Medical Genetics: Mental and Behavioral Diseases
Mental and behavioral diseases encompass a wide range of conditions that affect an individual's thoughts, emotions, and behavior. These conditions are characterized by their complexity, as they often result from a combination of genetic, environmental, and lifestyle factors. Understanding the genetic basis of these diseases is a challenging endeavor but one that holds great promise for the development of more effective therapies and interventions. This article embarks on a comprehensive review of the world of mental and behavioral disorders by taking a closer look at some of the most common diseases, illuminating the clinical presentations, linked genetic mutations, diagnostic processes, and hurdles faced by individuals affected by these conditions.
Types of Mental and Behavioral Diseases
Mental and behavioral diseases, often referred to as mental and behavioral disorders, are a broad category of conditions that affect an individual's thoughts, emotions, behaviors, and overall their mental well-being. Specifically, they are characterized by disturbances in thinking, feeling, and/or behavior that cause significant distress and result in impairment of the individual's ability to function. As a result, they often require medical intervention or specific clinical treatments.
There is a wide and complex range of mental diseases. Some of them are typically classified as mood, anxiety, personality, psychotic, and eating disorders, among others [Figure 1]. Schizophrenia is a severe and chronic mental disorder characterized by distorted thinking, hallucinations, delusions, and altered perceptions of reality. Other psychotic disorders may include similar symptoms to a lesser extent (Lewine & Hart, 2020). Mood disorders, such as depression and bipolar disorder, involve significant disturbances in a person's emotional state (Datta et al., 2021). Depression is defined by enduring emotions of sadness, despair, and a diminished enthusiasm or joy for activities. Bipolar disorder entails alternating between depression and mania periods characterized by elevated mood and high energy levels. In addition, there are many other disorders that may require attention, such as the neurodevelopmental ones (e.g., autism spectrum disorder, Fragile X syndrome and Rett syndrome).
Scientists are still studying the origins of mental diseases. There is not a singular cause; rather, there is usually a multifaceted blend of factors. These may encompass genetic predispositions as well as elements of social learning, such as one's upbringing and environment. This article will examine some of the most common mental and behavioral disorders in terms of their genetic factors.
Schizophrenia
Schizophrenia is a severe mental disorder characterized by disrupted thinking, hallucinations, and distorted perceptions of reality [Figure 2] (Schultz et al., 2007). It is a complex and multifactorial psychotic disorder with a genetic component. While the exact genetic underpinnings of schizophrenia remain the subject of ongoing research, several key points are known. Schizophrenia has a strong hereditary component. If an individual has a close relative (such as a parent or sibling) with schizophrenia, their risk of developing the disorder is significantly higher than in the general population (van de Leemput et al., 2016).
Several genes have been consistently associated with increased susceptibility to schizophrenia. Notable examples include DISC1 (disrupted in schizophrenia 1), COMT (catechol-O-methyltransferase), and NRGN (neurogranin). These genes play a role in neural development and neurotransmitter function. Many of the genes associated with schizophrenia are involved in the regulation of neurotransmitter metabolism, such as dopamine and glutamate. Dysregulation of these neurotransmitter systems is thought to contribute to the development of schizophrenia.
DISC1 was originally identified in a Scottish family with a high prevalence of psychotic disorders, including schizophrenia, bipolar disorder, and major depressive disorder. The gene was named "disrupted in schizophrenia 1" because of its apparent link to schizophrenia. While originally linked to schizophrenia, DISC1 has also been associated with other psychotic conditions, such as bipolar disorder, major depressive disorder, and autism spectrum disorders. This suggests that it may play a broader role in the etiology of mental conditions. DISC1 is located on chromosome 1 and it is involved in various aspects of neurodevelopment, including neuronal migration, axonal outgrowth, dendritic development, and synapse formation, acting as a coordinator of intracellular trafficking to shape neuronal development and connectivity [Figure 3]. These processes are crucial for the proper development and function of the nervous system. Several genetic variants in the DISC1 gene have been associated with an increased risk of psychotic disorders, particularly schizophrenia (Johnstone et al., 2011). These variants are represented by single nucleotide polymorphisms (SNPs) and other mutations.
COMT (catechol-O-methyltransferase) is an enzyme responsible for the breakdown and metabolism of catecholamines [Figure 4], which are neurotransmitters such as dopamine, norepinephrine, and epinephrine. These neurotransmitters play vital roles in regulating mood, cognition, stress response, and other brain functions. COMT enzymatic activity influences the levels of these neurotransmitters in the brain. Genetic variations in the COMT gene can lead to different levels of enzyme activity, affecting the breakdown of dopamine in particular. This genetic variability can result in altered neurotransmitter levels, impacting various cognitive and emotional processes (Williams et al., 2007).
A common genetic variation in the COMT gene involves a single nucleotide polymorphism (SNP) known as Val158Met. This particular variation impacts on the COMT enzyme activity. Individuals with the Val/Val genotype tend to develop a higher enzymatic activity, leading to a faster breakdown of dopamine, whereas those with the Met/Met genotype show a lower activity, resulting in slower dopamine breakdown. The Val/Met genotype falls in between. The link between COMT gene variations and neurological or psychiatric conditions, such as schizophrenia, bipolar disorder, anxiety, and attention-deficit/hyperactivity disorder (ADHD), has been studied extensively. For instance, selective studies suggest that the Met allele of the Val158Met polymorphism may be associated with an increased risk of schizophrenia, while the Val allele may be linked to better cognitive performance but a higher susceptibility to anxiety (Neuhaus et al., 2009).
NRGN (neurogranin) is a protein found in the brain, primarily in the dendrites of neurons. Its primary function is believed to involve signaling processes related to synaptic plasticity and memory formation. It plays a crucial role in regulating the signaling pathways involved in the strengthening or weakening of synaptic connections, which are fundamental for learning and memory. Some studies suggest that variations in the NRGN gene may be linked to an increased risk of developing schizophrenia. These variations could affect the expression or function of the NRGN protein, potentially influencing synaptic plasticity and neural circuitry in the brain (Smith et al., 2011).
Nowadays, schizophrenia is typically treated with a combination of medications, psychotherapy, and various forms of support. The primary goal of treatment is to manage symptoms, reduce the frequency of episodes, and help individuals lead productive lives. Further research is needed to fully understand the involvement of different genetic aspects and mutations and how they contribute to the pathophysiology of schizophrenia in order to develop more targeted treatments in the future.
Depression
Depression is a complex mental health disorder influenced by a combination of genetic, environmental, and psychological factors. The role of genetics in depression has been studied extensively and has shown that genetic factors contribute to a person's susceptibility to the condition. Research suggests that there is a hereditary predisposition to depression. Individuals with a family history of depression are more likely to experience depression themselves, and having a first-degree relative (parent or sibling) with depression increases this risk. However, estimates of heritability suggest that genetic factors may contribute to approximately 30–40% of the risk of developing depression [Figure 5] (Otte et al., 2016). This indicates that while genetics play an important role, environmental influences also have a significant impact on the development of the disorder. Depression is considered a polygenic disorder, meaning that it involves the interaction of multiple genes, each contributing a small amount to the overall risk of developing depression. There is no single gene responsible for depression, but rather a combination of genetic variations across several genes.
Studies have focused on certain candidate genes associated with depression, including genes involved in neurotransmitter regulation (e.g., serotonin, dopamine), the hypothalamic-pituitary-adrenal (HPA) axis involved in stress response, neurotrophic factors such as BDNF (brain-derived neurotrophic factor), and genes related to synaptic plasticity and inflammation (Norkeviciene et al., 2022). SLC6A4 (serotonin transporter gene) encodes the serotonin transporter protein, which regulates the reuptake of serotonin, a neurotransmitter involved in mood regulation. Variations, such as the serotonin transporter gene-linked polymorphic region (5-HTTLPR) have been extensively studied for their potential role in depression susceptibility. BDNF is a neurotrophin that supports the survival and growth of neurons. Genetic variations in the BDNF gene have been linked to altered levels of BDNF protein, which may affect mood regulation and neural plasticity, potentially contributing to the development of depression. FKBP5 (FK506 binding protein 5) is involved in the regulation of the stress response and HPA axis function. Variations in FKBP5 have been associated with altered stress reactivity and susceptibility to depression, particularly in individuals exposed to early life stress or trauma.
Imbalances of neurotransmitters (such as serotonin, dopamine, and norepinephrine) in the brain are associated with depression. Disruptions in the functioning of these chemical messengers can affect mood regulation. Depression can be effectively treated, and various options are available to help manage symptoms [Figure 6]. Psychotherapy, such as cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), or psychodynamic therapy, can help individuals learn coping strategies, identify thought patterns, and address underlying issues that contribute to depression. Antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and others, are commonly prescribed to help regulate neurotransmitter levels and alleviate symptoms (Nedic Erjavec et al., 2021).
Understanding the genetic basis of depression contributes to ongoing research aiming to identify biological pathways, potential biomarkers, and personalized treatments for individuals affected by depression. However, much remains to be understood about the complex interplay between genetics and other factors that contribute to depression.
Bipolar Disorder
Bipolar disorder is a complex mental condition characterized by alternating periods of mood swings between extreme highs (mania or hypomania) and lows (depression) (Tondo et al., 2017) [Figure 7]. Bipolar disorder often shows familiar patterns, suggesting a genetic predisposition. A family history of the condition increases the likelihood of developing bipolar disorder. Studies have estimated that genetic factors contribute significantly to the risk of bipolar disorder, with heritability estimates ranging from 60–80% (Gordovez and McMahon, 2020). Similar to depression, bipolar disorder is considered to be a polygenic disorder.
Bipolar disorder is a complex mental condition influenced by a variety of biological, genetic, environmental, and psychosocial factors. Although the precise biological causes of bipolar disorder are not fully understood, several biological factors are thought to contribute to its development (Sigitova et al., 2017). Imbalances in neurotransmitters, including dopamine, serotonin, and norepinephrine, are believed to play a role in bipolar disorder. Fluctuations in the levels of these neurotransmitters can affect mood regulation and contribute to cycling between manic and depressive episodes. Structural and functional abnormalities in certain brain regions involved in mood regulation and emotional processing have been observed in individuals with bipolar disorder. Irregularities in the body's internal biological clock, which regulates sleep-wake cycles and other physiological processes, are typically detected in individuals with bipolar disorder. Disruptions in circadian rhythms may contribute to mood fluctuations seen in this disorder.
Researchers have identified several candidate genes associated with bipolar disorder, and ongoing studies aim to understand their roles [Figure 8]. These genes are involved in various biological pathways, including neurotransmitter regulation, circadian rhythm, ion channel functioning, and neuronal signaling (Smedler et al., 2019). CACNA1C (calcium voltage-gated channel subunit alpha-1C) encodes a subunit of a calcium channel involved in neuronal signaling. Variations in CACNA1C have been associated with bipolar disorder in multiple studies, suggesting its potential role in mood dysregulation and susceptibility to the condition. ANK3 (ankyrin-3) encodes a protein involved in maintaining the structure of neurons and in regulating ion channels. Variations in ANK3 have been implicated in bipolar disorder, potentially affecting neuronal excitability and signaling. GRM3 (glutamate metabotropic receptor 3) encodes a glutamate receptor involved in neurotransmission, and abnormalities in glutamate signaling have been implicated in mood disorders. DAOA (D-amino acid oxidase activator) has been studied for its involvement in regulating the activity of the D-amino acid oxidase enzyme, which plays a role in neurotransmitter metabolism.
Treatment for bipolar disorder typically involves a combination of medications, psychotherapy, lifestyle changes, and support. There are some medications that can manage mood episodes, reduce their frequency and severity, and improve overall quality of life. However, additional research is essential to unravel the complexities of this matter and develop more precise interventions tailored to specific needs.
Autism Spectrum Disorder (ASD)
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by challenges with social communication and interactions, repetitive behaviors, and often restricted interests or activities [Figure 9]. ASD is a spectrum disorder, meaning it affects individuals differently and to varying degrees, ranging from mild to severe (Sharma et al., 2018). Genetics play a significant role in the development of ASD. While the exact causes of ASD are not entirely understood, research has shown that genetic factors significantly concur to its development. Several genes have been implicated in ASD, and it is believed that a combination of genetic variations or mutations, along with environmental factors, contribute to the risk of developing ASD.
Certain rare and spontaneous mutations such as de novo mutations, that occur for the first time in an affected individual and are not inherited from the parents and copy number variations (CNVs), have been linked to ASD (Wang et al., 2016) [Figure 10]. Some of the de novo mutations associated with ASD are in the SHANK3 gene, which is involved in synaptic function and plays a role in maintaining the structure and function of synapses; the ADNP gene, which is essential for brain development and is engaged in regulating the expression of other genes critical for neuronal function; and the CHD8 gene, which is associated with chromatin remodeling and gene regulation during brain development. Changes in CNVs, such as deletions or duplications, specifically in the 16p11.2 region, have been associated with ASD because changes in this genomic region can affect the expression of genes related to brain development and synaptic function (Varghese et al., 2017).
Common genetic variants are variations in DNA that are relatively common in the general population. Unlike the rare and highly penetrant mutations seen in some cases of ASD, these common variants individually contribute only a small increase in the risk of developing ASD [Figure 10]. Collectively, however, they may have a more significant impact on susceptibility to ASD. Several genes have been identified where common genetic variants may play a role in the risk of ASD. These include CDH10 and CDH9, which encode cadherin proteins involved in cell adhesion and neural connectivity; CNTNAP2, which encodes a protein that is part of the neurexin family and plays a role in neural development and communication between neurons; ASTN2, a gene involved in neuronal migration and organization of the cerebral cortex; and NRXN1, which contributes to synaptic function and connectivity between neurons. These common genetic variants are thought to contribute to the risk of ASD through more subtle effects on brain development, neuronal connectivity, and synaptic function. However, each individual variant confers only a small increase in risk, and their combined effects in interaction with environmental factors and other genetic variations contribute to the overall risk of developing ASD (Grove et al., 2019).
It is important to note that while genetics contribute significantly to ASD, environmental factors also play a role [Figure 10]. Factors such as prenatal complications, maternal health, exposure to certain environmental toxins or infections during pregnancy, and early childhood experiences may also influence the development of ASD. The genetic landscape of ASD is highly complex, and the interplay between various genetic and environmental factors is still an area of active research. The heterogeneity of ASD—its diverse symptoms and severity among affected individuals—suggests that multiple genetic pathways and interactions contribute to its development (Masini et al., 2020). Understanding the genetic basis of ASD is crucial for advancing research into potential treatments, early interventions, and personalized approaches to support individuals affected by ASD. However, due to the complex and multifaceted nature of ASD, further research is necessary to unravel its intricacies and develop more targeted interventions.
Fragile X Syndrome
Fragile X syndrome is caused by a mutation in the FMR1 gene located on the X chromosome. The mutation in the FMR1 gene results in the silencing or reduced production of a protein called FMRP (fragile X mental retardation protein). The clinical features of Fragile X syndrome vary in severity, but commonly include intellectual disability, social and communication difficulties, hyperactivity, sensory sensitivities, and repetitive behaviors. Physical characteristics may include a long face, large ears, and a prominent jaw or forehead. Affected individuals may also exhibit behavioral challenges, such as anxiety, social avoidance, and mood instability (Hagerman et al., 2017). The prevalence of Fragile X syndrome is 1 in 4,000 males and 1 in 6,000 females worldwide (Salcedo-Arellano et al., 2020), and boys are typically diagnosed at approximately 35 to 37 months of age, while girls are diagnosed at approximately 42 months of age.
The syndrome gets its name from a mutation that leads to a minor break in one of the arms of the X chromosome, referred to as the fragile site [Figure 11]. Within the FMR1 gene, there is a specific segment with a repeating genetic sequence known as the CGG trinucleotide. In individuals unaffected by Fragile X syndrome, this sequence repeats between 5 and 40 times. However, when the number of repeats surpasses this range, it leads to a modification in the gene's genetic code. This triggers a cascade of molecular processes that leads to the complete inactivation of the gene and the cessation of its corresponding protein production. Furthermore, when the CGG sequence is repeated between 45 and 200 times, it is called a premutation, and individuals with this condition do not develop the disease because the functionality of the gene remains relatively intact, but they can pass it on to their offspring. In contrast, those with more than 200 repeats are considered to have a complete mutation, which leads to the development of the disease (Tabolacci et al., 2022).
FMRP is distributed throughout the body, with the highest concentrations in the brain and testes. Its primary role is to selectively bind to approximately 4% of mRNA in the mammalian brain, facilitating the transport of this mRNA from the cell nucleus to presynaptic cell endings. Most of these mRNA targets are located in the dendrites of neurons. Brain tissue from individuals with Fragile X syndrome and mouse models exhibits irregular dendritic spines, which are crucial for enhancing connections with other neurons. As a consequence, these anomalies in synaptic formation and function, along with the development of neural circuits, lead to compromised neuroplasticity, a fundamental aspect of memory and learning (Richter & Zhao, 2021).
This condition also has a significant impact on the reproductive health of both carriers and patients. Women who carry the premutation face an elevated risk of experiencing early ovarian failure and a reduced ovarian reserve, which can ultimately lead to the onset of premature menopause [Figure 12]. This condition affects approximately 20% of Fragile X carriers (Gleicher & Barad, 2010). In cases where the ovarian reserve is prematurely depleted, the primary reproductive solution available to these women is oocyte donation treatment. In situations where a man is affected by Fragile X syndrome, the use of donor sperm may be considered to prevent the transmission of the genetic disorder to their offspring. These reproductive alternatives are highly effective, and ensure that children are not affected by the condition. Both egg and sperm donors will undergo rigorous screening to detect the presence of this genetic alteration.
Fragile X syndrome lacks a definitive cure for its inherent defects. The approach to managing this condition typically involves a multifaceted strategy that encompasses speech therapy, behavioral therapy, occupational therapy, specialized education, and customized educational plans. In cases where physical abnormalities are present, appropriate treatment may also be administered. For individuals with a family history of Fragile X syndrome, genetic counseling is recommended to assess the risk of inheriting the condition to their offspring and to gauge the potential severity of impairments in affected descendants.
Rett Syndrome
Rett syndrome is a rare and complex neurodevelopmental disorder that predominantly affects girls (Percy, 1995). It was first identified and described by the Austrian physician Andreas Rett in 1966. The disorder is characterized by a period of apparently normal development in early infancy, followed by a regression of acquired skills, particularly in language and motor function. Symptoms typically manifest between six months and two years of age. One of the hallmark features is repetitive hand movements such as handwringing, clapping, or rubbing. In addition, individuals with Rett syndrome often experience a loss of purposeful hand skills and may develop gait abnormalities and muscle stiffness. Beyond motor symptoms, Rett syndrome can also present with various other features, including breathing irregularities (such as hyperventilation and breath-holding), seizures, social withdrawal, intellectual disability, and difficulties with communication and social interaction (Banerjee et al., 2019) [Figure 13].
The majority of Rett syndrome cases are caused by mutations in the MECP2 gene (methyl-CpG-binding protein 2). The MECP2 gene provides instructions for producing a protein that plays a crucial role in the proper functioning of nerve cells, particularly in the brain. This gene is located on the X chromosome and encodes the MECP2 protein (Kyle et al., 2018) [Figure 14]. The MECP2 protein is involved in regulating the activity of other genes by binding to methylated regions of DNA. Methylation is a chemical modification that can affect gene expression without altering the underlying DNA sequence. The MECP2 protein helps interpret these methylated signals and influences the expression of genes involved in brain development and function. MECP2 is essential for various neurological processes, including the formation and maintenance of synapses (the connections between nerve cells), neuronal maturation, and overall brain development. It regulates the expression of many genes critical for neuronal function and supports the proper functioning of neurons. Mutations in the MECP2 gene disrupt the normal function of the MECP2 protein, leading to an array of neurological and developmental symptoms characteristic of Rett syndrome and other disorders (Chin & Goh, 2019).
The severity and specific symptoms of Rett syndrome can vary widely among affected individuals. While there is no cure for Rett syndrome, various therapies, and interventions, including physical therapy, speech therapy, and supportive care, are used to manage symptoms and improve the quality of life for individuals with the condition. Ongoing research continues to focus on understanding the underlying mechanisms of the disorder and exploring potential treatments and interventions.
Conclusion
The realm of mental and behavioral diseases presents a complex landscape shaped by a multitude of factors, including genetics, environment, and individual lifestyle. This comprehensive review delved into the intricate nature of these conditions, exploring their diverse clinical manifestations, associated genetic mutations, diagnostic challenges, and the significant hurdles they pose to affected individuals. While understanding the genetic underpinnings of mental and behavioral diseases remains a challenging pursuit, it holds immense promise for advancing our knowledge and fostering the development of more targeted and effective therapies. The intricate interplay between genetic susceptibility and environmental influences underscores the need for multifaceted approaches to diagnosis, treatment, and support for those grappling with these conditions.
Bibliographical References
Banerjee, A., Miller, M.T., Li, K., Sur, M., & Kaufmann, W.E. (2019). Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder. Brain 142(2), 239–248. https://doi.org/10.1093/brain/awy323
Chin, E.W.M., & Goh, E.L.K. (2019). MeCP2 Dysfunction in Rett Syndrome and Neuropsychiatric Disorders. Methods in Molecular Biology 2011, 573–591. https://doi.org/10.1007/978-1-4939-9554-7_33
Datta, S., Suryadevara, U., & Cheong, J. (2021). Mood Disorders. Continuum 27(6), 1712–1737. https://doi.org/10.1212/con.0000000000001051
Gleicher, N., & Barad, D.H. (2010). The FMR1 gene as regulator of ovarian recruitment and ovarian reserve. Obstetetrical & Gynecological Survey 65(8), 523–530. https://doi.org/10.1097/ogx.0b013e3181f8bdda
Gordovez, F.J.A., & McMahon, F.J. (2020). The genetics of bipolar disorder. Molecular Psychiatry 25(3), 544–559. https://doi.org/10.1038/s41380-019-0634-7
Grove, J., Ripke, S., Als, T.D., Mattheisen, M., Walters, R.K., Won, H., Pallesen, J., Agerbo, E., Andreassen, O.A., Anney, R., et al. (2019). Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics 51(3), 431–444. https://doi.org/10.1038/s41588-019-0344-8
Hagerman, R.J., Berry-Kravis, E., Hazlett, H.C., Bailey, D.B.J., Moine, H., Kooy, R.F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J.L., et al. (2017). Fragile X syndrome. Nature Reviews. Disease Primers 3, 17065. https://doi.org/10.1038/nrdp.2017.65
Johnstone, M., Thomson, P.A., Hall, J., McIntosh, A.M., Lawrie, S.M., & Porteous, D.J. (2011). DISC1 in schizophrenia: genetic mouse models and human genomic imaging. Schizophrenia Bulletin 37(1), 14–20. https://doi.org/10.1093/schbul/sbq135
Kyle, S.M., Vashi, N., & Justice, M.J. (2018). Rett syndrome: a neurological disorder with metabolic components. Open Biology 8(2), 170216. https://doi.org/10.1098/rsob.170216
van de Leemput, J., Hess, J.L., Glatt, S.J., & Tsuang, M.T. (2016). Genetics of Schizophrenia: Historical Insights and Prevailing Evidence. Advances in Genetics 96, 99-141 99–141.https://doi.org/10.1016/bs.adgen.2016.08.001
Lewine, R., & Hart, M. (2020). Schizophrenia spectrum and other psychotic disorders. Handbook of Clinical Neurology 175, 315–333. https://doi.org/10.1016/b978-0-444-64123-6.00022-9
Masini, E., Loi, E., Vega-Benedetti, A.F., Carta, M., Doneddu, G., Fadda, R., & Zavattari, P. (2020). An Overview of the Main Genetic, Epigenetic and Environmental Factors Involved in Autism Spectrum Disorder Focusing on Synaptic Activity. International Journal of Molecular Sciences 21(21), 8290. https://doi.org/10.3390/ijms21218290
Nedic Erjavec, G., Sagud, M., Nikolac Perkovic, M., Svob Strac, D., Konjevod, M., Tudor, L., Uzun, S., & Pivac, N. (2021). Depression: Biological markers and treatment. Progress in Neuro-psychopharmacology & Biological Psychiatry 105, 110139. https://doi.org/10.1016/j.pnpbp.2020.110139
Neuhaus, A.H., Opgen-Rhein, C., Urbanek, C., Hahn, E., Ta, T.M.T., Seidelsohn, M., Strathmann, S., Kley, F., Wieseke, N., Sander, T., et al. (2009). COMT Val 158 Met polymorphism is associated with cognitive flexibility in a signal discrimination task in schizophrenia. Pharmacopsychiatry 42(4), 141–144. https://doi.org/10.1055/s-0028-1112132
Norkeviciene, A., Gocentiene, R., Sestokaite, A., Sabaliauskaite, R., Dabkeviciene, D., Jarmalaite, S., & Bulotiene, G. (2022). A Systematic Review of Candidate Genes for Major Depression. Medicina. 58(2), 285. https://doi.org/10.3390/medicina58020285
Otte, C., Gold, S.M., Penninx, B.W., Pariante, C.M., Etkin, A., Fava, M., Mohr, D.C., & Schatzberg, A.F. (2016). Major depressive disorder. Nature Reviews. Disease Primers 2, 16065. https://doi.org/10.1038/nrdp.2016.65
Percy, A.K. (1995). Rett syndrome. Current Opinion in Neurology 8(2), 156–160. https://doi.org/10.1097/00019052-199504000-00013
Richter, J.D., & Zhao, X. (2021). The molecular biology of FMRP: new insights into fragile X syndrome. Nature Reviews. Neuroscience 22(4), 209–222. https://doi.org/10.1038/s41583-021-00432-0
Salcedo-Arellano, M.J., Hagerman, R.J., & Martínez-Cerdeño, V. (2020). Fragile X syndrome: clinical presentation, pathology and treatment. Gaceta Medica de Mexico 156(1), 60–66. https://doi.org/10.24875/gmm.19005275
Schultz, S.H., North, S.W., & Shields, C.G. (2007). Schizophrenia: a review. American Family Physician 75(12), 1821–1829. https://www.aafp.org/link_out?pmid=17619525
Sharma, S.R., Gonda, X., & Tarazi, F.I. (2018). Autism Spectrum Disorder: Classification, diagnosis and therapy. Pharmacology & Therapeutics 190, 91–104. https://doi.org/10.1016/j.pharmthera.2018.05.007
Shea, S.E. (2012). Intellectual disability (mental retardation). Pediatrics in Review 33(3), 110–111. https://doi.org/10.1542/pir.33-3-110
Sigitova, E., Fišar, Z., Hroudová, J., Cikánková, T., & Raboch, J. (2017). Biological hypotheses and biomarkers of bipolar disorder. Psychiatry and Clinical Neurosciences 71(2), 77–103. https://doi.org/10.1111/pcn.12476
Smedler, E., Bergen, S.E., Song, J., & Landén, M. (2019). Genes, biomarkers, and clinical features associated with the course of bipolar disorder. European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology 29(10), 1152–1160. https://doi.org/10.1016/j.euroneuro.2019.07.132
Smith, R.L., Knight, D., Williams, H., Dwyer, S., Richards, A., Kirov, G., O’Donovan, M.C., & Owen, M.J. (2011). Analysis of neurogranin (NRGN) in schizophrenia. American Journal of Medical Genet. Part B, Neuropsychiatry Genetics: the Official Publication of the International Society of Psychiatry Genetics 156B(5), 532–535. https://doi.org/10.1002/ajmg.b.31191
Tabolacci, E., Nobile, V., Pucci, C., & Chiurazzi, P. (2022). Mechanisms of the FMR1 Repeat Instability: How Does the CGG Sequence Expand? International Journal of Molecular Sciences 23(10), 5425. https://doi.org/10.3390/ijms23105425
Tondo, L., Vázquez, G.H., & Baldessarini, R.J. (2017). Depression and Mania in Bipolar Disorder. Current Neuropharmacology 15(3), 353–358. https://doi.org/10.2174/1570159x14666160606210811
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D.L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J.D., et al. (2017). Autism spectrum disorder: neuropathology and animal models. Acta Neuropathologica 134(4), 537–566. https://doi.org/10.1007/s00401-017-1736-4
Wang, T., Guo, H., Xiong, B., Stessman, H.A.F., Wu, H., Coe, B.P., Turner, T.N., Liu, Y., Zhao, W., Hoekzema, K., et al. (2016). De novo genic mutations among a Chinese autism spectrum disorder cohort. Nature Communications 7, 13316. https://doi.org/10.1038/ncomms13316
Williams, H.J., Owen, M.J., & O’Donovan, M.C. (2007). Is COMT a susceptibility gene for schizophrenia? Schizophrenia Bulletin 33(3), 635–641. https://doi.org/10.1093/schbul/sbm019
Visual Sources
Cover Image: [Artistic representation of genetics and mental disorders]. [Image]. Mount Sinai. Retrieved on 17th November, 2023 from https://www.mountsinai.org/about/newsroom/2023/researchers-identify-novel-genes-that-may-increase-risk-for-schizophrenia
Figure 1: [Types of mental disorders] [Image]. (Verywell Health, 2022). Retrieved on 17th November, 2023 from https://www.verywellhealth.com/top-mental-health-disorders-a-mental-illness-list-5210092
Figure 2: [Symptoms of schizophrenia]. [Image]. Cleveland Clinic, n.d.. Retrieved on 17th November, 2023 from https://my.clevelandclinic.org/health/diseases/4568-schizophrenia
Figure 3. (Devine, 2016) [DISC1 is a coordinator of intracellular trafficking to shape neuronal development and connectivity] [Image]. The Journal of Physiology. Retrieved on 17th November, 2023 from https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP272187
Figure 4: [COMT enzyme activity] [Image]. Genetic Lifehacks, 2020. Retrieved on 17th November, 2023 from https://www.geneticlifehacks.com/comt-genetic-connections-to-neurotransmitter-levels/
Figure 5: (Sullivan, 2000) [Estimates of the depression heritability]. [Image] Retrieved on 17th November, 2023 from https://doi.org/10.1176/appi.ajp.157.10.1552
Figure 6: (Garcia-Arocena, 2015) [The role of neurotransmitters in normal and depressed people with or without treatment]. [Image] The Jackson Laboratory. Retrieved on 17th November, 2023 from https://www.jax.org/news-and-insights/jax-blog/2015/december/happy-or-sad-the-chemistry-behind-depression
Figure 7. [Bipolar disorder symptoms]. [Image] Verywell Health, 2023. Retrieved on 17th November, 2023 from https://www.verywellhealth.com/bipolar-disorder-5090253
Figure 8. [Individuals diagnosed with bipolar disorder exhibit a higher likelihood of possessing multiple uncommon variations of genes that regulate the activity of nerve cells]. [Image] ScienceNews, 2015. Retrieved on 17th November, 2023 from https://www.sciencenews.org/article/bipolar-risk-boosted-accumulation-rare-versions-genes
Figure 9: (Rudy, 2023) [Symptoms of autism] [Image] Verywell Health, 2023. Retrieved on 17th November, 2023 from https://www.verywellhealth.com/the-spectrum-of-autism-symptoms-5094373
Figure 10: (Huguet, 2016) [Relative contributions of genetics and environment in ASD]. [Image] Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability. Retrieved on 17th November, 2023 from https://www.sciencedirect.com/science/article/abs/pii/B9780128001097000029
Figure 11: [Comparison between normal chromosome and fragile X chromosome]. [Image] InviTRA, 2022. Retrieved on 17th November, 2023 fromhttps://www.invitra.com/en/fragile-x-syndrome/
Figure 12: [Premature ovarian failure]. [Image] Bridge Clinic, 2020. Retrieved on 17th November, 2023 fromhttps://www.thebridgeclinic.com/blog/unravelling-the-mystery-behind-premature-ovarian-failure
Figure 13: [Rett syndrome symptoms]. [Image] Psychiatrist, 2023. Retrieved on 17th November, 2023 from https://www.psychiatrist.com/news/a-reason-for-hope-in-rett-syndrome-new-medications-novel-gene-therapies/ Figure 14: (Verhoeven et al., 2010) [Schematic representation of the location of the MECP2 gene on the long arm of the X chromosome]. [Image]. Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment. Retrieved on 17th November, 2023 from https://www.researchgate.net/figure/Rett-syndrome-and-the-MECP2-Gene-Schematic-representation-of-the-location-of-the-MECP2_fig3_221914164
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