A class of drugs known as serotonin reuptake inhibitors (SSRIs) is widely popular around the world for the treatment of depression, anxiety disorders, and a few other medical conditions. These drugs work by preventing the speedy breakdown of serotonin, a neurotransmitter associated with feelings of happiness and well-being. The more serotonin a person has in the synapses (tiny gaps between nerve cells), the happier they seem to be.

Unfortunately, SSRIs don’t work for everybody. Dr. Jeremy D. Coplan, of the Department of Psychiatry and Behavioral Sciences at the State University of New York, Brooklyn, noticed SSRIs often don’t work on depression patients who had experienced early life stresses (adverse childhood experiences, or ACEs, according to the American Academy of Pediatrics [AAP]). He assembled a team of researchers from all across the United States and Brazil to see if there was a connection.

The Coplan research team used bonnet macaques (monkeys) for their study. To simulate the experience of childhood trauma in 22 macaques between 2 and 6 months of age, the researchers created an environment in which the mother macaques would have a hard time finding enough food for themselves and their babies. The mothers often had to neglect their babies in order to find enough food. This group was the VFD group (variable foraging demand). A second, non-VFD group of 14 baby monkeys lived in an environment where food was readily available at all times.

When all the baby macaques were approximately 2.6 years old, their cerebrospinal fluid (CSF) was tested for the presence of 5-hydroxyindoleacetic acid (5-HIAA), which indicates how rapidly brain cells are processing serotonin. To test 5-HIAA levels, the researchers used a lumbar puncture which allowed them to extract CSF from a puncture in the lower back into the spine.

The researchers also used magnetic resonance imaging (MRI) scans to measure the volume of the hippocampus of each baby macaque; emotions are processed in the hippocampus.

The CSV levels of 5-HIAA were not significantly different between the VFD and non-VFD groups but the left lobes of the hippocampus were smaller in the VFD group. When serotonin is passed from one nerve cell to the next, it is broken down into smaller elements, including 5-HIAA. The smaller hippocampus indicates greater 5-HIAA activity which itself is an indicator of rapid processing of serotonin. The SSRI class of antidepressants slow the processing of serotonin so it stays intact longer and contributes to the feeling of happiness.

The CSV taken with lumbar puncture contains fluids from all parts of the brain and spinal cord. Coplan suggests that by the time 5-HIAA travels from the hippocampus to the lumbar region, it has mixed with 5-HIAA from other regions, masking the serotonin processing in the hippocampus alone. His research indicates the measure of 5-HIAA in the CSV should not be taken as an accurate measure of the effectiveness of SSRI medications when taken by someone who experienced early childhood trauma.


  1. Coplan, Jeremy D, et al. "Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following early life stress and inverse association with hippocampal volume: preliminary implications for serotonin-related function." Frontiers in Behavioral Neuroscience. Frontiers Media SA, 23 Dec. 2014. Frontiers. Web. 13 Mar. 2015.
  2. "Adverse Childhood Experiences and the Lifelong Consequences of Trauma (.pdf)." American Academy of Pediatrics. US Department of Health and Human Services, 2014. Web. 13 Mar. 2015.