Australian researchers have identified a new subtype of depression, termed "circadian depression," which they say is driven by disruptions in the body’s internal clock rather than solely by brain chemistry. The findings, emerging from studies conducted at the University of Sydney’s Brain and Mind Centre, offer fresh insights into why some patients do not respond to traditional antidepressant treatments and could pave the way for revised clinical approaches.
Circadian depression is associated with alterations in an individual’s circadian rhythms—the biological processes that regulate sleep-wake cycles, hormone release, metabolism, and other physiological functions. The researchers note that this subtype can be influenced by factors such as exposure to light, seasonal variations, and irregular sleep patterns. People affected by circadian depression often experience symptoms including persistent fatigue, difficulty concentrating, disrupted sleep, and changes in appetite.
Professor Ian Hickie, a clinical psychiatrist and co-director of the Brain and Mind Centre, explained that when circadian clocks are misaligned, individuals may feel "jetlagged all the time," exhibiting a range of symptoms beyond mood disturbance, such as weight gain and behavioral changes. “The coordination of those clocks underpins your mood, your metabolism, your concentration, your sleep-wake cycle, and many other key factors,” he said.
The study analysed data from more than 10,000 participants in the Australian Genetics of Depression Study. Researchers outlined six key features characteristic of the circadian depression subtype: mood and behavioral changes tied to seasonal patterns; delayed sleep onset leading to later wake times; social jet lag caused by varying sleep schedules between workdays and non-workdays; a preference for evening activity (being an “evening person”); hypersomnia or excessive sleep during depressive episodes; and waking feeling unrefreshed even after extended sleep.
Genetic analysis revealed that individuals with circadian depression carry higher genetic risks not only for mental health disorders such as ADHD, depression, anxiety, and bipolar disorder but also for metabolic and inflammatory conditions, according to Dr Emiliana Tonini, the study’s lead author. Approximately 25% of participants were classified within this newly proposed subtype.
Dr Tonini noted that patients with circadian depression tended to experience an earlier onset of depressive symptoms and a more complex illness trajectory, including higher rates of recurrent episodes, suicidality, and symptoms resembling hypomania or psychosis. This suggests an underlying biological distinction between circadian depression and other forms of depression, reinforcing the validity of viewing it as a separate clinical entity.
The researchers emphasised the importance of further investigations to validate these findings and identify optimal treatment strategies. Co-author Dr Jacob Crouse highlighted the potential for therapies targeting circadian rhythms, such as light therapy and melatonin supplementation, to become standard early interventions. “We hope that by giving these people targeted therapies that work on sleep-wake cycles, as well as pharmacological treatments to strengthen their circadian rhythms, we can improve their depression more effectively,” he said.
Professor Hickie added that patients involved in related studies expressed both frustration with previous care and relief at the recognition of the circadian component. He criticised a tendency within clinical practice to overlook sleep disruptions, often treating mood symptoms in isolation. “They may have been asked about their sleep simply in passing and, I think quite wrongly, told, ‘if you just fix the mood, you can sleep and everything else will get better,’” he said. The findings signal a potential shift towards more holistic, biologically informed approaches to diagnosing and treating depression.