Dopamine and Psychosis

By Sally Robertson, B.Sc.Reviewed by Dr. Jennifer Logan, MD, MPH

Psychosis is a mental health disorder where an individual perceives or understands things differently from how other people do.

Image Credit: SergeyTarasov/Shutterstock.com

The two main symptoms are delusions and hallucinations. In the case of delusion, a person strongly believes in the truth of things that other people around them do not. One common delusion a person with psychosis may have is believing that people are planning to harm them.

In the case of hallucination, the individual hears, sees and sometimes even smells, feels or tastes things that are not there. One common example of hallucination is hearing voices.

When a person experiences delusions and/or hallucination, they can become very distressed and may start to change their behaviour. The occurrence of psychotic symptoms is often called a psychotic episode.

What causes psychosis?

Psychosis can be caused by a mental (psychological) condition, a general medical condition, or alcohol or drug misuse.

The cause of psychosis may be a mental health condition such as schizophrenia, bipolar disorder or severe anxiety, stress, or depression. The cause of the psychosis often determines what type of symptoms a person has.

Grandiose delusions are common in bipolar disorder and persecutory delusions are common in schizophrenia and depression. Grandiose delusions refer to when someone believes they have more power or authority than they do, such as believing they are a world leader or can revive dead people.

Persecutory delusions refer to conspiratorial thinking, where someone believes someone in authority is trying to harm them, for example.

Psychosis may also be caused by a general health condition such as Parkinson’s disease, malaria, multiple sclerosis or a brain tumor. Other causes include substance misuses such as drinking too much alcohol or taking drugs such as cocaine, MDMA or amphetamine.

A psychotic episode can also be triggered by suddenly stopping taking drugs or drinking alcohol after having done so for a long time. More rarely, psychosis can manifest as a side effect of taking certain medications or overdosing on them.

The ”dopamine hypothesis”

Scientists have conducted a lot of research into the effects of psychosis on the brain and the brain changes that may trigger psychotic episodes. They believe that the neurotransmitter dopamine plays a key role.

A neurotransmitter is a chemical agent that nerve cells use to transmit information to other nerve cells or muscle or gland cells. Dopamine modulates many brain functions, with dopamine pathways regulating motor control, motivation, interest, reward and activities such as walking and talking. Impairment of such brain functions may underlie the symptoms of psychosis.

Evidence that has led researchers to posit “the dopamine hypothesis” in conditions such as schizophrenia and bipolar disorder is based on several sources, including studies of brain scans and drugs that affect dopamine levels in the brain.

The dopamine hypothesis in schizophrenia

Schizophrenia is the leading cause of admissions to mental health hospitals and it accounts for even more of the permanent populations in such hospitals.

It is a severe and often chronic condition that is associated with more severe levels of impairment and personality disorder than in any other mental health condition. The main symptoms of schizophrenia include hallucinations, delusions, incoherent thought processes, a reduced ability to feel normal and a withdrawal from reality.

Although understanding the neurobiology of schizophrenia still presents a challenge, one feature that remains unchanged is the involvement of dopamine dysfunction.

Disruption to the dopamine system is the result of dopamine dysfunction in the following brain regions: the striatum, the prefrontal cortex, the hippocampus, and the substantia nigra.

In the case of schizophrenia, the dopamine hypothesis proposes that dopamine transmission is overactive in the mesolimbic areas and underactive in the prefrontal cortex. Dopamine dysregulation is also seen in the amygdala, which is involved in emotional processing.

Studies of positron emission tomography (PET) scans have also found differences in the dopamine system in certain brain regions between patients with schizophrenia and neuropsychiatric healthy individuals. In particular, the dopamine system is overactive in the hippocampus among patients with schizophrenia.

The dopamine hypothesis in bipolar disorder

Bipolar disorder is a common mental health condition characterized by changes in mood, which is characterized by episodes of feeling manic and overactive, but patients may also experience depressive episodes in bipolar disorder. Episodes of depression or mania can last for days or weeks.

Although the neurobiological mechanisms underlying bipolar disorder are not fully understood, the dopamine hypothesis has been a key theory for more than 40 years.

A 2017 systematic review published in Molecular Psychiatry, which looked at findings from pharmacological and biomedical imaging studies, found that the studies supported the hypothesis that a state of hyperdopaminergic underlies mania and that increased dopaminergic transporter levels underlie depression.

Interestingly, Oliver Howes and colleagues found that, according to the pharmacological evidence, both dopamine agonists and antidopaminergics may improve symptoms in bipolar depression.

The researchers say the evidence suggested a model where increased dopamine D2/3 receptor levels in the striatum would increase dopaminergic neurotransmission and lead to mania, while increased dopamine transporter (DAT) levels in the striatum would reduce dopaminergic function and cause depression.

According to the researchers, this suggests that the pathological mechanism underlying bipolar disorder may be failed dopamine receptor and transporter homeostasis. If this model could be confirmed, they add, it would have implications for the development of new therapeutic approaches such as decreasing synthesis in mania and inhibiting DAT in depression.

Other neurotransmitters

Recent research has suggested that dopamine perturbations alone may not fully account for the clinical features of psychosis. Ongoing research aims to determine what role, if any, serotonin, acetylcholine, glutamate, and GABA may play in psychosis.

Further Reading

• All Dopamine Content
• What is Dopamine?
• Dopamine Biochemistry
• Dopamine Therapeutic Use
• Dopamine Functions