AMMAR AHMED KHAN
KARACHI: A generation ago, depression as the main form of grief was viewed as an unwanted guest: a gloomy presence that might appear in the wake of a loss or a grave disappointment and was slow to find the door.
The people it haunted could acknowledge the poor company without worrying that they had become chronically ill.
For decades, researchers have debated the various types of depression, from mild to severe to “endogenous,” a rare, near-paralyzing despair. Hundreds of studies have been conducted, looking for markers that might predict the course of depression and identify the best paths to recuperation.
But treatment largely remains a process of trial and error. A drug that helps one person can make another worse. The same goes for talk therapies: some patients do very well, others don’t respond at all.
A study in Biological Psychiatry has shown that exposure to violence early in life — such as physical, emotional, or sexual abuse — is associated with faster biological aging, including pubertal development and a cellular metric of biological aging called epigenetic age. In contrast, children exposed to forms of early life adversity involving deprivation — such as neglect and food insecurity — showed signs of delayed pubertal development compared with their peers.
“[The findings] demonstrate that different types of early-life adversity can have different consequences for children’s development,” said senior author Katie McLaughlin, Ph.D., who completed the study at the University of Washington. Poor physical and mental health outcomes associated with early life adversity have been attributed to accelerated development. However, the new findings show that violence- and deprivation-related adversity have different effects on development, indicating that the specific type of adversity should be considered to better understand how an experience will affect a child later in life.
In children who experienced early life violence, accelerated epigenetic aging was associated with increased symptoms of depression. According to the authors, this means that faster biological aging may be one way that early life adversity “gets under the skin” to contribute to later health problems.
The 247 children and adolescents involved in the study were 8-16 years old. “These findings indicate that accelerated aging following exposure to violence early in life can already be detected in children as young as 8 years old,” said Dr. McLaughlin.
“With each new study, it seems that our appreciation grows of the enormous and persisting impact of early life exposure to violence. This new knowledge calls for increased societal investment in reducing the exposure of children to violence and for biomedical and psychological research to reduce the impact of these experiences throughout the lives of these vulnerable individuals,” said John Krystal, MD, Editor of Biological Psychiatry.
Scientists from the Neural Computational Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), in collaboration with their colleagues at Nara Institute of Science and Technology and clinicians at Hiroshima University, have for the first time identified three sub-types of depression. They found that one out of these sub-types seems to be untreatable by Selective Serotonin Reuptake Inhibitors (SSRIs), the most commonly prescribed medicines for the condition. The study was published in the journal Scientific Reports.
Serotonin is a neurotransmitter that influences our moods, interactions with other people, sleep patterns and memory. SSRIs are thought to take effect by boosting the levels of serotonin in the brain. However, these drugs do not have the same effect on everyone, and in some people, depression does not improve even after taking them. “It has always been speculated that different types of depression exist, and they influence the effectiveness of the drug. But there has been no consensus,” says Prof. Kenji Doya.
For the study, the scientists collected clinical, biological, and life history data from 134 individuals — half of whom were newly diagnosed with depression and the other half who had no depression diagnosis- using questionnaires and blood tests. Participants were asked about their sleep patterns, whether or not they had stressful issues or other mental health conditions.
Researchers also scanned participants’ brains using magnetic resonance imaging (MRI) to map brain activity patterns in different regions. The technique they used allowed them to examine 78 regions covering the entire brain, to identify how its activities in different regions are correlated. “This is the first study to identify depression sub-types from life history and MRI data,” says Prof. Doya.
With over 3000 measurable features, including whether or not participants had experienced trauma, the scientists were faced with the dilemma of finding a way to analyze such a large dataset accurately. “The major challenge in this study was to develop a statistical tool that could extract relevant information for clustering similar subjects together,” says Dr. Tomoki Tokuda, a statistician and the lead author of the study. He, therefore, designed a novel statistical method that would help detect multiple ways of data clustering and the features responsible for it. Using this method, the researchers identified a group of closely-placed data clusters, which consisted of measurable features essential for accessing the mental health of an individual. Three out of the five data clusters were found to represent different sub-types of depression.
The three distinct sub-types of depression were characterized by two main factors: functional connectivity patterns synchronized between different regions of the brain and childhood trauma experience. They found that the brain’s functional connectivity in regions that involved the angular gyrus — a brain region associated with processing language and numbers, spatial cognition, attention, and other aspects of cognition — played a large role in determining whether SSRIs were effective in treating depression.
Patients with increased functional connectivity between the brain’s different regions who had also experienced childhood trauma had a sub-type of depression that is unresponsive to treatment by SSRIs drugs, the researchers found. On the other hand, the other two subtypes — where the participants’ brains did not show increased connectivity among its different regions or where participants had not experienced childhood trauma — tended to respond positively to treatments using SSRIs drugs.
This study not only identifies sub-types of depression for the first time but also identifies some underlying factors and points to the need to explore new treatment techniques. “It provides scientists studying neurobiological aspects of depression a promising direction in which to pursue their research,” says Prof. Doya. In time, he and his research team hope that these results will help psychiatrists and therapists improve diagnoses and treat their patients more effectively.
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Story Source:
Okinawa Institute of Science and Technology (OIST) Graduate University.
Journal Reference:
- Tomoki Tokuda, Junichiro Yoshimoto, Yu Shimizu, Go Okada, Masahiro Takamura, Yasumasa Okamoto, Shigeto Yamawaki, Kenji Doya. Identification of depression subtypes and relevant brain regions using a data-driven approach. Scientific Reports, 2018; 8 (1) DOI: 1038/s41598-018-32521-z
- Jennifer A. Sumner, Natalie L. Colich, Monica Uddin, Don Armstrong, Katie A. McLaughlin. Early Experiences of Threat, but Not Deprivation, Are Associated With Accelerated Biological Aging in Children and Adolescents. Biological Psychiatry, 2018; DOI: 1016/j.biopsych.2018.09.008
