Genetic Links Found for Autism and Schizophrenia

Mental health and human brain

Since the completion of the human genome project, researchers have been discovering changes to hundreds of places in the DNA. Some of these variants have been associated with psychiatric diseases such as autism spectrum disorder and schizophrenia. Researchers have found a roadmap for the development of new generation therapy for psychiatric conditions. In the last decade, scientists have conducted genetic studies of people with a psychiatric disease, comparing results to healthy individuals to find genes that have different sequencing in those diseases. This paper helps to explain the roles of tens of thousands of sections of regulatory DNA and proteins in the brain. Once again this study is but a jumping off place for further studies (Geschwind et al, 2018). Dendritic structure (dendrite is a short branched extension of a nerve cell along which impulses received from other cells at synapses are transmitted to the cell body) is tightly coupled with synaptic function in basal conditions. Many brain disorders are associated with an aberrant regulation of F-actin and impaired signaling. These alterations likely underlie the aberrant spine morphology found in these disorders. Further studies on the mechanism of structural plasticity of dendritic spines will provide new therapeutic targets and methods for the treatment of neuropsychiatric disorders (Borovac et al, 2018).


Evolution usually deals in genomic trade-offs: changes in the genome that are beneficial overall persist even though they cause disease in a subset of individuals. This includes the key genes that helped with the expansion of the brain and the wonderful cognitive capacities are significant contributors to autism and schizophrenia. This is not the first study to say this either. Other studies have found the same genes that are involved in schizophrenia are also crucial to the rapid expansion of the human brain. An example of this tradeoff is sickle cell disease. In areas where malaria is endemic (regularly found among certain people or certain areas), the same genes that can cause sickle cell in some individuals can also provide resistance to malaria. So the variant persists in this population even though in some people it has a harmful side effect.

This study found the support of the Olduvai protein family underlies a cognitive genomic tradeoff in our species. Specifically, these sequences can play both a beneficial role (in brain evolution and cognition) and a harmful role (in autism and schizophrenia) and which outcome occurs depends on which, where, how, and when copies are changing. It is felt this duality of effect could potentially be the reason for the central paradox of why autism and schizophrenia persist at high frequency across human populations. It may well be a steep price paid placed on the human brain by evolution and these researchers feel compelled to show those afflicted compassion for those who must somehow live with these disorders (Sikela & Quick, 2018).

What are schizophrenia and autism
Schizophrenia and autistic spectrum disorder are two of the most important neurodevelopmental disorders encountered in clinical psychiatric practice. Both are diagnosed by clinical history, symptoms, and behavior. These behaviors include hallucinations, delusions, and thought disorder as well as withdrawal from society and a range of cognitive abnormalities; attention, memory, and executive function. Autism spectrum disorder is characterized by abnormalities of social communication and interactive and repetitive patterns of interest and behavior. Both occur in early adulthood and have neurodevelopmental origins. And they both have strong familial ties; up to 80% for schizophrenia and 80-90% for autism. Both disorders are formidable challenges for those aiming to find methods to diagnose and treat these diseases. With current developments of groups like CRISPER that threshold may be met soon (St. Clair & Johnson, 2018).

Difficulties faced with these diseases
Severe mental illness schizophrenia is recognized as a leading cause of morbidity and ranks as one of the most costly disorders to affect humans. And while there is still a huge amount of study needing to be done, translating genetic findings to improve clinical practice for patients with schizophrenia it is hoped this genetic study can lead to more efficient treatment strategies for cognitive dysfunction. Cognitive dysfunction is important in schizophrenia but the question continues why some people with schizophrenia do not have cognitive deficits and why is the development of psychosis only associated with some diseases? Going forward will be important to implement a cross-disciplinary approach across current research fields and disease specific treatment programs to get a clearer the picture of what is involved with development of cognitive deficits in schizophrenia (Smeland & Andreassen, 2018).

Schizophrenia is a severe mental illness with complex genetic architectures. Recent studies have shown different variants are involved in the cause of this disorder. Schizophrenia has shown to have high heritability suggesting it has a role in inherited variants in genetic predisposition to schizophrenia. And though many studies have been done there still remains the difficulty in finding a way to translate the genetic findings into molecular risk models. There continues to be difficulties in pinpointing the casual gene at each risk locus. And they usually contain multiple genetic variants. While this study did result in promising data, there were some limitations. The researchers recommend further biological experiments to demonstrate the role of prioritized genes in schizophrenia (Ma et al, 2018).

Autism affects 1% of world population and has become a pressing medical and social problem worldwide. Thus far, a coherent understanding of autistic spectrum disorder biology has not been achieved. It is a complex genetic disorder. Thousands of autistic families have been analyzed yet a single cause is still to be found. After analyzing thousands of mutations the results suggest that isolated rare mutation events are actually connected and recurrent at gene levels. Valid method and reproducible results are critical for genome-scale studies. The researchers found several pathways that may cause the disease as supported by multiple independent studies. These pathways present a catalog of autistic genetic associations and also connect hundreds of interacting genes and variants into a multi-scale system. All the mutated pathways or functions converge to synaptic biology. This function is disrupted in these cases (Luo et al, 2018).

Autism spectrum disorder and schizophrenia have complex inheritance patterns with multiple genetic and environmental factors influencing disease risk. Although autism and schizophrenia are distinct disorders available evidence suggest that genetic overlap is present. These disorders co-occur at a higher rate than would be expected in the general population. A recent study showed that a family history of schizophrenia in first-degree relatives (mother, father, brother, sister and any offspring of the brothers and sisters) was also a risk of autism. These autism/schizophrenia associations are also implicated in other neurodevelopmental disorders including intellectual disability and attention deficit hyperactivity disorder. This study identified biologic pathways common to both disorders including the stress response. Well-established genes for autism and schizophrenia were found in the human cerebral cortex specific functional interaction network. This helped to add validity to the study (Kushima et al, 2018).

Research showing promise
Familial clustering of schizophrenia bipolar disorder, and major depressive disorder have been systematically reported and with evidence from genetics there are intrinsic connections between these three major psychiatric disorders. Schizophrenia is a severe mental disorder characterized by disruptive thought processes that can cause delusions and hallucinations. It is noted in molecular genetics with a disequilibrium has been found in some individuals over last two decades. Links have been identified chromosomal regions for schizophrenia and autism. Schizophrenia is a devastating mental illness with overlapping genetic components. Susceptibility genes on chromosome 3 for schizophrenia were systematically indentified in a relative homogeneous population in China. The gene NLGN1 has been identified being associated with schizophrenia and autism (Chen et al, 2018).

Gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, and schizophrenia have accelerated and proven hard to generate specific hypothesis without corresponding datasets at protein complex. The global burden of mental illness is enormous. This issue is further compounded by poor access to care, particularly in developing countries. Recent advances in gene discovery have set the stage for a better understanding of neuropsychiatric disorders. And while this progress is exciting translating the findings to a better understanding of the underlying pathobiology of neuropsychiatric disorders remain largely unrealized. Despite the challenges, this field is at a potential tipping point in the endeavor to understanding the pathobiology of these disorders. There is now an unprecedented opportunity to bridge the gap between gene discovery and translational biology (Willsey, et al, 2018).

The human brain contains over 200 billion cells therefore studying the human brain development has become very challenging given all the data available from different studies. Recent stem cell methods may give rise to possibility of modeling neurodevelopmental diseases associated with genetic defects. Besides autism, diseases such as schizophrenia and Rett syndrome display symptoms in common with autism. These include cognitive dysfunctions with mental retardation and dysmorphia. In addition, epilepsy, motor coordination, and sensorial hypersensitivity were also found. Advances in genome editing technologies allow the genetic manipulation of iPSC. These steps should provide new plausible models to study human neurodevelopmental diseases and additional opportunities for future drug development as well (Vitrac & Clo√ęz-Tayarani, 2018). Neuropsychiatric disorders are highly heritable. And while there have been new chances to decipher disease progress have been limited in part because of the multi loci and hundreds of candidate genes. In addition shared genetic predisposition indicates that some genes contribute to general brain health while others influence specific disease manifestations. This study found there is substantial overlap in risk factors for neuropsychiatric disorders. One of these is epilepsy. Symptoms of temporal lobe epilepsy and children diagnosed with it are at a higher risko of developing schizophrenia. In addition to this autism was found to share genetic risk architecture with schizophrenia. By the end of the study they found associated genome for bipolar, depression and sleep disorders in addition to autism and schizophrenia (Thyme et al, 2018).


Works Cited
Borovac, J. et al. (2018). Regulation of actin dynamics during structural plasticity of dendrite spines: Signaling messengers and actin-binding proteins. Science Direct.

Chen,X. et al. (2018). A novel relationship for schizophrenia bipolar and major depressive disorder Part 3: Evidence from chromosome 3 high density association screen. Journal of Comparative Neurology.

Geschwind, D. et al. (2018). Researchers uncover molecular mechanisms linked to autism and schizophrenia. University of California-Los Angeles Health Services.

Kushima, I. et al. (2018). Comparative analysis of copy-number variation in autism spectrum disorder and schizophrenia reveal etiological overlap and biological insights. Cell Reports, 24(11).

Luo, W. et al. (2018). Systemic reconstruction of autism biology from massive genetic mutation profiles. Science Advances.

Ma, C. et al. (2018). Integrated landscapes of causual genes and pathways in schizophrenia. Translational Psychiatry, 8(67).

Sikela, J. M. & Quick, V.B.S. (2018). Genomic trade-offs are autism and schizophrenia the steep price of the human brain? Human Genetics,137 (1).

Smeland, O.B. & Andreassen, O.A> (2018). How can genetics help understand the relationship between cognitive dysfunction and schizophrenia. Scandinavian Journal of Psychology, 59(1).

St. Clair, D. & Johnstone, M. (2018). Using mourse transgenic and human stem cells tech to model genetic mutations associated with schizophrenia and autism. Philosophical Transactions of the Royal Society B: Biologic Sciences,373(1742).

Thyme, S.B. et al. (2018). Phenotype landscape of schizophrenia-associated genes defines candidates and their shared functions. bioRxiv.

Vitrac, A. & Cloez-Tayarani, I. (2018). Induced pluripotent stem cell as a tool to study brain circuits in autism-related disorders. Stem Cell Research & Therapy

Willsey, A.J. et al. (2018). The psychiatric cell map initiative: A convergent systems biological approach to illuminating key molecular pathways in neuropsychiatric disorders. Cell.