- Email: [email protected]
Right, left, and bilateral ECT revisited
Depression
aio~. ~vCmATRY 1991;29:43A- |85A
133A
193 REDUCED BETA-I ADRENOCEPTORS IN DEPRESSION Gregory A. Ordway, Ph.D., Angelos E. Halaras, M.D., Ph.D. Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH 44109. The role of norepinephrine in depression has been debated for many yeats, ha rat ~ , the density of noradrenergic receptors (AIRs) is regulated by changes in concentrations of norepinephrine. We o b t a i ~ postmortem tissue to autoradiographically measure ARs in several brain regions from v i ~ of suicide and age-matched controls. Binding to [3 adrenoceptor subtypes or a2 ARs was measured using the ~ antagonist '~l-iodopindolol (IPIN) or the a2 agonist [ml]iodoclonidine (PIC), respectively. There was a trend for lower binding of IPIN in most regions of brain from suicide victims relative to controls, but this difference did not reach statistical significance. By contrast, IPIN binding [St ARs in the amygdala was s i ~ f i ~ y lower ( - 28%1 in brains from victims of suicide with histories of depression compared to age-matched controls (n = 6, p < 0.01). The binding of IPIN to [~2 ARs and the binding of PIC to a2 ARs were not significantly different in any brain region comparing suicides to controls, including in sections of the amygdala adjacent to those in which IPIN binding to [~ ARs was measured. Reduced a m y g ~ o i d [~t ARs implies overacfivity of noradrenergic neurons projecting to this IL,'abic b~-ainregion in depression.
194 UFC AS A PREDICTOR OF RESPONSE IN MAJOR DEPRESSION WITH PSYCHOTIC FEATURES W.H. Carson, M.D., R.F. Anton, M.D., E.A. Burch, Jr., M.D. Medical University of South Carolina, Charleston, SC 29425, and Tulane University School of Medicine, New Orleans, LA. Major depression with psychotic features (MDPF) is a distinct clinical entity, in which elevated cortL~l production as measured by 24-hr urinary free cortisol (UFC) and lack of dexamethasone suppression is common. To determine whether hypercortesolemia is predictive we evaluated the relationship of pretreatment 24-hr UFC determinations to treatment response in 30 inpatients who met DSM-I~ criteria for MDPF. Urine was collected during a placebo washout period over 24 .ha"on ice, refrigerated, ali~oted, and frozen until extraction and assay of free cortisol. Twenty-four-hour UFC was normalized for the amount of creatinine excretion. In a double-blind manner, patients were rated at baseline and over 4 weeks of treatment (with either amoxipine 400 mg or amitrip~fine/perphenazine 200 rag/32 mg daily) for depression (HRSD), psychosis (BPRS), and clinical improvement (CGI). Since there was no significant difference in overall response between the two medication groups the data for both groups were combined. Patients who showed marked overall clinical improvement tended (p = 0.091 to have higher UFC (53 -+ 33 lxg/mg) than those who showed less improvement (36 -+ 191. 73% of the patients with UFC above the median had marked clinical improvement compared with 40% of patients with UFC below the median (p = 0.06). In addition, there was a significant correlation between ;.mprovement in the HRSD scores and b a s e ~ e UFC (p = 0.04) but no significant correlation between improvement in BrKa . . scores . and . baseline . . UFC ~p = 0. 'L,,o.~"These data suggest that UFC may have some predictive power for treating depressive symptoms, in patients with MDPF.
195 RIGHT, LEFT, AND BILATERAL ECT REVISITED Victor Milstein, Ph.D., Joyce G. Small, M.D., Iver F. Small, M.D., Marietta H. Klapper, M.A. (by invitation), Marvin J. Miller, M.D. (by invitation), Jon D. Marhenke, M.D. (by invitation) Indiana University School of Medicine a,ut Larne D. Carter Memorial Hospital, Indianapolis, IN 46202. In previous investigations of nondominant and bilaterally induced ECT we observed that right brain functions improved more in affective disorders whereas dominant hemispheric functions were enhanced in schizophrenia. We investigated these relationships further in a new patient cohort in which unilateral induction
134A
BIOL PSYCHIATRY 1991 ;29:43A- 185A
Depression
was switched from the nondominant to the dominant side and stimulating electrode placements were changed from Lancaster to D'Elia positions. Clinical assessments by blind raters, neuropsychological tests, and clinical and topographic EEG studies were done as before. Patients were assessed prior to ECT, on a nontreatment day following the fifth or sixth ECT and 2-3 weeks after completion of the series. Data obtained were compared with findings from the earlier series. Effects of right- versus left-sided electrical induction were examined in different diagnostic categories. Findings were evaluated in terms of the previously advanced hypotheses about restoration of hemispheric equilibrium with ECT.
i96 PITFALLS IN TREATMENT OF ATYPICAL BIPOLAR DISORDER Richard Jaffe, M.D., Wendy Rives, M.D., Richard Roemer, D.M.S., Ph.D., William R. Dubin, M.D. Philadelphia Ps3~chiatricCenter, Philadelphia, PA 19131. Two patients, initially diagnosed as recurrent unipolar depressives were referred for ECT. Both had histories of poor response to antidepressant medications. Both patients showed similar responses to ECT, with rapid improvements but abrupt relapses, leading to protracted, unstable courses. Ultimately, both patients responded dramatically to pharmacotherapy with lithium, plus carbamazepine or valproic acid. Retrospective evaluation revealed no formal manic episodes, although limited evidence of post-ECT hypomania was observed in both~ Both patients were "'retrospectively" diagnosed as atypical bipolars. Their clinical courses con~asts with a more typical bipolar patient who has been successfully treated with outpatient maintenance ECT for several years. We consider the phenomenon of ECT-induced mania or hypomania, and abrupt relapse, as possibly indicative of a subset of patients with atypical bipolar disorder in whom ECT should be replaced promptly by mood-stabilizing medications.
197 CIRCULATING NATURAL KILLER CELL PHENOTYPES IN
MALES AND FEMALES WITH MAJOR DEPRESSION: RELATION TO CYTOTOXIC ACTIVITY AND SEVERITY OF DEPRESSION John M. Petitto, M.D., James D. Folds, Ph.D., Howard Ozer, M.D., Ph.D., Susan Gray Silva_ M_S , Cared Mnmhv 52 M. Dwight L. Evans, M.D. .
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Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160. Several recent studies suggest that natural killer activity (NKA) is reduced in patients with depression. Alterations in circulating NK cell phenotypes may underlie these changes in NKA. Therefore, we examined both peripheral blood NK cell phenotypes and NKA in major depressed and normal control subjects. Depressed subjects exhibited (!! reductions in Leu-ll (CDI6) NK effector cells and NKA, and (2) a dissociation of the normal positive correlation between the percent of Leu-l I lymphocytes and NKA, thus suggesting that alterations in both the killing capacity and availability of circulating Leu-l I N K cells appear to be responsible for depression-related reductions in NKA. Moreover, when the data were analyzed by gender, male major depressed subjects showed marked reductions in Leu-I l cells, NKA, and Leu-7 (HNKl) lymphocytes compared with normal male controls. By contrast, depressed females did not differ significantly from normal female controls on any of these three immune parameters studied. Severity of depression as assessed by Hamilton depression (HAM-D) rating was not associated with NKA or Leu-7 lymphocyte levels in either major depressed male or female subjects. HAM-D severity ratings were, however, strongly correlated with lower Leu-11 lymphocyte levels among mr~jor depressed men, but not women. These data begin to elucidate the immunologic mechanisms by which NKA is altered in depression, and suggest that
aio~. ~vCmATRY 1991;29:43A- |85A
133A
193 REDUCED BETA-I ADRENOCEPTORS IN DEPRESSION Gregory A. Ordway, Ph.D., Angelos E. Halaras, M.D., Ph.D. Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH 44109. The role of norepinephrine in depression has been debated for many yeats, ha rat ~ , the density of noradrenergic receptors (AIRs) is regulated by changes in concentrations of norepinephrine. We o b t a i ~ postmortem tissue to autoradiographically measure ARs in several brain regions from v i ~ of suicide and age-matched controls. Binding to [3 adrenoceptor subtypes or a2 ARs was measured using the ~ antagonist '~l-iodopindolol (IPIN) or the a2 agonist [ml]iodoclonidine (PIC), respectively. There was a trend for lower binding of IPIN in most regions of brain from suicide victims relative to controls, but this difference did not reach statistical significance. By contrast, IPIN binding [St ARs in the amygdala was s i ~ f i ~ y lower ( - 28%1 in brains from victims of suicide with histories of depression compared to age-matched controls (n = 6, p < 0.01). The binding of IPIN to [~2 ARs and the binding of PIC to a2 ARs were not significantly different in any brain region comparing suicides to controls, including in sections of the amygdala adjacent to those in which IPIN binding to [~ ARs was measured. Reduced a m y g ~ o i d [~t ARs implies overacfivity of noradrenergic neurons projecting to this IL,'abic b~-ainregion in depression.
194 UFC AS A PREDICTOR OF RESPONSE IN MAJOR DEPRESSION WITH PSYCHOTIC FEATURES W.H. Carson, M.D., R.F. Anton, M.D., E.A. Burch, Jr., M.D. Medical University of South Carolina, Charleston, SC 29425, and Tulane University School of Medicine, New Orleans, LA. Major depression with psychotic features (MDPF) is a distinct clinical entity, in which elevated cortL~l production as measured by 24-hr urinary free cortisol (UFC) and lack of dexamethasone suppression is common. To determine whether hypercortesolemia is predictive we evaluated the relationship of pretreatment 24-hr UFC determinations to treatment response in 30 inpatients who met DSM-I~ criteria for MDPF. Urine was collected during a placebo washout period over 24 .ha"on ice, refrigerated, ali~oted, and frozen until extraction and assay of free cortisol. Twenty-four-hour UFC was normalized for the amount of creatinine excretion. In a double-blind manner, patients were rated at baseline and over 4 weeks of treatment (with either amoxipine 400 mg or amitrip~fine/perphenazine 200 rag/32 mg daily) for depression (HRSD), psychosis (BPRS), and clinical improvement (CGI). Since there was no significant difference in overall response between the two medication groups the data for both groups were combined. Patients who showed marked overall clinical improvement tended (p = 0.091 to have higher UFC (53 -+ 33 lxg/mg) than those who showed less improvement (36 -+ 191. 73% of the patients with UFC above the median had marked clinical improvement compared with 40% of patients with UFC below the median (p = 0.06). In addition, there was a significant correlation between ;.mprovement in the HRSD scores and b a s e ~ e UFC (p = 0.04) but no significant correlation between improvement in BrKa . . scores . and . baseline . . UFC ~p = 0. 'L,,o.~"These data suggest that UFC may have some predictive power for treating depressive symptoms, in patients with MDPF.
195 RIGHT, LEFT, AND BILATERAL ECT REVISITED Victor Milstein, Ph.D., Joyce G. Small, M.D., Iver F. Small, M.D., Marietta H. Klapper, M.A. (by invitation), Marvin J. Miller, M.D. (by invitation), Jon D. Marhenke, M.D. (by invitation) Indiana University School of Medicine a,ut Larne D. Carter Memorial Hospital, Indianapolis, IN 46202. In previous investigations of nondominant and bilaterally induced ECT we observed that right brain functions improved more in affective disorders whereas dominant hemispheric functions were enhanced in schizophrenia. We investigated these relationships further in a new patient cohort in which unilateral induction
134A
BIOL PSYCHIATRY 1991 ;29:43A- 185A
Depression
was switched from the nondominant to the dominant side and stimulating electrode placements were changed from Lancaster to D'Elia positions. Clinical assessments by blind raters, neuropsychological tests, and clinical and topographic EEG studies were done as before. Patients were assessed prior to ECT, on a nontreatment day following the fifth or sixth ECT and 2-3 weeks after completion of the series. Data obtained were compared with findings from the earlier series. Effects of right- versus left-sided electrical induction were examined in different diagnostic categories. Findings were evaluated in terms of the previously advanced hypotheses about restoration of hemispheric equilibrium with ECT.
i96 PITFALLS IN TREATMENT OF ATYPICAL BIPOLAR DISORDER Richard Jaffe, M.D., Wendy Rives, M.D., Richard Roemer, D.M.S., Ph.D., William R. Dubin, M.D. Philadelphia Ps3~chiatricCenter, Philadelphia, PA 19131. Two patients, initially diagnosed as recurrent unipolar depressives were referred for ECT. Both had histories of poor response to antidepressant medications. Both patients showed similar responses to ECT, with rapid improvements but abrupt relapses, leading to protracted, unstable courses. Ultimately, both patients responded dramatically to pharmacotherapy with lithium, plus carbamazepine or valproic acid. Retrospective evaluation revealed no formal manic episodes, although limited evidence of post-ECT hypomania was observed in both~ Both patients were "'retrospectively" diagnosed as atypical bipolars. Their clinical courses con~asts with a more typical bipolar patient who has been successfully treated with outpatient maintenance ECT for several years. We consider the phenomenon of ECT-induced mania or hypomania, and abrupt relapse, as possibly indicative of a subset of patients with atypical bipolar disorder in whom ECT should be replaced promptly by mood-stabilizing medications.
197 CIRCULATING NATURAL KILLER CELL PHENOTYPES IN
MALES AND FEMALES WITH MAJOR DEPRESSION: RELATION TO CYTOTOXIC ACTIVITY AND SEVERITY OF DEPRESSION John M. Petitto, M.D., James D. Folds, Ph.D., Howard Ozer, M.D., Ph.D., Susan Gray Silva_ M_S , Cared Mnmhv 52 M. Dwight L. Evans, M.D. .
.
.
.
.
.
.
.
.
.
.
•
-
IL' ""
J
'
. . . . .
'
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160. Several recent studies suggest that natural killer activity (NKA) is reduced in patients with depression. Alterations in circulating NK cell phenotypes may underlie these changes in NKA. Therefore, we examined both peripheral blood NK cell phenotypes and NKA in major depressed and normal control subjects. Depressed subjects exhibited (!! reductions in Leu-ll (CDI6) NK effector cells and NKA, and (2) a dissociation of the normal positive correlation between the percent of Leu-l I lymphocytes and NKA, thus suggesting that alterations in both the killing capacity and availability of circulating Leu-l I N K cells appear to be responsible for depression-related reductions in NKA. Moreover, when the data were analyzed by gender, male major depressed subjects showed marked reductions in Leu-I l cells, NKA, and Leu-7 (HNKl) lymphocytes compared with normal male controls. By contrast, depressed females did not differ significantly from normal female controls on any of these three immune parameters studied. Severity of depression as assessed by Hamilton depression (HAM-D) rating was not associated with NKA or Leu-7 lymphocyte levels in either major depressed male or female subjects. HAM-D severity ratings were, however, strongly correlated with lower Leu-11 lymphocyte levels among mr~jor depressed men, but not women. These data begin to elucidate the immunologic mechanisms by which NKA is altered in depression, and suggest that