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Cortical function in schizophrenia during blood flow activation
606
Abstracts
BlOL PSYCHIATRY 1996:39:SlJO-666
levels similar to those of age-matched mcn in most brain regions. In this regard, ANCOVA detected significant ll£c-by-gender interactions in the amygdalae and thalamus (p<0.05) where postmenopausal women showed binding levels below those of age-matched men. These data imply that both :age and gender an: important variables to consider in the inlerpretation of brain function studies in which the opioid syslem may play II role. Additionally. hormone-mediated olter..ltions in the opioid system during the menopause may be involved in the cognitive and affective changes described during this phase of human aging.
358. CORTICAL FUNCTION IN SCHIZOPHRENIA DURING BLOOD FLOW ACTIVATION 1
I
')
S. F, Tay Ior , R. Tandon , & RA. Koeppe-
'Univef!iiit)' of Michigan Department of Psychiutry, Ann Arbor, Ml 48109-0116; 2University of Michigtln Depurtmcnt of Internal Merlicine. Division of Nuclear Medicine The interpretation of abnormal cerebral blood now (CSF) activation in schizophrenic ptltients performing complex tasks has not been slmightforward. Even during simple sensory and motor tllsks. recent studies have found abnormal :lctivotion responses in schizophrenill. To cvoluate the functiontll integrity of cortical CBF change in schizophrcnio, we utilized a non-patterned photic stimulus :It several stimulation rates (0, 1, 3, 8 & 30 hz), known (0 produce reliable CBF activation in the visuul cortex at vllr)'ing levels of intensity. We also used systemic infusion of neetazolamide. which increases CSP viu non-neuml mcch:lnisms, to llssess the vascular integrity of COF chanse. Seven medicated schizophrenic and se\'en healthy control subjecls (uge :lnd gender motched) were studied with quantitative [1.101H 20 PET methodology. The schizophrenic subjects exhibitcd discrete activation of the striate cortex at uti levels of stimulation, us did the normal controls. We found no evid.cnce for deficient nctivulion in a visual stimulation task, lind at the lowest level of stimulation. schizophrenics had (nOli-significantly) higher CSP increase in the striate cortex than the controls (13.1 % vs 9.0%). During the acetazolamide infusion, the schizophrenic patients had a foctll CBP increase in the medial frontal/anterior cingulllte cortex, relative to the unstimulated state, which represented underperfusion of this region in the s.chilophrcnics, compared with the nonnal controls, during the unstimulated stllte. This area of cortex has m'cn implicated in the mediation of emoIional responses 10 stimuli, and cerebral metnbolic llnd neuropathologic studies of s,hizophrenia suggest un important role for this region in pathophysiologkal mechnnisrns of the illness.
359. CAUDATE NUCLEUS AND PUTAMEN ABNORMALITIES IN PEDIATRIC OeD D. Rosenberg, M. Keshavan, W. Bagwell, A. Seymour. K. O'Hearn, E. Dick t B. Birmaher, & J. Sweeney University of Pittsburgh Medicnl C,nter, 381 I O'Hara Street, Pittsburgh. PA 15213 Thc most widely accepted neurobiological model of obsessive compulsive disorder (OeD) is that abnormalities in bm;nl snnSlia-rrontal conex
inter:lction arc involved in causing obsessive and compulsive symptoms. Indirect support for this hypothesis comes from observations of increased mtcs of obsessive and compulsive symptoms in neuropsychiatric disorders that result primarily from btlsal ganglia disease (e.g., Tourelte's Syndrome, Sydenhtlm's Chorea). many of which occur in childhood. More direct evidence comes from structural :lnd functiontll neuroimaging studies which have demonstrated disturbances in fronto-slritltal circuitry. Funher. although OeD commonly emerges during childhood or adolescence, no study to our knowledge has examined psychotropic-naive pediatric OCD patients ncar the onscl of illness to study the role of atypical dcvelopmental pTOl:esscs. MRI scans from 16 medication-naive, non-depressed OCD patients 7.2-16.9 years ofagc. and 16 cu.';e-mlltched hcalthy comparison subjects were analyzed to delermine the volumes or the following structures: prefrontal cortex. caudate nucleus, putamen, ond intracr.mitll volume. Because of the wide age ronge. ANCOVA with intmcranial volume as U covtlriate measurement was perfonned. OeD patients had significantly smaller left caudate nucleus and left putumcn volumes than controls (F == 4.07. P 0.03 and F == 4.20, P 0.Q2. respectively). but did not differ in right caudate and pUlamen volumes, prefrontal cortex or intracranial volume. Structural volumes were not significantly correlated with the duration or severity of OCD symptoms. In a previous study of many of the same casc·control pairs, a selective deficit in oculomotor response inhibition was observed in OCD ptltients but not controls. We perfonned cOlTClations between oculomotor response suppression elTors and structural volumetric measurements nnd observed significant correlations in OCD patients between riSht and left caudate volumes (r : 0.60, p = 0.04 and r == 0.63. p == 0.03. respectively), left putomen (r = .0.60, P 0,04) as well llS wilh prefrontal eortical gray mtlUer and tOlal prefrontal conical volume (r = 0.80, P = 0.003 nnd r 0.72. P 0.01. respectively) but not right putamen. Behavioral response inhibition nbnonnalities in OCD may be relmed to failures in deve[opmental motumtion of fronto-striatal circuitry. particularly orbiltll prefronlal-ventral striatal cireuits. Our findings provide adrlitional evidence for pathological involvement of thc caudaIe nucleus and putamen in OCD.
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360. A PET STUDY OF PET FDOPA UPTAKE
IN ABSTAINING COCAINE ADDICTS K.M .Bell, E.A. Klein. J.e. WU t C.B. Widmark, A. Najafi, & D, Keator Brain Imuging Center. Department of Psychiatry. University of Califomia at Irvine. Irvine, CA 92717 The objective of this study was to ussess dopnminergic function with PET in cocaine addicts during a period of withdrawal from cocaine usc. Seven cocaine-dependent subjllcts in acute withdrawal «30 days since last usc) were stmlied usint:; FDOPA uptake. Inclusion criteria were I) DSM·III-R diat:;nostic criteria for active cocaine dependency, 2) continuous usc of coctline for at least the prior six months with claimed cocaine use of at lenst "2 grams" II week (estimated cost of $2001week), PET studies were performed on 11 Neuroecat IV system with FWHM of 7.6mm in-plane. Each subject received 2.0-4.0 mCi of 6-FD. Twelve IO-minute scans were perfonned. FDOPA uptake was delennined (Martin et al 1989). FDOPA uptake wn.~ graphically represented pixel by pixel. Normal controls have tl significantly higher mOPA uptake in the right anterior cingultlte, righl cambte llnd right putamen compared with cocaine addicts nbsttllning from cocaine lise for up to one month (p<0.02). This suppression of prcs)'n:lptic dopamine nctivity may be the result of tl compensatory down-regula.tion initiated by the system in response to blockage of rcuptnke transportcrs anti may predispose llddicts to cocaine craving.
Abstracts
BlOL PSYCHIATRY 1996:39:SlJO-666
levels similar to those of age-matched mcn in most brain regions. In this regard, ANCOVA detected significant ll£c-by-gender interactions in the amygdalae and thalamus (p<0.05) where postmenopausal women showed binding levels below those of age-matched men. These data imply that both :age and gender an: important variables to consider in the inlerpretation of brain function studies in which the opioid syslem may play II role. Additionally. hormone-mediated olter..ltions in the opioid system during the menopause may be involved in the cognitive and affective changes described during this phase of human aging.
358. CORTICAL FUNCTION IN SCHIZOPHRENIA DURING BLOOD FLOW ACTIVATION 1
I
')
S. F, Tay Ior , R. Tandon , & RA. Koeppe-
'Univef!iiit)' of Michigan Department of Psychiutry, Ann Arbor, Ml 48109-0116; 2University of Michigtln Depurtmcnt of Internal Merlicine. Division of Nuclear Medicine The interpretation of abnormal cerebral blood now (CSF) activation in schizophrenic ptltients performing complex tasks has not been slmightforward. Even during simple sensory and motor tllsks. recent studies have found abnormal :lctivotion responses in schizophrenill. To cvoluate the functiontll integrity of cortical CBF change in schizophrcnio, we utilized a non-patterned photic stimulus :It several stimulation rates (0, 1, 3, 8 & 30 hz), known (0 produce reliable CBF activation in the visuul cortex at vllr)'ing levels of intensity. We also used systemic infusion of neetazolamide. which increases CSP viu non-neuml mcch:lnisms, to llssess the vascular integrity of COF chanse. Seven medicated schizophrenic and se\'en healthy control subjecls (uge :lnd gender motched) were studied with quantitative [1.101H 20 PET methodology. The schizophrenic subjects exhibitcd discrete activation of the striate cortex at uti levels of stimulation, us did the normal controls. We found no evid.cnce for deficient nctivulion in a visual stimulation task, lind at the lowest level of stimulation. schizophrenics had (nOli-significantly) higher CSP increase in the striate cortex than the controls (13.1 % vs 9.0%). During the acetazolamide infusion, the schizophrenic patients had a foctll CBP increase in the medial frontal/anterior cingulllte cortex, relative to the unstimulated state, which represented underperfusion of this region in the s.chilophrcnics, compared with the nonnal controls, during the unstimulated stllte. This area of cortex has m'cn implicated in the mediation of emoIional responses 10 stimuli, and cerebral metnbolic llnd neuropathologic studies of s,hizophrenia suggest un important role for this region in pathophysiologkal mechnnisrns of the illness.
359. CAUDATE NUCLEUS AND PUTAMEN ABNORMALITIES IN PEDIATRIC OeD D. Rosenberg, M. Keshavan, W. Bagwell, A. Seymour. K. O'Hearn, E. Dick t B. Birmaher, & J. Sweeney University of Pittsburgh Medicnl C,nter, 381 I O'Hara Street, Pittsburgh. PA 15213 Thc most widely accepted neurobiological model of obsessive compulsive disorder (OeD) is that abnormalities in bm;nl snnSlia-rrontal conex
inter:lction arc involved in causing obsessive and compulsive symptoms. Indirect support for this hypothesis comes from observations of increased mtcs of obsessive and compulsive symptoms in neuropsychiatric disorders that result primarily from btlsal ganglia disease (e.g., Tourelte's Syndrome, Sydenhtlm's Chorea). many of which occur in childhood. More direct evidence comes from structural :lnd functiontll neuroimaging studies which have demonstrated disturbances in fronto-slritltal circuitry. Funher. although OeD commonly emerges during childhood or adolescence, no study to our knowledge has examined psychotropic-naive pediatric OCD patients ncar the onscl of illness to study the role of atypical dcvelopmental pTOl:esscs. MRI scans from 16 medication-naive, non-depressed OCD patients 7.2-16.9 years ofagc. and 16 cu.';e-mlltched hcalthy comparison subjects were analyzed to delermine the volumes or the following structures: prefrontal cortex. caudate nucleus, putamen, ond intracr.mitll volume. Because of the wide age ronge. ANCOVA with intmcranial volume as U covtlriate measurement was perfonned. OeD patients had significantly smaller left caudate nucleus and left putumcn volumes than controls (F == 4.07. P 0.03 and F == 4.20, P 0.Q2. respectively). but did not differ in right caudate and pUlamen volumes, prefrontal cortex or intracranial volume. Structural volumes were not significantly correlated with the duration or severity of OCD symptoms. In a previous study of many of the same casc·control pairs, a selective deficit in oculomotor response inhibition was observed in OCD ptltients but not controls. We perfonned cOlTClations between oculomotor response suppression elTors and structural volumetric measurements nnd observed significant correlations in OCD patients between riSht and left caudate volumes (r : 0.60, p = 0.04 and r == 0.63. p == 0.03. respectively), left putomen (r = .0.60, P 0,04) as well llS wilh prefrontal eortical gray mtlUer and tOlal prefrontal conical volume (r = 0.80, P = 0.003 nnd r 0.72. P 0.01. respectively) but not right putamen. Behavioral response inhibition nbnonnalities in OCD may be relmed to failures in deve[opmental motumtion of fronto-striatal circuitry. particularly orbiltll prefronlal-ventral striatal cireuits. Our findings provide adrlitional evidence for pathological involvement of thc caudaIe nucleus and putamen in OCD.
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=
=
=
=
360. A PET STUDY OF PET FDOPA UPTAKE
IN ABSTAINING COCAINE ADDICTS K.M .Bell, E.A. Klein. J.e. WU t C.B. Widmark, A. Najafi, & D, Keator Brain Imuging Center. Department of Psychiatry. University of Califomia at Irvine. Irvine, CA 92717 The objective of this study was to ussess dopnminergic function with PET in cocaine addicts during a period of withdrawal from cocaine usc. Seven cocaine-dependent subjllcts in acute withdrawal «30 days since last usc) were stmlied usint:; FDOPA uptake. Inclusion criteria were I) DSM·III-R diat:;nostic criteria for active cocaine dependency, 2) continuous usc of coctline for at least the prior six months with claimed cocaine use of at lenst "2 grams" II week (estimated cost of $2001week), PET studies were performed on 11 Neuroecat IV system with FWHM of 7.6mm in-plane. Each subject received 2.0-4.0 mCi of 6-FD. Twelve IO-minute scans were perfonned. FDOPA uptake was delennined (Martin et al 1989). FDOPA uptake wn.~ graphically represented pixel by pixel. Normal controls have tl significantly higher mOPA uptake in the right anterior cingultlte, righl cambte llnd right putamen compared with cocaine addicts nbsttllning from cocaine lise for up to one month (p<0.02). This suppression of prcs)'n:lptic dopamine nctivity may be the result of tl compensatory down-regula.tion initiated by the system in response to blockage of rcuptnke transportcrs anti may predispose llddicts to cocaine craving.