Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder

Abstract

<p>Background Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the a-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying a-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an a-synucleinopathy.Methods In this case-control-family study, a combination of family history and family study method was used to measure the a-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of a-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls.Results There was an increase of a-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression.Conclusion Patients with psy-RBD are familially predisposed to a-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying a-synucleinopathy neurodegeneration.<br></p>