Schizophrenia: The Dopamine Hypothesis

Dopamine, a major excitatory neurotransmitter, may play a key role in schizophrenia. According to the dopamine hypothesis, the symptoms of schizophrenia - particularly positive symptoms (e.g. delusions and hallucinations), are produced by over-activity of the dopamine in areas of the brain that regulate emotional expression, motivated behaviour and cognitive functioning.

 

Having "too much" of this neurotransmitter is probably too simplistic; the better term is a functional excess (Lieberman, 1990). This may be caused by a failure of any of the many processes involved in breaking down and re-creating the neurotransmitter, or disruption to the receptor system (such as the receptor functioning "too well"), or there may be problems with re-uptake into the presynaptic membrane.

 

Dopamine Pathways

People diagnosed with schizophrenia have more dopamine receptors on neuron membranes than do non-schizophrenics, and these receptors seem to be over-active to dopamine stimulation (Wong, 1986). Additional support comes from the finding that the effectiveness of antipsychotic drugs used to treat schizophrenia is positively related to their ability to reduce dopamine-produced synaptic activity (Green, 1997).

 

The hypothesis that dopamine and dopaminergic mechanisms are central to schizophrenia has been one of the most enduring ideas about the illness. It was not until the 1970's, however, that the dopamine hypothesis was finally crystallized with the finding that the clinical effectiveness of antipsychotic drugs was directly related to their affinity for dopamine receptors. To date, their have been more than 6800 articles on the topic of dopamine and schizophrenia since 1991.

 

In summary, molecular imaging studies show that presynaptic striatal dopaminergic function is elevated in patients with schizophrenia; however blockade of this heightened transmission, either by decreasing dopamine levels or blocking dopamine transmission, leads to a resolution of symptoms for most patients (Howes, 2009).  

Neuroleptic-Induced Dystonia

Dystonia is a neurological movement disorder which may affect anyone at any age. It is characterised by involuntary muscle contractions which force certain parts of the body into abnormal, sometimes painful, movements or postures. Dystonia can affect any part of the body including the arms and legs, trunk, neck, eyelids, face, or vocal cords.



The disordered tonicity of muscles that occurs in dystonia can also be associated with neuroleptics, a dopamine antagonist drug. This secondary, or acquired dystonia, can be a problem encountered specifically with the use of antipsychotic medication (Hansen, 1997), as one side effect of these drugs is debilitating movement disorders known as extrapyramidal symptoms (Yamamoto & Inada, 2012). Drugs that decrease the effectiveness of neurotransmission are known as antagonists. Antipsychotic medication blocks dopamine receptors and this in turn can lead to the dystonic reactions.

With Parkinson’s, the disease is caused by cell death in the substantia nigra, which has dopamine producing functions. This loss of dopamine activity results in a decreased stimulation of the motor cortex which can lead to movement disruptions in the body. Similarly, the dopamine blockade effect of neuroleptic antagonists reduces the activity of transmitters in the synapse causing involuntary muscle contractions (Hansen, 1997). Therefore the severe disturbances of motor behaviour are often caused by the drug-induced dysfunction of the dopaminergic extrapyramidal system, which plays a vital role in movement control (Smelser & Baltes, 2001).

Extrapyramidal symptoms can be categorised as acute and tardive. Acute dystonia has a sudden onset and is often seen within the first five days of starting an antipsychotic course of treatment. Conversely, tardive begins after a long-term use of dopamine antagonist medication (Van Harten & Kahn, 1999).

Neuroleptic-Induced acute dystonia can result in abnormal positioning or spasm of muscles in the head, such as the eyes (oculogyric), neck (impaired swallowing), limbs, and trunk. Acute dystonic reactions generally disappear once the drug dose is lowered or there is complete cessation of the antipsychotic (Yamamodo & Inada, 2012). With tardive dystonia there is currently no established course of treatment, however administration of clozapine has been cited as the only drug helpful if it is tolerated by the patient.

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''Life has many twists and turns.

But when it literally involves your body, then the above saying takes on a whole different meaning''