A 25-year-year old graduate student is brought to the emergency department by his roommate for "acting weird.” The roommate reports that over the last 4 months, he has frequently been found to be talking to himself and speaking to the air. He has also refused to leave his room for several weeks recently because he believes that once he is out of his room people will extract his thoughts and he will be followed by some “villains.” A psychiatric consultation is obtained, and he is diagnosed with schizophrenia and is started on treatment with haloperidol. Upon follow-up he is noted to have a blunted affect and reports that he is less motivated to do things and is less active.
These negative symptoms are caused by which of the following?
The correct answer is:
A) Decreased dopamine activity in the mesocortical pathway
First-generation (typical) antipsychotics demonstrate clinical efficacy in treating positive symptoms of schizophrenia such as hallucinations and delusions, while they are largely ineffective and may worsen negative symptoms such as blunted affect and social withdrawal, as well as cognitive function. The positive symptoms of schizophrenia are associated with hyperdopaminergic neurotransmission in the brain, particularly in the mesolimbic dopamine pathway, while the negative symptoms and cognitive deficits associated with schizophrenia may be caused by hypodopaminergic activity in the mesocortical pathway. Dopamine D2 receptor antagonists, such as chlorpromazine and haloperidol, have demonstrated clinical efficacy in the reduction of positive symptoms, but they do not work well in treating negative symptoms and may exacerbate negative symptoms and cognitive deficits associated with schizophrenia.
Second-generation (atypical) antipsychotics such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine, and ziprasidone block serotonin 2A (5-HT2A) receptors and alpha-1 and H1 receptors in addition to D2 receptors.
Key Learning Point
The negative symptoms and cognitive deficits associated with schizophrenia may be caused by hypodopaminergic activity in the mesocortical pathway.
