Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia.

BACKGROUND: Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown. METHODS: Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis. RESULTS: We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance. CONCLUSIONS: This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

Association between degree centrality and neurocognitive impairments in patients with Schizophrenia: A Longitudinal rs-fMRI Study.

BACKGROUND: Evidence indicates that patients with schizophrenia (SZ) experience significant changes in their functional connectivity during antipsychotic treatment. Despite previous reports of changes in brain network degree centrality (DC) in patients with schizophrenia, the relationship between brain DC changes and neurocognitive improvement in patients with SZ after antipsychotic treatment remains elusive. METHODS: A total of 74 patients with acute episodes of chronic SZ and 53 age- and sex-matched healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS), Symbol Digit Modalities Test, digital span test (DST), and verbal fluency test were used to evaluate the clinical symptoms and cognitive performance of the patients with SZ. Patients with SZ were treated with antipsychotics for six weeks starting at baseline and underwent MRI and clinical interviews at baseline and after six weeks, respectively. We then divided the patients with SZ into responding (RS) and non-responding (NRS) groups based on the PANSS scores (reduction rate of PANSS ≥50%). DC was calculated and analyzed to determine its correlation with clinical symptoms and cognitive performance. RESULTS: After antipsychotic treatment, the patients with SZ showed significant improvements in clinical symptoms, semantic fluency performance. Correlation analysis revealed that the degree of DC increase in the left anterior inferior parietal lobe (aIPL) after treatment was negatively correlated with changes in the excitement score (r = -0.256, p = 0.048, adjusted p = 0.080), but this correlation failed the multiple test correction. Patients with SZ showed a significant negative correlation between DC values in the left aIPL and DST scores after treatment, which was not observed at the baseline (r = -0.359, p = 0.005, adjusted p = 0.047). In addition, we did not find a significant difference in DC between the RS and NRS groups, neither at baseline nor after treatment. CONCLUSIONS: The results suggested that DC changes in patients with SZ after antipsychotic treatment are correlated with neurocognitive performance. Our findings provide new insights into the neuropathological mechanisms underlying antipsychotic treatment of SZ.

Analysis of EEG features and study of automatic classification in first-episode and drug-naïve patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) has a high incidence and an unknown mechanism. There are no objective and sensitive indicators for clinical diagnosis. OBJECTIVE: This study explored specific electrophysiological indicators and their role in the clinical diagnosis of MDD using machine learning. METHODS: Forty first-episode and drug-naïve patients with MDD and forty healthy controls (HCs) were recruited. EEG data were collected from all subjects in the resting state with eyes closed for 10 min. The severity of MDD was assessed by the Hamilton Depression Rating Scale (HAMD-17). Machine learning analysis was used to identify the patients with MDD. RESULTS: Compared to the HC group, the relative power of the low delta and theta bands was significantly higher in the right occipital region, and the relative power of the alpha band in the entire posterior occipital region was significantly lower in the MDD group. In the MDD group, the alpha band scalp functional connectivity was overall lower, while the scalp functional connectivity in the gamma band was significantly higher than that in the HC group. In the feature set of the relative power of the ROI in each band, the highest accuracy of 88.2% was achieved using the KNN classifier while using PCA feature selection. In the explanatory model using SHAP values, the top-ranking influence feature is the relative power of the alpha band in the left parietal region. CONCLUSIONS: Our findings reveal that the abnormal EEG neural oscillations may reflect an imbalance of excitation, inhibition and hyperactivity in the cerebral cortex in first-episode and drug-naïve patients with MDD. The relative power of the alpha band in the left parietal region is expected to be an objective electrophysiological indicator of MDD.

Sex differences in the association between suicidal ideation and neurocognitive function in Chinese patients with schizophrenia.

There is increasing evidence that sex differences exist in many clinical manifestations of patients with schizophrenia, including suicidal ideation (SI) and neurocognitive function. The present study was performed to explore the sex differences in the association between SI and neurocognitive function in Chinese patients with schizophrenia. A total of 1188 inpatients with schizophrenia were recruited from multicenter psychiatric hospitals. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to evaluate the neurocognitive function of all patients. The Positive and Negative Syndrome Scale (PANSS) was utilized to assess the psychopathology of patients. The Beck Scale for Suicide Ideation (BSSI) was used to assess the severity of SI. In male patients, the suicide risk score was significantly associated with PANSS negative symptoms (r = 0.167, p = 0.043), visuospatial subscale (r = - 0.261, p = 0.001), and RBANS total scores (r = - 0.172, p = 0.037). Furthermore, multivariate linear regression analysis showed that the visuospatial subscale (ß = - 0.490, t = - 3.273, p = 0.001) was independently associated with the suicide risk score in male patients. In female patients, the suicide risk score was significantly correlated with PANSS positive symptoms (r = 0.249, p = 0.021), negative symptoms (r = 0.394, p < 0.001), general psychopathology (r = 0.276, p = 0.01) and PANSS total score (r = 0.365, p = 0.001). Multivariate linear regression analysis showed that PANSS negative symptoms (ß = 1.849, t = 3.933, p = 0.001) were significantly associated with suicide risk scores in female patients. Our findings indicate that there are sex differences in the association between SI and neurocognitive function in patients with schizophrenia. Based on the findings of our study, gender-specific prevention and intervention strategies may make a difference in reducing SI in Chinese schizophrenia patients.

A Case Report of Sinus Bradycardia after the Addition of Lurasidone in a Patient with Bipolar Disorder.

To date, tachycardia and orthostatic hypotension have been reported as one of the negative cardiovascular complications of antipsychotics. The aim of this study was to report a case of sinus bradycardia caused by the addition of lurasidone. The patient, a 46-year-old bipolar disorder female, was admitted to the Affiliated Brain Hospital of Guangzhou Medical University with 28 years of alternating euphoric and dysphoria. On the basis of lithium carbonate 1,200 mg/day and sodium valproate 1,500 mg/day, the patient was given lurasidone 80 mg/day. After 5 days of medication, her heart rate (HR) became 48 beats per minute (beats/min). As a result, lurasidone treatment was held. On 5th day after discontinuing lurasidone, the HR reached 80 beats/min. This case report notifies that although the cardiovascular effects of lurasidone are not significant, it is also important to monitor HR status after the first administration of lurasidone.

The percentage and clinical correlates of alexithymia in stable patients with schizophrenia.

Alexithymia is a common, but less-recognized affective deficit in patients with schizophrenia. To date, no definitive conclusions have been drawn about the relationship between alexithymia and the clinical symptoms or their clinical correlates, particularly in stable patients with schizophrenia. The purpose of this study was to investigate the link between alexithymia and psychopathological symptoms, as well as any associated correlates, in stable patients with schizophrenia. A total of 435 Chinese patients with schizophrenia were recruited. The Positive and Negative Symptoms Scale (PANSS) was used to evaluate each patient's psychopathological symptoms. The Toronto Alexithymia Scale (TAS-20) was used to measure alexithymia. The percentage of alexithymia was 35.2% in stable patients with schizophrenia. Compared to non-alexithymia patients, patients with alexithymia had higher PANSS total scores, negative subscores, depressive subscores, and cognitive subscores (all p < 0.05). Multivariate regression analysis revealed that the following variables were positively associated with TAS-20 total scores: PANSS negative subscores (ß = 0.274, t = 3.198, p = 0.001) and PANSS depressive subscores (ß = 0.366, t = 2.500, p = 0.013). Education years (ß = - 0.453, t = - 2.824, p = 0.005) was negatively associated with TAS-20 total scores. Our results suggest that the percentage of alexithymia was relatively higher in stable patients with schizophrenia. Education levels, negative symptoms, and depressive symptoms were independently associated with alexithymia in this specific population.

Association between fractional amplitude of low-frequency fluctuation (fALFF) and facial emotion recognition ability in first-episode schizophrenia patients: a fMRI study.

It was still unclear that the correlation between the resting-state intrinsic activity in brain regions and facial emotion recognition (FER) ability in patients with first-episode schizophrenia (FSZ). Our aim was to analyse the correlation between the fractional amplitude of low-frequency fluctuation (fALFF) and FER ability in FSZ patients. A total of 28 patients with FSZ and 33 healthy controls (HCs) completed visual search tasks for FER ability. Regions of interest (ROIs) related to facial emotion were obtained from a previous meta-analysis. Pearson correlation analysis was performed to understand the correlation between fALFF and FER ability. Our results indicated that the patients performed worse than the HCs in the accuracy performances of happy FER and fearful FER. The previous meta-analysis results showed that the brain regions related to FER included the bilateral amygdala (AMY)/hippocampus (HIP), right fusiform gyrus (FFG), and right supplementary motor area (SMA). Partial correlation analysis showed that the fALFF of the right FFG was associated with high-load fearful FER accuracy (r = - 0.60, p = 0.004). Our study indicated that FER ability is correlated with resting-state intrinsic activity in brain regions related to facial emotion, which may provide a reference for the study of FER deficiency in schizophrenia.

Prediction of Facial Emotion Recognition Ability in Patients With First-Episode Schizophrenia Using Amplitude of Low-Frequency Fluctuation-Based Support Vector Regression Model.

Objective: There were few studies that had attempted to predict facial emotion recognition (FER) ability at the individual level in schizophrenia patients. In this study, we developed a model for the prediction of FER ability in Chinese Han patients with the first-episode schizophrenia (FSZ). Materials and Methods: A total of 28 patients with FSZ and 33 healthy controls (HCs) were recruited. All subjects underwent resting-state fMRI (rs-fMRI). The amplitude of low-frequency fluctuation (ALFF) method was selected to analyze voxel-level spontaneous neuronal activity. The visual search experiments were selected to evaluate the FER, while the support vector regression (SVR) model was selected to develop a model based on individual rs-fMRI brain scan. Results: Group difference in FER ability showed statistical significance (P < 0.05). In FSZ patients, increased mALFF value were observed in the limbic lobe and frontal lobe, while decreased mALFF value were observed in the frontal lobe, parietal lobe, and occipital lobe (P < 0.05, AlphaSim correction). SVR analysis showed that abnormal spontaneous activity in multiple brain regions, especially in the right posterior cingulate, right precuneus, and left calcarine could effectively predict fearful FER accuracy (r = 0.64, P = 0.011) in patients. Conclusion: Our study provides an evidence that abnormal spontaneous activity in specific brain regions may serve as a predictive biomarker for fearful FER ability in schizophrenia.

Kynurenine pathway metabolites are associated with gray matter volume in subjects with schizophrenia.

Background: There has been growing evidence of the existence of abnormalities in the kynurenine pathway (KP) and structural gray matter volume (GMV) in schizophrenia (SCZ). Numerous studies have suggested that abnormal kynurenine metabolism (KM) in the brain is clearly associated with the pathogenesis of schizophrenia and may be one of the pathological mechanisms of SCZ. In this pilot study, we investigated whether there was a correlation between KP and GMV in schizophrenia patients. Methods: The plasma levels of KM were measured in 41 patients who met the Structured Clinical Interview of the Diagnostic IV criteria for schizophrenia and 60 healthy controls by using liquid chromatography-tandem mass spectrometry, and cortical thickness (as measured via magnetic resonance imaging) was obtained. Results: Our study showed no statistically significant differences in the concentrations of kynurenine (KYN), tryptophan (TRP), and KYNA/TRP (all p > 0.05), but kynurenic acid (KYNA) and the KYNA/KYN ratio were significantly higher in the schizophrenia subjects than in the healthy controls (F = 4.750, p = 0.032; F = 6.153, p = 0.015, respectively) after controlling for age and sex. Spearman's tests showed that KYN concentrations in SCZ patients were negatively correlated with GMV in the left front cingulate belt (r = -0.325, p = 0.046) and that KYN/TRP was negatively correlated with GMV in the left island (r = -0.396, p = 0.014) and right island (r = -0.385, p = 0.017). Conclusion: Our findings appear to provide new insights into the predisposition of an imbalance in the relative metabolism of KYN/TRP and KYN to GMV in schizophrenia.

Increased plasma level of kynurenic acid in drug-free patients with first-episode schizophrenia compared to patients with chronic schizophrenia and healthy controls: preliminary data.

BACKGROUND: Kynurenic acid (KYNA) is a metabolite of tryptophan (TRP). KYNA levels have been reported with controversial findings in patients with schizophrenia. AIM: This study aimed to investigate the probable effects of medication and illness chronicity on peripheral KYNA levels in schizophrenia. METHODS: We assessed peripheral (plasma) TRP metabolite levels in 38 drug-free patients with first-episode schizophrenia (FES), 65 patients with chronic schizophrenia (CHS), and 70 healthy controls by using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The symptom severity of patients was evaluated by using the Positive and Negative Syndrome Scale (PANSS). Finally, we analyzed the association of TRP metabolites with symptom severity. RESULTS: We found significantly higher KYNA levels in FES patients than in both healthy controls (p < 0.01) and CHS patients (p < 0.05). No significant association was observed between plasma TRP metabolite levels and PANSS scores in either FES or CHS patients. CONCLUSIONS: In conclusion, elevated plasma KYNA levels may be a promising biomarker in FES patients. Medication and illness chronicity may affect peripheral KYNA levels with a currently unknown mechanism.

Violence, neurocognitive function and clinical correlates in patients with schizophrenia.

Background: Schizophrenia patients with violent behavior are a severe public health concern, but the correlates of this violent behavior are unknown. Additionally, the relationship between neurocognitive function and violent behavior in Chinese patients with schizophrenia has not yet been investigated. Methods: A total of 337 schizophrenia inpatients were recruited. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathological symptoms. Neurocognitive functioning was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results: The percentage of violent behavior was 10.4% in patients with schizophrenia. Patients with violent behavior had higher PANSS-positive, excited, and total subscale scores than patients who did not show violent behavior. Patients with violent behavior also had lower RBANS language, semantic fluency, and total subscale scores. Gender (OR = 0.066∼0.819, p = 0.023), illness duration (OR = 0.876∼0.971, p = 0.002), smoking (OR = 1.127∼2.950, p = 0.014), the PANSS positive subscale (OR = 1.050∼1.197, p = 0.001), and the RBANS language subscale (OR = 0.927∼0.987, p = 0.005) significantly contributed to the development of violent behavior in schizophrenia patients. Conclusion: Our findings revealed that cognitive and clinical assessments should be considered in comprehensive assessments of future risks of violence in schizophrenia patients.

Restless arms syndrome with oral olanzapine: case based review.

Background: Restless arms syndrome (RAS) is a specific variant of restless legs syndrome (RLS). RAS is characterised by an uncomfortable, painful, burning or uneasy sensation confined to the arm. Case presentation: We report a case of RAS with oral olanzapine, which improved with medication reduction. In addition, all reported cases of RAS were reviewed to explore the underlying mechanisms, diagnosis and treatment for psychiatric drug-induced RAS. The literature review and new case suggest that iron deficiency may be a predisposing factor for RAS. Psychiatric medications are closely associated with RAS, especially olanzapine, quetiapine, and mirtazapine. Discontinuation is the recommended treatment for psychotropic drug-induced RAS, while α2δ calcium channel ligand drugs and benzodiazepines may be considered. Conclusion: In conclusion, psychiatrists should be alert to the possibility of RAS when administering psychiatric medications for the first time to psychiatric patients with iron deficiency.

Association between plasma homocysteine levels and cognitive deficits in Han Chinese patients with schizophrenia across age groups.

It was still unclear how homocysteine (Hcy) levels and cognitive deficits change in patients with schizophrenia of various ages. The present article attempts to assess the relationship between Hcy levels and cognitive deficits in patients with schizophrenia across age groups, especially in young people. Totals of 103 patients and 122 healthy controls were included. All participants were stratified into four groups according to their age: 18-29 years, 30-39 years, 40-49 years, and 50-59 years. Clinical data, plasma Hcy levels, and cognitive function score were collected. Cognitive function was evaluated using the MATRICS Consensus Cognitive Battery of tests assessing speed of processing, verbal learning and memory, visual learning and memory, working memory, and attention/vigilance. Compared with the healthy group, Hcy levels increased significantly, and all the measured cognitive function score were significantly lower in all age groups of patients with schizophrenia (p < 0.001). Hcy levels were negatively associated with speed of processing (SoP), working memory (WM), and visual learning and memory (Vis Lrng) score in 18-29 years. Further multiple regression analysis showed that SoP were independently associated with Hcy levels in patients with schizophrenia aged 18-29 years (B = 0.74, t = 3.12, p = 0.008). Based on our results, patients with schizophrenia performed worse on cognitive assessments and Hcy levels were more closely related to cognition in young patients.

Suicide Attempts, Neurocognitive Dysfunctions and Clinical Correlates in Middle-Aged and Elderly Chinese Schizophrenia Patients.

Background: Suicide is a common and complex symptom of schizophrenia that may be related to clinical variables and neurocognitive function. This study aimed to investigate the associated correlates of suicide attempts in Chinese middle-aged and elderly inpatients with schizophrenia, including demographic and clinical characteristics and cognitive level, which has not yet been reported. Methods: A total of 426 schizophrenia inpatients were recruited for this study. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Neurocognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results: The prevalence of suicide attempts in middle-aged and elderly Chinese schizophrenia patients was 13.3%. Female patients had a higher suicide rate than male patients. Patients with suicide attempts had significantly higher PANSS-positive subscores, depressive subscores, and RBANS-story recall than non-attempter patients (all p < 0.05). Multiple logistic regression showed that gender, positive subscore, depressive subscore and RBANS-story recall (OR = 1.10-2.19, p < 0.05) were independently associated with suicide attempts in middle-aged and elderly schizophrenia patients. Conclusions: Our study showed that the rate of suicide attempts in Chinese middle-aged and elderly schizophrenia patients is high. Compared to non-attempters, there are less cognitive impairments, more clinical symptoms, and more female patients in the suicide attempters.

Association of plasma VEGF levels and the antidepressant effects of ketamine in patients with depression.

AIMS: Growing evidence suggests that vascular endothelial growth factor (VEGF) may be involved in the neuronal mechanisms underlying both depression aetiology and the response to ketamine treatments. The aim of this study was to examine whether changes in plasma VEGF levels are associated with the antidepressant effects of repeated ketamine infusions in patients with depression. METHODS: Ninety-six patients with depression were enrolled and received six ketamine infusions during a 12-day period. Depressive symptom severity and plasma VEGF levels were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and an enzyme-linked immunosorbent assay (ELISA) respectively, at baseline, 13 days and 26 days. RESULTS: Despite a significant improvement in MADRS scores after patients received six ketamine infusions (p < 0.001), no changes in plasma VEGF levels were observed at 13 days when compared with baseline. Moreover, no significant difference in plasma VEGF levels at baseline and 13 days was found between ketamine responders and nonresponders. No association was found between the antidepressant effects of repeated ketamine treatments and plasma VEGF levels. CONCLUSION: This study indicated that VEGF may not be a potential predictor of antidepressant response to repeated intravenous administration of ketamine in patients with depression.

Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression.

OBJECTIVES: Accumulating evidence has implicated that brain derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of depression, but its correlation with ketamine's antidepressant efficacy focusing on Chinese individuals with depression is not known. This study was aim to determine the correlation of plasma BDNF (pBDNF) concentrations and ketamine's antidepressant efficacy. METHODS: Ninety-four individuals with depression received six intravenous infusions ketamine (0.5 mg/kg). Remission and response were defined as Montgomery-Asberg Depression Rating Scale (MADRS) scores less than 10 and a reduction of 50% or more in MADRS scores, respectively. Plasma was collected at baseline and at 24 h and 2 weeks after completing six ketamine infusions (baseline, 13 d and 26 d). RESULTS: A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all ps < 0.05). Higher baseline pBDNF concentrations were found in ketamine responders/remitters (11.0 ± 6.2/10.1 ± 5.8 ng/ml) than nonresponders/nonremitters (8.0 ± 5.5/9.2 ± 6.4 ng/ml) (all ps < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d (t =  - 2.011, p = 0.047) or 26 d (t =  - 2.398, p = 0.019) in depressed patients (all ps < 0.05). Subgroup analyses found similar results in individuals suffering from treatment refractory depression. CONCLUSION: This preliminary study suggests that baseline pBDNF concentrations appeared to be correlated with ketamine's antidepressant efficacy in Chinese patients with depression.

Serum BDNF levels and the antidepressant effects of electroconvulsive therapy with ketamine anaesthesia: a preliminary study.

OBJECTIVE: To firstly examine the relationship between serum brain-derived neurotrophic factor (BDNF) levels and antidepressant response to ketamine as an anaesthesia in electroconvulsive therapy (ECT) in Chinese patients with treatment-refractory depression (TRD). METHODS: Thirty patients with TRD were enrolled and underwent eight ECT sessions with ketamine anaesthesia (0.8 mg/kg) alone. Depression severity, response and remission were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17). Enzyme-linked immunosorbent assay (ELISA) was applied to examine serum BDNF levels in patients with TRD at baseline and after the second, fourth and eighth ECT sessions. Baseline serum samples were also collected for 30 healthy controls. RESULTS: No significant differences were observed in serum BDNF levels between patients with TRD and healthy controls at baseline (p > 0.05). The remission rate was 76.7% (23/30) after the last ECT treatment, although all patients with TRD obtained antidepressant response criteria. Serum BDNF levels were not altered compared to baseline, even between remitters and nonremitters (all p > 0.05), despite the significant reduction in HAMD-17 and Brief Psychiatric Rating Scale (BPRS) scores after ECT with ketamine anaesthesia (all p < 0.05). The antidepressant effects of ECT with ketamine anaesthesia were not correlated with changes in serum BDNF levels (all p > 0.05). CONCLUSION: This preliminary study indicated that serum BDNF levels do not appear to be a reliable biomarker to determine the antidepressant effects of ketamine as an anaesthesia in ECT for patients with TRD. Further studies with larger sample sizes are warranted to confirm these findings.

A Preliminary Study of Adjunctive Nonconvulsive Electrotherapy for Treatment-Refractory Depression.

Nonconvulsive electrotherapy (NET) defined as electrical brain stimulation administered like standard electroconvulsive therapy (ECT), but below seizure threshold, could be effective for patients with treatment-refractory depression (TRD) with fewer adverse neurocognitive outcomes. However, there is a lack of studies in Chinese patients with TRD. Thus, this study was conducted to examine the efficacy and safety of adjunctive NET for Chinese patients with TRD. Twenty TRD patients were enrolled and underwent six NET treatments. Depressive symptoms, response, and remission were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 1, 3, and 6 NET treatments. Neurocognitive function was assessed by the Wisconsin Card Sorting Test (WCST) at baseline and after the completion of six NET treatments. Mean HAMD-17 scores declined significantly from 26.2 to 10.4 (p < 0.001) after post-NET. The rates of response and remission were 60.0% (95% CI: 36.5-83.5) and 10.0% (95% CI: 0-24.4), respectively. Neurocognitive performance improved following a course of NET. No significant association was found between changes in depressive symptoms and baseline neurocognitive function. Adjunctive NET appeared to be effective for patients with TRD, without adverse neurocognitive effects. Randomized controlled studies were warranted to confirm these findings.

Association between plasma levels of BDNF and the antisuicidal effects of repeated ketamine infusions in depression with suicidal ideation.

BACKGROUND: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation. METHODS: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery-Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days. RESULTS: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p < 0.05). CONCLUSION: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation.