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Treatment-resistant schizophrenia and DAT and SERT polymorphisms.
Petar Bilic1, Vlado Jukic1, Maja Vilibic1
1University Psychiatric Hospital Vrapce, Zagreb, Croatia.
Gene
|April 1, 2014
Summary
Genetic variations in serotonin and dopamine genes are linked to treatment-resistant schizophrenia (TRS). Specific combinations of SERT-in2 and DAT-VNTR genotypes increase the likelihood of developing TRS, offering insights into treatment resistance.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Treatment-resistant schizophrenia (TRS) presents a significant clinical challenge, affecting one-fifth to one-third of patients.
- Genetic factors, particularly involving serotonin and dopamine systems, are investigated for their role in TRS.
- Previous studies on dopamine transporter (DAT) and serotonin transporter (SERT) gene polymorphisms in TRS have yielded conflicting results.
Purpose of the Study:
- To explore the association between specific polymorphisms in the DAT-VNTR, SERT-PR, and SERT-in2 genes and treatment-resistant schizophrenia (TRS).
- To investigate potential interactions between SERT-in2 and DAT polymorphisms in relation to TRS.
- To provide a potential explanation for contradictory findings in prior research.
Main Methods:
- Clinical evaluation of 173 schizophrenia patients using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions (CGI) scales.
- Stratification of patients into treatment-resistant schizophrenia (TRS) (92 patients) and non-resistant groups.
- Analysis of DAT-VNTR, SERT-PR, and SERT-in2 gene polymorphisms to identify associations with TRS.
Main Results:
- Patients with a combination of SERT-in2 ll genotype and specific DAT-VNTR genotypes (9/10, 9/11, 9/9, 6/6) showed a significantly higher likelihood of TRS (OR=5.1).
- In patients with DAT 10/10 or 10/12 genotypes, carrying SERT-in2 ls or ss genotypes increased the odds of TRS compared to the ll genotype (OR=2.7).
- These findings suggest a potential interaction between SERT-in2 and DAT polymorphisms in the development of TRS.
Conclusions:
- The interaction between SERT-in2 and DAT gene polymorphisms may play a crucial role in treatment resistance in schizophrenia.
- This interaction model could help reconcile previous inconsistent findings regarding the roles of DAT and SERT in TRS.
- Further research is warranted to validate these genetic associations and their clinical implications for managing TRS.
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