Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Alterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. METHODS: We recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. RESULTS: First-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LIMITATIONS: The relatively large "pure" MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. CONCLUSION: These findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Divergent effects of sex on hippocampal subfield alterations in drug-naive patients with major depressive disorder.

BACKGROUND: The hippocampus is a crucial brain structure in etiological models of major depressive disorder (MDD). It remains unclear whether sex differences in the incidence and symptoms of MDD are related to differential illness-associated brain alterations, including alterations in the hippocampus. This study investigated divergent the effects of sex on hippocampal subfield alterations in drug-naive patients with MDD. METHODS: High-resolution structural MR images were obtained from 144 drug-naive individuals with MDD early in their illness course and 135 age- and sex-matched healthy controls (HCs). Hippocampal subfields were segmented using FreeSurfer software and analyzed in terms of both histological subfields (CA1-4, dentate gyrus, etc.) and more integrative larger functional subregions (head, body and tail). RESULTS: We observed a significant overall reduction in hippocampal volume in MDD patients, with deficits more prominent deficits in the posterior hippocampus. Differences in anatomic alterations between male and female patients were observed in the CA1-head, presubiculum-body and fimbria in the left hemisphere. Exploratory analyses revealed different patterns of clinical and memory function correlations with histological subfields and functional subregions between male and female patients primarily in the hippocampal head and body. LIMITATIONS: This cross-sectional study cannot clarify the causality of hippocampal alterations or their association with illness risk or onset. CONCLUSIONS: These findings represent the first reported sex-specific alterations in hippocampal histological subfields in patients with MDD early in the illness course prior to treatment. Sex-specific hippocampal alterations may contribute to diverse sex differences in the clinical presentation of MDD.

Multivariate association between psychosocial environment, behaviors, and brain functional networks in adolescent depression.

BACKGROUND: Adolescent depression shows high clinical heterogeneity. Brain functional networks serve as a powerful tool for investigating neural mechanisms underlying depression profiles. A key challenge is to characterize how variation in brain functional organization links to behavioral features and psychosocial environmental influences. METHODS: We recruited 80 adolescents with major depressive disorder (MDD) and 42 healthy controls (HCs). First, we estimated the differences in functional connectivity of resting-state networks (RSN) between the two groups. Then, we used sparse canonical correlation analysis to characterize patterns of associations between RSN connectivity and symptoms, cognition, and psychosocial environmental factors in MDD adolescents. Clustering analysis was applied to stratify patients into homogenous subtypes according to these brain-behavior-environment associations. RESULTS: MDD adolescents showed significantly hyperconnectivity between the ventral attention and cingulo-opercular networks compared with HCs. We identified one reliable pattern of covariation between RSN connectivity and clinical/environmental features in MDD adolescents. In this pattern, psychosocial factors, especially the interpersonal and family relationships, were major contributors to variation in connectivity of salience, cingulo-opercular, ventral attention, subcortical and somatosensory-motor networks. Based on this association, we categorized patients into two subgroups which showed different environment and symptoms characteristics, and distinct connectivity alterations. These differences were covered up when the patients were taken as a whole group. CONCLUSION: This study identified the environmental exposures associated with specific functional networks in MDD youths. Our findings emphasize the importance of the psychosocial context in assessing brain function alterations in adolescent depression and have the potential to promote targeted treatment and precise prevention.

Distinctive intrinsic functional connectivity alterations of anterior cingulate cortex subdivisions in major depressive disorder: A systematic review and meta-analysis.

Evidence of whether the intrinsic functional connectivity of anterior cingulate cortex (ACC) and its subregions is altered in major depressive disorder (MDD) remains inconclusive. A systematic review and meta-analysis were therefore performed on the whole-brain resting-state functional connectivity (rsFC) studies using the ACC and its subregions as seed regions in MDD, in order to draw more reliable conclusions. Forty-four ACC-based rsFC studies were included, comprising 25 subgenual ACC-based studies, 11 pregenual ACC-based studies, and 17 dorsal ACC-based studies. Specific alterations of rsFC were identified for each ACC subregion in patients with MDD, with altered rsFC of subgenual ACC in emotion-related brain regions, of pregenual ACC in sensorimotor-related regions, and of dorsal ACC in cognition-related regions. Furthermore, meta-regression analysis revealed a significant negative correlation between the pgACC-caudate hypoconnectivity and percentage of female patients in the study cohort. This meta-analysis provides robust evidence of altered intrinsic functional connectivity of the ACC subregions in MDD, which may hold relevance to understanding the origin of, and treating, the emotional, sensorimotor and cognitive dysfunctions that are often observed in these patients.

Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Suprachiasmatic nucleus functional connectivity related to insomnia symptoms in adolescents with major depressive disorder.

Background: Insomnia is a commonly seen symptom in adolescents with major depressive disorder (MDD). The suprachiasmatic nucleus (SCN), which is the circadian rhythm regulation center, plays a crucial role in the regulation of sleep-wake circulation. Nevertheless, how SCN function contributes to the exact neural mechanisms underlying the associations between insomnia and depressive symptoms has not been explored in adolescents. In the current study, we aimed to explore the relationship between SCN functional connectivity (FC) and insomnia symptoms in adolescents with MDD using a seed-based FC method. Methods: In the current study, we recruited sixty-eight first-episode drug-naïve adolescents with MDD and classified them into high insomnia (MDD-HI) and low insomnia (MDD-LI) groups according to the sleep disturbance subscale of the Hamilton Depression Rating Scale (HAMD-S). Forty-three age/gender-matched healthy controls (HCs) were also recruited. SCN FC maps were generally for all subjects and compared among three groups using one-way ANOVA with age, gender and adjusted HAMD score as covariates. We used partial correlations to explore associations between altered FC and clinical symptoms, including sleep quality scores. Results: Adolescents with MDD showed worse sleep quality, which positively correlated with the severity of depression. Compared to MDD-LI and HCs, MDD-HI adolescents demonstrated significantly decreased FC between the right SCN and bilateral precuneus, and there was no significant difference between the MDD-LI and HC groups. The HAMD-S scores were negatively correlated with bilateral SCN-precuneus connectivity, and the retardation factor score of HAMD was negatively correlated with right SCN-precuneus connectivity. Conclusion: The altered FC between the SCN and precuneus may underline the neural mechanism of sleep-related symptoms in depressive adolescents and provide potential targets for personalized treatment strategies.

Abnormal focal segments in left uncinate fasciculus in adults with obsessive-compulsive disorder.

Background: Although the specific role of the uncinate fasciculus (UF) in emotional processing in patients with obsessive-compulsive disorder (OCD) has been investigated, the exact focal abnormalities in the UF have not been identified. The aim of the current study was to identify focal abnormalities in the white matter (WM) microstructure of the UF and to determine the associations between clinical features and structural neural substrates. Methods: In total, 71 drug-naïve patients with OCD and 81 age- and sex-matched healthy controls (HCs) were included. Automated fiber quantification (AFQ), a tract-based quantitative approach, was adopted to measure alterations in diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), along the trajectory of the UF. Additionally, we utilized partial correlation analyses to explore the relationship between the altered diffusion parameters and clinical characteristics. Results: OCD patients showed significantly higher FA and lower RD at the level of the temporal and insular portions in the left UF than HCs. In the insular segments of the left UF, increased FA was positively correlated with the Hamilton Anxiety Scale (HAMA) score, while decreased RD was negatively correlated with the duration of illness. Conclusion: We observed specific focal abnormalities in the left UF in adult patients with OCD. Correlations with measures of anxiety and duration of illness underscore the functional importance of the insular portion of left UF disturbance in OCD patients.

Construction and evaluation of DNA vaccine encoding Crimean Congo hemorrhagic fever virus nucleocapsid protein, glycoprotein N-terminal and C-terminal fused with LAMP1.

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe hemorrhagic fever in humans and is mainly transmitted by ticks. There is no effective vaccine for Crimean-Congo hemorrhagic fever (CCHF) at present. We developed three DNA vaccines encoding CCHFV nucleocapsid protein (NP), glycoprotein N-terminal (Gn) and C-terminal (Gc) fused with lysosome-associated membrane protein 1 (LAMP1) and assessed their immunogenicity and protective efficacy in a human MHC (HLA-A11/DR1) transgenic mouse model. The mice that were vaccinated three times with pVAX-LAMP1-CCHFV-NP induced balanced Th1 and Th2 responses and could most effectively protect mice from CCHFV transcription and entry-competent virus-like particles (tecVLPs) infection. The mice vaccinated with pVAX-LAMP1-CCHFV-Gc mainly elicited specific anti-Gc and neutralizing antibodies and provided a certain protection from CCHFV tecVLPs infection, but the protective efficacy was less than that of pVAX-LAMP1-CCHFV-NP. The mice vaccinated with pVAX-LAMP1-CCHFV-Gn only elicited specific anti-Gn antibodies and could not provide sufficient protection from CCHFV tecVLPs infection. These results suggest that pVAX-LAMP1-CCHFV-NP would be a potential and powerful candidate vaccine for CCHFV.

Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

Hippocampal adaptation to high altitude: a neuroanatomic profile of hippocampal subfields in Tibetans and acclimatized Han Chinese residents.

The hippocampus is highly plastic and vulnerable to hypoxia. However, it is unknown whether and how it adapts to chronic hypobaric hypoxia in humans. With a unique sample of Tibetans and acclimatized Han Chinese individuals residing on the Tibetan plateau, we aimed to build a neuroanatomic profile of the altitude-adapted hippocampus by measuring the volumetric differences in the whole hippocampus and its subfields. High-resolution T1-weighted magnetic resonance imaging was performed in healthy Tibetans (TH, n = 72) and healthy Han Chinese individuals living at an altitude of more than 3,500 m (HH, n = 27). In addition, healthy Han Chinese individuals living on a plain (HP, n = 72) were recruited as a sea-level reference group. Whereas the total hippocampal volume did not show a significant difference across groups when corrected for age, sex, and total intracranial volume, subfield-level differences within the hippocampus were found. Post hoc analyses revealed that Tibetans had larger core hippocampal subfields (bilateral CA3, right CA4, right dentate gyrus); a larger right hippocampus-amygdala transition area; and smaller bilateral presubiculum, right subiculum, and bilateral fimbria, than Han Chinese subjects (HH and/or HP). The hippocampus and all its subfields were found to be slightly and non-significantly smaller in HH subjects than in HP subjects. As a primary explorational study, our data suggested that while the overall hippocampal volume did not change, the core hippocampus of Tibetans may have an effect of adaptation to chronic hypobaric hypoxia. However, this adaptation may have required generations rather than mere decades to accumulate in the population.

An algal lectin griffithsin inhibits Hantaan virus infection in vitro and in vivo.

Hantaan virus (HTNV) is the etiological pathogen of hemorrhagic fever with renal syndrome in East Asia. There are currently no effective therapeutics approved for HTNV and other hantavirus infections. We found that griffithsin (GRFT), an algae-derived lectin with broad-spectrum antiviral activity against various enveloped viruses, can inhibit the growth and spread of HTNV. In vitro experiments using recombinant vesicular stomatitis virus (rVSV) with HTNV glycoproteins as a model revealed that the GRFT inhibited the entry of rVSV-HTNV-G into host cells. In addition, we demonstrated that GRFT prevented authentic HTNV infection in vitro by binding to the viral N-glycans. In vivo experiments showed that GRFT partially protected the suckling mice from death induced by intracranial exposure to HTNV. These results demonstrated that GRFT can be a promising agent for inhibiting HTNV infection.

Disorganized functional architecture of amygdala subregional networks in obsessive-compulsive disorder.

A precise understanding of amygdala-centered subtle networks may help refine neurocircuitry models of obsessive-compulsive disorder (OCD). We applied connectivity-based parcellation methodology to segment the amygdala based on resting-state fMRI data of 92 medication-free OCD patients without comorbidity and 90 matched healthy controls (HC). The amygdala was parcellated into two subregions corresponding to basolateral amygdala (BLA) and centromedial amygdala (CMA). Amygdala subregional functional connectivity (FC) maps were generated and group differences were evaluated with diagnosis-by-subregion flexible factorial ANOVA. We found significant diagnosis × subregion FC interactions in insula, supplementary motor area (SMA), midcingulate cortex (MCC), superior temporal gyrus (STG) and postcentral gyrus (PCG). In HC, the BLA demonstrated stronger connectivity with above regions compared to CMA, whereas in OCD, the connectivity pattern reversed to stronger CMA connectivity comparing to BLA. Relative to HC, OCD patients exhibited hypoconnectivity between left BLA and left insula, and hyperconnectivity between right CMA and SMA, MCC, insula, STG, and PCG. Moreover, OCD patients showed reduced volume of left BLA and right CMA compared to HC. Our findings characterized disorganized functional architecture of amygdala subregional networks in accordance with structural defects, providing direct evidence regarding the specific role of amygdala subregions in the neurocircuitry models of OCD.

Abnormal resting-state functional connectivity of the insula in medication-free patients with obsessive-compulsive disorder.

BACKGROUND: The function of the insula has been increasingly mentioned in neurocircuitry models of obsessive-compulsive disorder (OCD) for its role in affective processing and regulating anxiety and its wide interactions with the classic cortico-striato-thalamo-cortical circuit. However, the insular resting-state functional connectivity patterns in OCD remain unclear. Therefore, we aimed to investigate characteristic intrinsic connectivity alterations of the insula in OCD and their associations with clinical features. METHODS: We obtained resting-state functional magnetic resonance imaging data from 85 drug-free OCD patients and 85 age- and sex-matched healthy controls (HCs). We performed a general linear model to compare the whole-brain intrinsic functional connectivity maps of the bilateral insula between the OCD and HC groups. In addition, we further explored the relationship between the intrinsic functional connectivity alterations of the insula and clinical features using Pearson or Spearman correlation analysis. RESULTS: Compared with HCs, patients with OCD exhibited increased intrinsic connectivity between the bilateral insula and bilateral precuneus gyrus extending to the inferior parietal lobule and supplementary motor area. Decreased intrinsic connectivity was only found between the right insula and bilateral lingual gyrus in OCD patients relative to HC subjects, which was negatively correlated with the severity of depression symptoms in the OCD group. CONCLUSION: In the current study, we identified impaired insular intrinsic connectivity in OCD patients and the dysconnectivity of the right insula and bilateral lingual gyrus associated with the depressive severity of OCD patients. These findings provide neuroimaging evidence for the involvement of the insula in OCD and suggest its potential role in the depressive symptoms of OCD.

Brain morphometric abnormalities and their associations with affective symptoms in males with methamphetamine use disorder during abstinence.

Background: Methamphetamine (METH) use induces neurotoxic effects in brain structures and affective symptoms that persist during abstinence. However, the brain morphometry of individuals with METH use disorder (MUD) remains unclear, as well as their associations with affective symptoms during abstinence. Methods: Forty-eight abstinent males with MUD and 66 age-, sex-, and education-matched healthy controls (HCs) underwent high-resolution T1-weighted magnetic resonance imaging. Cortical thickness, surface area, volume, local gyrification index (LGI), and subcortical volume were obtained with FreeSurfer software. Brain morphometry differences between groups and their associations with affective symptoms and drug abuse history within the males with MUD were examined, with intracranial volume, age, and years of education as covariates. Results: Compared with the HCs, the individuals with MUD showed a significantly higher LGI in the right cuneus gyrus, left lingual gyrus, bilateral supramarginal gyrus, right inferior parietal gyrus (IPG), and right dorsal anterior cingulate cortex (clusterwise p < 0.05, Monte Carlo-corrected), as well as a smaller volume of the left nucleus accumbens (NAcc) (p < 0.05, FDR-corrected). However, there were no significant group differences in cortical thickness, area or volume. In addition, the LGI in the right IPG was positively associatedwith the severity of depression and anxiety symptoms in MUDs (p < 0.05, FDR-corrected). Conclusion: Brain morphometric abnormalities in abstinent males with MUD were characterized by hypergyrification across multiple mid-posterior brain regions anda smaller volume of the left NAcc.Gyrification of the right IPG may be a potential neural substrate underlying the affective symptoms experienced by MUDs during abstinence.

Worldwide Research Trends on Artemisinin: A Bibliometric Analysis From 2000 to 2021.

Objective: Artemisinin is an organic compound that comes from Artemisia annua. Artemisinin treatment is the most important and effective method for treating malaria. Bibliometric analysis was carried out to identify the global research trends, hot spots, scientific frontiers, and output characteristics of artemisinin from 2000 to 2021. Methods: Publications and their recorded information from 2000 to 2021 were retrieved through the Web of Science Core Collection (WoSCC). Using VOSviewer and Citespace, the hotspots and trends of studies on artemisinin were visualized. Results: A total of 8,466 publications were retrieved, and for the past 22 years, the annual number of publications associated with artemisinin kept increasing. The United States published most papers. The H-index and number of citations of the United States ranked first. The University of Oxford and MALARIA JOURNAL were the most productive affiliation and journal, respectively. A paper written by E.A. Ashley in 2011 achieved the highest global citation score. Keywords, such as "malaria," "artesunate," "plasmodium-falciparum," "in-vitro," "artemisinin resistance," "plasmodium falciparum," "resistance," and "artemether-lumefantrine," appeared most frequently. The research on artemisinin includes clinical research and animal and cell experiments. Conclusion: The biosynthesis, drug resistance mechanism, and combination of artemisinin have become more popular than before. Studies on artemisinin treating coronavirus disease 2019 (COVID-19) have been carried out, and good research results have been obtained.

Abnormal resting-state functional connectivity in patients with obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) displays widespread disruption across brain regions revealed by resting-state functional connectivity (rsFC) with inconsistent results between studies. We performed a systematic review of 47 seed-based rsFC studies (1863 patients; 1795 healthy controls) to explore brain intrinsic connectivity alterations. Quantitative coordinate-based meta-analysis was conducted for seed regions in the striatum (putamen, caudate, nucleus accumbens [Nac]), thalamus, and anterior cingulate cortex (ACC) because there were an adequate number of studies. We found that OCD patients demonstrated (1) characteristic dysconnectivity between striatum and cortical networks (i.e., caudate hyperconnectivity with the fronto-limbic network and hypoconnectivity with frontoparietal network regions; Nac hypoconnectivity with fronto-limbic network regions), (2) hypoconnectivity between thalamus and striatum (putamen and caudate), and (3) dysconnectivity between the ACC and fronto-limbic network regions. Furthermore, there were negative correlations between particular connectivities and symptom severity and onset age. Our results characterize the traditional cortico-striato-thalamo-cortical circuit model of OCD pathophysiology through the cerebral intrinsic connectivity, and unified neurocircuitry and brain network models into one integrity to elaborate the neural mechanism of OCD.

Sex-specific alterations of cortical morphometry in treatment-naïve patients with major depressive disorder.

Major depressive disorder (MDD) shows sex differences in terms of incidence and symptoms, but the neurobiological basis underlying these sex differences remains to be clarified. High resolution T1-weighted Magnetic Resonance Imaging (MRI) scans were obtained from 123 non-comorbid treatment-naïve individuals with MDD and 81 age-, sex-, and handedness-matched healthy controls (HCs). MRI data were preprocessed with FreeSurfer software and four cortical measures were extracted: cortical thickness (CT), surface area (SA), cortical volume (CV), and local gyrification index (LGI). We tested for both sex-specific and sex-nonspecific patterns of cortical anatomic alterations. Regardless of sex, individuals with MDD showed significantly higher LGI in posterior cortex relative to HCs. Significant sex-by-group interactions were observed, and subsequent post-hoc analyses revealed that female individuals with MDD showed significantly lower SA in left ventrolateral prefrontal cortex (vlPFC), lower CV in right rostromedial prefrontal cortex (rmPFC), and higher LGI in left visual cortex compared with sex-matched HCs, whereas the opposite patterns of significant effects were seen in male individuals with MDD relative to their sex-matched HCs. Thus, sex-nonspecific and specific morphometric differences from HCs were found in posterior cortex, while in PFC alterations were highly sex-specific early in the illness course. This may involve sex-specific alterations in brain development or processes related to illness onset. These findings highlight the presence and regional distribution of generalized as well as sex-specific alterations of brain neurobiology in MDD.

Alterations in functional network centrality in first-episode drug-naïve adolescent-onset schizophrenia.

Schizophrenia is a disorder resulting from aberrant brain networks and circuits. In the current study, we aimed to investigate specific network alterations in adolescent-onset schizophrenia (AOS) and to help identify the neurophysiological mechanisms of this adolescent disorder. We recruited forty-one subjects, including 20 AOS patients and 21 matched healthy controls (HCs), and we acquired brain images to examine the specific changes in functional network patterns using degree centrality (DC), which quantifies the strength of the local functional connectivity hubs. Whole-brain correlation analysis was applied to assess the relationships between clinical characteristics and DC measurements. The AOS group exhibited increased DC in the right inferior frontal lobe, right fusiform gyrus and right thalamus (p < 0.05, AlphaSim correction). Whole-brain correlation analysis found that the DC value in the right parahippocampus was positively correlated with PANSS-positive symptom scores (r = 0.80); DC in the right superior parietal lobe (SPL) was positively correlated with PANSS-negative symptom scores (r = 0.79); DC in the left precuneus was positively correlated with self-certainty (SC) scores (r = 0.70); and DC in the left medial frontal gyrus (MFG) was negatively correlated with self-reflectiveness (SR) scores (r = 0.69). We conclude that frontoparietal network and cortico-thalamo-cortical pathway disruptions could play key roles in the neurophysiological mechanisms underlying AOS. In AOS patients, the right parahippocampus and SPL are important structures associated with positive and negative symptoms, respectively, and the left precuneus and MFG contribute to deficits in cognitive insights.

Distinct alterations of amygdala subregional functional connectivity in early- and late-onset obsessive-compulsive disorder.

BACKGROUND: Age of onset may be an important feature associated with distinct subtypes of obsessive-compulsive disorder (OCD). The amygdala joined neurocircuitry models of OCD for its role in mediating fear and regulating anxiety. The present study aims to identify the underlying pathophysiological specifics in OCD with different onset times by assessing amygdala subregional functional connectivity (FC) alterations in early-onset OCD (EO-OCD) and late-onset OCD (LO-OCD). METHODS: Resting-state functional magnetic resonance imaging data were acquired from 88 medication-free OCD patients (including 30 EO-OCD and 58 LO-OCD) and age- and sex-matched healthy controls (HC) for each patient group. Onset-by-diagnosis interactions were examined and comparisons between each OCD group and the corresponding HC group were performed regarding the FC of amygdala subregions including the basolateral amygdala (BLA), centromedial amygdala (CMA), superficial amygdala (SFA) and amygdalostriatal transition area (Astr). RESULTS: Significant onset-by-diagnosis interactions were found in FC between bilateral SFA, right CMA, left Astr and the cerebellum. EO-OCD patients showed abnormally increased BLA/SFA-cerebellum, BLA-precuneus and BLA/SFA-fusiform connectivity in addition to decreased BLA/SFA-orbitofrontal cortex connectivity. In contrast, LO-OCD patients exhibited increased CMA/Astr-precentral/postcentral gyrus and CMA-cuneus connectivity as well as decreased CMA/Astr-cerebellum and BLA-striatum connectivity. LIMITATIONS: The exclusion of comorbidity may reduce the generalizability of our results. CONCLUSIONS: These findings emphasized the different patterns of amygdala subregional connectivity alterations associated with EO-OCD and LO-OCD patients. These results provide unique insights into constructing evidence-based distinct OCD subtypes based on brain intrinsic connectivity and point to the need of specified management for EO-OCD and LO-OCD in clinical setting.