Striatal D_2/3Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome

Abstract

One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D2/3 receptor binding potential (BPp) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D2/3 receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [123I]iodobenzamide ([123I]-IBZM) was used to examine striatal D2/3 receptor BPp. Patients were examined before and after 6 weeks of treatment with the D2/3 receptor antagonist amisulpride. There was a significant negative correlation between striatal D2/3 receptor BPp at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BPp in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BPp of dopamine D2/3 receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BPp have a better treatment response than patients with a high BPp. The results further suggest that functioning may decline at high levels of dopamine receptor blockade.

Amotivation is associated with smaller ventral striatum volumes in older patients with schizophrenia

“…However, treatment with antipsychotics, which antagonize D 2/3 R, does not seem to significantly worsen nor improve motivational deficits in patients with schizophrenia . Consistently, several studies suggest that occupancy of striatal D 2/3 R by antipsychotics is related to improvements in positive symptoms, with no relationship to negative symptoms . In a sample of older, chronically treated patients, estimated antipsychotic occupancy of D 2/3 R in the VS was not found to be related to amotivation .…”

“…18 Consistently, several studies suggest that occupancy of striatal D 2/3 R by antipsychotics is related to improvements in positive symptoms, with no relationship to negative symptoms. [19][20][21][22] In a sample of older, chronically treated patients, estimated antipsychotic occupancy of D 2/3 R in the VS was not found to be related to amotivation. 23 Reducing the dose of antipsychotics in the same sample failed to significantly improve motivation.…”

Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment

“…Reward data on a subgroup of the participants (22 patients) and data on other modalities have been presented elsewhere. 29,[40][41][42][43] A flowchart of patient recruitment is provided in Figure 1.…”

Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

“…Poor response to treatment in the chronic phase of schizophrenia has been associated with increased levels of glutamate in the anterior cingulate cortex (ACC) concurrent with relatively unaffected striatal dopamine function (Demjaha et al, 2014;Mouchlianitis et al, 2015). Recent findings suggest that glutamate and γ-aminobutyric acid (GABA) levels also are increased in antipsychotic-naïve or minimally treated non-responding patients when compared with levels in responders (de la Fuente-Sandoval et al, 2017;Egerton et al, 2018), whereas responding patients have higher striatal dopamine activity than nonresponding patients (Wulff et al, 2015(Wulff et al, , 2019. These findings suggest the existence of a subgroup of non-responding patients with higher glutamate levels compared with responders.…”