Dopamine theory – that’s all for schizophrenia?

Scientists know that pathology in the mesolimbic and mesocortical pathways causes schizophrenia, or simply called psychosis. Are there any other neurotransmitters causing the disease? I will start with the hypothesis that “Dopamine involves with schizophrenia.” Scientists found evidences that support this hypothesis, and it becomes the most fully developed more than several hypotheses. If I were about to test the hypothesis, first, I would think that if I introduce a drug that will enhance DA releasing in the brain to schizophrenics and non-schizophrenics, at a certain level of the drug, I would be able to see aggravation of the symptoms in schizophrenics group and I would expect to see schizophrenia-like symptoms in non-schizophrenics group. Second, if I use DA blocking agents in schizophrenics their symptoms would be alleviated. Third, I am going to do positron emission tomography (PET) to see the difference in DA receptors density in schizophrenics and non-schizophrenics. Actually, scientists have done these experiments and they confirm that DA involves in schizophrenia. They have also investigated postmortem brains and found the increase in DA receptors density in schizophrenics who have not been treated with antipsychotic drugs. Another evidence that support DA theory is changing in the level of homovanillic acid (HVA), a metabolite of DA, in the cerebrospinal fluid, plasma, and urine in the patients who were successfully treated. These experiments confirm that DA involves in schizophrenia, but can we make a conclusion that DA system is the system and the only system that plays an important role in schizophrenia? In greater detail are there any subtypes of DA receptors that play different roles? These questions arose because antipyschotic drugs did not give therapeutic results as good as they were expected. For examples, in a group of patients who have had the psychosis for ten to thirty years, a PET (Positron Emission Topography) scan revealed 90% of D2 receptor binding of antipsychotic drugs but the patients had minimal reduction in psychoses. However, the PET scan in a group of first-episode patients showed 60-70% D2 receptor binding, but the patients responded to low dose antipsychotics. In addition, it is found that typical antipsychotics selectively bind to D2 receptor 50 times more than binding to D1 and D3 receptors. These data support a hypothesis that selective D2 blocking has no significant in increasing antipsychotic activity, and therefore the research trend, in stead of focusing only on improving selectivity and potency of blocking D2 receptor, has been changed to a broader consideration–new drugs with less D2 selectivity.

Below is a nice illustration and explanation of DA receptor subtypes borrowed from www.cnsforum.com. I am going to discuss about this slide and other pathways that involve schizophrenia on Monday. Have a nice weekend.

“There are two types of dopamine receptor, D1-like and D2-like receptors. The D1-like receptors comprise D1- and D5-receptor subtypes that are associated with stimulation of adenylate cyclase. The D2-like receptors comprise D2-, D3- and D4-receptor subtypes and these are associated with inhibition of adenylate cyclase. The known functions of dopamine appear to be mediated mainly by D2-like receptors. All dopamine receptor subtypes are expressed in the brain in distinct but overlapping areas. D1 receptors are the most abundant and widespread in areas receiving dopaminergic innervation (the striatum, limbic system, thalamus and hypothalamus); D2 receptors are widespread in these areas, as well as the pituitary gland. D3 and D4 receptors are present in the limbic system. Schizophrenia is associated with dopaminergic hyperactivity. Dopamine antagonists used as antipsychotic drugs (eg chlorpromazine, haloperidol, risperidone) exert their effects mainly by blocking D2-like receptors. Dopamine agonists, such as apomorphine and bromocriptine, also have greater potency at D2-like receptors. Bromocriptine is used clinically to suppress prolactin secretion arising from tumours of the pituitary gland.”

Fight Schizophrenia!

People with schizophrenia need support from their families and people around them. There is no absolute cure for the disease, but there are ways to help them overcoming the symptoms and preventing a recurrence of the symptoms. When talking about schizophrenia, I think about these: first, the pathology of dopamine pathways. Second, the first agents–reserpine and chlopromazine that was found to alleviate the symptoms since 1950’s, and they are called typical antipsychotic drugs. Third, atypical antipsychotic drugs which are newer agents that have less side effects than the typical one. Fourth, the side effects of antipsychotic medications. Fifth, the drug interactions with this type of medication. And the lastly, sixth, how long people with schizophrenia should take the medications.

Many books use slightly different terminology for dopamine (DA) pathways; however, they base on the same concept in which the pathways are named after the area of the brain that neurons that release DA innervate. Here is the illustration borrowed from the Genetic Science Learning Center of the University of Utah.

[LEFT] The first–nigrostriatal pathway–extends from the substantia nigra to the caudate nucleus-putamen (neostriatum) and is concerned with sensory stimuli and movement. The death of neurons in this pathway can result in Parkinson’s disease.

[MIDDLE] The second–mesolimbic and mesocortical pathway–projects from the ventral tegmentum to the mesolimbic forebrain and is thought to be associated with memory, motivation, emotional response, reward, desire, and addiction. Pathology in this area causes schizophrenia.

[RIGHT] The third pathway, known as the tubero-infundibular system, extends from hypothalamus to pituitary gland, and is responsible for hormone regulation, maternal behavior (nurturing), pregnancy and sensory processes.

Now we know that the pathology in the mesolimbic and mesocortical pathway causes schizophrenia. Tomorrow I am going to write about DA theory in the mesolimbic and mesocortical pathway and how typical and atypical antipsychotic drugs act on this pathway.

Answers – Quiz i – Schizophrenia

i) 1. positive symptoms 2. negative symptoms 3. cognitive symptoms

Positive symptoms are obvious because normal people would not exhibit those kinds of behaviors. The symptoms involve hallucination, delusion, thought disorders, and movement disorders. These symptoms can come and go. Sometimes they are hardly to find in people with schizophrenia if they are taking medications.

ii) A hallucination is something a person sees, hears, smells, or feels that no one else can see, hear, smell, or feel. “Voices” are the most common type of hallucination in schizophrenia.

A delusion is a false personal belief that is not part of the person’s culture and do not change, even when other people present proof that the belief is not true or logical.

iii) A young man has difficulty in organizing his thoughts or connecting them logically. His speech is garbled and hard to understand.

iv) Movement disorders in people with schizophrenia are unreasonable or illogical. Sometimes they look clumsy because of their depression. Sometimes they exhibit the same movement over and over. For example a young man usually sit and look at the same spot for 10 minutes without moving. He looks like he is losing his mind. He answered questions incoherently.

Catatonia is a state of immobility and unresponsiveness.

vi) True

vii) Cognitive symptoms

viii) False

ix) True

x) False

How many scores you get?

Quize I Schizophrenia – symptoms

i. The symptoms of schizophrenia are categorized into three major groups:

1)___________ 2)_____________ 3)______________

ii. Explain “hallucination,” and “delusion.”

iii. Give two examples of thought disorders.

iv. Explain and give an example of movement disorders. What is catatonia?

v. Give examples of negative symptoms of schizophrenia.

vi. Cognitive symptoms are often detected only when neuropsychological tests are performed. (True or False)

vii. An inability to absorb and interpret an information, and make decisions based on the information is (Negative symptoms or Cognitive symptoms)

viii. People with schizophrenia can keep recently learned information in mind and use it right away. (True or False)

ix. An inability to focus on one thing is one of the characters of schizophrenia. (True or False)

x. Cognitive impairment usually does not cause emotional distress to people with schizophrenia because they do not know about their well-being. (True of False)

Check your answers tomorrow.