Camilo de la Fuente-Sandoval1, Francisco Reyes-Madrigal2, Xiangling Mao3, Pablo León-Ortiz4, Oscar Rodríguez-Mayoral5, Helgi Jung-Cook6, Rodolfo Solís-Vivanco7, Ariel Graff-Guerrero8, Dikoma C Shungu3. 1. Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. Electronic address: fcamilo@unam.mx. 2. Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. 3. Department of Radiology, Weill Cornell Medical College, New York, New York. 4. Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Department of Education, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. 5. Early Psychosis Intervention Department, Hospital Fray Bernardino Álvarez, Mexico City, Mexico; Palliative Care Unit, Instituto Nacional de Cancerología, Mexico City, Mexico. 6. Laboratory of Neuropsychopharmacology, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. 7. Neuropsychology Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. 8. Multimodal Neuroimaging Schizophrenia Group, Research Imaging Centre, Geriatric Mental Health Program at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND: Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. METHODS: Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. RESULTS: At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. CONCLUSIONS: The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment.
BACKGROUND: Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. METHODS: Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. RESULTS: At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. CONCLUSIONS: The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment.
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