Young people with severe depression experience disruptions in the way regions of their brain communicate with each other which are distinct from those observed in adults, a study has found.
The research published on Tuesday in Nature Mental Health could be used to identify potential targets for brain stimulation therapies, extending their existing application from adults to youth.
The study analysed the brain scans of 810 young people aged 12-25, of which 440 had major depressive disorder (MDD) and 370 were healthy comparison individuals.
The study led by the University of Melbourne found that in those with MDD, some densely connected regions of the brain (known as hubs) showed stronger connectivity and others showed weaker connectivity compared with youth without depression.
Prof Andrew Zalesky, the supervising researcher, said they found the connectivity was particularly strong in the part of the brain associated with someone’s internalised thoughts and rumination. “We see that in youth with depression, the default mode is more strongly connected, it’s more activated, which suggests that there is a greater focus on self-thought and self-reflection,” Zalesky said.
The study, whose first author was third-year PhD student at the University of Melbourne, Nga (Connie) Yan Tse, also found the extent of these differences could reliably predict how severe a person’s depressive symptoms were.
The researchers achieved what Zalesky called “the largest sample size of youth with depression and healthy comparison” with data from previous independent studies from six sites in Australia, China, the UK and the US.
Brain stimulation therapies can be targeted to repair specific brain circuits as an alternative approach to treating depression, when someone doesn’t respond to first-line treatments, such as antidepressants, Zalesky said.
However, they have been more commonly given as treatment to adults because researchers know which circuits are disrupted.
Targets developed to treat adult depression with transcranial magnetic stimulation (TMS) have been used to treat youth as a “best-guess approach”, the paper found.
TMS is only recommended for adults by Australia’s medicines regulator, the Therapeutic Goods Administration, but it can be made available to youth at the clinician’s discretion, Zalesky said.
“The assumption is that the same circuits would be affected in youth with depression, and our work shows that that’s not necessarily the case.
“While there is some overlap with the connectivity disruptions that we see in adults, there are also unique and specific circuit disruptions that we only see in youth with depression.”
For example, the network responsible for helping identify the most relevant piece of information at any given time, the researchers found was extensively implicated in youth MDD, whereas findings were mixed in adult depression, Zalesky said.
Further studies would need to be conducted to test the efficacy and safety of brain stimulation therapies in youth for it to be more widely practised among clinicians, “but this is a necessary first step towards providing targets”, Zalesky said.
Dr Hollie Byrne, a postdoctoral research associate at the Matilda Centre for Research in Mental Health and Substance Use at the University of Sydney, who was not involved in the research, said while it provides “essential evidence for identifying potential therapeutic targets” for brain stimulation therapies, “it is important to remember there is no ‘one-size-fits-all’ approach to the treatment of depression”.
“Currently, neuro-modulatory therapeutics are recommended to be utilised in conjunction with other treatment options as part of a comprehensive, personalised treatment plan, or in cases where other treatment options have been exhausted,” Byrne said.
Dr Stevan Nikolin, a neuroscience fellow at the Black Dog Institute, said “the work described in this study extends findings in adult individuals with MDD to adolescent/young-adult depression”.
“It furthers our understanding of the disorder in young people, and with that understanding future interventions may be conceived to specifically address the pathological brain activity identified ,” Nikolin said.
The authors also acknowledge limitations of the study, including only looking at each youth with depression at one point in time.
Zalesky acknowledged that, without undertaking further clinical trials, any inferences about brain stimulation still need to be taken with some caution.
