28 June 2013. Attention-deficit hyperactivity disorder (ADHD) and schizophrenia share genetic roots, according to two studies published May 23 in the British Journal of Psychiatry. One study, led by Henrik Larsson of the Karolinska Institute, found that first-degree relatives of people diagnosed with ADHD were about twice as likely to have schizophrenia or bipolar disorder as relatives of controls. The second study, led by Nick Craddock of Cardiff University, U.K., found that risk alleles previously associated with schizophrenia were enriched in children with ADHD compared to controls. These schizophrenia-derived genetic risk factors accounted for only a tiny portion of ADHD risk, however.
The results support previous hints of an association between the two disorders. Smaller studies have found that people with schizophrenia are more likely to have been diagnosed with ADHD as children than the general population (Peralta et al., 2011), and children with ADHD who have a parent with schizophrenia are at increased risk for schizophrenia compared to their siblings without ADHD (Keshavan et al., 2008). But whether this reflects genuine shared genetic factors or a syndrome in which both diseases travel together in certain families has been unclear. Larsson and colleagues’ new family study, based on Swedish national registers, argues for shared genetic risk because it studied 61,187 people with ADHD only and found that their first- but not second-degree relatives were at increased risk for schizophrenia.
The new genetic study from Craddock and colleagues uncovers evidence for this shared genetic risk among common variants, which adds to previous genetic overlaps between ADHD and schizophrenia found among the rarer copy number variants (Williams et al., 2010). The new study looked at risk alleles discovered by the Psychiatric Genomewide Association Study Consortium (PGC) for schizophrenia (see SRF related news story) and found that the summed contributions of these alleles in ADHD were greater than those in controls. This “polygene” analysis argues that many genes of small effect contribute to a disorder, and in this case, the cumulative effect of the schizophrenia-defined genes accounted for less than 1 percent for the overall risk for ADHD.
Still, the findings are consistent with a study published earlier this year which detected four chromosomal regions that contributed to risk for schizophrenia, autism, ADHD, bipolar disorder, and major depressive disorder combined (see SRF related news story). As genetic findings continue to blur the diagnostic boundaries between psychiatric disorders, the link between ADHD and schizophrenia highlighted by these new studies suggests that this holds true even for childhood-onset and adult-onset disorders.—Michele Solis.
Hamshere ML, Stergiakouli E, Langley K, Martin J, Holmans P, Kent L, Owen MJ, Gill M, Thapar A, O'Donovan M, Craddock N. A shared polygenic contribution between childhood ADHD and adult schizophrenia. Br J Psychiatry. 2013 May 23. Abstract
Larsson H, Rydén E, Boman M, Långström N, Lichtenstein P, Landén M. Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder. Br J Psychiatry. 2013 May 23. Abstract