A connectome-wide association study of altered functional connectivity in schizophrenia based on resting-state fMRI.

BACKGROUND: Aberrant resting-state functional connectivity is a neuropathological feature of schizophrenia (SCZ). Prior investigations into functional connectivity abnormalities have primarily employed seed-based connectivity analysis, necessitating predefined seed locations. To address this limitation, a data-driven multivariate method known as connectome-wide association study (CWAS) has been proposed for exploring whole-brain functional connectivity. METHODS: We conducted a CWAS analysis involving 46 patients with SCZ and 40 age- and sex-matched healthy controls. Multivariate distance matrix regression (MDMR) was utilized to identify key nodes in the brain. Subsequently, we conducted a follow-up seed-based connectivity analysis to elucidate specific connectivity patterns between regions of interest (ROIs). Additionally, we explored the spatial correlation between changes in functional connectivity and underlying molecular architectures by examining correlations between neurotransmitter/transporter distribution densities and functional connectivity. RESULTS: MDMR revealed the right medial frontal gyrus and the left calcarine sulcus as two key nodes. Follow-up analysis unveiled hypoconnectivity between the right medial frontal superior gyrus and the right fusiform gyrus, as well as hypoconnectivity between the left calcarine sulcus and the right lingual gyrus in SCZ. Notably, a significant association between functional connectivity strength and positive symptom severity was identified. Furthermore, altered functional connectivity patterns suggested potential dysfunctions in the dopamine, serotonin, and gamma-aminobutyric acid systems. CONCLUSIONS: This study elucidated reduced functional connectivity both within and between the medial frontal regions and the occipital cortex in patients with SCZ. Moreover, it indicated potential alterations in molecular architecture, thereby expanding current knowledge regarding neurobiological changes associated with SCZ.

Acute stress impairs intentional memory suppression through aberrant prefrontal cortex activation in high trait ruminators.

Objective: Research shows that the effect of acute stress on intentional memory suppression could be modulated by individual differences in psychological traits. However, whether acute stress distinctly affects intentional memory suppression in high trait ruminators, a high at-risk group of stress-related disorders, and the neural correlations, remains unclear. Method: 55 healthy college students were divided into high and low trait ruminators (HTR and LTR), Following stress manipulation, a Think/No Think task assessed the memory suppression performance. Functional near-infrared spectroscopy was applied to explore the neural correlates. Psychophysiological interaction analyses were used to assess how the functional connectivity between a seed region and another brain region was modulated by tasks during memory suppression, further mediating memory suppression performance and state rumination. Results: The HTR exhibited poorer memory suppression performance than the LTR under the stress condition. Aberrant activation patterns and task-modulated functional connectivity in the dorsal prefrontal cortex (DLPFC) and superior temporal gyrus (STG) were observed only in the HTR during memory suppression under the stress condition. The effect of memory suppression performance on the state rumination of individuals was significantly mediated by the task-modulated functional connectivity between the DLPFC and STG. Conclusions: The findings could provide insights for prevention or early intervention in the development of stress-related disorders in HTR.

Aberrant positive affect dynamics in individuals with subthreshold depression: Evidence from laboratory and real-world assessments / Dinámica aberrante del afecto positivo en individuos con depresión subumbral: evidencia de evaluaciones de laboratorio y del mundo real

Background/Objective: Reduced positive affect (PA) is a core feature of major depressive disorder (MDD). However, the precursor of MDD, subthreshold depression (StD), has received less attention in this regard. Therefore, we examined PA dynamics in StD, integrating laboratory-based and ecological momentary assessment (EMA) approaches. Method: Participants were college students recruited from Chinese universities (31 with StD, and 39 healthy controls (HC)). Positive mood was induced in the laboratory by an eight-minute comedy clip used to assess PA reactivity and maintenance. To extend findings to the real world and explore mechanisms of PA maintenance, 53 participants with StD and 64 HC reported their emotional states 14 times daily for one week via EMA. Multilevel models were used to test for predictors of PA inertia. Results: In the laboratory, participants with StD achieved the same PA reactivity as HC when facing positive stimuli, yet the curve-fitting revealed difficulties for the StD group in maintaining PA over time. Such reduced capacity was further observed in real-world settings, manifesting in significantly greater PA inertia. Conclusions: High PA inertia in daily life may reflect resistance to mood change in StD, explaining anhedonia and difficulties with emotional maintenance, and highlighting the need for early identification.(AU)

Aberrant positive affect dynamics in individuals with subthreshold depression: Evidence from laboratory and real-world assessments.

Background/Objective: Reduced positive affect (PA) is a core feature of major depressive disorder (MDD). However, the precursor of MDD, subthreshold depression (StD), has received less attention in this regard. Therefore, we examined PA dynamics in StD, integrating laboratory-based and ecological momentary assessment (EMA) approaches. Method: Participants were college students recruited from Chinese universities (31 with StD, and 39 healthy controls (HC)). Positive mood was induced in the laboratory by an eight-minute comedy clip used to assess PA reactivity and maintenance. To extend findings to the real world and explore mechanisms of PA maintenance, 53 participants with StD and 64 HC reported their emotional states 14 times daily for one week via EMA. Multilevel models were used to test for predictors of PA inertia. Results: In the laboratory, participants with StD achieved the same PA reactivity as HC when facing positive stimuli, yet the curve-fitting revealed difficulties for the StD group in maintaining PA over time. Such reduced capacity was further observed in real-world settings, manifesting in significantly greater PA inertia. Conclusions: High PA inertia in daily life may reflect resistance to mood change in StD, explaining anhedonia and difficulties with emotional maintenance, and highlighting the need for early identification.

Global-brain functional connectivity related with trait anxiety and its association with neurotransmitters and gene expression profiles.

BACKGROUND: Numerous studies have explored the neural correlates of trait anxiety, a predisposing factor for several stress-related disorders. However, the findings from previous studies are inconsistent, which might be due to the limited regions of interest (ROI). A recent approach, named global-brain functional connectivity (GBC), has been demonstrated to address the shortcomings of ROI-based analysis. Furthermore, research on the transcriptome-connectome association has provided an approach to link the microlevel transcriptome profile with the macroscale brain network. In this paper, we aim to explore the neurobiology of trait anxiety with an imaging transcriptomic approach using GBC, biological neurotransmitters, and transcriptome profiles. METHODS: Using a sample of resting-state fMRI data, we investigated trait anxiety-related alteration in GBC. We further used behavioral analysis, spatial correlation analysis, and postmortem gene expression to separately assess the cognitive functions, neurotransmitters, and transcriptional profiles related to alteration in GBC in individuals with trait anxiety. RESULTS: GBC values in the ventromedial prefrontal cortex and the precuneus were negatively correlated with levels of trait anxiety. This alteration was correlated with behavioral terms including social cognition, emotion, and memory. A strong association was revealed between trait anxiety-related alteration in GBC and neurotransmitters, including dopaminergic, serotonergic, GABAergic, and glutamatergic systems in the ventromedial prefrontal cortex and the precuneus. The transcriptional profiles explained the functional connectivity, with correlated genes enriched in transmembrane signaling. LIMITATIONS: Several limitations should be taken into account in this research. For example, future research should consider using some different approaches based on dynamic or task-based functional connectivity analysis, include more neurotransmitter receptors, additional gene expression data from different samples or more genes related to other stress-related disorders. Meanwhile, it is of great significance to include a larger sample size of individuals with a diagnosis of major depression disorder or other disorders for analysis and comparison and apply stricter multiple-comparison correction and threshold settings in future research. CONCLUSIONS: Our research employed multimodal data to investigate GBC in the context of trait anxiety and to establish its associations with neurotransmitters and transcriptome profiles. This approach may improve understanding of the neural mechanism, together with the biological and molecular genetic foundations of GBC in trait anxiety.

The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population.

BACKGROUND: Subthreshold depression could be a significant precursor to and a risk factor for major depression. However, reliable estimates of the prevalence and its contribution to developing major depression under different terminologies depicting subthreshold depression have to be established. METHODS: By searching PubMed and Web of Science using predefined inclusion criteria, we included 1 129 969 individuals from 113 studies conducted. The prevalence estimates were calculated using the random effect model. The incidence risk ratio (IRR) was estimated by measuring the ratio of individuals with subthreshold depression who developed major depression compared to that of non-depressed individuals from 19 studies (88, 882 individuals). RESULTS: No significant difference in the prevalence among the different terminologies depicting subthreshold depression (Q = 1.96, p = 0.5801) was found. By pooling the prevalence estimates of subthreshold depression in 113 studies, we obtained a summary prevalence of 11.02% [95% confidence interval (CI) 9.78-12.33%]. The youth group had the highest prevalence (14.17%, 95% CI 8.82-20.55%), followed by the elderly group (12.95%, 95% CI 11.41-14.58%) and the adult group (8.92%, 95% CI 7.51-10.45%). Further analysis of 19 studies' incidence rates showed individuals with subthreshold depression had an increased risk of developing major depression (IRR = 2.95, 95% CI 2.33-3.73), and the term minor depression showed the highest IRR compared with other terms (IRR = 3.97, 95% CI 3.17-4.96). CONCLUSIONS: Depression could be a spectrum disorder, with subthreshold depression being a significant precursor to and a risk factor for major depression. Proactive management of subthreshold depression could be effective for managing the increasing prevalence of major depression.

Distinct neural activation patterns of age in subcomponents of inhibitory control: A fMRI meta-analysis.

Inhibitory control (IC) is a fundamental cognitive function showing age-related change across the healthy lifespan. Since different cognitive resources are needed in the two subcomponents of IC (cognitive inhibition and response inhibition), regions of the brain are differentially activated. In this study, we aimed to determine whether there is a distinct age-related activation pattern in these two subcomponents. A total of 278 fMRI articles were included in the current analysis. Multilevel kernel density analysis was used to provide data on brain activation under each subcomponent of IC. Contrast analyses were conducted to capture the distinct activated brain regions for the two subcomponents, whereas meta-regression analyses were performed to identify brain regions with distinct age-related activation patterns in the two subcomponents of IC. The results showed that the right inferior frontal gyrus and the bilateral insula were activated during the two IC subcomponents. Contrast analyses revealed stronger activation in the superior parietal lobule during cognitive inhibition, whereas stronger activation during response inhibition was observed primarily in the right inferior frontal gyrus, bilateral insula, and angular gyrus. Furthermore, regression analyses showed that activation of the left anterior cingulate cortex, left inferior frontal gyrus, bilateral insula, and left superior parietal lobule increased and decreased with age during cognitive inhibition and response inhibition, respectively. The results showed distinct activation patterns of aging for the two subcomponents of IC, which may be related to the differential cognitive resources recruited. These findings may help to enhance knowledge of age-related changes in the activation patterns of IC.

Charting the neural circuits disruption in inhibitory control and its subcomponents across psychiatric disorders: A neuroimaging meta-analysis.

BACKGROUND: Inhibitory control, comprising cognitive inhibition and response inhibition, showed consistent deficits among several major psychiatric disorders. We aim to identify the trans-diagnostic convergence of neuroimaging abnormalities underlying inhibitory control across psychiatric disorders. METHODS: Inhibitory control tasks neuroimaging, including functional magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography articles published in PubMed and Web of Science before April 2020 comparing healthy controls with patients with several psychiatric disorders were searched. RESULTS: 146 experiments on 2653 patients with different disorders and 2764 control participants were included. Coordinates of case-control differences coded by diagnosis and inhibitory control components were analyzed using activation likelihood estimation. A robust trans-diagnostic pattern of aberrant brain activation in the bilateral cingulate gyri extending to medial frontal gyri, right insula, bilateral lentiform nuclei, right inferior frontal gyrus, right precuneus extending to inferior parietal lobule, and right supplementary motor area were detected. Frontostriatal pathways are the commonly disrupted neural circuits in the inhibitory control across psychiatric disorders. Furthermore, Patients showed aberrant activation in the dorsal frontal inhibitory system in cognitive inhibition, while in the frontostriatal system in response inhibition across disorders. CONCLUSION: Consistent with the Research Domain Criteria initiative, current findings show that psychiatric disorders may be productively formulated as a phenotype of trans-diagnostic neurocircuit disruption. Our results provide new insights for future research into mental disorders with inhibition-related dysfunctions.

The inter-relationships of the neural basis of rumination and inhibitory control: neuroimaging-based meta-analyses.

Rumination, as a clinical manifestation and pathogenic factor of depression, has long been the focus of psychological research regarding its causes and ameliorating approaches. Behavioral studies have shown that rumination is related to inhibitory control deficits, which provides ideas for reducing it. However, the neural relationship between them has not been clearly discussed. In this study, we first used multi-level kernel density analysis to conduct two meta-analyses of published functional magnetic resonance imaging studies: one was rumination comprising 17 studies with 180 foci, and the other was inhibitory control comprising 205 studies with 3791 foci. Conjunction analysis was then performed to explore the common brain regions and further decode them through Neurosynth to confirm the cognitive specificity. Results showed that rumination was mainly related to the default mode network (DMN), while inhibitory control was associated with the frontoparietal network (FPN). In addition, the common activation areas were mainly concentrated in the bilateral precuneus, right superior frontal gyrus, bilateral median cingulate, paracingulate gyri, and the left triangular part of inferior frontal gyrus (IFG). Decoding results also revealed they were involved in inhibition, memory retrieval, and self-related processes. Our findings support that rumination is associated with inhibitory control and can be explained neurologically by an antagonistic relationship between the DMN and FPN. In sum, inhibitory control may be related to rumination via inhibiting task-unrelated attention and controlling self-related processing. This research will help us understand and predict rumination from the perspective of inhibitory control and reduce rumination through behavioral training of inhibitory control or the application of neuromodulation techniques to common activation regions.