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Earlier onset, higher severity may indicate genetic risk for MDD

Among individuals with major depressive disorder, those with early age at onset and higher symptom severity had increased genetic risk for depression, bipolar disorder and schizophrenia.

“This study supports the idea that psychiatric disorders are heterogeneous and that the early onset and more severe forms of depression are the ones with greater heritability,” John Krystal, MD, editor of Biological Psychiatry, said in a press release.

John Krystal

To determine associations between clinical characteristics of major depressive disorder (MDD) and genetic risk for MDD, bipolar disorder and schizophrenia, researchers assessed data from two large cohort studies in the Netherlands for 1,539 individuals with MDD and 1,792 controls. Genomic profile risk scores were determined by meta-analysis results from the Psychiatric Genomics Consortium.

Genomic profile risk scores for MDD explained 1% of MDD variance and 1.5% for MDD endorsing nine DSM symptoms.

Genomic profile risk scores for bipolar disorder explained 0.6% of MDD variance and 1.1% for MDD with an onset age less than 18 years.

Genomic profile risk cores for schizophrenia explained 2% of MDD variance and 2.6% for MDD with higher symptom severity and 2.3% for MDD endorsing nine DSM symptoms.

An independent analysis replicated these associations among individuals with more DSM symptoms of MDD and genomic profile risk scores for schizophrenia.

“Our results showed that MDD patients with an early [age at onset], high number of DSM symptoms, and moderate-to-severe symptoms across years have the highest genetic risk. Our results suggest that in genetic studies for depression, in conjunction with a continuous effort in increasing sample sizes, it may be useful to create more homogenous subgroups based on those phenotypical characteristics in search for genes associated with MDD,” the researchers concluded. – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.