Neurobiology of Psychosis

In addition to bipolar type 1 and bipolar type 2, bipolar disorder can be further divided into two categories: bipolar disorder with psychosis and bipolar disorder without psychosis. Many genes are currently being studied to determine their role in psychosis, including D-amino acid oxidase, group II metabotropic glutamate receptors, ZNF804A, and catechol-O-methyltransferase (COMT). The neurotransmitter dopamine, when in excess, is believed to be the underlying cause of psychosis. However, this excess in dopamine is found in psychotic patients before they are in a psychotic episode, so dopamine is more of a prerequisite of psychosis than a cause or a result of psychosis. Dopaminergic drugs, like cocaine and amphetamine, can induce psychotic symptoms, especially in schizophrenic and bipolar patients. A common symptom of psychosis is inappropriate attribution of salience to nonsalient stimuli. Alterations in dopamine in the associative striatum likely contribute to this (Winton-Brown, Fusar-Poli, Ungless & Howes, 2014). The associative striatum, the connection between the frontal and parietal associative cortices, is important for goal-directed action and behavioral flexibility. A network model has been proposed that dysfunction in a circuit that includes the associative striatum, prefrontal cortex, and thalamus is a primary trigger of psychosis (Kesby, Eyles, McGrath & Scott, 2018). Auditory hallucinations have been associated with altered connectivity between the hippocampus and the thalamus (Amad et al., 2014). During visual hallucinations, activity between the striatum, thalamus and hippocampus has been found to be increased (Silbersweig et al., 1995). Delusions have been associated with overactivity in the prefrontal cortex (Larivière et al. 2017). People with lesions in the basal ganglia and the caudate nucleus also present with hallucinations and delusions (McMurtray et al., 2014).

Amad, A. et al. The multimodal connectivity of the hippocampal complex in auditory and visual hallucinations. Mol. Psychiatry 19, 184–191 (2014).

Kesby, J. P., Eyles, D. W., McGrath, J. J., & Scott, J. G. (2018). Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience. Translational psychiatry, 8(1), 1-12.

Larivière, S. et al. Altered functional connectivity in brain networks underlying self-referential processing in delusions of reference in schizophrenia. Psychiatry Res. 263, 32–43 (2017).

Silbersweig, D. A. et al. A functional neuroanatomy of hallucinations in schizophrenia. Nature 378, 176–179 (1995).

McMurtray, A. et al. Acute Psychosis Associated with Subcortical Stroke: Comparison between Basal Ganglia and Mid-Brain Lesions. Case Rep. Neurol. Med. 2014, 428425 (2014).

Winton-Brown, T. T., Fusar-Poli, P., Ungless, M. A. & Howes, O. D. Dopaminergic basis of salience dysregulation in psychosis. Trends Neurosci. 37, 85–94 (2014).