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A mental disorder is an impairment of the mind disrupting normal thinking, feeling, mood, behavior, or social interactions, and accompanied by significant distress or dysfunction. The causes of mental disorders are very complex and vary depending on the particular disorder and the individual. Although the causes of most mental disorders are not fully understood, researchers have identified a variety of biological, psychological, and environmental factors that can contribute to the development or progression of mental disorders. Most mental disorders result in a combination of several different factors rather than just a single factor.
The serotonin transporter also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein that transports the neurotransmitter serotonin from the synaptic cleft back to the presynaptic neuron, in a process known as serotonin reuptake.
The candidate gene approach to conducting genetic association studies focuses on associations between genetic variation within pre-specified genes of interest, and phenotypes or disease states. This is in contrast to genome-wide association studies (GWAS), which is a hypothesis-free approach that scans the entire genome for associations between common genetic variants and traits of interest. Candidate genes are most often selected for study based on a priori knowledge of the gene's biological functional impact on the trait or disease in question. The rationale behind focusing on allelic variation in specific, biologically relevant regions of the genome is that certain alleles within a gene may directly impact the function of the gene in question and lead to variation in the phenotype or disease state being investigated. This approach often uses the case-control study design to try to answer the question, "Is one allele of a candidate gene more frequently seen in subjects with the disease than in subjects without the disease?" Candidate genes hypothesized to be associated with complex traits have generally not been replicated by subsequent GWASs or highly powered replication attempts. The failure of candidate gene studies to shed light on the specific genes underlying such traits has been ascribed to insufficient statistical power, low prior probability that scientists can correctly guess a specific allele within a specific gene that is related to a trait, poor methodological practices, and data dredging.
Gene–environment interaction is when two different genotypes respond to environmental variation in different ways. A norm of reaction is a graph that shows the relationship between genes and environmental factors when phenotypic differences are continuous. They can help illustrate GxE interactions. When the norm of reaction is not parallel, as shown in the figure below, there is a gene by environment interaction. This indicates that each genotype responds to environmental variation in a different way. Environmental variation can be physical, chemical, biological, behavior patterns or life events.
Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. A mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed.
The Dunedin Multidisciplinary Health and Development Study is a detailed study of human health, development and behaviour. Based at the University of Otago in New Zealand, the Dunedin Study has followed the lives of 1037 babies born between 1 April 1972 and 31 March 1973 at Dunedin's former Queen Mary Maternity Centre since their birth. Teams of national and international collaborators work on the Dunedin Study, including a team at Duke University in the United States. The research is constantly evolving to encompass research made possible by new technology and seeks to answer questions about how people's early years impact mental and physical health as they age.
Personality development encompasses the dynamic construction and deconstruction of integrative characteristics that distinguish an individual in terms of interpersonal behavioral traits. Personality development is ever-changing and subject to contextual factors and life-altering experiences. Personality development is also dimensional in description and subjective in nature. That is, personality development can be seen as a continuum varying in degrees of intensity and change. It is subjective in nature because its conceptualization is rooted in social norms of expected behavior, self-expression, and personal growth. The dominant viewpoint in personality psychology indicates that personality emerges early and continues to develop across one's lifespan. Adult personality traits are believed to have a basis in infant temperament, meaning that individual differences in disposition and behavior appear early in life, potentially before language of conscious self-representation develop. The Five Factor Model of personality maps onto the dimensions of childhood temperament. This suggests that individual differences in levels of the corresponding personality traits are present from young ages.
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter. Since the polymorphism was identified in the middle of the 1990s, it has been extensively investigated, e.g., in connection with neuropsychiatric disorders. A 2006 scientific article stated that "over 300 behavioral, psychiatric, pharmacogenetic and other medical genetics papers" had analyzed the polymorphism. While often discussed as an example of gene-environment interaction, this contention is contested.
Rs6265, also called Val66Met or G196A, is a gene variation, a single nucleotide polymorphism (SNP) in the BDNF gene that codes for brain-derived neurotrophic factor.
Scientific studies have found that different brain areas show altered activity in humans with major depressive disorder (MDD), and this has encouraged advocates of various theories that seek to identify a biochemical origin of the disease, as opposed to theories that emphasize psychological or situational causes. Factors spanning these causative groups include nutritional deficiencies in magnesium, vitamin D, and tryptophan with situational origin but biological impact. Several theories concerning the biologically based cause of depression have been suggested over the years, including theories revolving around monoamine neurotransmitters, neuroplasticity, neurogenesis, inflammation and the circadian rhythm. Physical illnesses, including hypothyroidism and mitochondrial disease, can also trigger depressive symptoms.
Cultural neuroscience is a field of research that focuses on the interrelation between a human's cultural environment and neurobiological systems. The field particularly incorporates ideas and perspectives from related domains like anthropology, psychology, and cognitive neuroscience to study sociocultural influences on human behaviors. Such impacts on behavior are often measured using various neuroimaging methods, through which cross-cultural variability in neural activity can be examined.
Kenneth S. Kendler is an American psychiatrist best known for his pioneering research in psychiatric genetics, particularly the genetic causes of schizophrenia. Kendler is one of the highest cited psychiatry researchers. Between 1990 and 1998 he was the 2nd highest cited psychiatrist, and for the 1997-2007 decade he was ranked 4th by Thomson Reuters' Science Watch. He has authored over 1,200 papers and in 2016 his h-index was 126. Kendler's group was also noted for the replication of a study of Avshalom Caspi on the interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression.
Terrie Edith Moffitt is an American-British clinical psychologist who is best known for her pioneering research on the development of antisocial behavior and for her collaboration with colleague and partner Avshalom Caspi in research on gene-environment interactions in mental disorders.
Barbara Maughan is a Professor of Developmental Epidemiology at the Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry. Her research focuses on mental health problems in children and adolescents.
Andri Steinþór Björnsson is a clinical psychologist and an associate professor of psychology at the University of Iceland. In addition to his work on body dysmorphic syndrome, he has hosted a series of radio programs on science and the scientific method broadcast by RÚV, as well as editing and writing books on science aimed at the general public.
Richie Graham Poulton is a New Zealand psychologist and the director of the University of Otago's Dunedin Multidisciplinary Health & Development Research Unit, which runs the Dunedin Multidisciplinary Health and Development Study. He is also a professor of psychology at the University of Otago, the 2007 founder and co-director of the National Centre for Lifecourse Research, the founder in 2011 of the Graduate Longitudinal Study, New Zealand, and the chief science adviser of the Ministry of Social Development in the New Zealand government.
Matthew C. Keller is an American behavioral and psychiatric geneticist. He is the Director of the Institute for Behavioral Genetics and a professor in the Department of Psychology and Neuroscience at the University of Colorado Boulder. He is known for his criticism of the candidate gene approach and for development of approaches in quantitative genetics.
Louise Arseneault is a Canadian psychologist and Professor of Developmental Psychology in the Social, Genetic & Developmental Psychiatry Centre in the Institute of Psychiatry, Psychology and Neuroscience at King's College London, where she has taught since 2001.
Candice Lynn Odgers is a developmental and quantitative psychologist who studies how early adversity and exposure to poverty influences adolescent mental health. Her team has developed new approaches for studying health and development using mobile devices and online tools, with a focus on how digital tools and spaces can be improved to support children and adolescents. Odgers is currently a professor of Psychological Science at the University of California, Irvine and a research professor at Duke University. Odgers is also the co-director of the Child and Brain Development Program at the Canadian Institute for Advanced Research.
Laura Tach is an American professor of policy analysis and management and sociology at Cornell University. She is the co-director with Rachel Dunifon of Cornell Project 2Gen, a research initiative supporting disadvantaged caregivers and children. In collaboration with the Cornell Cooperative Extension of Tompkins County, Tach studies the relationship between opioid abuse and child maltreatment. The study was funded by a multi-year grant from the William T. Grant Foundation. Tach has studied the relationship between "microenvironments", or the neighborhood blocks where one resides, affect educational success.
References
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- 1 2 Starr, Douglas (2018-01-30). "Two psychologists followed 1000 New Zealanders for decades. Here's what they found about how childhood shapes later life". Science. Retrieved 2018-04-12.
- ↑ Green, Penelope (2012-10-03). "One Shed Fits All: A Modernist Dogtrot Reborn". The New York Times. ISSN 0362-4331 . Retrieved 2018-04-12.
- ↑ Hamilton, Anita (2009-06-17). "Study: 'Depression Gene' Doesn't Predict the Blues". Time. ISSN 0040-781X . Retrieved 2018-04-12.
- ↑ Culverhouse, R. C.; Saccone, N. L.; Horton, A. C.; Ma, Y.; Anstey, K. J.; Banaschewski, T.; Burmeister, M.; Cohen-Woods, S.; Etain, B. (2017-04-04). "Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression". Molecular Psychiatry. 23 (1): 133–142. doi:10.1038/mp.2017.44. ISSN 1476-5578. PMC 5628077 . PMID 28373689.
- 1 2 Border, Richard; Johnson, Emma C.; Evans, Luke M.; Smolen, Andrew; Berley, Noah; Sullivan, Patrick F.; Keller, Matthew C. (May 2019). "No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples". American Journal of Psychiatry. 176 (5): 376–387. doi:10.1176/appi.ajp.2018.18070881. ISSN 0002-953X. PMC 6548317 . PMID 30845820.
- ↑ Duncan LE, Keller MC (October 2011). "A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry". The American Journal of Psychiatry. 168 (10): 1041–9. doi:10.1176/appi.ajp.2011.11020191. PMC 3222234 . PMID 21890791.
- ↑ Hewitt, John K. (2011). "Editorial Policy on Candidate Gene Association and Candidate Gene-by-Environment Interaction Studies of Complex Traits". Behavior Genetics. 42 (1): 1–2. doi:10.1007/s10519-011-9504-z. ISSN 0001-8244. PMID 21928046. S2CID 11492871.
- ↑ Johnson, Emma C.; Border, Richard; Melroy-Greif, Whitney E.; de Leeuw, Christiaan A.; Ehringer, Marissa A.; Keller, Matthew C. (2017). "No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes". Biological Psychiatry. 82 (10): 702–708. doi:10.1016/j.biopsych.2017.06.033. ISSN 0006-3223. PMC 5643230 . PMID 28823710.
- ↑ Frazier, Annabelle; Ferreira, Patricia A.; Gonzales, Joseph E. (2019-10-23). "Born this way? A review of neurobiological and environmental evidence for the etiology of psychopathy". Personality Neuroscience. 2: e8. doi:10.1017/pen.2019.7. ISSN 2513-9886. PMC 7219694 . PMID 32435743.
- ↑ "Biosketch" (PDF). Caspi Biosketch 2019. Retrieved 2 June 2021.
- ↑ "Dissertation". Moving Against and Moving Away. Retrieved 2 June 2021– via ProQuest.
- ↑ "Professor Avshalom Caspi". British Academy. Retrieved 2018-04-12.
- ↑ "APA Award for Distinguished Scientific Contributions". American Psychological Association. Retrieved 2018-04-12.
- ↑ "Avshalom Caspi Awards & Honors". Duke Moffitt & Caspi. Retrieved 2020-03-23.
- ↑ "The Dunedin Study wins Rutherford Medal and other Research Honours Aotearoa winners celebrated in Ōtepoti Dunedin". Royal Society Te Apārangi. Retrieved 2022-11-16.
