For the first time, scientists have identified a new subtype of depression that involves more pronounced cognitive dysregulation, with current treatment missing the mark on helping relieve these symptoms.
The researchers led by a team at Stanford Medicine used surveys, tests and brain imaging to chart cognitive impairment, which is characterized by behaviors such as difficulty in planning ahead, lack of self-control, poor focus and other executive function issues.
While executive function difficulties have been known to be a factor in major depressive disorder for some time, the scientists argue that for as many as 27% of sufferers, it’s the dominant issue that most current medication doesn’t target. While a minority, this still accounts for around five million people with depression in the US.
“Depression presents in different ways in different people, but finding commonalities – like similar profiles of brain function – helps medical professionals effectively treat participants by individualizing care,” said Leanne Williams, senior author and professor of psychiatry and behavioral sciences.
Commonly, selective serotonin reuptake inhibitors (SSRIs) are prescribed, but they are less effective for helping cognitive dysfunction.
For the study, 1,008 adults with unmedicated major depressive disorder were given one of three common antidepressants – escitalopram (aka Lexapro) and sertraline (Zoloft), which act on serotonin, and venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine. At the end of eight weeks, 712 participants had completed the study.
Before and after, participants had a clinician-administered and self-assessed survey to gauge various symptom levels, plus behaviors like changes in sleep or eating and social and work-life impacts. They were also subjected to cognitive tests measuring brain function such as working memory, decision speed and sustained attention.
Adding to this, 96 of these participants had their brains scanned by functional magnetic resonance imaging (fMRI), during which a reaction test allowed scientists to observe brain activity compared to those without depression.
After the eight weeks, the team found that 27% of participants had more significant cognitive impairment and reduced activity in specific frontal brain areas – namely, the dorsolateral prefrontal cortex and dorsal anterior cingulate regions. They also showed the least improvement from the SSRIs.
“This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions,” said Dr Laura Hack, lead author of the study and an assistant professor of psychiatry and behavioral sciences. “It’s mostly making observations and self-report measures. Imaging while performing cognitive tasks is rather novel in depression treatment studies.”
From this, the researchers hope tests can be developed to spot this dysregulation and change treatment to better suit this subtype of major depressive disorder.
“One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner,” Williams said. “Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”
Williams and Hack hope to do further studies on those with this cognitive biotype, using different treatments such as transcranial magnetic stimulation (TMS) and cognitive behavioral therapy (CBT), as well as other medications like guanfacine, which is more commonly associated with attention deficit hyperactivity disorder (ADHD).
Not surprisingly, these same brain regions identified in the study are also the areas impacted by ADHD and the poor executive function associated with it.
“I regularly witness the suffering, the loss of hope and the increase in suicidality that occurs when people are going through our trial-and-error process,” Hack said. “And it’s because we start with medications that have the same mechanism of action for everyone with depression, even though depression is quite heterogeneous. I think this study could help change that.”
The research was published in the journal JAMA Network Open.
Source: Stanford Medicine
