Altered brain responses to specific negative emotions in schizophrenia.
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ABSTRACT:
SUBMITTER: Garcia-Leon MA
PROVIDER: S-EPMC8640102 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia.
| S-EPMC4034208 | biostudies-other
Project description:Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.
| S-EPMC5022089 | biostudies-literature
Project description:ObjectiveTo investigate brain structural and functional characteristics of three brain functional networks including default mode network (DMN), central executive network (CEN), and salience network (SN) in persistent negative symptoms (PNS) patients.MethodsWe performed an activation likelihood estimation (ALE) meta-analysis of functional connectivity (FC) studies and voxel-based morphometry (VBM) studies to detect specific structural and functional alterations of brain networks between PNS patients and healthy controls.ResultsSeventeen VBM studies and twenty FC studies were included. In the DMN, PNS patients showed decreased gray matter in the bilateral medial frontal gyrus and left anterior cingulate gyrus and a significant reduction of FC in the right precuneus. Also, PNS patients had a decrease of gray matter in the left inferior parietal lobules and medial frontal gyrus, and a significant reduction of FC in the bilateral superior frontal gyrus in the CEN. In comparison with healthy controls, PNS patients exhibited reduced gray matter in the bilateral insula, anterior cingulate gyrus, left precentral gyrus and right claustrum and lower FC in these brain areas in the SN, including the left insula, claustrum, inferior frontal gyrus and extra-nuclear.ConclusionThis meta-analysis reveals brain structural and functional imaging alterations in the three networks and the interaction among these networks in PNS patients, which provides neuroscientific evidence for more personalized treatment.Systematic Review RegistrationThe PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42022335962).
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Project description:ObjectiveWhen people think about negative events that may occur in the future, they tend to overestimate their emotional reactions, and these "affective forecasts" can influence their present behavior (Wilson and Gilbert, 2003). The present research examined affective forecasting for COVID-19 infection including the associations between emotions and preventive intentions and behavior.MethodsIn two studies, we compared individuals' anticipated emotions and recalled emotions for COVID-19 infection. Study 1 asked college students (N = 219) and Study 2 asked general adults (N = 401) to either predict their emotions in response to a future COVID-19 infection or to recall their emotions associated with a previous infection.ResultsIn both studies, reliable differences in negative emotions emerged. Those who were predicting their feelings associated with a future infection anticipated more negative emotion than those who were recalling their feelings associated with a past infection reported. Greater negative emotion in both studies was significantly associated with being more likely to have been vaccinated as well as higher intentions to get the booster vaccine.ConclusionsThese findings suggest that compared to those who have had a COVID-19 infection, those who have not yet experienced infection anticipate they will experience greater negative emotion, and this may have implications for preventive behaviors. In general, these findings suggest that people may have an impact bias for COVID-19 infection.
| S-EPMC9873369 | biostudies-literature
Project description:BackgroundImpairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder.MethodsWe investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach.ResultsWhile making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex.DiscussionWe report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.
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Project description:Schizophrenia has a complex etiology and symptomatology that is difficult to untangle. After decades of research, important advancements toward a central biomarker are still lacking. One of the missing pieces is a better understanding of how non-linear neural dynamics are altered in this patient population. In this study, the resting-state neuromagnetic signals of schizophrenia patients and healthy controls were analyzed in the framework of criticality. When biological systems like the brain are in a state of criticality, they are thought to be functioning at maximum efficiency (e.g., optimal communication and storage of information) and with maximum adaptability to incoming information. Here, we assessed the self-similarity and multifractality of resting-state brain signals recorded with magnetoencephalography in patients with schizophrenia patients and in matched controls. Schizophrenia patients had similar, although attenuated, patterns of self-similarity and multifractality values. Statistical tests showed that patients had higher values of self-similarity than controls in fronto-temporal regions, indicative of more regularity and memory in the signal. In contrast, patients had less multifractality than controls in the parietal and occipital regions, indicative of less diverse singularities and reduced variability in the signal. In addition, supervised machine-learning, based on logistic regression, successfully discriminated the two groups using measures of self-similarity and multifractality as features. Our results provide new insights into the baseline cognitive functioning of schizophrenia patients by identifying key alterations of criticality properties in their resting-state brain data.
| S-EPMC8995790 | biostudies-literature
Project description:Epigenetics plays a crucial role in schizophrenia susceptibility. In a previous study, we identified over 4500 differentially methylated sites in prefrontal cortex (PFC) samples from schizophrenia patients. We believe this was the first genome-wide methylation study performed on human brain tissue using the Illumina Infinium HumanMethylation450 Bead Chip. To understand the biological significance of these results, we sought to identify a smaller number of differentially methylated regions (DMRs) of more functional relevance compared with individual differentially methylated sites. Since our schizophrenia whole genome methylation study was performed, another study analysing two separate data sets of post-mortem tissue in the PFC from schizophrenia patients has been published. We analysed all three data sets using the bumphunter function found in the Bioconductor package minfi to identify regions that are consistently differentially methylated across distinct cohorts. We identified seven regions that are consistently differentially methylated in schizophrenia, despite considerable heterogeneity in the methylation profiles of patients with schizophrenia. The regions were near CERS3, DPPA5, PRDM9, DDX43, REC8, LY6G5C and a region on chromosome 10. Of particular interest is PRDM9 which encodes a histone methyltransferase that is essential for meiotic recombination and is known to tag genes for epigenetic transcriptional activation. These seven DMRs are likely to be key epigenetic factors in the aetiology of schizophrenia and normal brain neurodevelopment.
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Project description:Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression.
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Project description:Abnormal functional brain connectivity could be considered an endophenotype of psychosis in schizophrenia. Identifying candidate endophenotypes may serve as a tool for elucidating its biological and neural mechanisms. The present study investigated the similarities and differences of features of brain network connectivity between patients and their first-degree relatives. Independent component analysis was conducted on imaging data collected from 34 healthy controls, 33 schizophrenia patients, and 30 unaffected first-degree relatives. The correlation between functional connectivity with neurocognitive performance and clinical symptoms were calculated. Abnormalities of between-network connectivity largely overlapped in patients and first-degree relatives, but the extent of such abnormalities was relatively minor in relatives. Negative connectivity between language networks and executive control networks was impaired in schizophrenia patients and their first-degree relatives, and this decreased connectivity was correlated with performance in language processing. Similar impairments were found in high-visual network and executive network coupling, and this decreased connection was correlated with the severity of positive symptoms in patients. The results indicated that abnormal functional connectivity within and between perceptual systems (i.e., high-visual and language) and executive control networks was related to the generic risk of schizophrenia, which makes it a potential endophenotype for schizophrenia.
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Project description:The impairment of multisensory integration in schizophrenia is often explained by deficits of attentional selection. Emotion perception, however, does not always depend on attention because affective stimuli can capture attention automatically. In our study, we specify the role of attention in the multisensory perception of emotional stimuli in schizophrenia. We evaluated attention by interference between conflicting auditory and visual information in two multisensory paradigms in patients with schizophrenia and healthy participants. In the first paradigm, interference occurred between physical features of the dynamic auditory and visual stimuli. In the second paradigm, interference occurred between the emotional content of the auditory and visual stimuli, namely fearful and sad emotions. In patients with schizophrenia, the interference effect was observed in both paradigms. In contrast, in healthy participants, the interference occurred in the emotional paradigm only. These findings indicate that the information leakage between different modalities in patients with schizophrenia occurs at the perceptual level, which is intact in healthy participants. However, healthy participants can have problems with the separation of fearful and sad emotions similar to those of patients with schizophrenia.
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