Dopamine Hypothesis of Schizophrenia

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The Dopamine Hypothesis of Schizophrenia

Anne Frederickson

Schizophrenia is a disease that has plagued societies around the world for centuries, although it was not given its formal name until 1911. It is characterized by the presence of positive and negative symptoms. Positive symptoms are so named because of the presence of altered behaviors, such as delusions, hallucinations (usually auditory), extreme emotions, excited motor activity, and incoherent thoughts and speech. (1,2) In contrast, negative symptoms are described as a lack of behaviors, such as emotion, speech, social interaction, and action. (1,2) These symptoms are by no means concrete. Not all schizophrenic patients will exhibit all or even a majority of these symptoms, and there is some disagreement in the psychiatric community as to the exact diagnostic criteria. In addition, there is a great deal of debate as to the causes of the disease. While some proposed causes have been proven false, such as bad parenting and poor will power (2), there are many theories that remain. One of the most famous and most debatable is the dopamine hypothesis. The proposed hypothesis states that the brain of schizophrenic patients produces more dopamine than normal brains. It is this increased dopamine that is believed to be responsible for the symptoms of the disease. However, the is much debate in the scientific community as to the exact mechanism by which altered dopamine levels, especially in the prefrontal cortex, striatum, and limbic system, produce schizophrenia. There is much clinical evidense that provides support for the dopamine hypothesis. The first evidense that dopamine may be involved in schizophrenia came from amphetamine users. Amphetamines work by causing the brain to produce more dopamine and have been shown to produce psychotic-like symptoms. (5) In addition, traditional anti-psychotic drugs, such as haloperdol and chlorpromazine, act by blocking dopamine receptors in the brain. (2) However, there are some problems with this evidense. Amphetamines only mimic the positive symptoms of schizophrenia. They do not produce any of the negative symptoms. Likewise, anti-psychotic drugs are only affective on the positive symptoms of the disease. There is still some evidense that schizophrenics do posess higher levels of dopamine, however, these increases are only found in the striatum of the brain (7). The striatum is a region of the brain that receives its inputs from and outputs to the cortex. Injury to the striatum results in problems with intiation and control of motor behavior. (9) Also, there is evidence that the prefrontal cortex produces lower levels of dopamine. (4) The prefrontal cortex is involved in the organization and coordination of information to and from the cortex. (7)

The major support and refutation of the dopamine hypothesis has come from the examination of dopamine receptors in these regions of the brain. There are two main types of dopamine receptors, D1 and D2. However, within the category of D2 receptors, there are three subtypes, D2, D3, and D4. (5) Through PET scan analysis of dopamine usage in the brain and post-mordum molecular analysis of brain tissue, researcher were able to determine relative levels of dopamine receptors in patients with schizophrenia compared to non-schizophrenics. Overall analysis of dopamine receptors in the brain indicate that the striatum, limbic system, and the cortex have more receptors than the rest of the brain, regardless of pathology. (6) Examination of the striatum (involved in production of emotions) does not show a difference in levels of any of the dopamine receptors in schizophrenic patients. However, a great deal of research indicates that the prefrontal cortex of schizophrenic patients has decreased levels of D1, D3, and D4 receptors. (3,4,6) One researcher was able to show that, in addition, the decreased level of D1 receptors was correlated with the severity of negative symptoms in patient. (3) Another researcher found that the control of production of D3 and D4 receptors could be altered by the alteration of levels of NMDA, a neurotransmitter that seems to have some regulatory control over the production of dopamine mRNAs. (6) Through the use of a NMDA antagonist, the researcher was able to decrease the level of D4 production and increase the level of D3 production in the limbic system. Administration of the NMDA antagonist also produced effects that mimic schizophrenia. Likewise, PCP, a drug that has its effects through the inhibition of NMDA, has been shown to produce effects that are similar to both the positive and negative symptoms of the disease. (5)

While all the research seems to indicate that dopamine is somehow involved in the production of the symptoms of schizophrenia, it is difficult to determine the exact involvment. It appears that the increased levels of dopamine in the striatum are responsible for some of the positive symptoms, particularly the overactivity. However, it also appears that the prefrontal cortex may be responsible for the activation of positive symptoms. The prefrontal cortex controls and organizes the information that goes to and from the cortex. Thus, a decrease in the activity in this region of the brain would result in a lack of organization of thought and perception. This would result in the hallucinations and disorganized thoughts that are often experienced by patients with schizophrenia. In addition, the correlation between D1 receptors and negative symptoms is explained by the fact that the prefrontal cortex outputs to the rest of the brain. D1 receptors may be involved in the production of movement from signals intiated in the cortex. A decrease in these receptors would result in an inhibiting effect on behavior that would be similar to the negative symptoms. Both the positive and negative emotional symptoms can be explained by the activity of dopamine in the limbic system. The limbic system has a particularly high concentraction of D3 and D4 receptors. (6) The two receptors seem to be involved in the production and inhibition of emotion. It would seem that one is responsible for the production and the other for the inhibition. Which is which is difficult to determine, since schizophrenics exhibit an alteration in both aspects of emotion. So, the question that remains is how can the brain have different levels of dopamine and different levels of the receptors. One researcher hypothesizes that during normal development, activity of dopamine in one region of the brain may have an inhibitory effect on the development of other dopaminergic pathways. (1) The evidence indicates that the lack of dopamine activity in the prefrontal cortex and limbic system results in a lack of inhibition in the production of dopaminergic pathways in the striatum. There is some evidence to support this. Patients with schizophrenia have smaller frontal lobes and larger ventricles. (1,8) They also have a higher incidence of head injury during childhood. (1) Each of these factors could result in damage to the prefrontal cortex which would then result in a decrease in activity. The inactivity would then result in a lack of inhibition of the striatal pathway. This would be particularly evident in adolescence, when the prefrontal cortex finishes its development. (1) It is the case that schizophrenia appears during adolescence and early adulthood. (2)

Schizophrenia can be a debilitating disease if it is not properly managed. For this reason, there is copious research into its causes and treatments. Much of the research points to alterations in dopaminergic pathways. However, each piece of research seems to refute other pieces of research. However examination of the role of each of the brain areas implicated and the role of dopamine within those areas shows that the dopamine hypothesis, in a slightly altered form, does in fact support much of the research that has been done.

 

References

(1) "Schizophrenia and the Brain" From Internet Mental Health

(2) "What is Schizophrenia"

(3) "Decreased prefronal dopamine D1 receptors in schizophrenia revealed by PET" From The Schizophrenia Homepage

(4) "Dopamine Receptor Transcript Expression in Striatum, Prefrontal and Occipital Cortex: Focal Abnormalities in Orbitofrontal Cortex in Schizophrenia" From Meador-Woodruff Laboratory Homepage (University of Michigan)

(5) "Detailed Description of Our Studies" From Meador-Woodruff Laboratory

(6) "Dopamine, Glutamate, and the Neurochemical Circuitry of Schizophrenia" From Department of Psychiatry Homepage (University of Michigan)

(7) "Schizophrenia 'Trigger' Described" From NARSAD Homepage

(8) "Altered Neural Circuits in Schizophrenia"

(9)Rosenzweig, M.R., Leiman, A.L., & Breedlove, A.M. Biological Psychology. Sinaur Associates Inc: Massachusetts, 1996

 

 

Comments made prior to 2007

Avolition in schizoprenia is ofen wrongly defined as "amotivational" or as "apathy". In fact many schizophenics are highly motivated and goal directed. Avolition ("dysbulia" is a near synonym and "abulia" is synonomous) is a lack of ability to turn desires or plans into bodily motion. The dysbulic or abulic cannot get his body to do what his "mind" wants it to do. This is a catastrophic "executive" symtom of schizophrenia that is absolutly baffling. The words "apathy" and "amotivational" should be used only when avolition is not present ... Garcia Frausto, 22 February 2004

Comments

alicia's picture

schizophrenia?

I have been diagnosed with bipolar disoder since i was 20 yrs old when i was in first grade they told me i had add so i was put on meds then. I got tired of taking the medicine thought i could function without it.And i did. But about a couple years ago i started hearing vioces and seeing hallucinations. I dont understand why they wont completly go away on there own when im getting 8 hrs of sleep. The visual hallucinations have gone away like 95% but the voices i just cant function with them,there no way i can live for the rest of my life hearing voices since i just read this article i now know its schizophrenia and i need meds.

may 21 2011's picture

schizophrenia

there is alot of reasons why differnt people have mental illness, the frist major reason is because of there relationship with god. the other reasons are from drug abuse, being exposed to poisons, toxins, trama, anxiety, ect, nothing is wrong with the person themselfs.

the problem, is, the world. the world, and are hearts is what causes mental breakdown, because the world, and are hearts are very, very sinful.
there is a cure to mental illness, the cure is gods mercy.
the meds help yes! but, they are not the cure. the human body was designed to cure itself, and it does, but our continous actions, against the body, greatly disturb the recovery of the illness.

Serendip Visitor's picture

schizophrenia

Your comments are not completely without ignorance. God is not a cure for mental illness any more than other ailments or diseases. My uncle has severe schizophrenia and he is one of the most righteous, good, god fearing people I have ever known. I do believe that much depression and other mild mental disorders do have a lot to do with attitude and faith. However, some of these illnesses are serious and cannot be cured with our way of thinking, or even by our faith.

Maurice 's picture

very informal

i've been living with schizophrenia for 2 yrs now and i knew that there was more depth to my symptoms than just my former delusions as well as auditoy and visual hallucinations i knew that the fact that how everyday i felt diff when i woke up in the morning i still hear voices im often anxious & paranoid too yet i believe in that taking my meds helps me from being in the psychotic mind state i developed due to schizophrenia i've changed alot now that im aware of my illness but i fell like i lost a huge part of my old self i was more fun outgoing & social before my symptoms now im too anxious & paranoid not of violence but of peoples personalities that the may get the best of me in some way so now my emotions are more extreme if someone is real calm im nervous if they're too arrogant im shy too aggressive im anxious too much of a joker im uptight and vice versa but they always seem to outdo me they seem to no themselves socially better than me now but before my symptoms i always got to walk away with my headup

Anonymous's picture

I am sorry but your reply

I am sorry but your reply isn't very formal as well.

Luke's picture

Did you try vipassana

Did you try vipassana meditation? It help a lot to observe and kbow our states of mind and not act blinding on them, because once you are aware of it you can actually do something about before the reaction get in to the vocal or fisic active. Stay well

Luke

Sam P's picture

Thanks

Thank you for this excellent report. It was clearly layed out and easy to read. Much appreciated

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