Pre-treatment functional connectivity of the cingulate cortex predicts anti-suicidal effects of serial ketamine infusions.

BACKGROUND: Although ketamine can rapidly decrease suicidal ideation (SI), its neurobiological mechanism of action remains unclear. Several areas of the cingulate cortex have been implicated in SI; therefore, we aimed to explore the neural correlates of the anti-suicidal effect of ketamine with cingulate cortex functional connectivity (FC) in depression. METHODS: Forty patients with unipolar or bipolar depression with SI underwent six infusions of ketamine over 2 weeks. Clinical symptoms and resting-state functional magnetic resonance imaging data were obtained at baseline and on day 13. Remitters were defined as those with complete remission of SI on day 13. Four pairs of cingulate cortex subregions were selected: the subgenual anterior cingulate cortex (sgACC), pregenual anterior cingulate cortex (pgACC), anterior mid-cingulate cortex (aMCC), and posterior mid-cingulate cortex (pMCC), and whole-brain FC for each seed region was calculated. RESULTS: Compared with non-remitters, remitters exhibited increased FC of the right pgACC-left middle occipital gyrus (MOG) and right aMCC-bilateral postcentral gyrus at baseline. A high area under the curve (0.91) indicated good accuracy of the combination of the above between-group differential FCs as a predictor of anti-suicidal effect. Moreover, the change of SI after ketamine infusion was positively correlated with altered right pgACC-left MOG FC in remitters (r = 0.66, p = 0.001). CONCLUSIONS: Our findings suggest that the FC of some cingulate cortex subregions can predict the anti-suicidal effect of ketamine and that the anti-suicidal mechanism of action of ketamine may involve alteration of FC between the right pgACC and left MOG.

Functional connectivity differences in the amygdala are related to the antidepressant efficacy of ketamine in patients with anxious depression.

BACKGROUND: The antidepressant effects of ketamine in patients with anxious depression (AD) remain unclear. Functional connectivity (FC) differences in the amygdala have been linked to depression improvement after ketamine treatment in depressed patients, but their role in AD patients is uncertain. We investigated the correlation between depression improvement after ketamine treatment and amygdala FC in AD patients. METHODS: Thirty-one AD patients and 18 non-anxious depression (NAD) patients received six intravenous ketamine infusions (0.5 mg/kg) over two weeks. AD patients were further divided into responders (defined as a ≥50% MADRS total score reduction on day 13) and non-responders. The FC of the amygdala subregions, including the laterobasal amygdala (LBA), centromedial amygdala (CMA), and superficial amygdala, were compared between the groups. Receiver operating characteristic curves were used to predict treatment response after ketamine infusions. RESULTS: The baseline FC difference in the left LBA and the left precuneus between responders and non-responders among AD patients was found to be associated with depression improvement and was a significant predictor of treatment response to ketamine. A marked reduction in baseline LBA-precuneus FC after ketamine infusion was observed in responders. Unlike in patients with NAD, a lower right CMA-right middle temporal gyrus FC was found in AD patients. LIMITATIONS: The sample size is rather small. CONCLUSIONS: Our findings may suggest that amygdala FC is a significant predictor of treatment response to ketamine infusions in patients with AD. Further studies exploring the potential antidepressant mechanisms of ketamine may aid in the treatment of AD patients.

A precise language network revealed by the independent component-based lesion mapping in post-stroke aphasia.

Brain lesion mapping studies have provided the strongest evidence regarding the neural basis of cognition. However, it remained a problem to identify symptom-specific brain networks accounting for observed clinical and neuroanatomical heterogeneity. Independent component analysis (ICA) is a statistical method that decomposes mixed signals into multiple independent components. We aimed to solve this issue by proposing an independent component-based lesion mapping (ICLM) method to identify the language network in patients with moderate to severe post-stroke aphasia. Lesions were first extracted from 49 patients with post-stroke aphasia as masks applied to fMRI data in a cohort of healthy participants to calculate the functional connectivity (FC) within the masks and non-mask brain voxels. ICA was further performed on a reformatted FC matrix to extract multiple independent networks. Specifically, we found that one of the lesion-related independent components (ICs) highly resembled classical language networks. Moreover, the damaged level within the language-related lesioned network is strongly associated with language deficits, including aphasia quotient, naming, and auditory comprehension scores. In comparison, none of the other two traditional lesion mapping methods found any regions responsible for language dysfunction. The language-related lesioned network extracted with the ICLM method showed high specificity in detecting aphasia symptoms compared with the performance of resting ICs and classical language networks. In total, we detected a precise language network in patients with aphasia and proved its efficiency in the relationship with language symptoms. In general, our ICLM could successfully identify multiple lesion-related networks from complicated brain diseases, and be used as an effective tool to study brain-behavior relationships and provide potential biomarkers of particular clinical behavioral deficits.

Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis.

BACKGROUND: Previous studies have shown that psilocybin has antidepressant effects. In the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients). METHODS: Published studies concerning psilocybin for depression were retrieved. In accordance with PRISMA guidelines, 6 databases (PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov 2.3 and WanFang database) were searched for research studies published or still in progress from inception to 30 November, 2020, with language restricted to English and Chinese. Hedges' g of Beck Depression Inventory (BDI) score changes was calculated as the primary outcome. RESULTS: 7 articles were finally included, with a total of 136 participants. In terms of efficacy, Hedges' g was 1.289 (95%CI=[1.020, 1.558], heterogeneity I2=50.995%, p<0.001). As psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. Subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: Hedges' g=3.059, 95%CI=[2.269, 3.849], p<0.001), long-term (>1month: Hedges' g=1.123, 95%CI=[0.861, 1.385], p<0.001) and when used in primary depression patients (Hedges' g=2.190, 95%CI=[1.423, 2.957], p<0.001). LIMITATIONS: Only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary. CONCLUSIONS: Our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. The optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect.

Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine.

BACKGROUND: Recently, an animal model for depression has shown that ketamine, an N-methyl- d-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce. METHODS: This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis. RESULTS: In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders. CONCLUSIONS: These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.

Observing time effect of SSRIs on suicide risk and suicide-related behaviour: a network meta-analysis protocol.

INTRODUCTION: Suicide is a serious problem worldwide and 90% cases are associated with pre-existing or underlying mental illness. As a common treatment for depressive symptoms that suicidal people may receive, selective serotonin reuptake inhibitors (SSRIs) have been linked to a possible increase in suicide rates. Studies focusing on SSRIs and suicide have produced inconsistent results, suggesting that use of SSRIs decreases, increases, has no effect on suicide rates, or that the effect of SSRIs on suicide is age-dependent. This protocol of network meta-analysis aims to precisely evaluate the time effects of SSRIs by observing weekly changes of suicidality in the first 2 months of the treatment, and consequently, to explore whether the effect of the SSRIs on suicide varies depending on the stages of the treatment; if so, we will identify the turning point. METHODS AND ANALYSIS: We will search in the following databases: PubMed, Web of science, China National Knowledge Infrastructure and Wanfang Data, from dates of inception to 9 July 2021, with language restricted to English and Chinese. Studies focusing on the time effect of SSRIs on suicide will be retrieved. Then, the study selection process will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, and the quality assessment will be conducted with Cochrane Collaboration's tool. Two researchers will work independently on data extraction using a standardised data extraction spreadsheet. Any disagreement between two researchers will be discussed and determined by a third researcher. ETHICS AND DISSEMINATION: This work does not require ethics approval as it will be based on published studies. This review will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021244779.

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method.

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.

Working memory associated with anti-suicidal ideation effect of repeated-dose intravenous ketamine in depressed patients.

Suicide is a tremendous threat to global public health, and a large number of people who committed suicide suffered the pain of mental diseases, especially major depressive disorder (MDD). Previous study showed that ketamine could reduce suicidal ideation (SI), potentially by improving the impaired working memory (WM). The objective of current study was to illuminate the relationship between WM and SI in MDD with repeated ketamine treatment. MDD patients with SI (n = 59) and without SI (n = 37) completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Day 1, 3, 5, 8, 10 and 12). The severity of depressive symptoms, SI and WM were assessed at baseline, day 13 and day 26. We found that WM was significantly improved after 6 ketamine infusions (F = 161.284, p = 0.009) in a linear mixed model. Correlation analysis showed that the improvement of depressive symptom was significantly associated with WM at baseline (r = - 0.265, p = 0.042) and the reduction in SSI-part I was related to the change of WM (r = 0.276, p = 0.034) in the MDD patients with SI. Furthermore, Logistic regression analysis showed that improvement in WM might predict the anti-SI response of ketamine. Our findings suggest that the improvement of working memory may partly account for the anti-SI effect of ketamine, and intervention of improving working memory function may be capable of reducing suicidal ideation.

Functional MRI in the effect of transcranial magnetic stimulation therapy for patients with schizophrenia: a meta-analysis protocol.

INTRODUCTION: Schizophrenia is a psychiatric illness associated with brain function alterations and varying degree of treatment resistance, often leading to severe social malfunctioning. In recent decades, numerous studies have been investigating the therapeutic potential of transcranial magnetic stimulation (TMS) as a non-invasive therapy for schizophrenia. However, its clinical efficacy remains controversial, as a number of clinical trials indicated moderate therapeutic effect while others failed to reproduce the positive result. Moreover, the neurobiological mechanism of action remains unclear, possibly constricting the application of TMS in clinical practice. The present protocol of meta-analysis aims to investigate the TMS-related functional neuroimaging (ie, functional MRI) features and alterations in subjects with schizophrenia, and to discuss the potential of functional MRI in TMS researches. METHODS AND ANALYSIS: The study selection process will follow the Preferred Reporting Items for Meta-Analyses guideline and quality assessment will be conducted with a customised checklist. We plan to search in the following databases: PubMed, Embase, OVID, China National Knowledge Infrastructure and Wanfang Data, from their respective dates of inception to 1 May 2020, with language restricted to English and Chinese. Studies focusing on the brain functional alterations in patients with schizophrenia treated by TMS will be retrieved. ETHICS AND DISSEMINATION: This work does not require ethics approval as it will be based on published studies. This systematic review will be publicly disseminated in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020166288.

A magnetic separator for efficient microalgae harvesting.

A magnetic separator, which consisted of permanent magnet drum, separation chamber and scraper blade, was manufactured for efficient microalgae harvesting. The harvesting efficiency of Chlorella ellipsoidea cells reached more than 95% within forty seconds in each batch operation of microalgae harvesting. In the continuous operation of microalgae harvesting, the harvesting efficiency decreased with increasing the liquid flow rate through the separation chamber and remained more than 95% at the liquid flow rate less than 100mL/min. The developed magnetic separator together with functional magnetic nanoparticles provided a promising method for efficient microalgae harvesting in practice.

Scale-up cultivation of Chlorella ellipsoidea from indoor to outdoor in bubble column bioreactors.

The cultivation of Chlorella ellipsoidea in bubble column bioreactors was investigated at different scales under indoor and outdoor conditions. The algal cells were able to quickly adapt to the outdoor conditions and achieved a growth rate of 31.55mg L(-1)day(-1). Due to differences in light and temperature, the outdoor culture produced a higher percentage of unsaturated fatty acids compared to the indoor cultures, while the amino acid composition was unaffected. The overall cost of the biomass produced by the 200L outdoor cultivation (58.70US$/kg-dry weight) was estimated to be more than 7 times lower than that of the 20L indoor cultivation (431.39US$/kg-dry weight). Together these results provide a basis for the cultivation of C. ellipsoidea for the large-scale production of biofuels, high-value nutrients and/or recombinant proteins.

Magnetic flocculant for high efficiency harvesting of microalgal cells.

Magnetic flocculant was synthesized for the highly efficient recovery of microalgal cells. The highest flocculation was achieved using the magnetic flocculant synthesized with iron oxide and 0.1 mg/mL cationic polyacrylamide (CPAM). This resulted in a recovery efficiency of more than 95% within 10 min using a dosage of 25 mg/L for Botryococcus braunii and 120 mg/L for Chlorella ellipsoidea. For both species, the adsorption isotherm data fit the Freundlich model better than the Langmuir model, indicating that the adsorption process was a heterogeneous multilayer. The maximum adsorption capacity was 114.8 and 21.4 mg dry cells/mg-particles at pH 7 for B. braunii and C. ellipsoidea, respectively. The primary flocculation mechanism was bridging, which was assisted by the electrostatic interactions between the microalgal cells and the magnetic flocculant under acidic conditions. These results provide new opportunities and challenges for understanding and improving the harvesting of microalgae using magnetic separation.

Efficient harvesting of marine microalgae Nannochloropsis maritima using magnetic nanoparticles.

An efficient magnetic separation technology using Fe(3)O(4) nanoparticles was developed for harvesting marine microalgae Nannochloropsis maritima from culture broth. Recovery capacity of these nanoparticles was affected by microalgal growth phase and reached the peak value when the microalgal growth reached its maximal biomass after 18 days. The recovery efficiency of microalgal cells from the culture medium reached more than 95% at the particle dosage of 120 mg/L within 4 min. Electrostatic attraction at acidic pH and cell aggregation under neutral and alkaline conditions was beneficial for harvesting the algal cells. Higher operation temperature resulted in higher adsorption capacity of these nanoparticles for microalgawl cells. Reuse of the culture medium obtained from magnetic separation gave similar biomass production in comparison with that from centrifugation separation after 5 recycles. Together with these results provide a great potential in high-efficient and economical harvesting of tiny marine microalgae using magnetic separation technology in practice.

Enhanced phenol degradation in coking wastewater by immobilized laccase on magnetic mesoporous silica nanoparticles in a magnetically stabilized fluidized bed.

The immobilized laccase on magnetic mesoporous silica nanoparticles has been developed for efficient phenol degradation. The degradation rate of phenol by the immobilized laccase was 2-fold higher than that of the free laccase, and the immobilized laccase retained 71.3% of its initial degradation ability after 10 successive batch treatments of coking wastewater. The phenol degradation in the coking wastewater was enhanced in a continuous treatment process by the immobilized laccase in a magnetically stabilized fluidized bed (MSFB) because of good mixing and mass transfer. The degradation rate of phenol maintained more than 99% at a flow rate of less than 450mLh(-1) and decreased slowly to 91.5% after 40h of the continuous operation in the MSFB. The present work indicated that the immobilized laccase on magnetic mesoporous supports together with the MSFB provided a promising avenue for the continuous enzymatic degradation of phenolic compounds in industrial wastewater.