This is a good study, but it's important to understand that the study results [1] don't really contradict much of our current understanding of serotonin-related antidepressant activity. If you read through the actual study, you'll see that the authors aren't disagreeing with SSRI activity but rather attempting to gather more insight into the accepted anxiolytic activity of SSRIs.<p>Neurotransmitter reductionism is one of the more difficult pop-neuropsychiatry concepts to shake, because it's so tempting to think of neurotransmitters like serotonin in the same way we've come to think of more basic biomarkers like cholesterol levels or other hormone levels. Neurotransmitter function is several orders of magnitude more complex, and can't simply be summarized as "too much" or "too little."<p>For example, neurotransmitter signaling is often divided in to two components: Tonic and phasic release. Tonic signaling is lower frequency (think closer to DC current for a very crude analogy), while phasic release is higher frequency (think more along the lines of AC current). The balance of tonic vs phasic signaling often has a massive influence on the actual outcome of the signaling. SSRIs are frequently (and wrongly) thought of as generically "increasing serotonin levels" when what they're really doing is altering serotonin dynamics in the synaptic cleft. Inhibiting the serotonin reuptake pump causes the serotonin to stick around longer in the synaptic cleft, which (again, roughly speaking) slows the serotonin dynamics down a bit and moves toward tonic, rather than phasic, signaling. It's not difficult to find studies showing relationships between serotonin tonic and phasic signaling, SSRIs, and stress adaptation differences. See [2] for the first example I found in a quick search.<p>Another very important component of serotonin signaling are 5-HT1A autoreceptors located on presynaptic terminals. These are part of the feedback loop regulating serotonin release. Briefly, 5-HT1A autoreceptors bind serotonin in the synaptic cleft and apply negative feedback to serotonin release. More serotonin in the synaptic cleft results in more 5-HT1A autoreceptor activation, which will in turn slow serotonin release. SSRIs will increase extracellular serotonin area under the curve, which will result in additional 5-HT1A activation and altered serotonin release dynamics. This system will ultimately re-regulate to some other set-point after several weeks, which is theorized to be part of the reason for the therapeutic lag in SSRI treatment, and also thought to explain why SSRIs often initially cause more anxiety by acutely increasing serotonin levels before the system re-regulates. 5-HT1A autoreceptor modulation is also the theorized mechanism of action of anti-anxiety medications like Buspirone, and 5-HT1A modulation is a property of two of the most recent anti-depressant medications Vortioxetine and Vilazadone.<p>This is another good study to have, but it's important to not be too quick to think that this contradicts our current understandings.<p>[1] <a href="http://archpsyc.jamanetwork.com/article.aspx?articleid=2319711" rel="nofollow">http://archpsyc.jamanetwork.com/article.aspx?articleid=23197...</a><p>[2] <a href="http://www.ncbi.nlm.nih.gov/pubmed/22791197" rel="nofollow">http://www.ncbi.nlm.nih.gov/pubmed/22791197</a>