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 ). 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.