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Magnetic resonance spectroscopic inestigations of affective disorders
Abstracts
show the greatest deficits in the conditions requiring tliat contcxl be maintained over a delay, particularly when it must be used to elicit a context·medialed response in favor of a competing dominant response. To test these predictions, we modilied threc tasks - the AX·CPT. the Stroop ta."k, lmd a lexical disambiguation ta."k - and llliministered them to inpatient and outpaticnt schizophrenics, as well as patlenL.. with major depression and non-psychiatric controls. The results corroborated our predictions conccming schizophrenic pcrfonnancc in context-sensitive conditions of these tasks, and correlations of perfonnance in these condilions across tasks. These findings provide strong support for our hypothesis concerning a specific disturbance in the processing of context in schizophrenia.
371. MAGNETIC RESONANCE SPECTROSCOPIC INESTIGATIONS OF AFFECTIVE DISORDERS T. Kato
DlOL I'SVCHlATRY 19116:39:500-666
609
disorder. However, older generation brain imaging lechnlques. capablc of assessing brain anatomical struclure, hnve not identified consistcnt structural abnormalities. In this regards. the development of modem function:lI imaging techniques. such as. magnetic resonance spectroscopy (MRS) are beginning to elucldale underlying brain physiologic abnormalities which may be responsible for panic disorder. We hllve undertaken a series of studies of panic disonler using IH MRS to investigate brain metabolle responses to acute panic precipitated by chemical challenges, such as intravenous sodium lactate infusion or during controlled hyperventilation. Single voltel findings from the insular cOrle" region indic:lle execs:; brain lactale rise among panic subjects during panic precipitaled by lactale infusion :lnd continued rises post-infusion in relationship to decreasing blood lactate levels. Similarly, during vigorous hyperventilation contfCllled by capnometry, a...ymptomatie panic SUbjects dcmonstl'ilti:d significantty srealer brain lactate rise:; in comparison to matched controls. In tOlill. findings suggest brain metabolic abnormalities which may help to explain theories of "suffocation raise alurrn" (Klein, 1993) postulated to be responsible for sudden. overwhelming panic. In addition. preliminary findings using proton echo·planar spectroscopic imaging (PEPSI) to map out the underlying neuroanatomical substrntc in relationship to changing metabolic conditions during the precipitation of panic will be presented. These studies provide a model for unraveling underlying brain puthophysiological processes responsible for the pro· duction of panic. Work supported by NIMH (R01-MH50S79).
Department of Psychiatry, Shiga University of Medical Science. Otsu, Shigll, 520-21. Japlln Magnelic resonance spectroscopy (MRS) is a non·invasive tool for ill chemical analysis. We have been studying brnin metabolism in patients with ilffective disorders using :llp·MRS and IH·MRS. The results oflhese studies arc summarized as follows: (1) Phosphomonoester (PME) peak was elevated in manic patients with bipolar disorder (12.3::!: 1.9%. n"" 17). PME waq lower in the cuthymie statl.! (10.2± i.S%. n= 17) than that in rlonnal controls (l1.4± 1.6%, n= 17), (2) Phospho· creatine (PCr) WIIS lower in the left frontal lobe in bipollll depression (f( 4+ .!J\%.,"~:::::J.!l.!,(Imp.:!r!:d~.Hh ~t'\nn!!I.r.f.l!1!m!s (9.8:: Ll%, n=21), Decrease of PCr correlated wilh higher scores of Hamilton Depression Raling Scale (r= -0.75). PCr in the frontnl lobes was low in all psychiatric states in patients with bipolar lIl.1isorder. (3) Intmecllular pH was lower in cUlhymic patients with bipolnr disorder treuled wilh lithium (7.01 ::0,04. n=40) than normal controls (7.05::0.04. n=60). while it did not differ from controls in manic or depressive states. (4) The choline containing compounds (Cho) measured by I H·MRS was increased in both bipolar llnd unipolar depression in the basal ganglia. Decrease of PCr is of particular interest because PCr wns increased in the leC! frontal lobe in schizophrenia. This may provide a clue 10 clarify the biochemical dirfercnce in bipolar disorder and schizophrenia. Alteration of intracellular pH is also of interest beClluse it may rdate to cliniclli action of lithium. These findings will provide new research strategies to study the neurochemical basis of bipolar disorder. V;\'O
372. IH MRS INVESTIGATION OF PANIC DISORDER S.R. Dager l ,2, T.L. Richards l •3, K.I. Marro l ,2, W. Strauss 1•3, A. Heidi l ,3, A.A. Artrv. I,4, & S. Posses University of Washington School of Medicine, Depts. of 'psychiatry, 2Bloengineering, JRadiology, 4Aneslhesiology, Seattle, \VA 98105: ~Institut fUr Mcdizin, MR Research Cenler, JOllch, Gen11any There is increasing evidence to suggest the in.volvemcnt of bmin mechanism(s) in the ctiology of pllthological anxiety. pnrticularly panic
373. PROTON MRS OF HUMAN BASAL GANGLIA DURING ACUTE COCAINE ADMINISTRATION 2 , S.L. Rose I, J.D. Christensen.,I, MJ. Kaufmun ') 1 J.H. Mendelson-, S.E. Lukas-, C.M_Mccre.-. B.M. Cohen I, & P.F. Renshaw I
IBrnin Imaging Center und :!Akohol and Dmg Abuse Research Center. McLean Hospital. Harvard Medical School, Belmont. MA 02178
Proton mngnelic resonllnce spectroscopy ( IH Ml-I.S) wal> used to evaluatc change:; in basal gunglia chemislry occurring in response to intl1lvenous coclline administration. Twenty-seven healthy nnd neurologiclllly nonnal males, aged 28:!:5 years (melln±SD), provided lnfonncd consent to participale in lhe study. Subjects reported a history of casual cocaine use (l3:!: 14 lifetime exposures) and tested negative for tfle presence of drugs/alcohol immediately prior to the stud)'. All studies were performed using n 1.5T clinical MR scanner. PRESS localization was used to acquire 1H MRS signals from an 8 cm~ cubie volume surrounding the basal gangli:l. Unsuppressed water spcctr.t and water suppjcsscd spectra containing resonances for N·acdyi·asparlai~ (NAA). creatine+phosphocreutine (Cr), cylosolic choline-containing compounds (Cho), amI myo-inositol (Inos). Were obtained at 5 min intervals at baseline and following the inlravl!nous infusion (slow push over one minute) of placebo (n=7). 0.2 mglkg cocaine (n= 10) or 0.4 mglkg (n= 10). Following cocuinc administration, the signal intensities of aU intracellular resonances were increased in a dose·dependent manner. For the subjecls receiving placebo. the mean intensilies (::!:SD) of the resonance tines thiny minutes aner injection. expressed ali pcrcent of the baseline value were, NAA (99::8), Cho (97::!:8). Cr (l06±21), Inos (100::!::22). and water (100±2). Thirty minutes followinG the injection of 0.40 mgikg cocaine, cOfI'Csponding values were NAA (117.:!:28) Che (135::51). Cr (l12:!:24), Inos (l28±23), and water (100::2). The increases in the intracellular metabolite (N.~IA, Cho. Cr. IIml Inos) fCsonilnce intensities were all statistically Iiignilicalll. In contmst, the intensity of the water line remained constant, suggesting that cocaine
show the greatest deficits in the conditions requiring tliat contcxl be maintained over a delay, particularly when it must be used to elicit a context·medialed response in favor of a competing dominant response. To test these predictions, we modilied threc tasks - the AX·CPT. the Stroop ta."k, lmd a lexical disambiguation ta."k - and llliministered them to inpatient and outpaticnt schizophrenics, as well as patlenL.. with major depression and non-psychiatric controls. The results corroborated our predictions conccming schizophrenic pcrfonnancc in context-sensitive conditions of these tasks, and correlations of perfonnance in these condilions across tasks. These findings provide strong support for our hypothesis concerning a specific disturbance in the processing of context in schizophrenia.
371. MAGNETIC RESONANCE SPECTROSCOPIC INESTIGATIONS OF AFFECTIVE DISORDERS T. Kato
DlOL I'SVCHlATRY 19116:39:500-666
609
disorder. However, older generation brain imaging lechnlques. capablc of assessing brain anatomical struclure, hnve not identified consistcnt structural abnormalities. In this regards. the development of modem function:lI imaging techniques. such as. magnetic resonance spectroscopy (MRS) are beginning to elucldale underlying brain physiologic abnormalities which may be responsible for panic disorder. We hllve undertaken a series of studies of panic disonler using IH MRS to investigate brain metabolle responses to acute panic precipitated by chemical challenges, such as intravenous sodium lactate infusion or during controlled hyperventilation. Single voltel findings from the insular cOrle" region indic:lle execs:; brain lactale rise among panic subjects during panic precipitaled by lactale infusion :lnd continued rises post-infusion in relationship to decreasing blood lactate levels. Similarly, during vigorous hyperventilation contfCllled by capnometry, a...ymptomatie panic SUbjects dcmonstl'ilti:d significantty srealer brain lactate rise:; in comparison to matched controls. In tOlill. findings suggest brain metabolic abnormalities which may help to explain theories of "suffocation raise alurrn" (Klein, 1993) postulated to be responsible for sudden. overwhelming panic. In addition. preliminary findings using proton echo·planar spectroscopic imaging (PEPSI) to map out the underlying neuroanatomical substrntc in relationship to changing metabolic conditions during the precipitation of panic will be presented. These studies provide a model for unraveling underlying brain puthophysiological processes responsible for the pro· duction of panic. Work supported by NIMH (R01-MH50S79).
Department of Psychiatry, Shiga University of Medical Science. Otsu, Shigll, 520-21. Japlln Magnelic resonance spectroscopy (MRS) is a non·invasive tool for ill chemical analysis. We have been studying brnin metabolism in patients with ilffective disorders using :llp·MRS and IH·MRS. The results oflhese studies arc summarized as follows: (1) Phosphomonoester (PME) peak was elevated in manic patients with bipolar disorder (12.3::!: 1.9%. n"" 17). PME waq lower in the cuthymie statl.! (10.2± i.S%. n= 17) than that in rlonnal controls (l1.4± 1.6%, n= 17), (2) Phospho· creatine (PCr) WIIS lower in the left frontal lobe in bipollll depression (f( 4+ .!J\%.,"~:::::J.!l.!,(Imp.:!r!:d~.Hh ~t'\nn!!I.r.f.l!1!m!s (9.8:: Ll%, n=21), Decrease of PCr correlated wilh higher scores of Hamilton Depression Raling Scale (r= -0.75). PCr in the frontnl lobes was low in all psychiatric states in patients with bipolar lIl.1isorder. (3) Intmecllular pH was lower in cUlhymic patients with bipolnr disorder treuled wilh lithium (7.01 ::0,04. n=40) than normal controls (7.05::0.04. n=60). while it did not differ from controls in manic or depressive states. (4) The choline containing compounds (Cho) measured by I H·MRS was increased in both bipolar llnd unipolar depression in the basal ganglia. Decrease of PCr is of particular interest because PCr wns increased in the leC! frontal lobe in schizophrenia. This may provide a clue 10 clarify the biochemical dirfercnce in bipolar disorder and schizophrenia. Alteration of intracellular pH is also of interest beClluse it may rdate to cliniclli action of lithium. These findings will provide new research strategies to study the neurochemical basis of bipolar disorder. V;\'O
372. IH MRS INVESTIGATION OF PANIC DISORDER S.R. Dager l ,2, T.L. Richards l •3, K.I. Marro l ,2, W. Strauss 1•3, A. Heidi l ,3, A.A. Artrv. I,4, & S. Posses University of Washington School of Medicine, Depts. of 'psychiatry, 2Bloengineering, JRadiology, 4Aneslhesiology, Seattle, \VA 98105: ~Institut fUr Mcdizin, MR Research Cenler, JOllch, Gen11any There is increasing evidence to suggest the in.volvemcnt of bmin mechanism(s) in the ctiology of pllthological anxiety. pnrticularly panic
373. PROTON MRS OF HUMAN BASAL GANGLIA DURING ACUTE COCAINE ADMINISTRATION 2 , S.L. Rose I, J.D. Christensen.,I, MJ. Kaufmun ') 1 J.H. Mendelson-, S.E. Lukas-, C.M_Mccre.-. B.M. Cohen I, & P.F. Renshaw I
IBrnin Imaging Center und :!Akohol and Dmg Abuse Research Center. McLean Hospital. Harvard Medical School, Belmont. MA 02178
Proton mngnelic resonllnce spectroscopy ( IH Ml-I.S) wal> used to evaluatc change:; in basal gunglia chemislry occurring in response to intl1lvenous coclline administration. Twenty-seven healthy nnd neurologiclllly nonnal males, aged 28:!:5 years (melln±SD), provided lnfonncd consent to participale in lhe study. Subjects reported a history of casual cocaine use (l3:!: 14 lifetime exposures) and tested negative for tfle presence of drugs/alcohol immediately prior to the stud)'. All studies were performed using n 1.5T clinical MR scanner. PRESS localization was used to acquire 1H MRS signals from an 8 cm~ cubie volume surrounding the basal gangli:l. Unsuppressed water spcctr.t and water suppjcsscd spectra containing resonances for N·acdyi·asparlai~ (NAA). creatine+phosphocreutine (Cr), cylosolic choline-containing compounds (Cho), amI myo-inositol (Inos). Were obtained at 5 min intervals at baseline and following the inlravl!nous infusion (slow push over one minute) of placebo (n=7). 0.2 mglkg cocaine (n= 10) or 0.4 mglkg (n= 10). Following cocuinc administration, the signal intensities of aU intracellular resonances were increased in a dose·dependent manner. For the subjecls receiving placebo. the mean intensilies (::!:SD) of the resonance tines thiny minutes aner injection. expressed ali pcrcent of the baseline value were, NAA (99::8), Cho (97::!:8). Cr (l06±21), Inos (100::!::22). and water (100±2). Thirty minutes followinG the injection of 0.40 mgikg cocaine, cOfI'Csponding values were NAA (117.:!:28) Che (135::51). Cr (l12:!:24), Inos (l28±23), and water (100::2). The increases in the intracellular metabolite (N.~IA, Cho. Cr. IIml Inos) fCsonilnce intensities were all statistically Iiignilicalll. In contmst, the intensity of the water line remained constant, suggesting that cocaine