Body-clock profile links to harsher depression and weaker drug response

Researchers have identified a proposed body-clock-related profile in 2,604 adults with depression, linking sleep and timing traits to more severe illness and poorer reported responses to common antidepressants. ^[2][5]

The group accounted for 23% of the 11,380 participants analysed in the Australian Genetics of Depression Study. Its members reported earlier-onset depression, greater psychological distress and more side effects from treatment than other participants. ^[2][5]

Published online in the British Journal of Psychiatry on October 20, 2026, the study gives researchers a sizeable group in which to investigate whether treatments aimed at daily rhythms could improve depression care. The University of Sydney has identified melatonin, light therapy and behavioural changes as possible approaches, and a trial of melatonin and behavioural strategies is planned. ^[2][3][1]

The immediate clinical question is whether asking more carefully about sleep timing, morning tiredness and seasonal changes could help doctors recognise people whose treatment needs closer attention. First author Emiliana Tonini said the findings could help clinicians distinguish characteristics of depression and give people earlier access to treatments that may work for them. ^[3][6]

Six features, one proposed profile

To enter the proposed circadian group, participants had to meet at least three of six criteria. Circadian rhythms are the body's roughly 24-hour patterns, which help govern when we feel sleepy or alert. ^[2]

The criteria included an evening preference, a later midpoint of sleep and social jetlag, the mismatch between sleep schedules on workdays and free days. Researchers also counted seasonal changes, morning tiredness or difficulty becoming fully alert after waking, and sleeping more during depression. ^[2][5]

These are recognisable experiences rather than obscure laboratory findings. Someone may prefer late nights, struggle to get going in the morning and sleep longer during a depressive episode. Under the proposed system, that combination could be enough to place them in the circadian group. ^[2]

The researchers selected the criteria using the information available in the cohort, their knowledge of the field and clinical expertise. Participants supplied the information through online surveys, alongside accounts of depressive symptoms and experiences with antidepressants. The data were collected between September 2016 and September 2018. ^[2]

The sample was large, but selected. The analysis included adults of genetically inferred European ancestry who had complete genetic-risk data and information for at least three circadian criteria. Participants came from a nationwide cohort recruited through invitations linked to prescription records and through media outreach. ^[2]

They were also predominantly people with severe, recurrent depression. Only 4% reported having experienced a single depressive episode. The 23% figure therefore describes a pattern within this group, rather than the share of depression worldwide attributable to a body-clock problem. ^[2]

A harder course of illness

Participants meeting the proposed criteria reported more severe clinical features, including suicidal thoughts, physical complaints and experiences resembling symptoms of mania or psychosis. They also reported more weight gain during depressive episodes. ^[5]

Their accounts of treatment were less encouraging, too. The group reported poorer responses to SSRIs and SNRIs, two widely used classes of antidepressants, as well as more side effects. Those results came from participants' recollections and assessments, rather than a trial assigning treatments and measuring their effects. ^[4][5][6]

The genetic analysis supplied another line of investigation. The profile was associated with higher polygenic risk scores for depression, ADHD and bipolar disorder, among other traits. Such scores combine many genetic variants into an estimate of inherited susceptibility. ^[2][5]

Associations also appeared for insomnia, later sleep timing and metabolic traits, including body mass index and insulin resistance. The range of links gives researchers several possible routes to investigate, rather than a single biological explanation. ^[2][4][5]

The central uncertainty is whether these features identify a distinct form of depression. The study took a cross-sectional snapshot, so it cannot establish whether disrupted rhythms preceded depression or caused it.

It did not directly measure participants' body clocks, test alternative treatments or establish that the profile represents a separate disease mechanism. The authors describe the criteria as provisional and call for independent replication. ^[2][4][5]

Philip Mitchell, a psychiatrist who was not involved in the research, said the findings were thought-provoking but insufficient to bring the classification into clinical practice. He pointed to overlap with atypical depression and called for further international research. ^[6]

Sleep and circadian researcher Shanthakumar Wilson Rajaratnam, also uninvolved in the study, said the defining symptoms could reflect disturbed sleep. He supported addressing sleep and circadian complaints alongside depression treatment. ^[6]

The treatment test comes next

Co-author Sam Hockey described to ABC how oversleeping and waking unrefreshed had shaped his own experience. Later behavioural changes, including putting his bedside light on a timer, helped him regulate his body clock, he said. That is a personal account, not a treatment result. ^[6]

For clinicians, the useful lead is a set of questions about when patients sleep, how they wake and whether their symptoms shift with the seasons. The evidence supports investigating those patterns alongside established care. It does not support changing prescriptions on the strength of this classification alone. ^[2][4][6]

The university disclosed that senior author Ian Hickie had previously led pharmaceutical-industry-supported research, including work on agomelatine, a melatonin-focused antidepressant, and holds an equity interest in InnoWell. ^[3]

The next substantive step is to follow people forward and test whether the proposed profile predicts their course of illness or response to treatment. The planned trial of melatonin and behavioural strategies offers a route to answering the treatment question. No start date or results have been announced. ^[1][2]