Additional file 2: of Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

PRISMA CHECKLIST This additional file includes the PRISMA checklist for reporting systematic reviews; this has been completed for the current review, highlighting where in the review each item on the checklist is addressed. (DOCX 28 kb

Additional file 1: of Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

Appendix I: Search Strategies [Search terms used for databases]. Appendix II: Data Extraction Form [Form used to extract data from included studies]. Appendix III: Quality Assessment Tool [Adapted Newcastle-Ottawa Scale used for quality assessment of studies]. Appendix IV: Excluded Studies [Table listing all studies which underwent full-text screening and were subsequently excluded, with reasons for exclusion]. Appendix V: Included Studies [Table of all included studies with key details – study design, sample size, country, definitions of treatment-resistance and response, variables measured, full results, and overall quality assessment score]. Appendix VI: Quality Assessment for Included Studies [Tables outlining full quality assessment scoring for each included study]. (DOCX 180 kb

The relationship between striatal dopamine and anterior cingulate glutamate in first episode psychosis changes with antipsychotic treatment

The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Kicer) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks’ naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20). The relationship between both measures at baseline and follow-up, and the change in this relationship was analyzed using a mixed linear model. Neither anterior cingulate glutamate concentrations (p = 0.75) nor striatal Kicer (p = 0.79) showed significant change following antipsychotic treatment. The change in relationship between whole striatal Kicer and anterior cingulate glutamate, however, was statistically significant (p = 0.017). This was reflected in a significant difference in relationship between both measures for patients and controls at baseline (t = 2.1, p = 0.04), that was not present at follow-up (t = 0.06, p = 0.96). Although we did not find any effect of antipsychotic treatment on absolute measures of dopamine synthesis capacity and anterior cingulate glutamate, the relationship between anterior cingluate glutamate and striatal dopamine synthesis capacity did change, suggesting that antipsychotic treatment affects the relationship between glutamate and dopamine

Data_Sheet_1_The effect of antipsychotics on glutamate levels in the anterior cingulate cortex and clinical response: A 1H-MRS study in first-episode psychosis patients.docx

IntroductionGlutamatergic dysfunction is implicated in the pathophysiology of schizophrenia. It is unclear whether glutamatergic dysfunction predicts response to treatment or if antipsychotic treatment influences glutamate levels. We investigated the effect of antipsychotic treatment on glutamatergic levels in the anterior cingulate cortex (ACC), and whether there is a relationship between baseline glutamatergic levels and clinical response after antipsychotic treatment in people with first episode psychosis (FEP).Materials and methodsThe sample comprised 25 FEP patients; 22 completed magnetic resonance spectroscopy scans at both timepoints. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).ResultsThere was no significant change in glutamate [baseline 13.23 ± 2.33; follow-up 13.89 ± 1.74; t(21) = −1.158, p = 0.260], or Glx levels [baseline 19.64 ± 3.26; follow-up 19.66 ± 2.65; t(21) = −0.034, p = 0.973]. There was no significant association between glutamate or Glx levels at baseline and the change in PANSS positive (Glu r = 0.061, p = 0.777, Glx r = −0.152, p = 0.477), negative (Glu r = 0.144, p = 0.502, Glx r = 0.052, p = 0.811), general (Glu r = 0.110, p = 0.607, Glx r = −0.212, p = 0.320), or total scores (Glu r = 0.078, p = 0.719 Glx r = −0.155, p = 0.470).ConclusionThese findings indicate that treatment response is unlikely to be associated with baseline glutamatergic metabolites prior to antipsychotic treatment, and there is no major effect of antipsychotic treatment on glutamatergic metabolites in the ACC.</p