A group of Australian researchers has identified a new clinical subtype of depression, directly associated with alterations in the internal biological clock. The discovery comes from a study published in the British Journal of Psychiatry from the analysis of genetic and clinical data of over 11,000 Australian patients: circadian depression affects almost a quarter of the subjects examined. According to the authors of the study, the new subtype of depression could benefit from new therapeutic strategies aimed at restoring the body’s normal rhythm, while it rarely responds to standard treatments currently based mainly on traditional antidepressants.
The characteristics of the new phenotype
The link between mood disorders and the alteration of circadian rhythms has been known for some time, but until now there was a lack of sufficiently robust biological and genetic evidence to define an autonomous form of the pathology. To fill this gap, researchers at the University of Sydney examined a large cohort of patients with clinical pictures of severe and recurrent depression.
The researchers considered the presence of at least three out of six symptoms as a diagnostic criterion for circadian depression: a marked seasonality of mood disorders, a chronic delay in falling asleep, increased hours of sleep during depressive phases, a tendency to be nocturnal, persistent tiredness upon awakening and the presence of social misalignment between work and weekend rhythms.
A more severe clinical profile and distinct biological markers
The data analysis highlighted that patients classified within the circadian form of depression present an overall more complex clinical picture than those suffering from other forms of depression. The onset of symptoms tends to occur at a younger age, accompanied by a greater number of depressive episodes throughout life, more complex clinical trajectories, higher rates of suicide, and hypomanic (a form of hyperactivity less severe than true manic phases) or psychotic manifestations.
Alongside the symptomatic aspects, participants with circadian depression have other common characteristics: a greater genetic predisposition towards attention deficit hyperactivity disorder and other mood disorders, as well as specific metabolic and inflammatory indicators. “These are important factors – explains Emiliana Tonini, researcher at the Brain and Mind Center at the University of Sydney who participated in the study – because they indicate that circadian depression is not simply a form of depression that is accompanied by sleep disorders, but that it instead arises from a biological root that is very different from that of other forms of depression”.
New chronobiological perspectives
One of the most relevant consequences of the discovery concerns the response to first-line pharmacological treatments. Ian Hickie, psychiatrist and co-director of the Brain and Medical Center in Sydney, explains that selective serotonin reuptake inhibitors and other antidepressants commonly prescribed against depression show lower efficacy and a higher incidence of side effects in patients with the circadian subtype.
For this category of people, the therapeutic approach must be oriented towards chronobiological interventions. “Approaches aimed at realigning the sleep-wake rhythm in particular – concludes Hickie – which act on exposure to morning light, daily activities, the regularity of the sleep-wake rhythm and meal intake, are of critical importance”.