Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

Abstract

Studies with proton magnetic resonance spectroscopy (MRS) have reported abnormalities in N-acetyl-aspartate (NAA), amino acids (AA) and choline (Cho) to creatine (Cr) ratios associated with schizophrenia. We report data on the three ratios in a sample of 18 neuroleptic naive patients with first-episode schizophrenia (eight studied in the dorsolateral prefrontal and 10 in the midtemporal lobe) and 24 healthy controls (14 studied in prefrontal and 10 in midtemporal lobes). Frontal lobe proton spectra were acquired with the stimulated-echo acquisition mode (STEAM) pulse sequence (echo time 21 ms, repetition time 2 s). Temporal lobe proton spectra were acquired with the point-resolved spectroscopy (PRESS) pulse sequence (echo time 16-21 ms, repetition time 2 s). Upon comparison with KEY WORDS : Schizophrenia; Proton magnetic resonance spectroscopyMagnetic resonance imaging (MRI) and spectroscopy (MRS) provide noninvasive, risk-free methods with which to study the origins and the time course of progression of neuropsychiatric disorders. The development of spatial localization methods, which sample the relative levels of mobile metabolites from a volume of tissue defined from an MR image, has provided a basis for integrating the biochemical information obtained by MRS with the anatomical and pathological information obtained from MRI. In vivo MRS studies of schizophrenia have examined two primary nuclei, phosphorus (Calabrese et al. 1992;Deicken et al. 1995;Keshavan et al. 1993;Pettegrew et al. 1993Pettegrew et al. , 1995Pettegrew et al. , 1991Shioiri et al. 1994;Stanley et al. 1995b;Stanley et al. 1994) and proton (Bertolino et al. 1996, Buckley et al. 1994Choe et al. 1994;Fukuzako et al. 1995;Nasrallah et al. 1994;Radda and Taylor 1985;Stanley et al. 1996;Yurgelun-Todd et al. 1996;Yurgelun-Todd et al. 1993). Phosphorus MRS can detect alterations in the levels of compounds involved in the bioenergetics of cellular metabolism, such as inorganic phosphate, adenosine triphosphate (ATP), and phosphocreatine. Additional composite resonances from phosphorus monoesters (PME) and phosphorus diesters (PDE) can also be detected. Phosphorus MRS in schizophrenia research has revealed abnormalities with high-energy phosphates as well as alterations in membrane phospholipid metabolism (Pettegrew et al. 1995 (Birken and Oldendorf 1989), NAA/Cr levels may reflect neuronal viability and integrity. Creatine is a compound involved in the regulation of cellular energy metabolism. The creatine resonance observed by proton MRS, is a combination of creatine and phosphocreatine. Trimethyl ammonium residues primarily representing choline are detected with MRS. The choline resonance is a composite of a number of choline-containing compounds. These include phosphocholine, glycerophosphocholine, acetylcholine, and cytidine diphosphate choline, as well as choline itself. However, the most prominent form of choline in the brain, phosphatidylcholine, is, for the most part, not detected by MRS because of its restricted immobile form . Choline level...

Proton magnetic resonance spectroscopy of the frontal lobe in schizophrenics: a critical review of the methodology

“…The alterations most often found in the overall comparison of patients with healthy volunteers were a decrease of the NAA/Cr ratio [17][18][23][24][25][26][27][28][29] and of the NAA absolute value 19,30,31 . Regarding subgroup comparisons, Heimberg et al 32 , Bustillo et al 33 and Ende et al 34 found NAA differences between schizophrenics treated with atypical anti-psychotics as compared to schizophrenics under typical neuroleptics, and between each subgroup and its control.…”

“…Three of them used schizophrenic patients under no medication and, two of the studies were longitudinal. Cecil et al 25 and Choe et al 17 studied non-medicated patients and found NAA/Cr decrease. However, Bartha et al 42 did not find any NAA alteration in non-medicated schizophrenics.…”

“…Among 16 [18][19][22][23][24][25][26][28][29][30]34,[44][45][46][47][48] articles that have evaluated bilateral frontal lobe, in ten [18][19][22][23][24][25][26][28][29]34 the abnormalities were the same bilaterally and in two 30,47 studies NAA differences were found only on the left side. In the other four [44][45][46]48 studies no differences were found.…”

“…When only one side was selected, the left frontal lobe was clearly preferred for investigation (N= 10 4,27,31-33,37-38,41-43 ) as compared to the right frontal lobe (N=1 17 ). There were NAA abnormalities in 18 4,[18][19][22][23][24][25][26][27][28][29][30][31][32][33][34]38,47 (69%) out of 26 articles that evaluated the left side, whereas NAA differences occurred in 11 [17][18][19][22][23][24][25][26][28][29]34 (64%) out of 17 articles that studied the right side. Therefore, these results suggest that the NAA abnormalities in the frontal lobe are not influenced by brain laterality.…”

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

“…A decrease (22%) in creatine kinase activity was found in schizophrenia (3), an enzyme critical for maintaining stable adenosine triphosphate (ATP) levels during altered neuronal activity (3, 17, 18). Other MRS studies in medication naïve patients suggest that decreases in the availability of high-energy phosphates may be a core feature of the illness (19-21). …”