Alterations in Brain High-Energy Phosphate and Membrane Phospholipid Metabolism in First-Episode, Drug-Naive Schizophrenics

Pettegrew, Jay W.; Keshavan, Matcheri S.; Panchalingam, K.; Strychor, Sandra; Kaplan, David B.; Tretta, Marjorie; Allen, Maureen

doi:10.1001/archpsyc.1991.01810300075011

Cited by 457 publications

(112 citation statements)

References 46 publications

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“…Kraepelin (1919) originally proposed that schizophrenia 'attacks by preference the prefrontal cortex'. Interest in the role of the prefrontal cortex (PFC) in pathophysiology of schizophrenia has been rekindled by observations of consistently reduced metabolism in this region ('hypofrontality') from a variety of approaches, including positron emission tomography (PET) studies (Buchsbaum, 1993), single photon emission tomography (SPECT) studies (Andreasen et al 1992), magnetic resonance spectroscopy (MRS) studies (Pettegrew et al 1991), and electrophysiological studies of cortical coherence (Hoffman et al 1991). The PFC is the site of most intense cortical brain activity during the awake state in normal humans, and the reverse is true during SWS.…”

Section: Slow-wave Sleepmentioning

confidence: 99%

Sleep abnormalities in schizophrenia: pathophysiological significance

Keshavan¹,

Tandon²

1993

Psychol. Med.

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Section: Slow-wave Sleepmentioning

confidence: 99%

Sleep abnormalities in schizophrenia: pathophysiological significance

Keshavan¹,

Tandon²

1993

Psychol. Med.

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“…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). …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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Schizophrenia is a devastating illness that affects over 2 million people in the U.S. and costs society billions of dollars annually. New insights into the pathophysiology of schizophrenia are needed to provide the conceptual framework to facilitate development of new treatment strategies. We examined bioenergetic pathways in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and control subjects using western blot analysis, quantitative real-time polymerase chain reaction, and enzyme/substrate assays. Laser-capture microdissection-qPCR was used to examine these pathways at the cellular level. We found decreases in hexokinase (HXK) and phosphofructokinase (PFK) activity in the DLPFC, as well as decreased PFK1 mRNA expression. In pyramidal neurons, we found an increase in monocarboxylate transporter 1 mRNA expression, and decreases in HXK1, PFK1, glucose transporter 1 (GLUT1), and GLUT3 mRNA expression. These results suggest abnormal bioenergetic function, as well as a neuron-specific defect in glucose utilization, in the DLPFC in schizophrenia.

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“…Alterations in phosphodiesters have also been reported in patients with schizophrenia (107)(108)(109)(110)(111), but with some studies in disagreement (112)(113)(114)(115). As discussed by Stanley (102), some of the variability may arise from differing detection efficiencies of broad vs narrow phosphodiester peaks.…”

mentioning

confidence: 99%

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Mason

Krystal

2006

NMR Biomed.

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Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.

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Alterations in Brain High-Energy Phosphate and Membrane Phospholipid Metabolism in First-Episode, Drug-Naive Schizophrenics

Cited by 457 publications

References 46 publications

Sleep abnormalities in schizophrenia: pathophysiological significance

Sleep abnormalities in schizophrenia: pathophysiological significance

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

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

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