Does adjunctive electro-convulsive therapy improve the speed of treatment response in schizophrenia? A systematic review and week-by-week meta-analyses of controlled clinical trials.

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger’s regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = −0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant.

ObjectiveMajor depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD.MethodsIn total, 601 patients (aged 12–18) with MDD were recruited. The Patient Health Questionnaire – 9 items (PHQ – 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured.ResultsThe incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p < 0.05).ConclusionsPRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention.

P02-540 - Electroconvulsive Therapy and Depression with Psychotic Symptoms: a Case Report

Major depressive disorder (MDD) sufferers frequently have psychotic symptoms, yet the underlying triggers remain elusive. Prior research suggests a link between insulin resistance (IR) and increased occurrence of psychotic symptoms. Hence, this study sought to investigate the potential association between psychotic symptoms in Chinese patients experiencing their first-episode drug-naïve (FEDN) MDD and the triglyceride glucose (TyG) index, an alternative measure of insulin resistance (IR). Between September 2016 and December 2018, 1,718 FEDN MDD patients with an average age of 34.9 ± 12.4 years were recruited for this cross-sectional study at the First Hospital of Shanxi Medical University in China. The study collected clinical and demographic data and included assessments of anxiety, depression, and psychotic symptoms using the 14-item Hamilton Anxiety Rating Scale (HAMA), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the positive subscales of the Positive and Negative Syndrome Scale (PANSS), respectively. Measurements of metabolic parameters, fasting blood glucose (FBG), and thyroid hormones were also gathered. To assess the correlation between the TyG index and the likelihood of psychotic symptoms, the study used multivariable binary logistic regression analysis. Additionally, two-segmented linear regression models were employed to investigate possible threshold effects in case non-linearity relationships were identified. Among the patients, 9.95% (171 out of 1,718) exhibited psychotic symptoms. Multivariable logistic regression analysis showed a positive correlation between the TyG index and the likelihood of psychotic symptoms (OR = 2.12, 95% CI: 1.21-3.74, P = 0.01) after adjusting for confounding variables. Moreover, smoothed plots revealed a nonlinear relationship with the TyG index, revealing an inflection point at 8.42. Interestingly, no significant link was observed to the left of the inflection point (OR = 0.50, 95% CI: 0.04-6.64, P = 0.60), whereas beyond this point, a positive correlation emerged between the TyG index and psychotic symptoms (OR = 2.42, 95% CI: 1.31-4.48, P = 0.01). Particularly, a considerable 142% rise in the probability of experiencing psychotic symptoms was found with each incremental elevation in the TyG index. Understanding the non-linear link between the TyG index and the risk of psychotic symptoms in Chinese patients with FEDN MDD highlights the potential for targeted therapeutic approaches. By acknowledging the threshold effect observed, there is an opportunity to mitigate risk factors associated with IR-related psychiatric comorbidities through tailored interventions. These preliminary results stress the need for further longitudinal research to solidify these insights and contribute to more effective therapeutic strategies.

The aim of this study was to examine the efficacy and safety of electroconvulsive therapy (ECT) for psychotic symptoms of dementia with Lewy bodies (DLB), and also to determine its use as an adaptive criterion. Eight patients aged 66-83years old (mean 75.4±5.9years) diagnosed with probable DLB based on the criteria for DLB and who received ECT between September 2013 and December 2019 at Aichi Medical University were enrolled. The efficacy and safety of ECT were retrospectively examined. Psychotic symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS), while parkinsonism was evaluated based on Hoehn-Yahr (HY) stage, with both scores analyzed and comparedstatistically between before and after ECT. Additionally, a follow-up survey after undergoing ECT was performed. Two incidents occurred during ECT sessions, arrhythmia in one patient and respiratory arrest in another, both of whom quickly recovered. Following ECT, a significant improvement in BPRS score was noted (p<0.018, Wilcoxon signed rank test), whereas no significant difference was seen in regard to HY stage (p=0.059). Follow-up survey findings obtained after ECT (mean observation period 15.9±16.7months), showed that all eight patients were alive and none had a relapse of psychotic symptoms. The present results suggest that ECT for patients with mild to moderate DLB and drug therapy-resistant psychotic symptoms is safe, well tolerated and effective. We consider it worth considering as a DLB therapeutic option.

Background: Electroconvulsive therapy (ECT) is a clinically effective treatment for schizophrenia (SZD). However, studies have shown that only about 50 to 80% of patients show response to ECT. To identify the most suitable patients for ECT, developing biomarkers predicting ECT response remains an important goal. This study aimed to explore the quantitative electroencephalography (QEEG) biomarkers to predict ECT efficacy. Methods: Thirty patients who met DSM-5 criteria for SZD and had been assigned to ECT were recruited. 32-lead Resting-EEG recordings were collected one hour before the initial ECT treatment. Positive and negative symptoms scale (PANSS) was assessed at baseline and after the eighth ECT session. EEG data were analyzed using mutual information. Results: In the brain network density threshold range of 0.05 to 0.2, the assortativity of the right temporal, right parietal, and right occipital cortex in the response group was significantly higher than that in the non-response group (p < .05) in the beta band. In the theta band, the left frontal, parietal, right occipital cortex, and central area assortativity were higher in the response group than in the non-response group (p < .05). Conclusions: QEEG might be a useful approach to identify the candidate biomarker for ECT in clinical practice.

ECT led to better results than medication for treatment-resistant bipolar disorder, but remission rates did not differ between the two groups.

Patients with concurrent schizophrenic and mood symptoms are often treated with antipsychotics plus antidepressant or thymoleptic drugs. The authors review the literature on treatment of two overlapping groups of patients: those with schizoaffective disorder and those with schizophrenia and concurrent mood symptoms. MEDLINE searches (from 1976 onward) were undertaken to identify treatment studies of both groups, and references in these reports were checked. Selection of studies for review was based on the use of specified diagnostic criteria and of parallel-group, double-blind design (or, where few such studies addressed a particular issue, large open studies). A total of 18 treatment studies of schizoaffective disorder and 15 of schizophrenia with mood symptoms were selected for review. For acute exacerbations of schizoaffective disorder or of schizophrenia with mood symptoms, antipsychotics appeared to be as effective as combination treatments, and there was some evidence for superior efficacy of atypical antipsychotics. There was evidence supporting adjunctive antidepressant treatment for schizophrenic and schizoaffective patients who develop a major depressive syndrome after remission of acute psychosis, but there were mixed results for treatment of subsyndromal depression. There was little evidence to support adjunctive lithium for depressive symptoms and no evidence concerning its use for manic symptoms in patients with schizophrenia. Empirical data suggest that both groups of patients are best treated by optimizing antipsychotic treatment and that atypical antipsychotics may prove to be most effective. Adjunctive antidepressants may be useful for patients with major depression who are not acutely ill. Careful longitudinal assessment is required to ensure identification of primary mood disorders.

BackgroundSchizophrenia is a kind of intractable brain disorder. Electroconvulsive therapy (ECT) has been used to rapidly improve the clinical symptoms of patients with schizophrenia, but the effect of ECT on topological attributes of brain functional network in patients with schizophrenia has not been clear. The purpose of this study was to investigate the brain functional network mechanism of ECT against schizophrenia.MethodsThirty-one patients with schizophrenia and fifty healthy controls matching age, gender, and years of education were included. All participants underwent general data collection and magnetic resonance imaging scanning before ECT, and clinical symptoms were assessed using the Positive And Negative Syndrome Scale (PANSS). MRI and clinical symptoms were collected again after the first and eighth ECT application. The functional brain network was constructed on the basis of magnetic resonance imaging, and the global and node topological properties were analyzed. Repeated measure variance analysis was used to explore the changes of the topological attribute values and clinical symptom scores before and after ECT, and Bonferroni post hoc analysis was performed. The independent sample t-test was used to compare the differences in the topological attribute values between patients and healthy controls at three time points before and after ECT. Partial correlation analysis was performed for topological attribute values and clinical symptom scores of abnormal brain regions in the patient groups and their changes during ECT. A general linear regression model was used to predict the outcome after the final eighth ECT using the patient's response to the first ECT.Results(1) One ECT can restore the gamma(γ), lamuda(λ), sigma(σ), nodal global efficiency (Ne) of right insular gyrus ventral agranular insula (INS_R_vIa) and nodal local efficiency (NLe) of bilateral fusiform gyrus medioventral area37 (FuG_A37mv). Eight ECT can also restore the NLe of cortex rostral lingual gyrus (MVOcC _R_rLinG). Eight ECT did not improve the Ne of right superior parietal lobule rostral area 7 (SPL_R_A7r) and NLe of left superior frontal gyrus medial area 6 (SFG_L_A6m). (2) Even after only the first use of ECT, total PANSS scores began to decrease (mean ΔPANSSECT1 was 11.7%; Range, 2%-32.8%), decreased significantly after the eighth application (mean ΔPANSSECT8 was 86.0%; Range,72.5% to 97.9%). Five patients met the response criteria after ECT1 (20% reduction in PANSS total score), and all patients met the response criteria after ECT8. (3) Linear regression analysis showed that ΔPANSSECT1 was a significant predictor of ΔPANSSECT8 (F=5.387, P=0.028), and ΔPANSSECT1 explained 15.7% of the variance of ΔPANSSECT8 (R2=0.157).ConclusionsECT was able to normalize γ, λ, σ, Ne of INS_R_vIa, NLe of bilateral FuG_A37mv in SZ patients after the first treatment, and NLe of MVOcC_R_rLinG after the eighth ECT. ECT significantly alleviates psychotic symptoms in patients with SZ, and its efficacy after eight sessions can be predicted by the patient's response to the first session of ECT.

Objective To explore relationship of psychotic symptoms with childhood abuse and psychological resilience in patients with depression. Methods According to whether the psychotic symptoms exist, 160 patients with depression were divided into psychotic major depression (PMD group, n=80) and nonpsychotic major depression (NMD group, n=80). All patients were assessed with general information questionnaire, the childhood trauma questionnaire(CTQ)and the Conner-Davidson resilience scale(CD-RISC). Using logistic regression analysis to explore the influencing factors of psychiatric symptoms in depressive patients. Results There were significant differences in the emotional abuse ((17.80±2.78), (10.14±1.46)), the physical abuse ((16.98±3.21), (8.31±1.24)), the sexual abuse ((8.74±1.87), (7.85±1.71)), the emotional neglect ((21.46±1.95), (15.71±2.12)) and total score of childhood abuse ((81.98±9.88), (54.10±4.36)) between the two group (F=68.88, 70.91, 2.91, 45.93, 77.28, all P<0.01). There were significant differences in the resilience (F=4.47, P<0.01), the power (F=5.59, P<0.01), the optimism (F=2.35, P=0.033) and total score of psychological resilience (F=7.23, P<0.01) between the two group.Logistic regression analysis showed that attack in early age(B=2.57, P=0.024, OR(95%CI)=13.07(1.01-169.54))was a risk factor for psychotic symptoms in patients with depression.No experience of childhood abuse (B=-1.95, P=0.003, OR(95%CI)=0.14(0.04-0.52)), the higher psychological resilience level(B=-2.54, P<0.01, OR(95%CI)=0.08(0.02-0.27)), mild to moderate depression (B=-1.33, P=0.013, OR(95%CI)=0.27(0.09-0.76))were protective factors of psychotic symptoms in patients with depression. Conclusion Psychological resilience may be the protective factor for psychotic symptoms in patients with depression while childhood abuse may be a risk factor. Key words: Depression; Psychotic symptoms; Childhood abuse; Psychological resilience

The first- and second-generation antipsychotic drugs have become mainstay drug treatment for schizophrenia. However, patients who receive antipsychotic drugs differ with respect to treatment response and drug-induced adverse events. The biological predictors of treatment response are being researched worldwide, with emphasis on molecular genetic predictors of treatment response. Because of the rapid and exciting developments in the field, we reviewed the recent studies of the molecular genetic basis of treatment response in schizophrenia. The accumulating data suggest that DNA information in the pathways for drug metabolism and drug target sites may be an important predictor of treatment response in schizophrenia. The data suggest that clinicians may soon be using a patient's genotype to decide initial choice of antipsychotic drug treatment in schizophrenia. The pharmacogenetics of schizophrenia can improve the prospects of individualized treatment and drug discovery. Pharmacogenetic investigations of schizophrenia susceptibility loci, and genes controlling drug target site receptors, drug-metabolizing enzymes, the blood-brain barrier systems, and epigenetic mechanisms could lead to a molecular classification of treatment response and adverse events of psychotropic drugs.

Relationship between childhood trauma and psychotic symptoms in patients with schizophrenia

ObjectiveThis retrospective case series study of the effectiveness of electroconvulsive therapy (ECT) augmentation on clozapine-resistant schizophrenia was conducted by EMR review.MethodsClozapine-resistance was defined as persistent psychotic symptoms despite at least 12 weeks of clozapine administration with blood levels over 350 ng/mL in order to rule out pseudo-resistance. Seven in-patients who were taking clozapine and treated with ECT were selected. We analyzed the psychopathology and subscales changed by ECT.ResultsThe average number of ECT sessions was 13.4 (±4.6). Total Positive and Negative Syndrome Scale (PANSS) score was significantly reduced by 17.9 (±12.8) points (p=0.0384) on average, which represented a reduction of 25.5% (±14.3). 71.4% (5/7) of patients were identified as clinical remission, with at least a 20% reduction in PANSS score. PANSS reduction was associated with number of ECT sessions, stimulus level in the final session, and blood clozapine levels before ECT. However, the negative subscale on the PANSS were not reduced by ECT in any patient. We did not observe any persistent adverse cognitive effects.ConclusionThis study supports that ECT augmentation on clozapine-resistant schizophrenia reveals clinically effective and safe. Further research should be done involving a larger number of patients to investigate the effectiveness of clozapine/ECT combination therapy.

Investigating the relationship between premorbid functioning and treatment response in schizophrenia is relevant to understanding the illness and predicting treatment outcomes. To examine the relationship between premorbid characteristics and treatment response of people with recent-onset schizophrenia. Data came from a large, double-blind trial of recent-onset psychosis treated with a flexible dose of risperidone or haloperidol. Median treatment length was 206 days. Premorbid functioning was categorised using the Cannon-Spoor Premorbid Adjustment Scale. There were significant differences between the premorbid groups on change on the Positive and Negative Syndrome Scale, Clinical Global Impression severity and cognitive functioning and Extrapyramidal Symptoms Rating Scale. Patients in the ;stable-good' premorbid group (n = 251) improved more than those in the'stable-poor' (n = 198) and 'declining' (n = 81) groups. The ;stable-good' group received the lowest doses of antipsychotic and had the least extrapyramidal symptoms. Patients in the 'declining' group had the highest dosages and the most extrapyramidal symptoms. In first-episode psychosis good premorbid functioning is associated with better response to treatment and fewer extrapyramidal symptoms.

Antipsychotics are thought to improve schizophrenia symptoms through the antagonism of dopamine D2 receptors, which are abundant mainly in subcortical regions. By introducing functional gradient, a novel approach to identify hierarchy alterations by capturing the similarity of whole brain fucntional connectivity (FC) profiles between two voxels, the present study aimed to characterize how the subcortical gradient is associated with treatment effects and response in first-episode schizophrenia in vivo. Two independent samples of first-episode schizophrenia (FES) patients with matched healthy controls (HC) were obtained: the discovery dataset included 71 patients (FES0W) and 64 HC at baseline, and patients were re-scanned after either 6 weeks (FES6W, N = 33) or 12 months (FES12M, N = 57) of antipsychotic treatment, of which 19 patients finished both 6-week and 12-month evaluation. The validation dataset included 22 patients and 24 HC at baseline and patients were re-scanned after 6 weeks. Gradient metrics were calculated using BrainSpace Toolbox. Voxel-based gradient values were generated and group-averaged gradient values were further extracted across all voxels (global), three systems (thalamus, limbic and striatum) and their subcortical subfields. The comparisons were conducted separately between FES0W and HC for investigating illness effects, and between FES6W/FES12M and FES0W for treatment effects. Correlational analyses were then conducted between the longitudinal gradient alterations and the improvement of clinical ratings. Before treatment, schizophrenia patients exhibited an expanded range of global gradient scores compared to HC which indicated functional segregation within subcortical systems. The increased gradient in limbic system and decreased gradient in thalamic and striatal system contributed to the baseline abnormalities and led to the disruption of the subcortical functional integration. After treatment, these disruptions were normalized and the longitudinal changes of gradient scores in limbic system were significantly associated with symptom improvement. Similar illness and treatment effects were also observed in the validation dataset. By measuring functional hierarchy of subcortical organization, our findings provide a novel imaging marker that is sensitive to treatment effects and may make a promising indicator of treatment response in schizophrenia.