Dopamine

Gaum et al. (2017) assessed dopamine in their participants by measuring two of its metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), in urine.  They adjusted the levels for creatine as a marker of urine concentration, albumin to account for liver function, and also self-reported traumatic experiences, taking post-traumatic stress disorder into account as a factor in dopamine concentrations.  They note that VMA acid is also a metabolite of norepinephrine, which is made from dopamine, thus limiting its use in assessment of dopamine on its own.  They appreciate the non-invasiveness of urine as a method of assessment while acknowledging the observation that it is reflecting dopamine throughout the body, not just the small percentage that is in the brain and thus responsible for the symptoms they were investigating. 

 

In contrast, Lambert et al. (2000) measured HVA directly in the jugular vein from the brain by using a catheter, and compared this to levels at a catheter in the brachial artery.  They wanted to assess dopamine in the brain, and felt that metabolite levels in urine, peripheral blood, or even a spinal tap would be too reflective of dopamine activity throughout the rest of the body.  In recognition of the invasive nature of this method of assessment, the authors emphasized that the participants had been told that they were voluntarily participating in a research study and that the procedure was not a part of the treatment for their condition. 

 

Hartmann et al. (2020) assessed dopamine using tasks designed to measure working memory and reinforcement learning.  Reinforcement learning involves learning to anticipate rewards and punishments.  They accounted for the potential confounders of mood and well-being, but not for the effect that estradiol levels at different phases of the menstrual cycle would have on performance in these tasks.  Another indirect measure of dopamine that they used was serum levels of dopamine precursors.  They note the potential for the brain to have storage reservoirs that could buffer a temporary depletion of precursors.  It would be interesting to see if any of these methods had been validated against the more direct assessment methods.  The authors mention positron emission tomography (PET) scans as a way to more directly measure dopamine in the brain. 

 

Gaum et al. (2017) found that PCB exposure was associated with lower urinary HVA, and concluded that dopamine disruption is involved in the depression symptoms that have been seen with long term occupational exposure to PCBs.  They measured plasma PCBs and urinary HVA and VMA, as well as depression symptoms, on two occasions separated by a year in 178 participants who reported occupational PCB exposure.  They describe a mechanism proposed in other studies whereby PCBs may disrupt dopamine over the long term by blocking the dopamine vesicles from getting to the synapse, resulting in the dopamine getting metabolized inside the neurons with excessive reactive oxygen species actually causing the neurons to die off.  Thus the effects could be long term even if serum PCB levels are resolved. 

 

References:

 

Gaum, P. M., Gube, M., Schettgen, T., Putschögl, F. M., Kraus, T., Fimm, B., & Lang, J. (2017). Polychlorinated biphenyls and depression: cross-sectional and longitudinal investigation of a dopamine-related Neurochemical path in the German HELPcB surveillance program. Environmental Health: A Global Access Science Source, 16, 1–11. 

 

Hartmann, H., Pauli, L. K., Janssen, L. K., Huhn, S., Ceglarek, U., & Horstmann, A. (2020). Preliminary evidence for an association between intake of high-fat high-sugar diet, variations in peripheral dopamine precursor availability and dopamine-dependent cognition in humans. Journal of Neuroendocrinology, 32(12), e12917. 

Lambert, G., Johansson, M., Agren, H., & Friberg, P. (2000). Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Archives of General Psychiatry, 57(8), 787–793.