Abstract:
:All current antipsychotic drugs block dopamine (DA) receptors, but the nature of the DA dysfunction in schizophrenia has not been clear. However, consistent evidence now shows that presynaptic dopaminergic function is altered in schizophrenia, specifically in terms of increased DA synthesis capacity, baseline synaptic DA levels, and DA release. Furthermore, presynaptic dopaminergic function is already elevated in prodromal patients who later developed the disorder. Currently available antipsychotics act on postsynaptic receptors, not targeting presynaptic DA abnormalities. This has implications for understanding response and developing new treatments. The lack of normalization of the abnormal presynaptic function could explain why discontinuation is likely to lead to relapse, because the major dopaminergic function persists, meaning that once treatment stops there is nothing to oppose the dysregulated dopamine function reinstating symptoms. Furthermore, it suggests that drugs that target presynaptic dopaminergic function may constitute new treatment possibilities for schizophrenic patients, in particular, for those in whom antipsychotics are poorly effective. In addition, the longitudinal changes with the onset of psychosis indicate the potential to target a defined dynamic neurochemical abnormality to prevent the onset of psychosis.
journal_name
CNS Drugsjournal_title
CNS drugsauthors
Bonoldi I,Howes ODdoi
10.1007/s40263-014-0177-zsubject
Has Abstractpub_date
2014-07-01 00:00:00pages
649-63issue
7eissn
1172-7047issn
1179-1934journal_volume
28pub_type
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