Dopamine and response to antipsychotic medication

TY - CHAP

T1 - Dopamine and response to antipsychotic medication

AU - Ntephe, Chukwuma U.

AU - Demjaha, Arsime

N1 - Publisher Copyright: © Springer Nature Switzerland AG 2021. All rights reserved.

PY - 2020/12/14

Y1 - 2020/12/14

N2 - The precise molecular basis of schizophrenia is not completely understood. In this chapter, we will describe and examine the evidence from PET and SPECT imaging findings on the key role that dopamine, the neurotransmitter most strongly associated with schizophrenia, plays in its pathophysiology. We will review the evidence for presynaptic dopamine pathway dysfunction, which is most apparent in the associative striatum and involves abnormal elevations of dopamine synthetic capacity, dopamine release and synaptic dopamine levels. This dysfunction is well correlated with the increased likelihood, onset and worsening severity of schizophrenia. Furthermore, this association appears to be crucial in relation to the therapeutic response to dopamine antagonists. Here, in addition we review the evidence for the mechanism of action of current antipsychotics, by examining the roles that pre-and postsynaptic dopamine modulation play in their clinical efficacy. Furthermore treatment resistance, current understanding about its neurological underpinnings and treatment strategies will be outlined. Finally, we explore the dopamine and non-dopaminergic mechanisms of potential novel therapies.

AB - The precise molecular basis of schizophrenia is not completely understood. In this chapter, we will describe and examine the evidence from PET and SPECT imaging findings on the key role that dopamine, the neurotransmitter most strongly associated with schizophrenia, plays in its pathophysiology. We will review the evidence for presynaptic dopamine pathway dysfunction, which is most apparent in the associative striatum and involves abnormal elevations of dopamine synthetic capacity, dopamine release and synaptic dopamine levels. This dysfunction is well correlated with the increased likelihood, onset and worsening severity of schizophrenia. Furthermore, this association appears to be crucial in relation to the therapeutic response to dopamine antagonists. Here, in addition we review the evidence for the mechanism of action of current antipsychotics, by examining the roles that pre-and postsynaptic dopamine modulation play in their clinical efficacy. Furthermore treatment resistance, current understanding about its neurological underpinnings and treatment strategies will be outlined. Finally, we explore the dopamine and non-dopaminergic mechanisms of potential novel therapies.

KW - Dopamine

KW - Molecular imaging

KW - PET

KW - Schizophrenia

KW - SPECT

KW - Treatment-resistant schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85149297730&partnerID=8YFLogxK

U2 - 10.1007/978-3-030-57231-0_14

DO - 10.1007/978-3-030-57231-0_14

M3 - Chapter

AN - SCOPUS:85149297730

SN - 9783030572303

SP - 481

EP - 524

BT - PET and SPECT in Psychiatry

PB - Springer International Publishing

ER -