Psychiatric Neurogenetics

Section Head

Dr. James L. Kennedy

Contact 

Mary Smirniw, Administrative Secretary
Neurogenetics Section
Centre for Addiction and Mental Health
250 College Street
Toronto, Ontario M5T 1R8
Tel: (416) 535-8501 ext. 4807
mary_smirniw@camh.net 

Research Objective

The genetic factors in mental illness and the response of these illnesses to psychiatric medications are studied using brain imaging techniques to identify abnormal genes involved in the causes, expression, treatment, and possible cures for these disorders.

Summary of Activities 

CAMH scientists have amassed a collection of more than 11,000 DNA samples from psychiatric patients and control subjects. This collection is one of the largest in the world enabling researchers to examine not only the genetic risk factors within each illness, but also investigate the same symptom across several disorders.

The Krembil Family Epigenetics Laboratory is developing new methods to search the entire human genome for DNA sequences that have modifications influencing the manifestation of psychiatric illnesses. Epigenetics is a relatively new field of study that can help identify the cause of complex diseases and open new avenues for developing novel diagnostic and therapeutic approaches.

Attention Deficit Hyperactivity Disorder (ADHD)

CAMH scientists have shown that a dopamine D₄ receptor gene is involved with ADHD, prompting other groups to search for new medications for this disorder. The D₄ findings and added discoveries also show involvement of serotonin receptor genes in ADHD.

Autism

Research is focused on clarifying and understanding the genetics and molecular pathways of autism and other pervasive developmental disorders. Current projects and collaborations include:

• Identification of cytogenetic breakpoints and cloning and characterization of genes spanning breakpoints in autism and Rett patients.
• Functional and molecular studies of the MeCP2_E1 isoform, and identification of causative mutations in patients with Rett syndrome-like features.
• Fine-mapping of the X-chromosome in autism, also identification and characterization of genomic mutations on the X-chromosome in autism patients using 500K SNP microarray data, in order to identify autism candidate genes.
• Identification of disease loci in consanguineous autism/MR families from Pakistan, and functional characterization of disease genes.
• Genome scan and fine-mapping for autism susceptibility genes.
• Genetic mapping and identification of genes involved in hereditary neuropathies and neuromuscular disease.

Mood Disorders

Several neurotransmitter receptors have been identified that predict the risk for bipolar disorder. These include the subunit GRIN1 of the NMDA glutamate receptor, the D₄ receptor and genetic variants of the brain derived neurotrophic factor (BDNF). The glutamate system genes contribute to both schizophrenia and bipolar disorder and are an important area for further investigations. Investigations of suicide attempts in these mood disorder populations suggest a possible relationship with the BDNF gene for the trytophan hydroxylase 2 enzyme.

Examining the world’s largest collection of DNA samples from the child depression cases has also implicated the BDNF gene as a predictor of risk for depression.

Obsessive Compulsive Disorder (OCD)

Examining DNA samples from individuals diagnosed with OCD has shown that a serotonin 1B receptor gene is involved in OCD and the GRIN2B gene that plays a role in schizophrenia also contributes to OCD.

Schizophrenia

The examination of various neurotransmitter genes including those in the dopamine, serotonin, and glutamate systems have led to several findings. There is evidence that the dopamine D₃ receptor gene contributes to tardive dyskinesia, a serious neurological disorder caused by long-term use of medications to treat schizophrenia. The dopamine D₄ gene predicts positive symptoms in schizophrenia such as delusions and hallucinations and the subunit GRIN2B of NMDA, a glutamate receptor gene, predicts risk for this disorder and possibly treatment response. The glutamate hypothesis is the first priority for further study.

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