Question: The "chemical imbalance" model of depression (too little serotonin/dopamine) has been challenged in the last few years due to many antidepressants being as clinically effective as placebos (they are effective, but so are the placebos). (See the studies by Irving Kirsch, or read his book *The Emperor's New Drugs*.)
  
  How does this fit in with models of ADHD and medication? Do you find any validity in Kirsch's claims?
Answer: Though there are similar issues between over simplifying depression as merely a neurochemical problem and seeing ADHD as just a dopamine disorder, we have moved way beyond that implication now.  While ADHD does impact dopamine regulation, it also impacts norepinephrine (why atomoxetine may work) as well as GABA and even the alpha-2 system (why guanfacine may help).  But beyond that, neuroimaging studies and those involving white matter connectivity and functional connectivity all suggest myriad difficulties in the development and functioning of networks, not just chemicals.  And the risk genes we are discovering for ADHD implicate even other mechanisms.  For example, some of the genes involved in ADHD are responsible for nerve cell growth, migration, and density of connections to other nerves.  Others involve nerve cell support and nourishment.  So we know now there is a lot more to disputed brain development than just low dopamine or insensitivity to it.  That doesn't take away from the fact that dopanine drugs remain the most effective for ADHD most likely because the networks we see maldeveloping are dopamine and norepinephrine mediated ones.  But its not just neurochemicals any more in modeling ADHD.  Its networks, pathways, and their functional connectivity that is also at issue.
content: Q: The "chemical imbalance" model of depression (too little serotonin/dopamine) has been challenged in the last few years due to many antidepressants being as clinically effective as placebos (they are effective, but so are the placebos). (See the studies by Irving Kirsch, or read his book *The Emperor's New Drugs*.)
  
  How does this fit in with models of ADHD and medication? Do you find any validity in Kirsch's claims?
   Ans: Though there are similar issues between over simplifying depression as merely a neurochemical problem and seeing ADHD as just a dopamine disorder, we have moved way beyond that implication now.  While ADHD does impact dopamine regulation, it also impacts norepinephrine (why atomoxetine may work) as well as GABA and even the alpha-2 system (why guanfacine may help).  But beyond that, neuroimaging studies and those involving white matter connectivity and functional connectivity all suggest myriad difficulties in the development and functioning of networks, not just chemicals.  And the risk genes we are discovering for ADHD implicate even other mechanisms.  For example, some of the genes involved in ADHD are responsible for nerve cell growth, migration, and density of connections to other nerves.  Others involve nerve cell support and nourishment.  So we know now there is a lot more to disputed brain development than just low dopamine or insensitivity to it.  That doesn't take away from the fact that dopanine drugs remain the most effective for ADHD most likely because the networks we see maldeveloping are dopamine and norepinephrine mediated ones.  But its not just neurochemicals any more in modeling ADHD.  Its networks, pathways, and their functional connectivity that is also at issue.