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Review
. 2014 Apr 28;6(4):29.
doi: 10.1186/gm546. eCollection 2014.

Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice

Joanne L Doherty  1 , Michael J Owen  1
Affiliations
Review

Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice

Joanne L Doherty et al. Genome Med. .

Abstract

Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder are common and result in significant morbidity and mortality. Although currently classified into distinct disorder categories, they show clinical overlap and familial co-aggregation, and share genetic risk factors. Recent advances in psychiatric genomics have provided insight into the potential mechanisms underlying the overlap between these disorders, implicating genes involved in neurodevelopment, synaptic plasticity, learning and memory. Furthermore, evidence from copy number variant, exome sequencing and genome-wide association studies supports a gradient of neurodevelopmental psychopathology indexed by mutational load or mutational severity, and cognitive impairment. These findings have important implications for psychiatric research, highlighting the need for new approaches to stratifying patients for research. They also point the way for work aiming to advance our understanding of the pathways from genotype to clinical phenotype, which will be required in order to inform new classification systems and to develop novel therapeutic strategies.

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Figures

Figure 1
Figure 1
Simplified representation of the hypothesized relationship between the number and severity of deleterious genetic mutations and clinical syndromes. Psychiatric disorders as currently classified are shown as a neurodevelopmental continuum, with intellectual disability (ID) at one extreme and mood disorders at the other (see [130]). Domains of psychopathology overlap between the clinical syndromes, with the ultimate clinical phenotype being dependent on both genetic and environmental influences. Positive symptoms refer to abnormal thoughts, perceptions and behaviour, for example, hallucinations and delusions. Negative symptoms refer to disruption to normal emotions or behaviour, for example, apathy and lack of emotional reactivity. A gradient of mutational load and cognitive impairment is shown, with ID associated with the highest mutational load and most severe cognitive impairment, and mood disorders associated with the lowest mutational load/severity and least impaired cognitive function. The severity of individual syndromes is not represented. Owing to the lack of evidence from adequately powered genetic studies, attention-deficit/hyperactivity disorder (ADHD) has been omitted from the figure. ASD, autism spectrum disorder; BD, bipolar disorder; MDD, major depressive disorder; SZ, schizophrenia.
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