. Sasuga, N. Bodal]I, M. Asakura, A. Aoba. Department 01 Neuropsychiatry. St Marianna University School 01 Medicine, Kawasaki,

Japan A dysregulation in negative feedback of the hypothalamus-pituitary-adrenal (HPA) system is observed in a major depression. Recent studies have

Seasonal change and affective disorder

H.D. Yang. Shenyang Mental Health Center, Shenyang, P.R. China Recently foreign scholars find the certain relativity between affective disor• der and seasonal change through clinical observation, put forward circadian rhythm-melatonin hypothesis by biochemical studies. cure patients of affec• tive disorder with phototherapy clinically, and obtain certain therapeutical effect. By means of cUnical analysis to the relation between 56 cases of affective disorder attack and seasonal change, the paper proves the inter• nal relations surely exist between affective disorder Xattack and seasonal change. Mania attack is significantly higher in spring and summer (71.4%) than in faU and winter (28.6%), depressive attack is higher in fall and winter (63.4%) than In spring and summer (36.6%), which show there are clear re• lations between affective disorder attack and seasonal change, and support the circadian rhythm-melatonin hypothesis. In addition, this paper finds there are not gender differences between mania attack and depressive attack and seasonal change.

190-1041

A study on the correlation of hormonal status with depression-anxiety In menopausal women

B.S. Kee, J.Y. Cho, J.K. Lee, O.B. Pari<. Dept. of Psychiatry, Chung-Ang University HospItal, Seoul, Korea The purpose of this study is to investigale the correlation between the hormonal status and depression and anxiety In menopausal women. Methods: Among the women attending menopausal clinic. menopausal women, defined as who having a amenorrehea for more than 12 months, were selected as a study group (n .. 83). The control group (n .. 73), who visited to screen the cervix cancer with regular menstruation, had no history of hormone replacement therapy. Depression and anxiety were evaluated by Beck Depression Inventory (BDI) and State Trait Anxiety Inventory (STAI) respectively. The female hormones such as E2, FSH and LH were obtained by blood sampling at visiting clinic.

254S

BIOL. PSYCHIATRY

Poster session IV

1997;42:1S-297S

Results: In menopausal women the scores of BDI & STAI were significantly higher than in control group. There were significant differences between menopausal and control group by E2 and FSH. There was no correlation between female hormonal status and STAI and BDI scores in both group.

190-1 051

Collaborative study of nefazodone and CST-CD In chronically depressed patients

J.P. McCullough, M.B. Keller, R.M.A. Hirschfeld, J.M. Russell, DL Dunner, M.E. Thase, J.H. Kocsis. Department of Psychology, Virginia Commonwealth University. 808 W. Franklin St., Richmond, VA, USA A national, 12-site, collaborative combined treatment study investigating the therapeutic efficacy of the antidepressant nefazodone and a new psy• chotherapy model (Cognitive-Behavior Therapy for the Chronic Depressions: CBT-CD) is currently underway. Six-hundred-sixty chronically depressed out· patients will be recruited and they will be processed through an Acute Phase (12 weeks), Crossover Phase for nonresponders, Continuation Phase (16 weeks) and a Maintenance Phase (52 weeks). The project represents the largest combined study ever undertaken in psychiatry as well as the first investigation of its kind involving chronically depressed outpatients.

\90-1

07\

Adrenal volume In recurrent depression

A. Barocka, J. Walloch. University of Erlangen, Dept. of Psychiatry. 91054 Erlangen. Germany Until now there have been three studies demonstrating Increased adrenal volume in depressed patients using either Computed or Magnetic Resonance Tomography. However, the expected correlation of increased adrenal volume with endocrine tests for conisol regulation has not been found. We compared 10 female post-menopausal Inpatients. having undergone at least three episodes of DSM-IV Major Depression with Melancholic Features, with 10 age- and sex-matched controls. Mean adrenal volumes, measured with computed tomography, were 8.95 cm3 (sd 1.7) in patients and 6.68 cm3 (sd 2.01) In controls (p < 0.02). Adrenal volumes positively correlated with post-
190-1 oal

Acute (12 ......)

Response of patients with major depression and silent cerebral Infarction to antidepressant drug therapy

T. Fujikawa 1,2, N. Yokota 1, M. Muraoka 1 , S. Yamawakl 1 • 1 Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine. Hiroshima, Japan, 2 Department of Psychiatry. National Sanatorium Kama Hospital. Hiroshima, Japan The present study was designed to clarify the response to antidepressant pharmacotherapy In patients with major depression with silent cerebral Infarction (SCI) using magnetic resonance Imaging (MRI). Methods: Patients older than 50 years who were admitted for antidepres• sant drug therapy were studied retrospectively using clinical charts. Patients with focal neurological symptoms were excluded. All patients underwent MRI and were classified as SCI-negative or SCI-positive. The SCI-positive group was subclassified into those with moderate SCI and those with severe SCI. Duration of treatment in hospital and the Incidence of central nervous system (CNS) adverse reactions to the antidepressant drugs were compared. Results: The duration of hospital treatment In patients with severe SCI was significantly longer than that in those with moderate SCI. Incidence 01 CNS adverse reactions to antidepressant drugs was significantly higher In the SCI-positive group than In the SCI-negative group. Patients with severe SCI had significantly more adverse reactions than those with moderate SCI. These findings suggest that the depression associated with severe SCI may be resistant to treatment.

190-1091 The study design and the major research issues being investigated will be discussed. The Poster is shown on the attached sheet. The study is sponsored by BristOl-Myers Squibb.

190-1061

Treatment of dysthymic disorder with venlafaxlne

D.L. Dunner, H.E. Hendrickson, C.J. Bea, C.B. Budech. Genter for Anxiety and Depression, U of Washington, Seattle. WA, USA The aim of this study is to assess efficacy of venlafaxlne in patients with dysthymic disorder. Methods: Seventeen patients with dysthymic disorder were treated on an open label basis with venlafaxine up to 250 mg per day for 9 weeks. Outcome was assessed with HAMD17 and BDl. Resulta: Fourteen patients completed the trial and all improved over their baseline condition. Nine patients met response criteria for major depression (HAMD ~ 7, BDI ~ 8). Seven responders required the minimal dose (75 mg). Two patients discontinued after 1 week due to side effects; one patient improved In the first week but discontinued. Side effects due to medication were generally mild. Conclusion: Venlafaxlne Is useful In the treatment of patients with dys• thymic disorder and is well tolerated.

Predictors of response to long-term antidepressant therapy

J.M. Russell. A.M.A. Hirchfeld, M.B. Keller. A.F. Shatzberg, M.E. Thase, J.H. Kocsis, A. Gelenberg. UTMB, Assistant Professor, Galveston, T)(, USA Prediction of response to antidepressant therapy Is clinically very useful, especially so in patients with chronic depression. Predictors of long-term response to pharmacotherapy will be evaluated in a multicenter trial in the United States of chronic & double depression Involving setraline, Imipramine, and placebo. Methods: This double-blind, randomized, parallel design study observed patients with chronic or double depression who had responded either to 12 week course of sertrallne or Imipramine (or a crossover for nonresponders) and who had maintained this response throughout a 16 week continuation: Patients eligible for the maintenance study who had been taking sertraline at the end of the continuation phase were randomly assigned to double-blind treatment with either sertraline or placebo. and those taking Imipramine remained on the double-blind Imipramine treatment. These assignments were maintained for up to 78 weeks. Results: The poster will present results of analyses of long-term re• s~nse usln~ pretre.atment baseline predictors, inclUding soclodernographic vanables, cliOical historical variables, cross-sectional variables, diagnostic variables, and quality of life variables. In addition, we will look for predictors assessed at the beginning of the maintenance study, InclUding clinical and psychosocial status.