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Is a Neuroprotective Therapy Suitable for Schizophrenia Patients?

  • Michael S. RitsnerEmail author
Chapter

Abstract

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.

Keywords

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 

Abbreviations

AMPA

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

BDNF

Brain-derived neurotrophic factor

CANTAB

Cambridge Automated Neuropsychological Test Battery

CGI-S

Clinical Global Impression – Severity scale

CNS

Central Nervous System

CSF

Cerebrospinal fluid

Delta9-THC

Delta(9)-tetrahydrocannabinol

DHA

docosahexaenoic acid

DHEA

dehydroepiandrosterone

DHEAS

dehydroepiandrosterone sulfate

DHEA(S)

DHEA and DHEAS together

DSM-IV

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition

EPA

eicosapentaenoic acid

EPS

Extrapyramidal symptoms

ESRS

Extrapyramidal Symptom Rating Scale

GABAA

gamma-aminobutyric acid

HPA

hypothalamic-pituitary-adrenal axis

HRQL

the health-related quality of life

ICD-10

International Classification of Mental and Behavioural Disorders

NMDA

N-methyl-D-aspartate

PREG

pregnenolone

PREGS

pregnenolone sulphate

PREG(S)

PREG and PREGS together

PANSS

Positive and Negative Syndrome Scale

RARs

retinoic acid receptors

RXRs

retinoid X receptors

SANS

Scale for the Assessment of Negative Symptoms

Notes

Acknowledgments

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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