A pilot double-blind comparison of d-serine and high-dose olanzapine in treatment-resistant patients with schizophrenia

Ermilov, Marina; Gelfin, Evgenia; Levin, Raz; Lichtenberg, Pesach; Hashimoto, Kenji; Javitt, Daniel C.; Heresco-Levy, Uriel

doi:10.1016/j.schres.2013.09.018

Cited by 31 publications

(27 citation statements)

References 9 publications

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“…Very interestingly, a recent double-blind, placebo-controlled, randomized study showed that D-serine (60 mg/kg/day for 16 weeks) could prevent the conversion to psychosis in individuals at clinical high risk of schizophrenia52. These findings make D-serine an attractive prophylactic amino acid for early intervention in the onset of schizophrenia53, mainly because D-serine is effective for treating several symptoms in schizophrenia24252627282952.…”

Section: Discussionmentioning

confidence: 99%

“…First, there are reports showing lower levels of D-serine in the blood, cerebrospinal fluid (CSF), and postmortem brain tissue from patients with schizophrenia, relative to normal controls181920212223. Secondly, treatment with D-serine is beneficial for alleviating several symptoms associated with schizophrenia242526, even in treatment-resistant disease2728. Meta-analyses support these findings that D-serine is effective in treating schizophrenia2930, although D-serine is not approved as therapeutic drug for schizophrenia.…”

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confidence: 99%

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Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

Fujita

Ishima

Hashimoto

2016

Sci Rep

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Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus. Supplementing drinking water with D-serine (600 mg/L from P28 to P56) prevented the onset of cognitive deficits in adult offspring after MIA, in a significant manner. This study shows that supplementing offspring with D-serine during juvenile and adolescent stages could prevent the onset of psychosis in adulthood, after MIA. Therefore, early intervention with D-serine may prevent the occurrence of psychosis in high-risk subjects.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

Fujita

Ishima

Hashimoto

2016

Sci Rep

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“…Serum D-serine is typically reduced in adults with schizophrenia (Hashimoto et al, 2003; Calcia et al, 2012), and a recent meta-analysis found that serum levels of total serine are elevated in adults with schizophrenia (Brouwer et al, 2013). In addition, D-serine has been investigated as a monotherapy (Ermilov et al, 2013) and as adjunctive therapy (Heresco-Levy et al, 2005) in treatment-refractory adults with schizophrenia and found to be helpful in relieving negative symptoms.…”

Section: 0 1h-mrs In Schizophreniamentioning

confidence: 99%

In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: Application to schizophrenia

Wijtenburg

Yang

Fischer

et al. 2015

Neuroscience & Biobehavioral Reviews

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In vivo measurement of neurotransmitters and modulators is now feasible with advanced proton magnetic resonance spectroscopy (1H-MRS) techniques. This review provides a basic tutorial of MRS, describes the methods available to measure brain glutamate, glutamine, γ-aminobutyric acid, glutathione, N-acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3Tesla or higher, and summarizes the neurochemical findings in schizophrenia. Overall, 1H-MRS holds great promise for producing biomarkers that can serve as treatment targets, prediction of disease onset, or illness exacerbation in schizophrenia and other brain diseases.

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“…In a preliminary four week open-label study [65], it was shown that high dose DSR (≥60 mg/kg/day) improves neurocognitive functions as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. An additional controlled pilot investigation [93] compared the effectiveness of DSR (3 g/day) versus high-dose olanzapine (30 mg/day) as antipsychotic monotherapy in 18 treatment-resistant schizophrenia patients. The primary LOCF analysis indicated a lack of efficacy of DSR as compared to high-dose olanzapine ( Figure 3).…”

Section: Schizophreniamentioning

confidence: 99%

“…A potential concern with DSR use is nephrotoxicity [94,95] which has been reported in one patient receiving 120 mg/kg/day and resolved following DSR discontinuation [65]. This apparent paucity of side effects seems remarkable in view of the fact that both acute [65,96] and chronic [62,88,93] administration of 1-2 g DSR results in ≥100 times increases in DSR serum levels. Nevertheless, orally administered DSR is substantially metabolized by DAAO diminishing its bioavailability and necessitating the administration of gram level doses.…”

Section: Schizophreniamentioning

confidence: 99%

D-Serine in Neuropsychiatric Disorders: New Advances

Durrant

Heresco-Levy

2014

Advances in Psychiatry

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D-Serine (DSR) is an endogenous amino acid involved in glia-synapse interactions that has unique neurotransmitter characteristics. DSR acts as obligatory coagonist at the glycine site associated with the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) and has a cardinal modulatory role in major NMDAR-dependent processes including NMDAR-mediated neurotransmission, neurotoxicity, synaptic plasticity, and cell migration. Since either over-or underfunction of NMDARs may be involved in the pathophysiology of neuropsychiatric disorders; the pharmacological manipulation of DSR signaling represents a major drug development target. A first generation of proof-of-concept animal and clinical studies suggest beneficial DSR effects in treatmentrefractory schizophrenia, movement, depression, and anxiety disorders and for the improvement of cognitive performance. A related developing pharmacological strategy is the indirect modification of DSR synaptic levels by use of compounds that alter the function of main enzymes responsible for DSR production and degradation. Accumulating data indicate that, during the next decade, we will witness important advances in the understanding of DSR role that will further contribute to elucidating the causes of neuropsychiatric disorders and will be instrumental in the development of innovative treatments.

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A pilot double-blind comparison of d-serine and high-dose olanzapine in treatment-resistant patients with schizophrenia

Cited by 31 publications

References 9 publications

Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: Application to schizophrenia

D-Serine in Neuropsychiatric Disorders: New Advances

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