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Advancing Neuroprotective-Based Treatments for Schizophrenia

  • Michael S. RitsnerEmail author
  • Vladimir Lerner
Chapter

Abstract

Schizophrenia is a chronic, severe, and disabling brain disease. About one-third of all patients with schizophrenia do not respond adequately to drug treatment. Advances in neuroscience and clinical research have led to the introduction of a novel generation of compounds with neuroprotective properties. Despite numerous animal studies with promising neuroprotective agents, no successful strategy for neuroprotection from functional psychoses has been successfully demonstrated. There are two main targets for neuroprotective therapy: (1) neurodegenerative processes in schizophrenia (e.g. apoptosis, excitotoxicity, oxidative stress, stress sensitization, and alteration of neurosteroids); and (2) phenotypic presentations of illness including psychopathological symptoms, significant decline in cognition, psychosocial functioning and in health related quality of life (HRQL). In this chapter substantial information about clinical trials with neurosteroids, vitamins, and some herbal supplements with neuroprotective properties in schizophrenia is presented. Neurosteroids such as pregnenolone (PREG), dehydroepiandrosterone (DHEA) and their sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability and synaptic plasticity. In addition, vitamins and herbal supplements are important for regular cell function, growth and development. As a rule, vitamins promote the activity of enzymes to improve their efficiency and in this role they are called coenzymes. The herbal supplements are active antioxidants with neuroptective properties. The authors hope that neuroprotective strategies will pave the way to the next generation of antipsychotic, sedative and mood stabilizer medications. The clinical effects of neuroprotective agents clearly merit further clinical trials for the treatment of mental disorders.

Keywords

Clinical trial Dehydroepiandrosterone Folic acid Ginkgo biloba L-theanine Neuroptotection Omega-3 Pregnenolone Retinoids Schizophrenia Vitamin B6 Vitamin B12 Vitamin C Vitamin D Vitamin E 

Abbreviations

AA

Arachidonic acid

AIMS

Abnormal involuntary movement scale

BARS

Barnes Akathisia rating scale

BDNF

Brain-derived neurotrophic factor

CANTAB

Cambridge automated neuropsychological test battery

CGI-S

Clinical global impression severity scale

CNS

Central nervous system

CSDS

Calgary scale for depression in schizophrenia

DHA

Docosahexaenoic acid

DHAs

Docosahexaenoic acids

DHEA

Dehydroepiandrosterone

DHEA(S)

Both DHEA and DHEAS

DHEAS

Dehydroepiandrosterone sulfate

DNA

Deoxyrybonucleic acid

DPA

Docosapentaenoic acid

EGb

Extract of gingko biloba

EPA

Eicosapentaenoic acid

EPS

Medication-induced extrapyramidal symptoms

EPUFAs

Essential polyunsaturated fatty acids

ESRS

Extrapyramidal symptom rating scale

FGAs

First-generation antipsychotics

GABA

Gamma-aminobutyric acid

GABAA

Gamma-aminobutyric acid receptor type A

HAM-A

Hamilton scale for anxiety

Hcy

Homoysteine

HPA

Hypothalamic-pituitary-adrenal axis

LDL

Low-density lipoprotein

NMDA

N-methyl-D-aspartate

PANSS

Positive and negative symptom scale

PD

Parkinson’s disease

PREG

Pregnenolone

PREG(S)

Both PREG and PREGS

PREGS

Pregnenolone sulfate

PUFA

Polyunsaturated fatty acids

QLS

Quality of life scale for rating the schizophrenic deficit syndrome

SAM

S-adenosylmethionine

SANS

Scale for the assessment of negative symptoms

SAPS

Scale for the assessment of positive symptoms

SAS

Simpson-Angus scale

SD

Standard deviation

SGAs

Second-generation antipsychotics

SOD

Superoxide dismutase

TD

Tardive dyskinesia

Notes

Acknowledgments

We thank our collaborators Dr. Anatoly Gibel, Dr. Ekateryna Kovalyonok, Dr. Chanoch Miodownik, Dr. Yael Ratner, Dr. Tatyana Shleifer and Professor Abraham Weizman in the reviewed studies for fruitful cooperation. DHEA, L-theanine and vitamin B6 studies were supported by grants from the Stanley Foundation.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of Psychiatry, Rappaport Faculty of MedicineTechnion – Israel Institute of TechnologyHaifaIsrael
  2. 2.Acute DepartmentSha’ar Menashe Mental Health CenterHaderaIsrael
  3. 3.Division of Psychiatry, Ministry of HealthBe’er Sheva Mental Health CenterBe’er ShevaIsrael
  4. 4.Faculty of Health SciencesBen-Gurion University of the NegevBe’er ShevaIsrael

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