Neural network analysis in pharmacogenetics of mood disorders.
BACKGROUND
The increasing number of available genotypes for genetic studies in humans requires more advanced techniques of analysis. We previously reported significant univariate associations between gene polymorphisms and antidepressant response in mood disorders. However the combined analysis of multiple gene polymorphisms and clinical variables requires the use of non linear methods.


METHODS
In the present study we tested a neural network strategy for a combined analysis of two gene polymorphisms. A Multi Layer Perceptron model showed the best performance and was therefore selected over the other networks. One hundred and twenty one depressed inpatients treated with fluvoxamine in the context of previously reported pharmacogenetic studies were included. The polymorphism in the transcriptional control region upstream of the 5HTT coding sequence (SERTPR) and in the Tryptophan Hydroxylase (TPH) gene were analysed simultaneously.


RESULTS
A multi layer perceptron network composed by 1 hidden layer with 7 nodes was chosen. 77.5 % of responders and 51.2% of non responders were correctly classified (ROC area = 0.731--empirical p value = 0.0082). Finally, we performed a comparison with traditional techniques. A discriminant function analysis correctly classified 34.1 % of responders and 68.1 % of non responders (F = 8.16 p = 0.0005).


CONCLUSIONS
Overall, our findings suggest that neural networks may be a valid technique for the analysis of gene polymorphisms in pharmacogenetic studies. The complex interactions modelled through NN may be eventually applied at the clinical level for the individualized therapy.
Serretti
Alessandro
A
Istituto Scientifico Universitario Ospedale San Raffaele, Department of Neuropsychiatric Sciences, Milano, Italy. serretti.alessandro@hsr.it
Smeraldi
Enrico
E
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D017668:Age of Onset; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D016571:Neural Networks, Computer; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins; D014158:Transcription, Genetic / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics
D020121:5' Untranslated Regions; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase