Genetic Etiology of Mental Health Disorders

[Pages:68]Genetic Etiology

of Mental Health Disorders

Prepared by: James J. Messina, Ph.D., CCMHC, NCC, DCMHS Assistant Professor, Troy University, Tampa Bay Site

5 Mental Health Disorders Found Share Genetic Etiology

1. Autism 2. ADHD 3. Schizophrenia 4. Bipolar Disorder 5. Major Depressive Disorder

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.

2013 Study by Hong et al-What did they study? First what's SNPs?

Hong et al, 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

2013 Study by Hong et al-What did they study? Five psychiatric disorders

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)

2013 Study by Hong et al 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

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.

What was the thinking at the Beginning of this Century

In 2001, some examples of genes thought to be associated with different disorders or traits

Gene

Alleles

Dopamine D4 receptor (DRD4)

Serotonin transporter (5HTT)

Serotonin 2a receptor (5HT2a)

Long Short C polymorphism

Associated Disorder or Trait ADHD

Neuroticism Bipolar Disorder Schizophrenia

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.

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