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Advancing Neuroprotective-Based Treatments for Schizophrenia

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Handbook of Schizophrenia Spectrum Disorders, Volume III

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.

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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

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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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  1. Department of Psychiatry, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

    Michael S. Ritsner

  2. Acute Department, Sha’ar Menashe Mental Health Center, Hadera, Israel

    Michael S. Ritsner

  3. Division of Psychiatry, Ministry of Health, Be’er Sheva Mental Health Center, Be’er Sheva, Israel

    Vladimir Lerner

  4. Faculty of Health Sciences, Ben-Gurion University of the Negev, Be’er Sheva, Israel

    Vladimir Lerner

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  2. Vladimir Lerner
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Correspondence to Michael S. Ritsner .

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    Michael S. Ritsner

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Ritsner, M.S., Lerner, V. (2011). Advancing Neuroprotective-Based Treatments for Schizophrenia. In: Ritsner, M. (eds) Handbook of Schizophrenia Spectrum Disorders, Volume III. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0834-1_3

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