Dopamine plays a major role in the formation of acute psychosis, as indicated by the dopamine hypothesis of schizophrenia. The relationship between acute psychosis and the dopamine system provides insight into the effects of dopamine on brain function.　Acute psychosis is a combination of various symptoms, such as hallucinations and delusions, that impair one’s relationship to reality. This can be a symptom of a serious mental illness. However, acute psychosis can also result from physical illness as well as mental illness. Acute psychosis due to physical illness may also require antipsychotics when significant confusion is present. In general, low-dose, well-tolerated atypical antipsychotics can reduce future relapse of psychosis. Because antipsychotics are effective in acute psychosis, their pathophysiology may involve an increase in the dopaminergic neurotransmissions.

Fig. 1. Schematic diagram of the neuronal nuclei of the extrapyramidal tract

We have experienced acute psychotic states in a patient with Bickerstaff brainstem encephalitis (BBE). BBE is a rare autoimmune disease of the peripheral nervous system and brainstem that presents with an acute triad of ataxia, encephalopathy, and ocular muscle paralysis. In this case, inflammation in the brain stem region may have disrupted the cortico-basal ganglia loop and caused acute psychosis. In addition to BBE, we have experienced acute psychosis due to hormonal abnormalities such as cortisol deficiency and severe metabolic abnormalities such as diabetic ketoacidosis, all of which have in common an underlying systemic inflammation. The involvement of various inflammatory cytokines in psychosis has been demonstrated both in animal models and clinically.

Interestingly, both acute psychosis due to physical illness and first-episode drug naïve schizophrenia can exhibit extrapyramidal symptoms when examined carefully. Inflammation in the brainstem, as seen in BBE, can easily cause dysfunction of the extrapyramidal loop formed by the cortex and basal ganglia, including the striatum, resulting in extrapyramidal symptoms and psychosis (Fig. 1). The extrapyramidal tract forms the cortico-basal ganglia loop and regulates motor function as well as thought. This loop is a complex interplay of excitatory and inhibitory pathways, of which the dopamine D2 receptors in the indirect pathway play an important role in thought and behavior. There is an inverse correlation between glutamate in the dorsolateral prefrontal cortex and dopamine synthesis capacity in the striatum. An imbalance between cortical glutamatergic signaling and striatal dopaminergic signaling has been proposed as a model for psychosis. There is an indirect pathway from the prefrontal cortex to the midbrain involving GABAergic interneurons that regulates dopamine secretion. If the indirect pathway is predominant, a decrease in glutamatergic signaling releases the inhibition of dopaminergic neurons in the midbrain and increases D2 receptor signaling (Fig. 2). The extrapyramidal dopaminergic system modulates thought; for example, avoidance learning and flexibility of thought are impaired in mice lacking dopamine D2(L) receptors, which are receptors in the indirect pathway. Cytokine-induced neuronal dysfunction in the basal ganglia region can lead to excessive transmission of dopamine, causing inflexibility of thought and potentially inducing hallucinations and delusions.

Fig. 2. Schematic diagram of excitatory and inhibitory neurotransmissions in the cortico-basal ganglia loop.

Investigating the function of the cortico-basal ganglia loop in patients who develop acute psychosis from physical illness may provide insight into the mechanism of psychiatric symptoms.

Takahiko Nagamine
Sunlight Brain Research Center, Hofu, Yamaguchi, 747-0066, Japan

Publication

Acute psychosis secondary to atypical Bickerstaff brainstem encephalitis
Takahiko Nagamine
Asian J Psychiatr. 2019 Dec

Read offline:

Related Articles:

	Can reports of a homicide committed by a person with…Schizophrenia is a neurological disorder in which a combination of hallucinations and delusions lead the person to interpret reality abnormally. On May 29th 2009, a patient diagnosed with schizophrenia killed…
	Modulation of intracellular dopamine signaling by…Aripiprazole, a dopamine partial agonist, is one of the most widely prescribed atypical antipsychotics and its use in children and adolescents has become common. However, due to its favorable side…
	Left-handers are not at risk for mathematical learning…Nearly one in every ten people is left-handed, a number that seems to have remained the same through time and place. Interestingly, individuals with neurodevelopmental disorders, such as low functioning…
	Adverse Drug Reactions: power, harm reduction, regulation…Patients should be checked systematically to ensure that they are not being harmed by their medication. Through case studies of prescriptions of antipsychotics to older adults in the UK, we…
	Orexin-A regulates dopamine D2 receptor in the mesolimbic…Orexin-A (orx-A) is a neuropeptide expressed exclusively in hypothalamic neurons. Orx-A acts through the activation of type-1 (Orx1R) and -2 (Orx2R) receptors present in the mesolimbic circuit and in other…
	Gas types affect stability of microbubbles and ultrasound…Ultrasound (US) is used for clinical diagnosis and therapy. Microbubbles (MBs) as US-contrast agents are applied to detect micro blood flow or specific lesions. Recently, the combination of MBs and…