Genetics and mental health
Introduction (Psychology and Mental Health)
The idea that genes can influence mental health has been entertained from the early part of the twentieth century. Several studies have shown positive association of genetic components with various mental disorders such as schizophrenia and bipolar disorder. Although a plethora of evidence suggests that many mental and psychiatric diseases have tremendously influential genetic components, solid evidence pointing to specific genes as the direct cause of particular diseases is still lacking. Mental disorders are fairly complicated, because in most cases, diagnosis is based on self-reported symptoms (which could be subjective and overlap with other disorders) or clinical observations (which are hampered by the lack of sophisticated diagnostic and screening tools). Most mental disorders are complex in nature, with varying degrees of manifestations, onset times, and symptoms. Determining a genetic basis for such complex mental disorders becomes even more challenging because a disorder can be polygenic (more than one gene is responsible for the symptoms) or multifactorial in nature (both genetic and environmental factors are responsible), the genes may not adhere to Mendelian patterns of inheritance (the segregation of genes into the following generations is complex), and the loci of the risk alleles is heterogeneous in nature. Some researchers suspect that genes merely mediate some disorders rather than determine them.
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Structure of Genes (Psychology and Mental Health)
Knowledge of the structure and functioning of genes provides a better understanding of how complex diseases can have a genetic basis. Genes are made up of deoxyribonucleic acid (DNA), which consists of bases called nucleotides. Numerous nucleotides (called polynucleotides), interspersed with sugar molecules, are bound together through chemical bonds to form helical strands. Each DNA has two polynucleotide strands forming a double helical structure. Four bases have been identified—adenine (A), guanine (G), thiamine (T), and cytosine (C)—each of which has specific binding partners (A binds with T, and G binds with C).
Chromosomes consist of uninterrupted stretches of DNA molecules. During cell division, these DNA molecules get shuffled, and the resultant cells acquire a new combination of genes that are unique to an individual. This process is called recombination of DNA. Recombination occurs through independent segregation and assortment of genes so that the unique combination of genes in the offspring has a fair mixture of the parents’ DNA. In some cases, however, genes that are located in close proximity to each other stay together and do not segregate during cell division. These genes are said to be linked together, and the process of inheritance of a group of genes together is called linkage. Linkage aids enormously in studying the genetic basis of many phenomena, including the occurrence of diseases. Traits or...
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Mutations (Psychology and Mental Health)
Alterations to the DNA sequences (called mutations) can result in drastic changes, sometimes even changing a cell from a normal to a disease state. Mutations can be at the level of one base pair (for example, A can mutate to G, which when copied will bind with C, instead of T), and this one base pair change (called point mutation) changes the code to a different amino acid, which can result in a malfunctioning or nonfunctional protein. Proper functioning of specific proteins is key for a normal or healthy state, and a point mutation can very well change that state of a cell. Mutations can also be insertions or deletions, in which a few additional nucleotides are added or deleted. All these can lead to drastic changes in the physiology of the cell.
In addition, mutations can also occur at the level of whole chromosomes. Chromosomal aberrations—deletions, duplications, inversions, insertions, or translocations—alter a whole array of genes, resulting in significant abnormalities. A common example of this is Down syndrome, in which the affected individual possesses either an extra copy of chromosome 21 or an additional piece attached to that chromosome because of a translocation event. The translocation of chromosome that could be related to schizophrenia was first observed between chromosomes 1 and 11 in a large Scottish family study. Genes that elicited considerable interest in this region are DISC1 (Disrupted in...
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Penetrance and Expressivity (Psychology and Mental Health)
The extent to which a certain gene mutation results in symptoms varies between and within specific diseases. Some mutations lead to a distinctly altered physical manifestation (phenotype) or symptoms, and all individuals carrying a certain genetic composition (genotype) manifest those symptoms. Such mutations are called penetrant, and the state is called complete penetrance. Penetrance directly indicates the onset of an illness, which is the point at which the affected individual begins to show enough symptoms that a diagnosis can be made. If a certain illness affects the succeeding generation earlier than it did the previous one (a phenomenon called early onset or anticipation), the gene is said to be more penetrant. Early onset can somewhat simplify the identification of genes involved in mental disorders, but many individuals with the disease genes do not develop the disease until a later stage or do not develop the disease at all. Such incomplete penetrations pose serious problems, especially when conducting large family studies.
The degree of manifestation of the symptoms may range from mild to serious. This is referred to as the expressivity of the gene. Factors such as penetrance and expressivity complicate the understanding of the genetic bases of most diseases.
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Types of Genetic Analyses (Psychology and Mental Health)
Many types of genetic analyses are performed to identify the genes involved and to decipher their roles in mental illnesses. Chief among them are linkage analysis, family studies, association studies, twin studies, and the candidate gene approach.Linkage Analysis
Linkage analysis is a powerful statistical tool that bases its findings on linkage maps and deduces the combination of alleles that are inherited together from multiple loci (haplotypes). It uses the location of commonly known markers (such as color blindness) and attempts to map potential genes of interest in the chromosome. Linkage mapping helps reduce the number of genes that need to be studied in a certain chromosome. A variety of associated biomarker tests help in narrowing down the genes associated with illnesses. Data are mostly collected from large families with multiple members, consisting of cases and probands (the first member of the family who reported the disease). Data from large samples are pooled in meta-analyses, and statistical tests are applied to deduce the probability of certain genes being linked and cosegregated, and to exhibit certain disease phenotypes (called logarithm-of-odds ratio, or lod score). Most diseases that have a high degree of penetration use linkage studies for determining the relevant genes. Linkage studies, however, are limited by the number of genetic recombinations occurring within the specific set of chromosomes...
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Sources for Further Study (Psychology and Mental Health)
Andreasen, Nancy. Brave New Brain: Conquering Mental Illness in the Era of the Genome. New York: Oxford University Press, 2001. This book is a very interesting source for learning about mental illnesses. It provides an entire chapter that discusses the various approaches to studying the genetic basis of different mental disorders, with specific examples of real-life cases.
Collier, D. A., and T. Li. “The Genetics of Schizophrenia: Glutamate Not Dopamine?” European Journal of Pharmacology 480, nos. 1-3 (2003): 177-184. This article discusses the possibility of the involvement of the glutamatergic system in schizophrenia, showing how the genes that have strong linkage association with schizophrenia are related to the glutamatergic system.
Cowan, W. M., et al. “The Human Genome Project and Its Impact on Psychiatry.” Annual Review of Neuroscience 25 (2002): 1-50. This article discusses the advances made before the Human Genome Project on studies related to the genetic basis of mental disorders such as schizophrenia, bipolar disorder, and autism. It provides an extensive review of different genetic approaches used for investigations and their results.
Detera-Wadleigh, S. D., and F. J. McMahon. “Genetic Association Studies in Mood Disorders: Issues and Promise.” International Review of Psychiatry 16, no. 4 (2004): 301-310. This article provides an exhaustive...
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