A Beautiful Mind, A Dysfunctional Synapse

The dopaminergic projection pathways in the midbrain also play a crucial role in the development of schizophrenia. The midbrain has two distinct dopaminergic projection pathways: the nigrostriatal pathway and the mesolimbic pathway. The former is involved in motor control and is associated with Parkinson’s disease, the second most common neurodegenerative disease (after Alzheimer’s disease), while the latter is involved with addiction and reward behaviors and is therefore implicated in the development of schizophrenia.

The nigrostriatal pathway is compromised in Parkinson’s disease, which is often treated with L-DOPA, the precursor to dopamine, in order to stimulate the biosynthesis of dopamine within nerve terminals (dopamine is not administered because it cannot cross the blood-brain barrier). However, this increased biosynthesis of dopamine often leads to overstimulation of the mesolimbic pathway, which also utilizes dopamine, manifesting in schizophrenia-like side effects. Similarly, antagonists of the D2 dopamine receptor (called neuroleptics) used in the treatment of schizophrenia often result in side effects resembling Parkinson’s disease due to the unintended suppression of the nigrostriatal pathway. Abnormalities in other neurotransmitters, such as norepinephrine and glutamate, may also contribute to schizophrenia.

Knowing Neurons

JohnForbesNashJr2_300 John Forbes Nash, Jr.
Image courtesy of Princeton University.

“I felt like I might get divine revelation by seeing a certain number; a great coincidence could be interpreted as a message from heaven.”

– John Nash in “A Brilliant Madness”

John Forbes Nash Jr. was a 20-year-old graduate student when he came up with the mathematical theories that would win him the Nobel Prize in Economics 50 years later. His mathematical insight into game theory is often over-shadowed by accounts of the eccentric behavior, paranoia, and delusions that characterized his schizophrenia. Paranoid schizophrenia manifests in clinical terms as fixed beliefs that are over-imaginative and accompanied by experiences of hauntingly real perceptions of something not actually present. These hallucinations often take the form of auditory or visual disturbances and can be accompanied by a lack of motivation and clinical depression. In his own words in the documentary “A Brilliant Madness,” Nash…

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