The postgenomic era promises to revolutionize psychopathology research, with the complete mapping of the 3 billion base pairs of DNA in the human genome and their variations. This promise lies in the ability to identify genes associated with psychopathology, which will allow a deeper understanding of genetic influences on behavior. (Plomin & McGuffin, 2003)
Despite initial optimism, progress in identifying these genes has been slower than expected. The complexity of psychopathological phenotypes, influenced by multiple genes with small individual effects, explains this slowness. However, significant progress has been made in identifying genes related to dementia, reading difficulties, and hyperactivity. (Plomin & McGuffin, 2003)
The future of genetic research lies in functional genomics, which seeks to understand how genes work. Two complementary approaches stand out: functional genomics, which focuses on molecular mechanisms, and behavioral genomics, which investigates the pathways between genes and behavior at the psychological level. (Plomin & McGuffin, 2003)
Functional genomics uses techniques such as genetic manipulation, gene expression analysis and proteomics. Genetic manipulation, through gene knockouts and knock-ins in animal models, allows the impact of genetic alteration on behavior to be studied. Gene expression analysis, using microarrays, identifies genes that respond to specific events, such as alcohol exposure. Proteomics, in turn, studies the proteins produced by genes, revealing their function and interactions. (Plomin & McGuffin, 2003)
Behavioral genomics, on the other hand, takes a top-down approach, investigating how genetic effects interact with experience, influence development, and contribute to heterogeneity and comorbidity among disorders. (Plomin & McGuffin, 2003)
With the increasing accessibility of DNA collection, psychopathology research will be transformed. The routine inclusion of genetic information in psychological studies will allow for more accurate and personalized analyses. (Plomin & McGuffin, 2003)
The search for genes associated with psychopathology has focused on linkage and association methods. Linkage examines the cotransmission of DNA markers and disorder genes within families. Association, on the other hand, investigates the correlation between a specific allele and a trait in the population. (Plomin & McGuffin, 2003)
Although linkage is effective in identifying rare monogenic disorders such as Huntington’s disease, association has been shown to be more powerful in detecting QTLs (quantitative trait loci) with smaller effects, commonly associated with psychopathology. (Plomin & McGuffin, 2003)
QTL research aims to identify multiple genes that contribute to the variability of a trait, such as predisposition to disorders. However, identifying all genes involved in a complex trait is unlikely because of the difficulty in detecting genes with very small or non-additive effects. (Plomin & McGuffin, 2003)
The successful discovery of the APOE gene as a risk factor for late-life dementia illustrates the potential of QTL research. APOE-4, a specific allele of the APOE gene, increases the risk of dementia, although it is not a necessary or sufficient condition for the development of the disease. (Plomin & McGuffin, 2003)
Promising advances have also been made in identifying genes related to autism and reading difficulties, such as linkage on chromosome 7 for autism and on chromosome 6 for reading difficulties. (Plomin & McGuffin, 2003)
Research into communication and mental retardation has also benefited from the post-genomic era. The discovery of the FOXP2 gene, associated with a rare type of mental retardation with language impairment, and the identification of genes related to hyperactivity and alcoholism, such as the ALDH2 gene
2 that protects against alcoholism in Asian populations, demonstrate progress in this area. (Plomin & McGuffin, 2003)
In short, the postgenomic era offers an unprecedented opportunity to unravel the complex relationship between genes and psychopathology. The identification of genes, combined with an understanding of their functioning, promises to revolutionize mental health research and treatment in the coming decades. (Plomin & McGuffin, 2003)
Reference:
Plomin, R., & McGuffin, P. (2003). Psicopatologia na era pós-genômica. Revisão Anual de Psicologia, 54(1), 205-228. doi: 10.1146/annurev.psych.54.101601.145108
