Personalized Nutrition

A. P. Simopoulos, J. A. Milner

• Verlag: S. Karger
• Jahr: 2010
• ISBN:
  9783805594288
• Thema: Medicina
• Thema: Nutrición, dietética y bariatría

Awareness of the influence of our genetic variation to dietary response (nutrigenetics) and how nutrients may affect gene expression (nutrigenomics) is prompting a revolution in the field of nutrition. Nutrigenetics/Nutrigenomics provide powerful approaches to unravel the complex relationships among nutritional molecules, genetic variants and the biological system.This publication contains selected papers from the '3rd Congress of the International Society of Nutrigenetics/Nutrigenomics' held in Bethesda, Md., in October 2009. The contributions address frontiers in nutrigenetics, nutrigenomics, epigenetics, transcriptomics as well as non-coding RNAs and posttranslational gene regulations in various diseases and conditions. In addition to scientific studies, the challenges and opportunities facing governments, academia and the industry are included.Everyone interested in the future of personalized medicine and nutrition or agriculture, as well as researchers in academia, government and industry will find this publication of the utmost interest for their work.

Simopoulos AP, Milner JA (eds): Personalized Nutrition.
World Rev Nutr Diet. Basel, Karger, 2010, vol 101, pp 131–153

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Redox Dysregulation and Oxidative Stress in Schizophrenia: Nutrigenetics as a Challenge in Psychiatric Disease Prevention

Kim Q. Do^a,b · Philippe Conus^a,c · Michel Cuenod^a,b

^aDepartment of Psychiatry, ^bCenter for Psychiatric Neuroscience, and ^cService of General Psychiatry, Lausanne University Hospital, Lausanne, Switzerland

Schizophrenia is a major psychiatric brain disease with potentially devastating effects. It strikes in adolescence and young adulthood and can last a lifetime. It affects about 1% of the world’s population, is destructive for the individual, family and society, and constitutes a major costly public health problem. It develops progressively, most often undetected during childhood and adolescence in a pre-morbid phase. This usually leads to the onset of psychosis at between 18 and 25 years of age, often evolving toward invalidity. Approximately two-thirds of those who develop schizophrenia require assistance from health care providers (such as government and social security systems) within a few years of onset. The majority of people who develop schizophrenia are unable to return to work or school and may have difficulties in maintaining normal social interactions [1].

The symptoms of schizophrenia are classically divided into categories of positive symptoms (delusions, hallucinations, thought disorder) and negative ones (e.g. deficits in social abilities, poverty of speech, affective flattening). The patients also present other discrete, but more permanent dysfunctions, such as cognitive deficits (problems with attention, specific forms of memory, executive functions) and perceptual instability (basic symptoms) that are now thought to be central to patients’ behavioral disturbances and functional disability. Moreover, patients with schizophrenia also present non-specific symptoms such as anxiety, depression, obsessive behavior, drug and alcohol abuse and suicidal tendency (10% incidence). While present antipsychotic treatments are relatively effective against positive symptoms, they are almost ineffectual for negative and cognitive ones. Indeed, even in patients stabilized with present antipsychotics, these negative and cognitive symptoms are impediments to the social and professional integration of young individuals from the time of disease onset [1–3].

Despite a growing understanding of its neurochemical anomalies, schizophrenia remains an elusive and multifaceted disorder and available evidence regarding its onset and etiology point to a complex interplay of genetic, environmental and developmental factors. Various pathophysiological hypotheses have been put forward, which account for available evidence to varying degrees. Globally, they involve dysfunctions in neurotransmission and impairments of functional connectivity.

Genetic Factors

It is well established from twin and adoption studies that schizophrenia is highly heritable, but in a complex manner, with a concordance rate of ~50% for monozygotic twins and a heritability of 80% [4]. Numerous studies have focused on identifying genetic vulnerability factors. Results from several genome-wide scans [5–8] have identified chromosomal regions of interest, and cumulative evidence from replication efforts suggest that schizophrenia susceptibility genes may be found on chromosomes 1, 6, 8, 10, 13 and 22 [see reviews in 9–11]. Very recent studies from large genome-wide scans in multiple, large cohorts that have identified both rare high-risk mutations (RR: 2–14) [12–15] and common low-risk variations on chromosome 2 (ZnF804A) and 11 (RR: 1.09–1.19) [16] and in the HLA and histone regions on chromosome 6 [17]. Similarly, studies that have adopted a family-based approach have identified a balanced translocation that disrupts the DISC1 gene [18], as well as the neuregulin gene [19], while hypothesis-driven approaches based on biological findings of deficits in the ability to cope with oxidative stress in patients with schizophrenia have implicated gene variants in the biosynthesis of glutathione as susceptibility factors of the illness [20, 21]. Moreover, understanding how genetic variation at each locus confers susceptibility and/or protection, or what is the contribution of each gene, their relationship with the phenotype and their interaction with environmental risk factors [22, 23] remains a great challenge.

Environmental Factors

These include exposure to viral infections [24], autoimmune, toxic or traumatic insults and stress during gestation, birth or childhood [25–27] that have been implicated in the pathogenesis of schizophrenia. Recently, models based on epigenetic factors and an interaction between a susceptible genotype and environmental factors have been proposed for this puzzlingly complex disease [28].

Developmental Factors

In attempting to produce a unifying concept of the etiology of schizophrenia, researchers have posited that these biological mechanisms have their origins in developmental processes that emerge prior to the onset of clinical symptoms. Indeed, evidence for pre- and perinatal epidemiological risk factors of schizophrenia, and for premorbid dysfunction during infancy and childhood have led to the formulation of the so-called neurodevelopmental hypothesis: schizophrenia is viewed as resulting from etiological events acting between conception and birth, and interfering with normal maturational processes of the central nervous system [29–31]. Moreover, it is also hypothesized that the interaction between a hereditary predisposition and early neurodevelopmental insults results in defective connectivity between a number of brain regions, including the midbrain, nucleus accumbens, thalamus, temporo-limbic (including hippocampus) and prefrontal cortices [2, 32–34]. This defective neural circuitry is then vulnerable to dysfunction when unmasked by developmental processes and events of adolescence (myelination, synaptic pruning and hormonal effects of puberty on the central nervous system) and exposure to stressors as the individual enters high-risk ages [3, 31, 35].

Neurotransmission Dysfunction

A number of theories implicate aberrant neurotransmission systems in schizophrenia, in particular, aberrant dopaminergic [36–38], glutamatergic [39–41] and γ-aminobutyric acid (GABA)-ergic systems [42–46] involving dysfunctions in presynaptic storage, vesicular transport, release, re-uptake and metabolic mechanisms [3, 47]. It is unclear, however, to what extent such neurochemical findings reflect primary causes rather than secondary effects of the pathology, including compensatory mechanisms or environmental interactions.

Impaired Structural Connectivity

Multiple lines of evidence suggest that schizophrenia is associated with abnormalities in neural circuitry and impaired structural connectivity. Post-mortem histological studies have shown anomalies at the level of dendritic spines [48–51] and decreases in numbers of inhibitory GABA-parvalbumin interneurons in the prefrontal cortex [46, 52]. Moreover, recent advances in diffusion tensor imaging have allowed in vivo explorations of anatomical connectivity in the human brain. These have pointed to connectivity abnormalities in fronto-parietal and fronto-temporal circuitry in schizophrenia [for reviews see 53, 54]. Further evidence for anomalies in information integration across brain networks is accumulating.

Impaired Functional Connectivity

This is based on the study of dynamic, context-dependent processes, which require the preferential recruitment of context-relevant networks over others [55–57]. Evidence is emerging in schizophrenia for an impairment in both local and long-range synchronization in a range of cognitive and perceptual tasks [58–61]. Such perturbation of brain connectivity might be associated with functional anomalies of dopaminergic, glutamatergic and GABA-ergic systems [62–64]. The connectivity argument is reinforced by the fact that the age of onset of full-blown psychosis corresponds to the maturation of myelinated pathways, in particular those involving the prefrontal cortex.

In summary, existing neuroanatomical, neurochemical, neurophysiological and psychopathological arguments converge to suggest that schizophrenia may be considered as a developmental syndrome involving faulty connectivity and neurotransmissio...

Inhaltsverzeichnis

• Cover Page
• Front Matter
• Opportunities and Challenges in Nutrigenetics/Nutrigenomics and Health
• Genome-Wide Association Studies and Diet
• Copy Number Variation, Eicosapentaenoic Acid and Neurological Disorders.
• Nutrigenetics: A Tool to Provide Personalized Nutritional Therapy to the Obese
• Xenobiotic Metabolizing Genes, Meat-Related Exposures, and Risk of Advanced Colorectal Adenoma
• Strategies to Improve Detection of Hypertension Genes
• Diet, Nutrition and Modulation of Genomic Expression in Fetal Origins of Adult Disease
• Choline: Clinical Nutrigenetic/Nutrigenomic Approaches for Identification of Functions and Dietary Requirements
• Dietary Polyphenols, Deacetylases and Chromatin Remodeling in Inflammation
• Dietary Manipulation of Histone Structure and Function
• Changes in Human Adipose Tissue Gene Expression during Diet-Induced Weight Loss
• Toxicogenomics and Studies of Genomic Effects of Dietary Components
• Dietary Methyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis
• Redox Dysregulation and Oxidative Stress in Schizophrenia: Nutrigenetics as a Challenge in Psychiatric Disease Prevention
• Nutrigenomics and Agriculture: A Perspective
• Opportunities and Challenges in Nutrigenetics/Nutrigenomics: Building Industry-Academia Partnerships
• Tailoring Foods to Match People’s Genes in New Zealand: Opportunities for Collaboration
• Author Index
• Subject Index