scholarly journals Plasma dopa decarboxylase activity in treatment-resistant recent-onset psychosis patients

2019 ◽  
Vol 9 ◽  
pp. 204512531987234
Author(s):  
Marieke van der Pluijm ◽  
Arjen L. Sutterland ◽  
André B. P. van Kuilenburg ◽  
Lida Zoetekouw ◽  
Lieuwe de Haan ◽  
...  
Keyword(s):  
Surrogate Marker ◽  
Clinical Problem ◽  
Dopa Decarboxylase ◽  
Antipsychotic Treatment ◽  
Decarboxylase Activity ◽  
Treatment Resistant ◽  
Significant Group ◽  
Adequate Treatment ◽  
Recent Onset ◽  
Potential Biomarker

Treatment resistance (TR) in psychosis is a major clinical problem. A biomarker predicting TR against conventional antipsychotic drugs would be relevant, potentially reducing unnecessary delay to adequate treatment with clozapine. Dopa decarboxylase (DDC) activity in the striatum, measured with positron emission tomography, is elevated in responders, but not in treatment-resistant patients. Plasma DDC activity could be a surrogate marker for DDC brain activity, and thus a potential biomarker that could be used in daily clinical practice. Therefore, we determined plasma DDC activity in 40 male patients with recent-onset psychosis, of whom the majority had started treatment, whereby 21 turned out to be treatment responders and 19 treatment resistant during follow up. We observed no significant group differences. Furthermore, symptom severity was not associated with plasma DCC activity. We did observe a trend level difference in the distribution of plasma DDC activity across categories of medication, with subsequent post hoc analysis showing lower DDC activity in risperidone-using patients. This may suggest that risperidone could influence plasma DDC activity. Based on these results, plasma DDC activity does not appear to be a promising biomarker for TR in recent-onset psychosis patients who are already receiving antipsychotic treatment.

Is treatment-resistant schizophrenia associated with distinct neurobiological callosal connectivity abnormalities?

CNS Spectrums ◽  
2020 ◽  
pp. 1-5
Author(s):  
Idaiane Batista Assunção-Leme ◽  
André Zugman ◽  
Luciana Monteiro de Moura ◽  
João Ricardo Sato ◽  
Cinthia Higuchi ◽  
...  
Keyword(s):  
Time Course ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Significant Feature ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Adequate Treatment ◽  
Brain White Matter ◽  
Potential Biomarker

Abstract Background. Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non–treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. Methods. TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB’s Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. Results. We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. Conclusion. Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.

scholarly journals Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine

2021 ◽  
Vol 14 (4) ◽  
pp. e242495
Author(s):  
Nagara Takao ◽  
Toshiya Murai ◽  
Hironobu Fujiwara
Keyword(s):  
Animal Studies ◽  
Significant Proportion ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Receptor Density ◽  
Treatment Resistant ◽  
Psychomotor Activity ◽  
Receptor Blockers ◽  
Dopamine Supersensitivity

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.

scholarly journals Dopa-decarboxylase activity and 5-HTP decarboxylase activity in pregnant rats

1990 ◽  
Vol 52 ◽  
pp. 231
Author(s):  
Naova HAMAUE ◽  
Toru ENDO ◽  
Akiyoshi YANAI ◽  
Yasuteru SHIROSHITA ◽  
Yoshio MONMA ◽  
...  
Keyword(s):  
Dopa Decarboxylase ◽  
Decarboxylase Activity ◽  
Pregnant Rats

scholarly journals Dopa decarboxylase activity of the living human brain.

1991 ◽  
Vol 88 (7) ◽  
pp. 2721-2725 ◽  
Author(s):  
A. Gjedde ◽  
J. Reith ◽  
S. Dyve ◽  
G. Leger ◽  
M. Guttman ◽  
...  
Keyword(s):  
Human Brain ◽  
Dopa Decarboxylase ◽  
Decarboxylase Activity

scholarly journals Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia

2011 ◽  
Vol 199 (4) ◽  
pp. 275-280 ◽  
Author(s):  
Takefumi Suzuki ◽  
Gary Remington ◽  
Tamara Arenovich ◽  
Hiroyuki Uchida ◽  
Ofer Agid ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Time Course ◽  
Rating Scale ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Item Score ◽  
Double Blind ◽  
The Mean ◽  
Meta Regression ◽  
Item Scores

BackgroundImprovements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia.AimsTo address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia.MethodRandomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of meta-regression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment.ResultsStudy duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0–76%). The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression – Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356).ConclusionsOur findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early. More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.

scholarly journals Dopa-decarboxylase activity and plasma prolactin concentration in rats

1989 ◽  
Vol 49 ◽  
pp. 186
Author(s):  
Naoya Hamaue ◽  
Hiroyuki Sato ◽  
Haruko Kameda ◽  
Yoshio Monma ◽  
Masaru Minami ◽  
...  
Keyword(s):  
Dopa Decarboxylase ◽  
Decarboxylase Activity ◽  
Plasma Prolactin
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