Researchers at the University of Helsinki identified five different patterns of brain activity in people with the same diagnosis of major depressive disorder. In some participants, communication between brain regions was stronger than usual, while in others it was weaker. These differences were also linked to different combinations and levels of symptom severity. According to the researchers, the results support the view that depression may involve more than one distinct pattern of brain functioning.
The team examined 263 people with major depressive disorder and 75 healthy participants, who formed the comparison group. The question was whether the wide range of experiences described under the same diagnosis is also reflected in brain functioning: for example, whether persistent anxiety and recurring negative thoughts are accompanied by different patterns from symptoms related to trauma or substance abuse. The issue concerns a particularly widespread condition: according to WHO figures for 2025, around 332 million adults worldwide, or 5.2%, have depression. In Finland, it is the leading single cause of prolonged sick leave and retirement due to disability.
The analysis focused on functional connectivity, meaning the degree to which activity in different brain regions is coordinated. When two regions show synchronized activity, this suggests that they work together as part of a broader network. Stronger connectivity, however, does not necessarily mean better brain functioning. To classify the participants, the researchers examined both the strength of this coordination and the frequencies at which it occurred.
The first group showed relatively strong connectivity, which was linked to more severe symptoms of depression and anxiety, as well as more recurring unpleasant thoughts. Participants with this profile also had greater difficulty functioning in their daily lives. Persistent rumination involves repeatedly dwelling on worries, unpleasant experiences or thoughts that cause distress. By contrast, the second group was characterized by relatively weak connectivity and generally milder symptoms than the other groups.
In the third group, reduced connectivity extended across large parts of the brain. Symptoms of post-traumatic stress disorder were particularly pronounced in this profile. The fourth group showed a mixed pattern, with unusually strong connections in some regions and weaker ones in others. People in this group tended to have more severe depression, more substance abuse problems and lower overall well-being.
The fifth group had the strongest connectivity of all the profiles identified. Substance abuse was particularly evident, while trauma-related symptoms were less pronounced than in the other groups. All five groups differed from the healthy participants, and the differences went beyond the strength of the connections. The brain regions involved in this coordination and the frequencies at which their activity synchronized also differed.
The recordings were made using magnetoencephalography, a technique that detects the extremely weak magnetic fields produced by the brain's electrical activity. Satu Palva, director of the Neuroscience Center at the University of Helsinki, explains that the method allowed this activity to be tracked with millisecond precision. This temporal resolution helped the team examine rapid changes and the coordination of signals, which may be harder to distinguish using slower methods. Recordings were made both in participants with depression and in the comparison group.
According to the researchers, the opposing connectivity patterns offer a possible explanation for the conflicting findings of previous studies. If different studies include different combinations of patients, they may record different results even though everyone has the same diagnosis. The new study thus shows why a single description of brain activity in depression may not capture its full diversity. The profiles were linked to specific symptoms, but this does not mean they already provide a tool for selecting treatments.
The long-term prospect is that measurements of brain activity could provide additional information for more personalized care. Today, finding an effective approach may require trying different treatments and assessing each person's response. Palva stresses that the findings are not yet ready for clinical use, but point to a possible research direction for linking symptoms to the functioning of brain networks. The work was carried out in collaboration with Aalto University and the Helsinki and Uusimaa Hospital District (HUS) and published in Nature Mental Health.
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