Is a Neuroprotective Therapy Suitable for Schizophrenia Patients?

  • Michael S. RitsnerEmail author


Schizophrenia is a chronic and disabling mental disorder characterized by positive, negative and mood symptoms, disturbed coping abilities with elevated distress and a significant decline in cognition, quality of life and psychosocial functioning. About one-third of all patients with schizophrenia do not respond adequately to drug treatment. Today neuroscience and clinical research have sufficiently advanced to introduce a novel generation of compounds with neuroprotective properties. The use of neuroprotective agents in schizophrenia is not yet significantly established. An in-depth review of new compounds such as neurosteroids, estrogen, omega-3 fatty acids, S-adenosylmethionine, cannabinoids, piracetam, modafinil, L-theanine, bexarotene with neuroprotective properties is discussed. The mechanisms underlying the neuroprotective effects of these compounds vary and differ from classically defined dopamine and serotonin receptors. This review highlights selective evidence supporting a neuroprotective approach in the search for novel compounds, and suggests future directions for this exciting area. Neuroprotection strategy may be a useful paradigm for treatment of prodromal and first-episode schizophrenia patients and might have a significant impact on the subsequent course and outcome of the illness. The clinical effects of neuroprotective agents clearly merit further investigation in schizophrenia spectrum disorders.


Schizophrenia Neurodevelopmental model Neurodegenerative model Apoptosis Oxidative stress Excitotoxicity Stress sensitization Neurotrophic factor expression Alteration of neurosteroids Vulnerability model Neurocognitive domains Quality of life deficit Neuroprotective agents Neurosteroids Pregnenolone Dehydroepiandrosterone Bexarotene Theanine 



alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Brain-derived neurotrophic factor


Cambridge Automated Neuropsychological Test Battery


Clinical Global Impression – Severity scale


Central Nervous System


Cerebrospinal fluid




docosahexaenoic acid




dehydroepiandrosterone sulfate


DHEA and DHEAS together


Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition


eicosapentaenoic acid


Extrapyramidal symptoms


Extrapyramidal Symptom Rating Scale


gamma-aminobutyric acid


hypothalamic-pituitary-adrenal axis


the health-related quality of life


International Classification of Mental and Behavioural Disorders






pregnenolone sulphate


PREG and PREGS together


Positive and Negative Syndrome Scale


retinoic acid receptors


retinoid X receptors


Scale for the Assessment of Negative Symptoms



The author would like to express gratitude to my colleagues Drs. Anatoly Gibel, Yael Ratner, Professor Vladimir Lerner, and Professor Abraham Weizman for fruitful cooperation. Mrs. Rena Kurs provided outstanding editorial assistance. The author gratefully acknowledges the support of the team of clinical departments of Shaar Menashe Mental Health Center. Clinical trials with neuroprotective compounds were supported by generous grants from the Stanley Foundation.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Technion – Israel Institute of TechnologyHaifaIsrael
  2. 2.Acute Department, Sha’ar Menashe Mental Health CenterHaderaIsrael

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