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

Bustillo, Juan; Rowland, Laura M.; Jung, Rex E.; Brooks, William M.; Qualls, Clifford; Hammond, Roger; Hart, Blaine L.; Lauriello, John

doi:10.1038/sj.npp.1301631

Cited by 68 publications

(81 citation statements)

References 48 publications

(59 reference statements)

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“…We observed an effect of treatment irrespective of antipsychotic for NAA, Glx and Creatine, but this appears to be caused by higher doses pretreatment with other antipsychotics, as results disappeared after correction for baseline haloperidol equivalents. Other studies have also failed to show an effect of treatment on prefrontal NAA levels with both strong and weak D2 antagonists in recently medicated patients [37][38][39]. It has been reported that NAA did initially not decrease after treatment [34], but eventually did after multiple years [33], although the authors could not confirm whether these effects were specific to antipsychotic exposure.…”

Section: Researchcontrasting

confidence: 46%

The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

Liemburg¹,

Sibeijn-Kuiper²,

Knegtering³

et al. 2018

Neuropsychiatry

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ObjectiveGiven that aripiprazole acts as a partial agonist on the dopamine receptor, it may have unique effects on brain neuro-metabolism, specifically in the prefrontal cortex. In this exploratory study, we investigated the effect of aripiprazole compared to risperidone on prefrontal metabolite levels (Glx, NAA, Creatine, Choline and myo-Inositol) and changes in gray and white matter volume (GMV and WMV) in patients with a psychotic disorder. We hypothesized that patients treated with aripiprazole would show increased levels of Glx and NAA and preserved brain volumes, in contrast to risperidone. MethodsIn this randomized, single blind study, patients (n=24) treated with either risperidone or aripiprazole underwent magnetic resonance spectroscopy ( 1 H-MRS) and high-resolution anatomical scans (3T) at baseline and after 9 weeks. LC Model was used to determine the absolute spectral metabolite levels and SPM12 was to perform voxel based morphometry analyses. Both metabolite levels and brain volumes were compared between treatment groups. ResultsWe found a trend for a different effect of both antipsychotics on Glx levels, whereby risperidone reduced Glx levels compared to aripiprazole. Moreover, patients treated with aripiprazole showed a decreased GMV in the precentral gyrus, caudate and lateral frontal regions and increased WMV in the precentral gyrus and a non-significant but consistent pattern of prefrontal WM increases, in contrast to risperidone. ConclusionOur results point to possibility of different effects of aripiprazole on brain volume and metabolism compared to risperidone. Studies in larger samples are needed to shed more light on the robustness and nature of such differences.

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Section: Researchcontrasting

confidence: 46%

The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

Liemburg¹,

Sibeijn-Kuiper²,

Knegtering³

et al. 2018

Neuropsychiatry

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“…Although some markers (e.g., NAA) (Bustillo et al 2008) have been measured repeatedly, to date no studies have assessed the trajectory of neurobiological markers specifically associated with a psychotic episode and subsequent remission. The challenge for future research is to characterise the nature of brain trajectories (e.g., linear v. non-linear; acute v. gradual) occurring across the stages and phases of schizophrenia psychoses as well as in the context of neurodevelopment.…”

Section: A Guide For Future Imaging Workmentioning

confidence: 99%

Using longitudinal imaging to map the ‘relapse signature’ of schizophrenia and other psychoses

Cropley

Pantelis

2014

Epidemiol Psychiatr Sci

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Brain imaging studies in schizophrenia have typically involved single assessment and cross-sectional designs, while longitudinal studies rarely incorporate more than two time points. While informative, these studies do not adequately capture potential trajectories of neurobiological change, particularly in the context of a changing clinical picture. We propose that the analysis of brain trajectories using multiple time points may inform our understanding of the illness and the effect of treatment. This paper makes the case for frequent serial neuroimaging across the course of schizophrenia psychoses and its application to active illness epsiodes to provide a detailed examination of psychosis relapse and remission. First published online 22 May 2014Key words: Biomarkers, brain trajectories, inflammation, neurodevelopment, neuroimaging, psychosis relapse, psychosis remission.Over the past three decades, there has been much effort towards identifying neurobiological abnormalities in schizophrenia. Part of the appeal of neuroimaging is that it bridges the gap between psychiatry and the rest of medicine, and offers the potential for applying objective biological markers (biomarkers), rather than clinical history alone, to the diagnosis and clinical management of the illness. Nevertheless, despite three decades of research, neuroimaging has been limited in the extent to which it has improved our understanding of the pathophysiology of schizophrenia and is yet to have a major impact clinically.The large bulk of neuroimaging studies in schizophrenia and psychosis have involved cross-sectional comparisons between patients at various illness stages and healthy controls at a single point in time. Such studies have typically assessed regional grey matter or whole brain volume, although more recent studies have examined functional (i.e., functional magnetic resonance imaging (fMRI)) and neurochemical alterations including in N-acetyl-aspartate (NAA) (Kraguljac et al. 2012), glutamate (GLU) and dopamine (Urban & Abi-Dargham, 2010). Although abnormalities in these systems have been identified, the use of single assessments provides a simple snapshot in time and ignores the importance of the trajectory of change ). The importance of assessing the course of change is illustrated in Fig. 1a, in three hypothetical neurobiological (e.g., cognitive, imaging) outcomes (figure modified from Testa & Pantelis, 2009). For instance, patients and controls may not differ on a cognitive or neuroimaging outcome at a particular time point, despite each having a distinct developmental course (e.g., lag, arrest, degeneration). Furthermore, the timing of the imaging scan may influence the degree of difference in a neuroimaging outcome between patients and controls. Although individuals may follow the same 'course', they could have very different outcomes if they were all assessed at various points along their trajectory. We suggest that the analysis of brain trajectories may be more informative in delineating different populations of individuals ...

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“…There were no differences in gray matter, white matter, and cerebrospinal fluid (CSF) proportions at each time point between cytidine and placebo groups. Metabolite concentrations were arithmetically corrected for voxel CSF proportion assuming a metabolite concentration of zero in CSF (Bustillo et al, 2008;McLean et al, 2001).…”

Section: Mri/mrs Acquisition and Processingmentioning

confidence: 99%

Decreased Glutamate/Glutamine Levels May Mediate Cytidine’s Efficacy in Treating Bipolar Depression: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

Yoon

Lyoo

Haws

et al. 2009

Neuropsychopharmacol

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Targeting the glutamatergic system has been suggested as a promising new option for developing treatment strategies for bipolar depression. Cytidine, a pyrimidine, may exert therapeutic effects through a pathway that leads to altered neuronal-glial glutamate cycling. Pyrimidines are also known to exert beneficial effects on cerebral phospholipid metabolism, catecholamine synthesis, and mitochondrial function, which have each been linked to the pathophysiology of bipolar depression. This study was aimed at determining cytidine's efficacy in bipolar depression and at assessing the longitudinal effects of cytidine on cerebral glutamate/glutamine levels. Thirty-five patients with bipolar depression were randomly assigned to receive the mood-stabilizing drug valproate plus either cytidine or placebo for 12 weeks. Midfrontal cerebral glutamate/glutamine levels were measured using proton magnetic resonance spectroscopy before and after 2, 4, and 12 weeks of oral cytidine administration. Cytidine supplementation was associated with an earlier improvement in depressive symptoms (weeks 1-4; p ¼ 0.02, 0.001, 0.002, and 0.004, respectively) and also produced a greater reduction in cerebral glutamate/glutamine levels in patients with bipolar depression (weeks 2, 4, and 12; p ¼ 0.004, 0.004, and 0.02, respectively). Cytidinerelated glutamate/glutamine decrements correlated with a reduction in depressive symptoms (p ¼ 0.001). In contrast, these relationships were not observed in the placebo add-on group. The study results suggest that cytidine supplementation of valproate is associated with an earlier treatment response in bipolar depression. Furthermore, cytidine's efficacy in bipolar depression may be mediated by decreased levels of cerebral glutamate and/or glutamine, consistent with alterations in excitatory neurotransmission.

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

Cited by 68 publications

References 48 publications

The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

Using longitudinal imaging to map the ‘relapse signature’ of schizophrenia and other psychoses

Decreased Glutamate/Glutamine Levels May Mediate Cytidine’s Efficacy in Treating Bipolar Depression: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

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