Selective deficit of hippocampal N-acetylaspartate in antipsychotic-naive patients with schizophrenia

Fannon, Dominic; Simmons, Andrew; Tennakoon, Lakshika; O’Ceallaigh, S.; Sumich, Alexander; Doku, V.; Shew, Carl; Sharma, Tonmoy

doi:10.1016/s0006-3223(03)00185-9

Cited by 63 publications

(63 citation statements)

References 48 publications

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“…Choe et al (1996) found low frontal NAA/Cre at baseline with no further reductions after naturalistic treatment with typical and atypical agents (follow-up 1-6 months). Fannon et al (2003) reported reduced medial temporal NAA/Cre at baseline which was no longer statistically different from healthy subjects after 3 months of atypical antipsychotic treatment. In a study of chronically ill patients, Bertolino et al (2001) reported higher NAA/Cre in the dorsolateral prefrontal cortex in subjects treated with atypical antipsychotic medication compared to when they were medication free for at least 2 weeks.…”

Section: Discussionmentioning

confidence: 83%

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Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Bustillo

Rowland

Jung

et al. 2007

Neuropsychopharmacol

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Reduced brain N-acetyl-aspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. We studied 32 minimally treated schizophrenia patients and 21 healthy subjects with single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS) of the frontal and occipital lobes, caudate nucleus, and cerebellum. Concentrations of NAA, Choline, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind manner with either haloperidol or quetiapine. 1 H-MRS was repeated every 6 months for up to 2 years. There was a group main effect for baseline NAA with lower global NAA in schizophrenia subjects before treatment compared to healthy controls. Global NAA was directly related to measures of global cognitive performance in the whole subject sample. Following treatment with haloperidol or quetiapine, there were no changes in NAA in any of the regions studied. Early in the illness, schizophrenia patients already demonstrate subtle reductions in NAA. Treatment with typical or atypical antipsychotic medications for several months does not result in NAA changes.

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Section: Discussionmentioning

confidence: 83%

“…Of these, Choe et al (1996) found no changes in NAA with treatment, whereas Fannon et al (2003) found evidence that atypical antipsychotic treatment was associated with an increase in NAA. Our preliminary report (10 schizophrenia patients from the current sample) suggested NAA reductions with antipsychotic treatment (Bustillo et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Bustillo

Rowland

Jung

et al. 2007

Neuropsychopharmacol

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“…There is recent evidence that treatment with antipsychotic medication can have an effect on NAA levels in SZ patients (Fannon et al, 2003;Bertolino et al, 2001). Patients treated with atypical antipsychotics had higher levels of NAA in hippocampus than did patients treated with haloperidol (Fannon et al, 2003).…”

Section: White Mattermentioning

confidence: 99%

“…Patients treated with atypical antipsychotics had higher levels of NAA in hippocampus than did patients treated with haloperidol (Fannon et al, 2003). A longitudinal within-subjects design was used to evaluate 23 chronic SZ patients, first when they were drug free (either drug naïve or off medication for at least 2 weeks), then again after they had been stably medicated for at least 4 weeks.…”

Section: White Mattermentioning

confidence: 99%

Measurement of Brain Metabolites by 1H Magnetic Resonance Spectroscopy in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

Steen

Hamer

Lieberman

2005

Neuropsychopharmacol

245

183

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A systematic review of the literature identified 64 published English-language papers that used proton ( 1 H) magnetic resonance spectroscopy to measure N-acetylaspartate (NAA) concurrently in healthy controls and in patients with a diagnosis of schizophrenia (SZ). A total of 1209 controls and 1256 patients have been evaluated, with 88% of studies carried out at 1.5 T field strength, and 77% of studies focused on patients with chronic SZ. There is consistent evidence that NAA is reduced in a broad range of tissues in the SZ brain. Broad consensus (X10 studies) is emerging that NAA levels are reduced X5% in hippocampus and in both cortical gray matter (GM) and white matter (WM) of the frontal lobe. There is no evidence to support a hypothesis that relative NAA levels are reduced to a different degree in frontal lobe GM and WM, nor is there robust evidence of a difference in NAA levels between patients with firstepisode and chronic SZ. Study reliability may be a problem, as most studies appear to be underpowered. With simple assumptions about the inherent difference in NAA levels between patients and controls, it can be calculated that a minimum sample size of approximately 39 patients and 39 controls is required for acceptable statistical power. Only three of 64 studies included enough subjects to have 80% power to detect a 10% NAA reduction in patients, and no studies were adequately powered to detect a 5% NAA reduction with 80% power.

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“…Similarly, several studies reported decreased hippocampal NAA levels (4), and a few studies reported unaltered NAA levels in chronic patients (13,14) and in medicated and unmedicated FEPs (15)(16)(17). Contrasting the above results, FEPs and drug-naive schizophrenia patients showed decreased hippocampal NAA/Cre ratios compared to medicated FEP (18).…”

Section: Introductionmentioning

confidence: 82%

1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia patients

Kirtaş¹,

Karadağ²,

Şengül³

et al. 2016

Turk J Med Sci

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Selective deficit of hippocampal N-acetylaspartate in antipsychotic-naive patients with schizophrenia

Cited by 63 publications

References 48 publications

Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Measurement of Brain Metabolites by 1H Magnetic Resonance Spectroscopy in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia patients

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