Search

Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear.Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex (PFC) with a mass spectrometry-based lipidomic approach.Results: Similar to previous research outcomes, the current study also showed that (S)-ketamine reversed depressive-like behaviors in mice produced by CVS procedures. Moreover, CVS induced changes inthe lipid compositions of the hippocampus and PFC, notably in the contents of sphingolipids, glycerolipids, and fatty acyls. With the administration of (S)-ketamine, CVS-induced lipid disturbances were partially normalized, particularly in the hippocampus.Conclusion: Altogether, our results indicated that (S)-ketamine could rescue CVS-induced depressive-like behaviors in mice through region-specific modulation of the brain lipidome, contributing to the understanding of (S)-ketamine’s antidepressant effects.

BackgroundAuditory verbal hallucinations (AVH) are a core symptom of schizophrenia. Low-frequency (e.g., 1 Hz) repetitive transcranial magnetic stimulation (rTMS) targeting language processing regions (e.g., left TPJ) has been evident as a potential treatment for AVH. However, the underlying neural mechanisms of the rTMS treatment effect remain unclear. The present study aimed to investigate the effects of 1 Hz rTMS on functional connectivity (FC) of the temporoparietal junction area (TPJ) seed with the whole brain in schizophrenia patients with AVH.MethodsUsing a single-blind placebo-controlled randomized clinical trial, 55 patients with AVH were randomly divided into active treatment group (n = 30) or placebo group (n = 25). The active treatment group receive 15-day 1 Hz rTMS stimulation to the left TPJ, whereas the placebo group received sham rTMS stimulation to the same site. Resting-state fMRI scans and clinical measures were acquired for all patients before and after treatment. The seed-based (left TPJ) static and DFC was used to assess the connectivity characteristics during rTMS treatment in patients with AVH.ResultsOverall, symptom improvement following 1 Hz rTMS treatment was found in the active treatment group, whereas no change occurred in the placebo group. Moreover, decreased static FC (SFC) of the left TPJ with the right temporal lobes, as well as increased SFC with the prefrontal cortex and subcortical structure were observed in active rTMS group. Increased dynamic FC (DFC) of the left TPJ with frontoparietal areas was also found in the active rTMS group. However, seed-based SFC and DFC were reduced to a great extent in the placebo group. In addition, these changed FC (SFC) strengths in the active rTMS group were associated with reduced severity of clinical outcomes (e.g., positive symptoms).ConclusionThe application of 1 Hz rTMS over the left TPJ may affect connectivity characteristics of the targeted region and contribute to clinical improvement, which shed light on the therapeutic effect of rTMS on schizophrenia with AVH.

Suicidal ideation increases precipitously in patients with depression, contributing to the risk of suicidal attempts. Despite the recent advancement in transcranial magnetic stimulation, its effectiveness in depression disorder and its wide acceptance, the network mechanisms of the clinical response to suicidal ideation in major depressive disorder remain unclear. Independent component analysis for neuroimaging data allows the identification of functional network connectivity which may help to explore the neural basis of suicidal ideation in major depressive disorder. Resting-state functional magnetic resonance imaging data and clinical scales were collected from 30 participants (15 major depressive patients with suicidal ideation and 15 healthy subjects). Individual target-transcranial magnetic stimulation (IT-TMS) was then used to decrease the subgenual anterior cingulate cortex activity through the left dorsolateral prefrontal cortex. Thirty days post IT-TMS therapy, seven of 15 patients (46.67%) met suicidal remission criteria, and 12 patients (80.00%) met depression remission criteria. We found that IT-TMS could restore the abnormal functional network connectivity between default mode network and precuneus network, left executive control network and sensory-motor network. Furthermore, the changes in functional network connectivity between the default mode network and precuneus network were associated with suicidal ideation, and depressive symptoms were related to connectivity between left executive control network and sensory-motor network. These findings illustrate that IT-TMS is an effective protocol for the accurate restoration of impaired brain networks, which is consistent with clinical symptoms.

BackgroundLow-frequency transcranial magnetic stimulation (rTMS) over the left temporoparietal cortex reduces the auditory verbal hallucination (AVH) in schizophrenia. However, the underlying neural basis of the rTMS treatment effect for schizophrenia remains not well understood. This study investigates the rTMS induced brain functional and structural alternations and their associations with clinical as well as neurocognitive profiles in schizophrenia patients with AVH.MethodsThirty schizophrenia patients with AVH and thirty-three matched healthy controls were enrolled. The patients were administered by 15 days of 1 Hz rTMS delivering to the left temporoparietal junction (TPJ) area. Clinical symptoms and neurocognitive measurements were assessed at pre- and post-rTMS treatment. The functional (amplitude of low-frequency fluctuation, ALFF) and structural (gray matter volume, GMV) alternations were compared, and they were then used to related to the clinical and neurocognitive measurements after rTMS treatment.ResultsThe results showed that the positive symptoms, including AVH, were relieved, and certain neurocognitive measurements, including visual learning (VisLearn) and verbal learning (VerbLearn), were improved after the rTMS treatment in the patient group. Furthermore, the rTMS treatment induced brain functional and structural alternations in patients, such as enhanced ALFF in the left superior frontal gyrus and larger GMV in the right inferior temporal cortex. The baseline ALFF and GMV values in certain brain areas (e.g., the inferior parietal lobule and superior temporal gyrus) could be associated with the clinical symptoms (e.g., positive symptoms) and neurocognitive performances (e.g., VerbLearn and VisLearn) after rTMS treatment in patients.ConclusionThe low-frequency rTMS over the left TPJ area is an efficacious treatment for schizophrenia patients with AVH and could selectively modulate the neural basis underlying psychiatric symptoms and neurocognitive domains in schizophrenia.

ObjectivesTo investigate the improvement effect of occipital repetitive transcranial magnetic stimulation (rTMS) combined with escitalopram oxalate tablets on pre-attentive processing in patients with first-episode, medication-naive depression.MethodsPatients who were hospitalized between January and December 2019 were selected. They were randomly allocated to real occipital rTMS stimulation group with 27 cases receiving intermittent theta-burst (iTBS) and sham stimulation group with 24 cases over 20 days. The rTMS treatment target is located at the Oz point of the occipital region. Both groups took escitalopram oxalate tablets, and the average daily drug dose was 15.294 ± 5.041 mg. Hamilton Depression Rating Scale (HAMD) was used to assess the symptoms of depression before and after treatment, and mismatch negativity (MMN) was used to assess the improvement of pre-attentive processing before and after treatment.ResultsAfter 20 days of treatment, the total score of HAMD (13.495 ± 3.700) in both groups was significantly lower than that before treatment [21.910 ± 3.841, F(1, 49) = 46, 3.690, p < 0.001]. After treatment, the latency of MMN in the real stimulation group (182.204 ± 31.878 ms) was significantly lower than that in the sham stimulation group (219.896 ± 42.634 ms, p < 0.001), and the amplitude of MMN in the real stimulation group (−7.107 ± 3.374 ms) was significantly higher than that in the sham stimulation group (−2.773 ± 3.7 32 ms, p < 0.001).ConclusionOccipital rTMS treatment can enhance the early therapeutic effect and effectively improve the pre-attentive processing of patients with depression and provide a scientific basis for the new target of rTMS therapy in clinical patients with depression.

Schizophrenia (SCZ) is an inherited disease, with the familial risk being among the most important factors when evaluating an individual’s risk for SCZ. However, robust imaging biomarkers for the disease that can be used for diagnosis and determination of the prognosis are lacking. Here, we explore the potential of functional connectivity (FC) for use as a biomarker for the early detection of high-risk first-degree relatives (FDRs). Thirty-eight first-episode SCZ patients, 38 healthy controls (HCs), and 33 FDRs were scanned using resting-state functional magnetic resonance imaging. The subjects’ brains were parcellated into 200 regions using the Craddock atlas, and the FC between each pair of regions was used as a classification feature. Multivariate pattern analysis using leave-one-out cross-validation achieved a correct classification rate of 88.15% [sensitivity 84.06%, specificity 92.18%, and area under the receiver operating characteristic curve (AUC) 0.93] for differentiating SCZ patients from HCs. FC located within the default mode, frontal-parietal, auditory, and sensorimotor networks contributed mostly to the accurate classification. The FC patterns of each FDR were input into each classification model as test data to obtain a corresponding prediction label (a total of 76 individual classification scores), and the averaged individual classification score was then used as a robust measure to characterize whether each FDR showed an SCZ-type or HC-type FC pattern. A significant negative correlation was found between the average classification scores of the FDRs and their semantic fluency scores. These findings suggest that FC combined with a machine learning algorithm could help to predict whether FDRs are likely to show an SCZ-specific or HC-specific FC pattern.

Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ-according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, spectral DCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions.