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Insults to DNC in Mental Illness


Schizophrenia: Genetic Insults and Layer III of dlPFC

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Many layer III dlPFC DNC proteins are genetically altered in schizophrenia, and/or have documented changes in expression. A number of proteins that normally serve to strengthen synaptic efficacy, e.g. by regulating Ca2+-cAMP signaling, are lost or weakened in schizophrenia, while those molecules that decrease PFC network connectivity by activating Ca2+-cAMP signaling are often increased in the dlPFC of patients with schizophrenia.

If you are interested: Arnsten AFT, Wang MJ, Paspalas CD (2012) Neuromodulation of thought: Flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron 76: 223-239.

Genetic Insults to Molecules that Inhibit the Stress Response

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Many of the molecules that reign in the stress response are genetically altered in mental illness. For example, translocation in DISC1 is associated with a variety of mental illnesses including schizophrenia, depression and bipolar disorder; PDE4A is altered in schizophrenia, RGS4 is reduced in schizophrenia and bipolar disorder; and DGK has been associated with bipolar disorder where there may be excessive PKC signaling. The α2A-AR has been associated with ADHD. The loss of regulation of the stress response may contribute to PFC gray matter loss in these disorders.

If you are interested: Arnsten and Manji​(2008) Mania: A rational neurobiology. Future Neurology 3: 125-131. Arnsten (2011) Prefrontal cortical network connections: key site of vulnerability in stress and schizophrenia. Int J Dev Neuro. 29: 215-23.