Serotonin Is Still Alive and Well in Psychiatry Land

In the September, 2015 issue of JAMA Psychiatry, a team of Swedish researchers (see Frick et al.) published a study evaluating the serotonin system in persons with social anxiety.  They used Positron Emission Tomography an imaging technique wherein radio-active molecules that will bind in particular places in the brain and then allow for quantification of particular molecules in the brain are employed.  The researchers used two different molecules:  [¹¹C]5-HTP, which is a precursor to the production of serotonin and 5-hydoxytryptophan labeled with Carbon-11 that will bind to the serotonin transporter.

What the researchers found was an increase in both of these substances in brain areas that are known to be active during the experience of anxiety, viz.; the amygdala and the dorsal Anterior Cingulate Gyrus.  The researchers concluded, “Collectively, these findings suggest that extracellular serotonin in the amygdala and dorsal ACC is positively related to severity of social anxiety symptoms” (p. 789).  Translated into English, the researcher found that more serotonin release occurs during social anxiety.

Of course, the findings here are in direct contradiction to what the pharmaceutical companies would have us believe: that anxiety and depression are caused by deficit levels of serotonin.  There was an editorial by Stein and Andrews published in the same issue of JAMA Psychiatry in the “Clinical Review and Education” section which attempted to obfuscate the findings by referencing the heterogeneity in persons who exhibit social anxiety.

Unfortunately, neither the Frick et al. article or the editorial referenced the work of neuroscientist Steven Maier on learned helplessness.  Neuroscientists for the last 30 years have been investigating what happens in the brains of animals that are subjected to uncontrollable stress.  Given uncontrollable shock, for instance, animals appear depressed and essentially “give-up”; failing to make responses that could turn off the shock even when the opportunity is presented.  It turns out that one of the first areas to be activated by uncontrollable shock contains serotonin neurons in the caudal-dorsal raphe that project to the amygdala.  If these serotonergic neurons are destroyed, then; no learned helplessness.  The Frick et al. findings are very consistent with the animal work: serotonin creates anxiety/depression.

While the Frick et al. findings are consistent with data on learned helplessness, Chris Lowry, a colleague of Steven Maier at University of Colorado, has identified multiple serotonin circuits in the raphe.  While one of these circuits produces learned helplessness, another circuit turns it off.  Thus, serotonin is just another work-horse neurotransmitter capable of creating opposite effects.  It’s the connections among the neurons, not the particular chemical making the connections, that determines the outcome.  This is another “bad news” story for the pharmaceutical houses because ingesting a chemical such as an SSRI, which presumably elevates serotonin in all circuits, will yield unpredictable effects.  There is no way given current technology to target the serotonin neurons you want.

What is clear from the two articles in JAMA Psychiatry is that psychiatrists are still focused on serotonin.  Whatever glib statements psychiatry-spokespersons utter for the general public (“we always knew it was more complicated”), in the psychiatric journals, where psychiatrists talk to each other, they acknowledge having bought the assumption that low serotonin creates anxiety.  Indeed, Stein and Andrews reflect “how do we understand the apparent paradox that potentiated serotonin signaling might underlie increased anxiety-related endophenotypes and the possible predisposition for developing anxiety disorders with the fact that some patients respond to SSRIs, which presumably further increases extracellular serotonin levels?”  As they went through tortured possibilities they could not resolve the paradox.  If they read the animal literature, it’s far less confusing.

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References:

Frick, A., Åhs,F., Engman, J., Jonasson, M., Alaie, I., Bjöekstrand, J., Frans, O., Faria, V., Linnman, C., Appel, L., Wahlstedt, K., Lubberink, M., Fredrikson, M., & Furmark, T.  (2015).  Serotonin synthesis and reuptake in social anxiety disorder:  A positron emission tomography study.  JAMA Psychiatry, 77 (8), 794-802.

Stein, M. B., & Andrews, A. M.  (2015).  Serotonin states and social anxiety.  JAMA Psychiatry, 77 (8), 845-847.