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Changes in brain glutamate correlate with antidepressant response to total sleep deprivation: a 3 T 1H-MRS study
Clinical Neuropsychopharmacology syndrome in psychosis. This effect seems to be more important in male than in female patients.
References [1] Cota, D., Marsicano, G., Lutz, B., Vicennati, V., Stalla, G.K., Pasquali, R., Pagotto, U., 2003. Endogenous cannabinoid system as modulator of food intake. Int J Obesity 27, 289 301. [2] Broome, M.R., Woolley, J.B., Tabraham, O., Jhons, L.C., Bramon, E., Murray, G.K., Pariante, C.M., McGuire, RK., and Murray, R.M., 2005. What causes the onset of psychosis? Schizophr Res 79(1), 23-34. [3] Meyer, J.M., and Koro, C.E., 2004. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res 70(1), 1-17.
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Changes in brain glutamate correlate with antidepressant response to total sleep deprivation: a 3T 1H-MRS study
A. Bernasconi 1, G. Calabrese 1, E Benedetti 1, D. Radaelli 1, S. Dallaspezia 1, A. Falini 1, C. Colombo 1, M. Cadioli 1, G. Scotti 1, E. Smeraldi 1. IlRCCS Ospedale
San Raffaele, Psychiatry & Neuroradiology, Milan, Italy Glutamate (GLU) is the primary excitatory neurotransmitter of the human brain. Despite this predominant role, little is known about glutamatergic neurotransmission in mood disorders. Single-proton magnetic resonance spectroscopy (1H-MRS) allowed to start the study of the relative levels of brain GLU in mood disordered patients. Probably because of major methodological discrepancies, available studies are far from being consistent with each other. These contrasting results warranted interest for the study of glutamatergic neurotransmission in mood disorders, but led to contrasting hypotheses linking depression with a hyperglutamatergic activity, or conversely with a hypoglutamatergic activity, to be corrected by successful antidepressant treatment; and linking the observed dysfunctions in brain GLU to the mood illness, or to the effects of drugs. Aim: To investigate the possible correlation between brain biochemistry in specific areas and the clinical response to total sleep deprivation (TSD) in a sample of patients affected by bipolar depression. Method: We studied 19 patients with a diagnosis of bipolar disorder type I, depressive episode without psychotic features. 1H-MRS data were acquired on a 3 Tesla magnet before and after sleep deprivation treatment using a PRESS sequence (TR 2000ms, TE 30ms). A single VOI was positioned at the level of the anterior cingulate on the basis of previous literature data. Proton
$69
spectra were processed by an operator blind to the treatment status, using jMRUI program by appplication of 4Hz Gaussian apodization, Fourier transform and automatic zero-order phase correction. An automated curve fitting procedure was used for the following peak: creatine-phosphocreatin (Cr) at 3.0 ppm, GLU at 2.35 ppm. Peak assignment for GLU was done according to the criteria described by Hurd et al. (2004). Peak integral ratio for Glu/Cr was calculated. Mood was rated before and after the TSD treatment by administering in the morning a modified version of the 21-item HDRS (HDRS-NOW). In the same days selfratings of perceived mood levels were assessed by a selfadministered visual analogue scale (VAS). Results: Individual variability in the effect of treatment on GLU/Cr ratio was significantly correlated with the individual variability in the clinical effect of treatment: higher decrease in GLU/Cr, better decrease in depressive symptomatology on both objective (Delta HDRS scores: r=0.534, p=0.022) and self-rated (Delta VAS scores: r = 0.470, p = 0.049) measures of depression. Results were confirmed when stratifying the sample according to a categorical criterium of benefit (HDRS score reduction of at least 30%): patients who had some benefit (n = 14) had an higher decrease in glutamate than patients who did not (n=4) (p=0.023). Conclusions: The core finding of the present study is that a decrease in brain GLU levels is a neurometabolic correlate of antidepressant response to cronotherapeutic treatment of bipolar depression. This finding is in agreement with previous studies that found that brain GLU levels were higher than normal in bipolar disorder and that lithium decreases them in bipolar patients (Friedman et al., 2004).
References [1] Hurd R, Sailasuta N, Srinivasan R, Vigneron DB, Pelletier D, Nelson SJ, 2004. Measurement of brain glutamate using TE-averaged PRESS at 3 T. Magn Reson Med 51(3), 435-40. [2] Friedman SD, Dager SR, Parow A, Hirashima F, Demopulos C, Stoll AL, Lyoo IK, Dunner DL, Renshaw PF, 2004. Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder. Biol Psychiatr 2004 56(5), 340-8.
References [1] Cota, D., Marsicano, G., Lutz, B., Vicennati, V., Stalla, G.K., Pasquali, R., Pagotto, U., 2003. Endogenous cannabinoid system as modulator of food intake. Int J Obesity 27, 289 301. [2] Broome, M.R., Woolley, J.B., Tabraham, O., Jhons, L.C., Bramon, E., Murray, G.K., Pariante, C.M., McGuire, RK., and Murray, R.M., 2005. What causes the onset of psychosis? Schizophr Res 79(1), 23-34. [3] Meyer, J.M., and Koro, C.E., 2004. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res 70(1), 1-17.
F•-•
Changes in brain glutamate correlate with antidepressant response to total sleep deprivation: a 3T 1H-MRS study
A. Bernasconi 1, G. Calabrese 1, E Benedetti 1, D. Radaelli 1, S. Dallaspezia 1, A. Falini 1, C. Colombo 1, M. Cadioli 1, G. Scotti 1, E. Smeraldi 1. IlRCCS Ospedale
San Raffaele, Psychiatry & Neuroradiology, Milan, Italy Glutamate (GLU) is the primary excitatory neurotransmitter of the human brain. Despite this predominant role, little is known about glutamatergic neurotransmission in mood disorders. Single-proton magnetic resonance spectroscopy (1H-MRS) allowed to start the study of the relative levels of brain GLU in mood disordered patients. Probably because of major methodological discrepancies, available studies are far from being consistent with each other. These contrasting results warranted interest for the study of glutamatergic neurotransmission in mood disorders, but led to contrasting hypotheses linking depression with a hyperglutamatergic activity, or conversely with a hypoglutamatergic activity, to be corrected by successful antidepressant treatment; and linking the observed dysfunctions in brain GLU to the mood illness, or to the effects of drugs. Aim: To investigate the possible correlation between brain biochemistry in specific areas and the clinical response to total sleep deprivation (TSD) in a sample of patients affected by bipolar depression. Method: We studied 19 patients with a diagnosis of bipolar disorder type I, depressive episode without psychotic features. 1H-MRS data were acquired on a 3 Tesla magnet before and after sleep deprivation treatment using a PRESS sequence (TR 2000ms, TE 30ms). A single VOI was positioned at the level of the anterior cingulate on the basis of previous literature data. Proton
$69
spectra were processed by an operator blind to the treatment status, using jMRUI program by appplication of 4Hz Gaussian apodization, Fourier transform and automatic zero-order phase correction. An automated curve fitting procedure was used for the following peak: creatine-phosphocreatin (Cr) at 3.0 ppm, GLU at 2.35 ppm. Peak assignment for GLU was done according to the criteria described by Hurd et al. (2004). Peak integral ratio for Glu/Cr was calculated. Mood was rated before and after the TSD treatment by administering in the morning a modified version of the 21-item HDRS (HDRS-NOW). In the same days selfratings of perceived mood levels were assessed by a selfadministered visual analogue scale (VAS). Results: Individual variability in the effect of treatment on GLU/Cr ratio was significantly correlated with the individual variability in the clinical effect of treatment: higher decrease in GLU/Cr, better decrease in depressive symptomatology on both objective (Delta HDRS scores: r=0.534, p=0.022) and self-rated (Delta VAS scores: r = 0.470, p = 0.049) measures of depression. Results were confirmed when stratifying the sample according to a categorical criterium of benefit (HDRS score reduction of at least 30%): patients who had some benefit (n = 14) had an higher decrease in glutamate than patients who did not (n=4) (p=0.023). Conclusions: The core finding of the present study is that a decrease in brain GLU levels is a neurometabolic correlate of antidepressant response to cronotherapeutic treatment of bipolar depression. This finding is in agreement with previous studies that found that brain GLU levels were higher than normal in bipolar disorder and that lithium decreases them in bipolar patients (Friedman et al., 2004).
References [1] Hurd R, Sailasuta N, Srinivasan R, Vigneron DB, Pelletier D, Nelson SJ, 2004. Measurement of brain glutamate using TE-averaged PRESS at 3 T. Magn Reson Med 51(3), 435-40. [2] Friedman SD, Dager SR, Parow A, Hirashima F, Demopulos C, Stoll AL, Lyoo IK, Dunner DL, Renshaw PF, 2004. Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder. Biol Psychiatr 2004 56(5), 340-8.