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Respiratory sinus arrhythmia in schizophrenia and mania
Abstracts
DIaL PSYCIIIATRY 1996:39:500-666
180. AGE OF ILLNESS ONSET AND THE INPATIENT DRUG WASHOUT R.P. Sharma, S. Dowd, J.M. Davis, &
P.G~
Janicak
The Psychiatric Institute, Depa.'1ment of Psychiatry, University of Illinois tit ChicOlgo, Chicago, IL The authors examined the relationship between the uBc of illness onset and the abilily to tolerate a medication-frce period in a sample of acutely ill schizophrenic p:l1ients, Patients were admilted to an inpalient research unit for the treatment of acule tlnd recurrent psychiatrlc symptoms. Prior medications were disconlinued upon admission to the unit for purposes of clinical research and beh:!vioral assessment uncontamimued by medication side cffecls. The age of illness onset waS significantly and positively correlated with the duration of hospital willlhout. Furthennore, agc of illness onset was significantly correlated with the BPRS total score and the BPRS !lostility/suspiciousness faclOr measured at the end of washout. Our results suggest that early onset schizophrenics ddcrior.J.tc more rnpidly in an acute episode than do their later onset countel'Jlilt15.
181. RESPIRATORY SINUS ARRHYTHMIA IN SCHIZOPHRENIA AND MANIA S. Smith, D.B. Schnur, R. Yehuda, & P. Siddiqui Mt. Sinai School of Medicine. New York, NY 10029
The effect of labomtory manipulations on respirnlol)' sinus arrhythmia (RSA) was measured in schizophrenic, manic, and normal subjects as
pan of an ongoing sludy of psychophysiologic:!1 rcnctivity to labonltory strcssoIS. RSA ha,~ been shown previously to vary with ilvcrsivc stimulation. The sample consisted of21 schizophrenic. 14 manic. and 10 nonnal subjects. RSA was derived by discrele Fourier transronn llnd reported as spectral power within the 117-414 mHz band. RSA mcasurements were time·locked to mental urithmetie tasks with and wilhout distractor and a colli pressor Icst. Mental arithmetic did not produce robust chnnSes in RSA. RSA during the four minutcs hnmedialely following the cold pressor eKceeded both pre·cold pressor RSA (Wileo~on Z"" 3.19, p"'-O.OO t 4) and RSA during the subsequent four minutes (Wilcoxon Z=4.37, p=O.OOOOI). Diagnostic groups did not lIifrer significantly in this efrcct. The short-tived increase in RSA on release from the cold pressor test suggests thm cold pressor is an effeclive stressor for Use with this measure, but mental arithmetic did not cre3le alterations in RSA. RSA responsivity does not appellr to differentiate schizophrenic or mOlnic patient groups from controls. We will provide additional analyses with n larger samplc.
182. PROBABLE NEUROLEPTIC INDUCED TARDIVE DYSKINESIA IN ASSOCIATION WITH COMBINED FLUOXETINE AND RISPERIDONE TREATMENT
553
effects. Rispcridone is a Pllt3tively "atypical" antipsycholic wilh rela" tively high binding affinity to bOlh dopamine D·2 nnd serotonin SHT-2 receptors and a relatively low incidence of extl'llpyrnmidal side effects at therOlpeutic dosages. Auoxetine and other i1gents that selectively inhibit presynapt;c rcuptuke of serotonin may exacerbate molor symptoms when given in combination with antipsychotic medication. We describe an 18 year old Caucasian male who developed extrnpyramid.:ll side effects followed by persistent, dyskinelic tongue movements in association with combined Ouoxetine and risperidone treatment, Although only a single ca5~. the results are consistent with the notion th:n th~ complex dopamillergic nnd seroloninergic interactions producing motor ntypicality in an nntipsychotic may be relatively "fragile" and subject to disruplion by drug inll:rnctions.
183. NEUROLEPTIC EFFECTS ON THE RESPIRATORY CHAIN D.S. Higgins, Jr..,I, M. Garcia~Osuna2, &
J.T. Greenamyre-
IThe Ohio State University College of Medicine. Columbus. OH 43210; 2Emory University School of Medicine, Atlnma, GA 30322 Accumulnting evidence implicates metabolic defects in basal ganglia disorders. Antipsychotic indut'ed respiratory chain dysfunction has been recently described suggesting metabolic compromise in neuroleptic illlsocialed eXlrnpyrnmidal syndromes. We have examined the effect of c1assicOll (haloperidol & fluphenazine) :lOd Dtypical (c1ozapine) neuroleptics on the respiratory chnin. In a novel autorndiogrnphie assay, specific [JH)dihydrorotenone (f'HjDHR) binding to the "distal" segment of complex I was displaced with lhe rank order potency: haloperidol (31 J.LM) » nuphenazinc (384 IJ.M) > c10:lilpine (630 IJ.M). The physiologic relev:mce of this intel"'Jction was assessed during short (7 days) lind prolonged (28 days) dUlillion treatment parndigms. Short tenn hnlopcri. dol (I mglkg) signincanlly reduced [3H1DBR binding in the strinlum (-42%). dentale gyrus (-65%) anll cerebellum. molecular layer (-60%). []HIDHR binding also declined with short term fluphenazine (4 mglkg) ltnd clompinc (10 mglkg) although the effect did not achieve significance in the slnntum of the clozapine group. In contrast. prolol1ged neuroleplic e~posurc significimtly increased [JHj DHR binding in the striatum (+4549%) but was without effeci in Ihe cerebellum, molcl:ul3r layer (+414%). Complex It (succinate dehydrogenase) and complex IV (cytochrome oxidase). visualized histochemically. were unaltered by either short Or prolonged neuroleptic trcntmenl. Neuroleptics, notably the classical ltgents, can modify respiratory chain integrity having the greatest dfect on complllx I. The restricted effect of clozapine may llccount, in part, for the low frequency of movement disorders associated with this compound. The mechanism underlying the short lerm attenualion and prolonged potentiation of [JH)DHR binding is under invesligation. Supported by NARSAD
184. CBF ACTIVATION IN POST TRAUMATIC STRESS DISORDER: SPECT STUDIES I. Liberzon, L.M. Fig, S.F. Taylor, T.D. Jung, S, Minoshima, & R.A. Koeppe
'Washington Clinical Research Center. 6404-P Seven Comct!l Plnee. FOllis Church, VA 22044: :lCllnical Brain Disorders Branch DIRP. NlMH, Washinglon, DC
PSyt'hiatl)' and Nuclear Medicine. VAMC Olnd University of Michigan. Ann Arbor MI
In::rellsed risk of lardive dyskinesia has been linked to cumulalive neuroleptic exposure Dnd early development of extrapyrnmidal side
Post triluml1lic stress disorder (PTSD) patients exhibit memory abnormalities (inlrusive mcmories, nnshbacks llnd dreams), avoidance behav-
DIaL PSYCIIIATRY 1996:39:500-666
180. AGE OF ILLNESS ONSET AND THE INPATIENT DRUG WASHOUT R.P. Sharma, S. Dowd, J.M. Davis, &
P.G~
Janicak
The Psychiatric Institute, Depa.'1ment of Psychiatry, University of Illinois tit ChicOlgo, Chicago, IL The authors examined the relationship between the uBc of illness onset and the abilily to tolerate a medication-frce period in a sample of acutely ill schizophrenic p:l1ients, Patients were admilted to an inpalient research unit for the treatment of acule tlnd recurrent psychiatrlc symptoms. Prior medications were disconlinued upon admission to the unit for purposes of clinical research and beh:!vioral assessment uncontamimued by medication side cffecls. The age of illness onset waS significantly and positively correlated with the duration of hospital willlhout. Furthennore, agc of illness onset was significantly correlated with the BPRS total score and the BPRS !lostility/suspiciousness faclOr measured at the end of washout. Our results suggest that early onset schizophrenics ddcrior.J.tc more rnpidly in an acute episode than do their later onset countel'Jlilt15.
181. RESPIRATORY SINUS ARRHYTHMIA IN SCHIZOPHRENIA AND MANIA S. Smith, D.B. Schnur, R. Yehuda, & P. Siddiqui Mt. Sinai School of Medicine. New York, NY 10029
The effect of labomtory manipulations on respirnlol)' sinus arrhythmia (RSA) was measured in schizophrenic, manic, and normal subjects as
pan of an ongoing sludy of psychophysiologic:!1 rcnctivity to labonltory strcssoIS. RSA ha,~ been shown previously to vary with ilvcrsivc stimulation. The sample consisted of21 schizophrenic. 14 manic. and 10 nonnal subjects. RSA was derived by discrele Fourier transronn llnd reported as spectral power within the 117-414 mHz band. RSA mcasurements were time·locked to mental urithmetie tasks with and wilhout distractor and a colli pressor Icst. Mental arithmetic did not produce robust chnnSes in RSA. RSA during the four minutcs hnmedialely following the cold pressor eKceeded both pre·cold pressor RSA (Wileo~on Z"" 3.19, p"'-O.OO t 4) and RSA during the subsequent four minutes (Wilcoxon Z=4.37, p=O.OOOOI). Diagnostic groups did not lIifrer significantly in this efrcct. The short-tived increase in RSA on release from the cold pressor test suggests thm cold pressor is an effeclive stressor for Use with this measure, but mental arithmetic did not cre3le alterations in RSA. RSA responsivity does not appellr to differentiate schizophrenic or mOlnic patient groups from controls. We will provide additional analyses with n larger samplc.
182. PROBABLE NEUROLEPTIC INDUCED TARDIVE DYSKINESIA IN ASSOCIATION WITH COMBINED FLUOXETINE AND RISPERIDONE TREATMENT
553
effects. Rispcridone is a Pllt3tively "atypical" antipsycholic wilh rela" tively high binding affinity to bOlh dopamine D·2 nnd serotonin SHT-2 receptors and a relatively low incidence of extl'llpyrnmidal side effects at therOlpeutic dosages. Auoxetine and other i1gents that selectively inhibit presynapt;c rcuptuke of serotonin may exacerbate molor symptoms when given in combination with antipsychotic medication. We describe an 18 year old Caucasian male who developed extrnpyramid.:ll side effects followed by persistent, dyskinelic tongue movements in association with combined Ouoxetine and risperidone treatment, Although only a single ca5~. the results are consistent with the notion th:n th~ complex dopamillergic nnd seroloninergic interactions producing motor ntypicality in an nntipsychotic may be relatively "fragile" and subject to disruplion by drug inll:rnctions.
183. NEUROLEPTIC EFFECTS ON THE RESPIRATORY CHAIN D.S. Higgins, Jr..,I, M. Garcia~Osuna2, &
J.T. Greenamyre-
IThe Ohio State University College of Medicine. Columbus. OH 43210; 2Emory University School of Medicine, Atlnma, GA 30322 Accumulnting evidence implicates metabolic defects in basal ganglia disorders. Antipsychotic indut'ed respiratory chain dysfunction has been recently described suggesting metabolic compromise in neuroleptic illlsocialed eXlrnpyrnmidal syndromes. We have examined the effect of c1assicOll (haloperidol & fluphenazine) :lOd Dtypical (c1ozapine) neuroleptics on the respiratory chnin. In a novel autorndiogrnphie assay, specific [JH)dihydrorotenone (f'HjDHR) binding to the "distal" segment of complex I was displaced with lhe rank order potency: haloperidol (31 J.LM) » nuphenazinc (384 IJ.M) > c10:lilpine (630 IJ.M). The physiologic relev:mce of this intel"'Jction was assessed during short (7 days) lind prolonged (28 days) dUlillion treatment parndigms. Short tenn hnlopcri. dol (I mglkg) signincanlly reduced [3H1DBR binding in the strinlum (-42%). dentale gyrus (-65%) anll cerebellum. molecular layer (-60%). []HIDHR binding also declined with short term fluphenazine (4 mglkg) ltnd clompinc (10 mglkg) although the effect did not achieve significance in the slnntum of the clozapine group. In contrast. prolol1ged neuroleplic e~posurc significimtly increased [JHj DHR binding in the striatum (+4549%) but was without effeci in Ihe cerebellum, molcl:ul3r layer (+414%). Complex It (succinate dehydrogenase) and complex IV (cytochrome oxidase). visualized histochemically. were unaltered by either short Or prolonged neuroleptic trcntmenl. Neuroleptics, notably the classical ltgents, can modify respiratory chain integrity having the greatest dfect on complllx I. The restricted effect of clozapine may llccount, in part, for the low frequency of movement disorders associated with this compound. The mechanism underlying the short lerm attenualion and prolonged potentiation of [JH)DHR binding is under invesligation. Supported by NARSAD
184. CBF ACTIVATION IN POST TRAUMATIC STRESS DISORDER: SPECT STUDIES I. Liberzon, L.M. Fig, S.F. Taylor, T.D. Jung, S, Minoshima, & R.A. Koeppe
'Washington Clinical Research Center. 6404-P Seven Comct!l Plnee. FOllis Church, VA 22044: :lCllnical Brain Disorders Branch DIRP. NlMH, Washinglon, DC
PSyt'hiatl)' and Nuclear Medicine. VAMC Olnd University of Michigan. Ann Arbor MI
In::rellsed risk of lardive dyskinesia has been linked to cumulalive neuroleptic exposure Dnd early development of extrapyrnmidal side
Post triluml1lic stress disorder (PTSD) patients exhibit memory abnormalities (inlrusive mcmories, nnshbacks llnd dreams), avoidance behav-