Substantia nigra: Parkinson's disease, schizophrenia and dopamine

BRAIN AREA: Midbrain – Basal Ganglia – Substantia Nigra – Movement, learning and memory, aspects of behaviour

See Image 10

Parkinson's disease was originally described in 1817 by English doctor James Parkinson (1755–1824) who studied what was then known as 'the shaking palsy' and speculated that it might be curable in the early stages of the disease. While this is not yet possible, an early arrest of Parkinson's disease would prevent significant additional problems including intellectual deficits which worsen as the condition progresses. Contrary to Parkinson's belief that 'the … intellects being uninjured', careful testing has revealed many patients with the disease are also affected by cognitive impairment and between 25 and 40 percent eventually develop dementia.

The cause of Parkinson's disease remains uncertain. Although hereditary predisposition is implicated in approximately 15 percent of cases, experts believe most cases are due to a combination of genetic and environmental factors. Within the substantia nigra (see Image 10), the disease is marked by a reduction in dopamine and an increase in Lewy bodies leading to cell death, particularly in the pars compacta:

'In essence, the depletion of dopamine in Parkinson's disease closes the funnel that feeds activity to the supplementary motor area [of the cerebral cortex] via the basal ganglia and the [thalamus]. At the same time, dopamine inhibits the neurons in the striatum that send inhibitory outputs … to the external segment of the globus pallidus' (Neuroscience: Exploring the brain)

Dopamine has also been implicated in schizophrenia where an increase in the release of dopamine and synthesis in the striatum causes low dopamine activity in areas of the cerebral cortex, resulting in disordered thinking (cognitive deficits). However, it has not been conclusively established that reduced cortical dopamine influences symptoms such as hallucinations, delusions and racing thoughts. Causes of schizophrenia include genetic inheritance, environmental factors and drug use.

References & further reading

Parkinson's disease:

Bear, M. F., Connors, B. W., & Paradiso, M. A. (2016). Neuroscience: Exploring the brain. Wolters Kluwer.

Foltynie, T., Lewis, S., & Barker, R. A. (2003). Parkinson's disease: Your questions answered. Churchill Livingstone.

Hurwitz, B. (2014). Urban observation and sentiment in James Parkinson's Essay on the Shaking Palsy, 1817. Literature and Medicine, 32(1), 74–104.

Olanow, C. W., & Schapira, A. H. V. (2013). Parkinson's disease and other extrapyramidal movement disorders. In S. L. Hauser & S. A. Josephson (Eds.), Harrison's neurology in clinical medicine (3rd ed., pp. 333–356). McGraw-Hill.


Kambeitz, J., Abi-Dargham, A., Kapur, S., & Howes, O. D. (2014). Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: Systematic review and meta-analysis of imaging studies. The British Journal of Psychiatry, 204(6), 420–429.

Yoon, J. H., Minzenberg, M. J., Raouf, S., D’Esposito, M., & Carter, C. S. (2013). Impaired prefrontal-basal ganglia functional connectivity and substantia nigra hyperactivity in schizophrenia. Biological Psychiatry, 74(2), 122–129.