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Genetic Etiology of Mental Health Disorders


5 Mental Health Disorders Found Share Genetic Etiology ( Hong et al, 2013)
1.Autism
2.ADHD
3.Schizophrenia
4.Bipolar Disorder
5.Major Depressive Disorder

What's a SNP?
Hong et al, (2013) used SNPs to see if there was a common genetic link for the five psychiatric conditions.

Single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people

SNPs occur normally throughout a person’s DNA

They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome

Most commonly, these variations are found in the DNA between genes

They can act as biological markers, helping scientists locate genes that are associated with disease

When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function

SNPs can also be used to track the inheritance of disease genes within families


What did they study? 

Most psychiatric disorders are moderately to highly heritable, but the degree to which genetic variation is unique to individual disorders or shared across disorders is unclear


They examined shared genetic etiology, by using genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD)


What did they Find?

Genetic correlation calculated using common SNPs was

  • High between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.),
  • Moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.)
  • Low between schizophrenia and Autism Spectrum Disorder (ASD) (0.16 ± 0.06 s.e.)
  • Non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease


They concluded: This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology (classification of diseases) & encourages the investigation of common pathophysiologies for related disorders


Hong, L.S., Ripke, S., Neale, B.M., Faraone, S.V., Purcell, S.M., Perlis, R.H., Mowry, B.J., Thapar, A., Goodard, M.E., Witte, J.S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreasssen, O.A., Anjoriin, A., Anney, R., Anttila, V., Arking, D.E. & Asherson, P. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45(9), 984-994. 

At the Beginning of the 21st Century there was acceptance of Genetic Etiology of Mental Illness

Hyman (2000) concluded that:

It was well established that the risk of mental illness runs in families. Family, twin and adoption studies had shown that for:

  • Schizophrenia
  • Autism
  • Bipolar Disorder
  • Major Depression
  • Attention Deficit Hyperactivity Disorder (ADHD)
  • Panic Disorder
  • Other mental illnesses,
  • the transmission of risk is due to heredity


Hyman, S.E. (2000). The genetics of mental illness: Implications for practice. Bulletin of the World Health Organization, 78(4), 455-463.

Link to Chromosome 18?

Kamnasaren (2003) found that  linkage, association and chromosome aberration studies have suggested that intervals on both the short arm (p) and long arm (q) of chromosome 18 may contain genes for psychiatric disorders:

  • Autism
  • Schizophrenia
  • Affective disorders


Kamnasaran, D. (2003). 2003 Genetic analysis of psychiatric disorders associated with human chromosome 18. Clinical & Investigative Medicine, 26(6), 285-302.

Impact of Family, Twin & Adoption Studies in 2004

Shih et al (2004) concluded that:

Family, twin and adoption studies provided major evidence for the role of genetics in numerous psychiatric disorders including:

  • obsessive-compulsive disorder
  • panic disorder
  • major depressive disorder
  • bipolar disorder
  • schizophrenia
  • Alzheimer's disease.


Shih, R. A., Belmonte, P. L., & Zandi, P. P. (2004). A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders. International Review Of Psychiatry, 16(4), 260-283. doi:10.1080/0954026040001440

Cannon and Keller (2006) Used Endophenotypes to Analyze Genetic Etiology

Endophenotypes—intermediate phenotypes that form the causal links between genes and overt expression of disorders

Endophenotypes involve interaction of:

Gene
Protein
Cellular System & Signaling Pathway
Neural System Dysfunction
Cognitive Dysfunction
Symptoms
Syndrome


Cannon, T.D. & Keller, M.C. (2006). Endophenotypes in the genetic analyses of mental disorders. Annual Review of Clinical Psychology, 2, 267-290. 

doi: 10.1146/annurev.clinpsy.2.022305.095232


In 2008 Call went out for Use of other Factors in getting to Genetic Etiology of Disorders

Researchers stated that several psychiatric disorders — such as bipolar disorder, schizophrenia and autism — are highly heritable, yet identifying their genetic basis has been challenging, with most discoveries failing to be replicated

However, inroads had been made by the incorporation of:

1.Intermediate traits (endophenotypes)
2.Environmental factors into genetic analyses
3.Through the identification of rare inherited variants and novel structural mutations


Burmeister, M., McInnis, M. G., & Zöllner, S. (2008). Psychiatric genetics: progress amid controversy. Nature Reviews Genetics, 9(7), 527-540. doi:10.1038/nrg2381
Co-morbidity of Bipolar, Alcohol Use Disorder and other conditions 

Carmiol et al (2014) looked into Bipolar disorder and alcohol use disorder (AUD) due to their high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes


Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD


They examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process,

  • 32% of the sample met criteria for bipolar disorder
  • 17% had a lifetime AUD diagnosis
  • 32% met criteria for lifetime nicotine dependence
  • 21% had an anxiety disorder
  • AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives

All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders

The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety


Their findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.


Carmiol, N. N., Peralta, J. M., Almasy, L. L., Contreras, J. J., Pacheco, A. A., Escamilla, M. A., & ... Glahn, D. C. (2014). Shared genetic factors influence risk for bipolar disorder and alcohol use disorders. European Psychiatry, 29(5), 282-287. doi:10.1016/j.eurpsy.2013.10.001

Clinical Application of the Study of the Genetics of Mental Health Disorders

We will now explore the Genetic Etiology of the Following Mental Health Disorders:

1.Autism Spectrum Disorder
2.ADHD
3.Schizophrenia
4.Bipolar Disorder
5.Major Depressive Disorder
6.Anxiety Disorders

We found that since the Genome Study Report of 2004, there have been great advances in the identification of the genetic etiology of mental health disorders and it is important for us as mental health professionals to always do a thorough psychosocial assessment which includes the mental health and substance use disorder background of our client’s families going back at least three generations to pick up if there is a heritable trait in the family for the presenting condition

REFERENCES GENERAL GENETIC STUDY FOR MULTIPLE MENTAL DISORDERS


Burmeister, M., McInnis, M. G., & Zöllner, S. (2008). Psychiatric genetics: progress

amid controversy. Nature Reviews Genetics9(7), 527-540. doi:10.1038/nrg2381

 

Cannon, T.D. & Keller, M.C. (2006). Endophenotypes in the genetic analyses of mental

disorders. Annual Review of Clinical Psychology, 2, 267-290. doi: 10.1146/annurev.clinpsy.2.022305.095232

 

Carmiol, N. N., Peralta, J. M., Almasy, L. L., Contreras, J. J., Pacheco, A. A., Escamilla,

M. A., & ... Glahn, D. C. (2014). Shared genetic factors influence risk for bipolar disorder and alcohol use disorders. European Psychiatry29(5), 282-287. doi:10.1016/j.eurpsy.2013.10.001

 

Hong, L.S., Ripke, S., Neale, B.M., Faraone, S.V., Purcell, S.M., Perlis, R.H., Mowry,

B.J., Thapar, A., Goodard, M.E., Witte, J.S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreasssen, O.A., Anjoriin, A., Anney, R., Anttila, V., Arking, D.E. & Asherson, P. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45(9), 984-994.

 

Kamnasaran, D. (2003). Genetic analysis of psychiatric disorders associated with

human chromosome 18. Clinical & Investigative Medicine, 26(6), 285-302.

 

Mosing, M. A., Gordon, S. D., Medland, S. E., Statham, D. J., Nelson, E. C., Heath, A.

C., & ... Wray, N. R. (2009). Genetic and environmental influences on the co-morbidity between depression, panic disorder, agoraphobia, and social phobia: a twin study. Depression & Anxiety (1091-4269)26(11), 1004-1011. doi:10.1002/da.20611

 

Shih, R. A., Belmonte, P. L., & Zandi, P. P. (2004). A review of the evidence from family,

twin and adoption studies for a genetic contribution to adult psychiatric disorders. International Review Of Psychiatry, 16(4), 260-283. doi:10.1080/09540260400014401