I thank Drs Bulbena-Cabre & Bulbena for their comments on my editorial ‘Schizophrenia – an anxiety disorder?’.Reference Hall¹ In it they raise a number of interesting points.

The first is that there is likely a subgroup of patients with schizophrenia in whom high levels of anxiety are a particularly prominent feature. This is important as these individuals are those who are most likely to benefit from interventions to decrease anxiety as a potential secondary prevention measure for psychosis. Future possible trials aimed at testing whether anti-anxiety measures in psychosis targeted at decreasing anxiety could be effective would benefit from stratifying patients according to their pre-existing anxiety symptoms.

The second point they raise concerns the prevalence of anxiety and psychosis in joint hypermobility syndrome. They have themselves previously reviewed the literature showing an association between joint hypermobility syndrome and a range of psychiatric presentations including anxiety, psychosis and autism.Reference Baeza-Velasco, Pailhez, Bulbena and Baghdadli² Indeed, this association is one that many clinicians have noted in their own practice. Although the exact mechanism underlying this association is not known, it is notable that connective tissue proteins (mutations in which cause joint hypermobility syndrome) are present in the brain.Reference Bowen, Sobey, Burrows, Colombi, Lavallee and Malfait^3, Reference Heikkinen, Pihlajaniemi, Faissner and Yuzaki⁴ Furthermore, many are localised to the region of synapses, which are a key site of mutations related to psychiatric disorders.Reference Heikkinen, Pihlajaniemi, Faissner and Yuzaki⁴ Although genes encoding connective tissue proteins have not, as a class, been identified as associated with risk for disorders such as schizophrenia and autism, the present results suggest that they may alter synaptic function in susceptible populations and increase risk for disease. This is clearly an interesting area worthy of further investigation.

Overall the letter of Drs Bulbena-Cabre & Bulbena reinforces the point that anxiety contributes to pathology in patients with schizophrenia and related disorders, and may represent a treatment target in appropriate subgroups.