Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder
| Autor: | Robert H. Nadrich, K C Rilett, Valerie Drouet, James D. Clelland, Catherine L. Clelland, Amit Rajparia, Laura L. Read, Jennifer Smeed |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Bipolar Disorder Genotype Proline Catechol O-Methyltransferase behavioral disciplines and activities Polymorphism Single Nucleotide 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Proline dehydrogenase Internal medicine mental disorders medicine Humans Genetic Predisposition to Disease Bipolar disorder Biological Psychiatry Alleles Catechol-O-methyl transferase Middle Aged medicine.disease Psychiatry and Mental health 030104 developmental biology Endocrinology Schizophrenia Behavioral medicine Female Schizophrenic Psychology Original Article Psychopharmacology Psychology 030217 neurology & neurosurgery Clinical psychology |
| Zdroj: | Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val158Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (Pn=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions. |
| Databáze: | OpenAIRE |
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