There is strong evidence for a heritability of major depression as shown by family, twin- and adoption studies. Several studies suggest a heritability for unipolar depression between 35 and 75% which is much lower than the heritability of bipolar disorder or schizophrenia. There is no doubt, that major depression is not caused by any single gene but it is a disease with complex genetic features. Furthermore, some subtypes, as early-onset or recurrent depression may have a higher heritability than other forms of depression. Neuroticism as an intermediate phenotype of MDD, which is a trait that reflects a tendency toward negative mood states, and has been linked to internalizing depressive conditions. For these reasons Dan Rujescu will present genome-wide and candidate gene studies, demonstrating a genetic approach for discovering potentially important pathogenic pathways for which clinically powerful (bio)markers may eventually be developed. He will discuss neuroticism as an intermediate phenotype of MDD, which is a trait that reflects a tendency toward negative mood states and has been linked to internalizing depressive conditions.