Serum levels of interleukin 6 in schizophrenic patients during treatment augmentation with sarcosine (results of the <scp>PULSAR</scp> study)

Strzelecki, Dominik; Urban-Kowalczyk, Małgorzata; Wysokiński, Adam

doi:10.1002/hup.2652

Cited by 13 publications

(6 citation statements)

References 40 publications

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“…Evidence-based psychotherapies are broadly underutilized, 2 and existing data suggest that some dietary supplements are potentially useful and relatively safe. 2,3,4,5,24,25,26,27…”

Section: Discussionmentioning

confidence: 99%

Reimagining Roles of Dietary Supplements in Psychiatric Care

Messamore

2022

AMA Journal of Ethics

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“…Evidence-based psychotherapies are broadly underutilized, 2 and existing data suggest that some dietary supplements are potentially useful and relatively safe. 2,3,4,5,24,25,26,27…”

Section: Discussionmentioning

confidence: 99%

Reimagining Roles of Dietary Supplements in Psychiatric Care

Messamore

2022

AMA Journal of Ethics

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“…Along the same lines, a series of studies from the Polish Sarcosine Study in Schizophrenia (PULSAR) project illustrated that schizophrenic patients treated with sarcosine for 6 months displayed significant improvements in negative symptoms, general psychopathology and changes in glutamatergic transmission in the brain (190,192,193). However, no significant differences in cardiometabolic systems, body composition or neurochemical levels (e.g., BDNF, IL-6 and TNF-α) were found in PULSAR studies (191,(194)(195)(196)(197). Double-blind clinical studies revealed no beneficial effect of adjunctive sarcosine in drug-free schizophrenia patients or patients treated with clozapine (186,187,199).…”

Section: Indirect Modulation Of Nmdar Functions By Targeting Astrocytic Glyt1mentioning

confidence: 97%

Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia

et al. 2021

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Schizophrenia is a severe mental illness that affects ~1% of the world's population. It is clinically characterized by positive, negative, and cognitive symptoms. Currently available antipsychotic medications are relatively ineffective in improving negative and cognitive deficits, which are related to a patient's functional outcomes and quality of life. Negative symptoms and cognitive deficits are unmet by the antipsychotic medications developed to date. In recent decades, compelling animal and clinical studies have supported the NMDA receptor (NMDAR) hypofunction hypothesis of schizophrenia and have suggested some promising therapeutic agents. Notably, several NMDAR-enhancing agents, especially those that function through the glycine modulatory site (GMS) of NMDAR, cause significant reduction in psychotic and cognitive symptoms in patients with schizophrenia. Given that the NMDAR-mediated signaling pathway has been implicated in cognitive/social functions and that GMS is a potential therapeutic target for enhancing the activation of NMDARs, there is great interest in investigating the effects of direct and indirect GMS modulators and their therapeutic potential. In this review, we focus on describing preclinical and clinical studies of direct and indirect GMS modulators in the treatment of schizophrenia, including glycine, D-cycloserine, D-serine, glycine transporter 1 (GlyT1) inhibitors, and D-amino acid oxidase (DAO or DAAO) inhibitors. We highlight some of the most promising recently developed pharmacological compounds designed to either directly or indirectly target GMS and thus augment NMDAR function to treat the cognitive and negative symptoms of schizophrenia. Overall, the current findings suggest that indirectly targeting of GMS appears to be more beneficial and leads to less adverse effects than direct targeting of GMS to modulate NMDAR functions. Indirect GMS modulators, especially GlyT1 inhibitors and DAO inhibitors, open new avenues for the treatment of unmet medical needs for patients with schizophrenia.

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“…Several studies investigated sarcosine augmentation efficacy in schizophrenia patients [ 224 , 225 , 312 , 347 , 350 , 352 , 353 , 354 ]. The addition of sarcosine (2 g/day) to antipsychotic medications, including risperidone [ 350 ] and other atypicals [ 225 ] but not clozapine [ 347 ], was found to benefit schizophrenia patients.…”

Section: Other Modulators Of the Glycine B Site At Nmdarmentioning

confidence: 99%

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics

et al. 2022

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Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical–subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30–40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics’ effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.

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Serum levels of interleukin 6 in schizophrenic patients during treatment augmentation with sarcosine (results of the PULSAR study)

Abstract: Sarcosine does not significantly affect IL-6 concentrations but IL-6 may be involved in mechanisms related to the presence of positive symptoms.

Cited by 13 publications

References 40 publications

Reimagining Roles of Dietary Supplements in Psychiatric Care

Reimagining Roles of Dietary Supplements in Psychiatric Care

Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics

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