Our spirits may be regulated by the methylation of our genes. Methylation, acetylation, and other biochemical processes are the molecular switches for turning genes on and off. There is evidence now that certain behaviors, feelings, and psychiatric symptoms may be modified by turning various genes on or off. If classical genetics is the sequence of DNA that is inherited, then epigenetics is a parallel process determining whether a given gene (ie, a sequence of DNA coding for transcription) is expressed into its RNA or is silenced. Epigenetics is now entering psychiatry with the hypothesis that normal genes as well as risk genes can both contribute to a mental disorder. That is, it has long been hypothesized that when “abnormal” genes with an altered sequence of DNA are inherited as risk genes for a mental illness, these risk genes will make an abnormal gene product in neurons, contributing to inefficient information processing in various brain circuits and creating risk for developing a symptom of a mental illness. Now comes the role of epigenetic actions in mental illnesses.

Cerebrotendinous xanthomatosis (CTX) is a rare inborn disorder of sterol storage with autosomal recessive inheritance and a variable clinical presentation. We describe two siblings with an early psychiatric presentation of CTX-associated attention-deficit/hyperactivity disorder and oppositional defiant disorder, also associated with a mild intellectual disability and major behavioral impairments. In both cases, treatment with chenodeoxycholic acid improved externalized symptoms and a partial recovery of cognitive impairments was observed. This suggests that CTX is potentially reversible, demonstrating the need for early diagnosis and treatment of this disorder before irreversible neurological lesions can occur.

The duration of untreated illness (DUI), defined as the interval between the onset of a psychiatric disorder and the administration of the first pharmacological treatment, has been increasingly investigated in the last decade as a predictor of outcome across different psychiatric conditions including schizophrenia and psychotic disorders (duration of untreated psychosis), and mood and anxiety disorders. Converging evidence indicates that a prolonged DUI may be viewed as a negative prognostic factor in schizophrenia and increasing data point toward a similar conclusion in mood and anxiety disorders. Through a Medline search, the present article highlights the role of the DUI in this group of psychiatric disorders, focusing on social and psychopathological determinants of the DUI, as well as the clinical consequences related to a longer DUI in terms of outcome. Hypotheses on neurobiological mechanisms underpinning outcome differences in relation to a prolonged DUI are provided and methodological limitations related to the assessment of the DUI in published studies and clinical practice discussed. Finally, given that DUI is supposed to be a potentially modifiable prognostic factor, intervention programs aimed to reduce this variable are briefly considered and discussed.