Research by experts at the University of Sydney has identified a new subtype of depression called 'circadian depression'. 

The study used clinical and genetic data from more than 10,000 Australians to identify this new subtype, accounting for nearly a quarter of diagnoses in their study looking at people with severe, recurrent or persistent depression. 

Circadian depression is linked to the body’s 24-hour internal clock that regulates our sleep-wake cycle. It is characterised by being more resistant to treatment by common serotonin-based antidepressants but is more responsive to behavioural and medical therapies targeting the body clock’s unique brain circuits, such as melatonin, melatonin-targeted antidepressants and light therapy. 

The research, published in the British Journal of Psychiatry, provides greater understanding of the genetic mechanisms underpinning circadian depression and offers insights into why traditional treatments such as SSRIs (selective serotonin reuptake inhibitors) do not work as well for people with this subtype.

First author, Dr Emiliana Tonini from the Brain and Mind Centre, said: 

“Our research has identified circadian depression as a new subtype, affecting around a quarter of people in our study into those with severe, recurrent or persistent depression.

“Depression is not a uniform illness and understanding the characteristics of different subtypes mean that we can give people earlier access to treatments that will be most effective for them.”

How the study was carried out 

Researchers carried out clinical and genetic analysis of more than 10,000 people with depression using data from the nationwide Australian Genetics of Depression Study. 

Of these, nearly 25 percent (2,604 participants) were identified as having circadian depression, which includes symptoms such as a seasonal pattern of illness, sleeping longer when depressed, waking feeling very tired, and being a night owl.

People with circadian depression were more like to experience their depression emerging earlier in life and had more severe symptoms (such as mania and higher levels of suicidal thoughts). They also had a higher genetic risk for inflammatory and cardiovascular health problems and major neurodevelopmental disorders, including ADHD.

How to treat circadian depression 

Antidepressants such as SSRIs or SNRIs (serotonin and norepinephrine reuptake inhibitors) are usually considered the first option for treating depression but are less effective, and come with more side effects, for people with the circadian subtype.

Co-senior author Dr Jacob Crouse from the Brain and Mind Centre said: “Because circadian depression is linked to people’s internal body clock, treatments targeting the circadian rhythm, such as light therapy and melatonin, may be much more relevant, and clinicians should reach for these much earlier in people with this presentation.

“For those who find that antidepressants are not working for them, it is important to speak to your clinician for advice about your individual circumstances.”

Professor Ian Hickie, Co-Director of the Brain and Mind Centre and a clinical psychiatrist, emphasised that not recognising circadian depression in young people often led to early treatment failures and more side-effects. 

“We really want young people to receive the most appropriate treatment early in their course of illness. 

“Most young people will be offered SSRIs first up, but for at least a quarter there are better circadian-focused medical and behavioural options to help treat and manage their condition.”

Research: Tonini, E., Crouse, J., Hickie, I.B. ‘Clinical and genetic correlates of a circadian subtype of depression in the Australian Genetics of Depression Study’ (British Journal of Psychiatry, 2026)

DOI: 10.1192/bjp.2026.10798 

Declaration: 

The Australian Genetics of Depression Study was primarily funded by grant 1086683 from the National Medical Health and Research Council (NHMRC) of Australia. This work was further supported by philanthropic donations from families who are affected by mental illness (who would like to be left anonymous) awarded to Dr Mirim Shin.  NHMRC EL1 Investigator Grants awarded to Dr Jacob Crouse and Associate Professor Brittany Mitchell (GNT2008196 and GNT2017176, respectively). Professor Sarah Medland was awarded a Wellcome Trust Mental Health Award (227089/ Z/23/Z), and NHMRC L1 and L2 Investigator Grants (APP117291, APP2025674). Professor Ian Hickie was supported by an NHMRC L3 Investigator Grant (GNT2016346).

Professor Ian Hickie is Professor of Psychiatry and Co-Director of Health and Policy at the Brain and Mind Centre, University of Sydney. He has led major public health and health service developments in Australia, with a particular focus on early intervention for young people experiencing depression, suicidal thoughts and behaviours, and complex mood disorders. He has conducted investigator-led research on agomelatine (funded by Servier Pharmaceuticals), a melatonin-focused antidepressant medication. He is actively involved in the co-design, implementation, and continuous evaluation of innovative health information technologies and personal monitoring tools that support highly personalised, measurement-based care. He holds a 0.36 percent equity interest in Innowell Pty Ltd, a company focused on the digital transformation of mental health services.