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Amygdala functional dysconnectivity lies at the heart of the pathophysiology of bipolar disorder (BD). Recent preclinical studies suggest that the amygdala is a heterogeneous group of nuclei, whose specific connectivity could drive positive or negative emotional valence. We investigated functional connectivity (FC) changes within these circuits emerging from each amygdala's subdivision in 127 patients with BD in different mood states and 131 healthy controls (HC), who underwent resting-state functional MRI. FC was evaluated between lateral and medial nuclei of amygdalae, and key subcortical regions of the emotion processing network: anterior and posterior parts of the hippocampus, and core and shell parts of the nucleus accumbens. FC was compared across groups, and subgroups of patients depending on their mood states, using linear mixed models. We also tested correlations between FC and depression (MADRS) and mania (YMRS) scores. We found no difference between the whole sample of BD patients vs. HC but a significant correlation between MADRS and right lateral amygdala /right anterior hippocampus, right lateral amygdala/right posterior hippocampus and right lateral amygdala/left anterior hippocampus FC (r = -0.44, r = -0.32, r = -0.27, respectively, all pFDR<0.05). Subgroup analysis revealed decreased right lateral amygdala/right anterior hippocampus and right lateral amygdala/right posterior hippocampus FC in depressed vs. non-depressed patients and increased left medial amygdala/shell part of the left nucleus accumbens FC in manic vs non-manic patients. These results demonstrate that acute mood states in BD concur with FC changes in individual nuclei of the amygdala implicated in distinct emotional valence processing. Overall, our data highlight the importance to consider the amygdala subnuclei separately when studying its FC patterns including patients in distinct homogeneous mood states.
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OBJECTIVES: Bipolar disorder (BD) is a highly heritable disorder characterized by emotion dysregulation and recurrent oscillations between mood states. Despite the proven efficacy of early interventions, vulnerability markers in high-risk individuals are still lacking. BD patients present structural alterations of the hippocampus, a pivotal hub of emotion regulation networks composed of multiple subregions with different projections. However, the hippocampal dynamic functional connectivity (dFC) in BD remains unclear. We aim to investigate whether the dFC of hippocampal subdivisions differentiates BD patients, offspring of BD patients (BDoff), and healthy controls (HC); and whether it correlates with symptoms differently between these groups. METHODS: We studied for the first time the dFC of the hippocampus through a cutting-edge micro-co-activation patterns (µCAPs) analysis of resting-state functional MRI data of 97 subjects (26 BD, 18 BDoff, 53 HC). µCAPs allow a data-driven differentiation within the seed region. RESULTS: dFC between the hippocampal body and a somatomotor-µCAP was lower both in BD patients (p-valueFDR:0.00015) and in BDoff (p-valueFDR:0.020) than in HC. Inversely, dFC between the hippocampal head and a limbic-µCAP was higher in BD patients than in HC (p-valueFDR: 0.005). Furthermore, the correlations between a frontoparietal-µCAP and both depression and emotion dysregulation symptoms were significantly higher in BD than HC (p-valueFDR <0.02). CONCLUSION: Overall, we observed alterations of large-scale functional brain networks associated with decreased cognitive control flexibility and disrupted somatomotor, saliency, and emotion processing in BD. Interestingly, BDoff presented an intermediate phenotype between BD and HC, suggesting that dFC of hippocampal subregions might represent a marker of vulnerability to BD.
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Borderline personality disorder (BPD) is a debilitating psychiatric condition characterized by emotional dysregulation, unstable sense of self, and impulsive, potentially self-harming behavior. In order to provide new neurophysiological insights on BPD, we complemented resting-state EEG frequency spectrum analysis with EEG microstates (MS) analysis to capture the spatiotemporal dynamics of large-scale neural networks. High-density EEG was recorded at rest in 16 BPD patients and 16 age-matched neurotypical controls. The relative power spectrum and broadband MS spatiotemporal parameters were compared between groups and their inter-correlations were examined. Compared to controls, BPD patients showed similar global spectral power, but exploratory univariate analyses on single channels indicated reduced relative alpha power and enhanced relative delta power at parietal electrodes. In terms of EEG MS, BPD patients displayed similar MS topographies as controls, indicating comparable neural generators. However, the MS temporal dynamics were significantly altered in BPD patients, who demonstrated opposite prevalence of MS C (lower than controls) and MS E (higher than controls). Interestingly, MS C prevalence correlated positively with global alpha power and negatively with global delta power, while MS E did not correlate with any measures of spectral power. Taken together, these observations suggest that BPD patients exhibit a state of cortical hyperactivation, represented by decreased posterior alpha power, together with an elevated presence of MS E, consistent with symptoms of elevated arousal and/or vigilance. This is the first study to investigate resting-state MS patterns in BPD, with findings of elevated MS E and the suggestion of reduced posterior alpha power indicating a disorder-specific neurophysiological signature previously unreported in a psychiatric population.
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Transtorno da Personalidade Borderline , Humanos , Vigília , Nível de Alerta/fisiologia , EletroencefalografiaRESUMO
Adolescence is a vulnerable period for mental health. It is not easy to make a precise diagnosis during this period, as young people may present attenuated forms of psychiatric pathology, or on the contrary, a combination of several types of difficulties. Adopting a transdiagnostic and dimensional approach, based on clinical stages, and thus proposing interventions adapted to the severity of symptoms, is pertinent. As emotional dysregulation lies at the heart of many pathologies, it is a prime target for early intervention. Although interventions for adolescents are still underdeveloped, certain approaches derived from cognitive-behavioral therapies and the psychodynamic current have been adapted for adolescents and appear promising.
L'adolescence constitue une période vulnérable pour la santé mentale. Poser un diagnostic précis durant cette période n'est pas aisé car les jeunes peuvent présenter des formes atténuées de pathologies psychiatriques, ou, au contraire, une combinaison de plusieurs types de difficultés. Adopter une approche transdiagnostique et dimensionnelle, en fonction de stades cliniques, et ainsi proposer des interventions adaptées à la sévérité des symptômes est pertinent. La dysrégulation émotionnelle étant au cÅur de nombreuses pathologies, elle est une cible de premier choix pour des interventions précoces. Bien que les interventions pour les adolescents soient encore peu développées, certaines approches issues des thérapies cognitivo-comportementales et du courant psychodynamique ont été adaptées pour les adolescents et semblent prometteuses.
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Terapia Cognitivo-Comportamental , Regulação Emocional , Humanos , Adolescente , Coração , Saúde MentalRESUMO
OBJECTIVE: As part of a larger study investigating biological risk factors for bipolar disorder (BD) and borderline personality disorder (BPD), we investigated the prevalence of psychiatric diagnoses presented by young BD or BPD offspring. With respect to the scarcity of studies interested in psychiatric disorders among BPD offspring, we have chosen to report these results despite the small sample size for a prevalence study. METHOD: We recruited 21 BD and 22 BPD offspring and 23 control subjects. All subjects were assessed with a structured interview. RESULTS: Our main finding suggests that BPD offspring present a higher rate of psychiatric disorders compared to BD offspring. Attention deficit and hyperactivity disorder was the most prevalent disorder. CONCLUSION: Our results contribute to the evidence that offspring of patients with BPD, are at high risk with regard to their mental health and deserve both more research and special attention at the clinical level.
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Transtornos de Ansiedade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno Bipolar/epidemiologia , Transtorno da Personalidade Borderline/epidemiologia , Filho de Pais com Deficiência/estatística & dados numéricos , Transtorno Depressivo Maior/epidemiologia , Suscetibilidade a Doenças/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Prevalência , Adulto JovemRESUMO
Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed.
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Transtornos Cognitivos/fisiopatologia , Giro do Cíngulo/fisiopatologia , Inibição Psicológica , Transtornos do Humor/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Cognição/fisiologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Distribuição Aleatória , Tempo de Reação/fisiologiaRESUMO
BACKGROUND: Serotonin 3A receptor (5-HT3A R) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early-life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5-HT3A R and its association with clinical severity outcomes in relation with a functional genetic polymorphism. METHODS: Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5-HT3A R gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. RESULTS: Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5-HT3A R CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. CONCLUSIONS: This study shows that epigenetic modification of the 5-HT3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood.
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Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Bipolar/genética , Transtorno da Personalidade Borderline/genética , Maus-Tratos Infantis/psicologia , Metilação de DNA , Receptores 5-HT3 de Serotonina/genética , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Bipolar/psicologia , Transtorno da Personalidade Borderline/psicologia , Criança , Feminino , Humanos , Masculino , Polimorfismo Genético/genética , Índice de Gravidade de DoençaRESUMO
Theoretical models of hypnosis have emphasized the importance of attentional processes in accounting for hypnotic phenomena but their exact nature and brain substrates remain unresolved. Individuals vary in their susceptibility to hypnosis, a variability often attributed to differences in attentional functioning such as greater ability to filter irrelevant information and inhibit prepotent responses. However, behavioral studies of attentional performance outside the hypnotic state have provided conflicting results. We used fMRI to investigate the recruitment of attentional networks during a modified flanker task in High and Low hypnotizable participants. The task was performed in a normal (no hypnotized) state. While behavioral performance did not reliably differ between groups, components of the fronto-parietal executive network implicated in monitoring (anterior cingulate cortex; ACC), adjustment (lateral prefrontal cortex; latPFC), and implementation of attentional control (intraparietal sulcus; IPS) were differently activated depending on the hypnotizability of the subjects: the right inferior frontal gyrus (rIFG) was more recruited, whereas IPS and ACC were less recruited by High susceptible individuals compared to Low. Our results demonstrate that susceptibility to hypnosis is associated with particular executive control capabilities allowing efficient attentional focusing, and point to specific neural substrates in right prefrontal cortex. SIGNIFICANCE STATEMENT: We demonstrated that outside hypnosis, low hypnotizable subjects recruited more parietal cortex and anterior cingulate regions during selective attention conditions suggesting a better detection and implementation of conflict. However, outside hypnosis the right inferior frontal gyrus (rIFG) was more recruited by highly hypnotizable subjects during selective attention conditions suggesting a better control of conflict. Furthermore, in highly hypnotizable subjects this region was more connected to the default mode network suggesting a tight dialogue between internally and externally driven processes that may permit higher flexibility in attention and underlie a greater ability to dissociate.
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Atenção/fisiologia , Função Executiva/fisiologia , Hipnose , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Feminino , Giro do Cíngulo/fisiologia , Humanos , Masculino , Lobo Parietal/fisiologiaRESUMO
Spider-phobic individuals are characterized by exaggerated expectancies to be faced with spiders (so-called encounter expectancy bias). Whereas phobic responses have been linked to brain systems mediating fear, little is known about how the recruitment of these systems relates to exaggerated expectancies of threat. We used fMRI to examine spider-phobic and control participants while they imagined visiting different locations in a forest after having received background information about the likelihood of encountering different animals (spiders, snakes, and birds) at these locations. Critically, imagined encounter expectancies modulated brain responses differently in phobics as compared with controls. Phobics displayed stronger negative modulation of activity in the lateral prefrontal cortex, precuneus, and visual cortex by encounter expectancies for spiders, relative to snakes or birds (within-participants analysis); these effects were not seen in controls. Between-participants correlation analyses within the phobic group further corroborated the hypothesis that these phobia-specific modulations may underlie irrationality in encounter expectancies (deviations of encounter expectancies from objective background information) in spider phobia; the greater the negative modulation a phobic participant displayed in the lateral prefrontal cortex, precuneus, and visual cortex, the stronger was her bias in encounter expectancies for spiders. Interestingly, irrationality in expectancies reflected in frontal areas relied on right rather than left hemispheric deactivations. Our data accord with the idea that expectancy biases in spider phobia may reflect deficiencies in cognitive control and contextual integration that are mediated by right frontal and parietal areas.
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Viés , Mapeamento Encefálico , Encéfalo/patologia , Medo , Transtornos Fóbicos/patologia , Aranhas , Adulto , Animais , Encéfalo/irrigação sanguínea , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Transtornos Fóbicos/psicologia , Estimulação Luminosa , Adulto JovemRESUMO
Efficient perceptual identification of emotionally-relevant stimuli requires optimized neural coding. Because sleep contributes to neural plasticity mechanisms, we asked whether the perceptual representation of emotionally-relevant stimuli within sensory cortices is modified after a period of sleep. We show combined effects of sleep and aversive conditioning on subsequent discrimination of face identity information, with parallel plasticity in the amygdala and visual cortex. After one night of sleep (but neither immediately nor after an equal waking interval), a fear-conditioned face was better detected when morphed with another identity. This behavioral change was accompanied by increased selectivity of the amygdala and face-responsive fusiform regions. Overnight neural changes can thus sharpen the representation of threat-related stimuli in cortical sensory areas, in order to improve detection in impoverished or ambiguous situations. These findings reveal an important role of sleep in shaping cortical selectivity to emotionally-relevant cues and thus promoting adaptive responses to new dangers.
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Tonsila do Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Condicionamento Clássico/fisiologia , Face , Medo/fisiologia , Plasticidade Neuronal/fisiologia , Sono/fisiologia , Adulto , Discriminação Psicológica/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Distribuição Aleatória , Córtex Visual , Adulto JovemRESUMO
BACKGROUND: Early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic-pituitary-adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (NR3C1). AIMS: To investigate whether severity of childhood maltreatment is associated with increased methylation of the exon 1F NR3C1 promoter in bipolar disorder. METHOD: A sample of people with bipolar disorder (n = 99) were assessed for childhood traumatic experiences. The percentage of NR3C1 methylation was measured for each participant. RESULTS: The higher the number of trauma events, the higher was the percentage of NR3C1 methylation (ß = 0.52, 95% CI 0.46-0.59, P<<0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated with NR3C1 methylation status. CONCLUSIONS: Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder.
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BACKGROUND: Racing thoughts, crowded thoughts and flight of ideas are frequent symptoms in mood disorders, but the underlying subjective experience of overactivation of thought processes remains poorly documented. METHODS: Qualitative analysis of audiotaped interviews explored subjective experience of thought overactivation in patients with mood disorders (sample 1, n = 45). Quantitative analysis considered the properties of a newly developed rating scale in sample 1, in an additional sample of patients with mood disorders (sample 2, n = 37) and in healthy subjects (sample 3, n = 38). RESULTS: Qualitative analysis of individual interviews revealed that 5 conceptual categories characterized thought overactivation: sequential thought flow, overstimulation, competition for resource allocation, unexpected/unexplained onset, and association with mood and emotions. A principal component analysis of the initial 16-item rating scale indicated that a single component explained 55.9% of the variance, with major and exclusive contributions from 9 items, which were retained in the final 9-item Subjective Thought Overactivation Questionnaire (STOQ; Cronbach's α = 0.95). Total score correlated significantly with activation, depression and perceived conflict subscales of the Internal State Scale (ISS; rs = 0.57-0.66, p < 0.001). It was associated with decreased well-being (ISS; rs = -0.48, p = 0.001) and increased state anxiety (State-Trait Anxiety Inventory; rs = 0.60, p < 0.001). The STOQ score was significantly higher in patients than in healthy subjects. It allowed distinguishing between ISS mood states, with the highest median score in mixed states. LIMITATIONS: Sample size, representativeness, possible bias in qualitative analysis, and quality of expert consensus. CONCLUSIONS: Qualitative analysis of clinical interviews, together with a new short rating scale, contributed to a documentation of subjective thought overactivation, an important but often undetected feature in mood disorders.
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Transtornos do Humor/psicologia , Pensamento , Adulto , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Depressão/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação Pessoal , Inventário de Personalidade , Pesquisa Qualitativa , Tamanho da Amostra , Comportamento Social , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Emotion dysregulation (ED), the difficulty in modulating which emotions are felt, and when and how they are expressed or experienced, has been implicated in an array of psychological disorders. Despite potentially different manifestations depending on the disorder, this symptom is emerging as a transdiagnostic construct that can and should be targeted early, given the associations with various maladaptive behaviors as early as childhood and adolescence. As such, our goal was to investigate the psychotherapeutic interventions used to address ED and gauge their effectiveness, safety, and potential mechanisms across various populations. METHODS: This umbrella systematic review, pre-registered under PROSPERO (registration: CRD42023411452), consolidates evidence from systematic reviews and meta-analyses on psychotherapeutic interventions targeting ED, in accordance with PRISMA guidelines. RESULTS: Our synthesis of quantitative and qualitative evidence from 21 systematic reviews (including 11 meta-analyses) points-with moderate overall risk of bias-to the effectiveness of Dialectical Behavior Therapy and Cognitive Behavioral Therapy in reducing ED in a wide range of adult transdiagnostic psychiatric patients and healthy participants. Similar results have emerged in other less extensively researched methods as well. However, results on adolescents and children are sparse, highlighting the need for additional research to tailor these interventions to the unique challenges of ED in younger populations with diverse externalizing and internalizing disorders. CONCLUSIONS: These demonstrated transdiagnostic advantages of psychotherapy for ED underscore the potential for specifically designed interventions that address this issue directly, particularly for high-risk individuals. In these individuals, early interventions targeting transdiagnostic core dimensions may mitigate the emergence of full-blown disorders. Future research on the mediating factors, the durability of intervention effects, and the exploration of understudied interventions and populations may enhance prevention and treatment efficiency, enhancing the quality of life for those affected by varied manifestations of ED.
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Regulação Emocional , Humanos , Regulação Emocional/fisiologia , Terapia Cognitivo-Comportamental/métodos , Sintomas Afetivos/terapia , Sintomas Afetivos/etiologia , Terapia do Comportamento Dialético , Psicoterapia/métodosRESUMO
Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.
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Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies. Systematic review registration: https://osf.io/, identifier (ycqpz).
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Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13-15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.
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Hidrocortisona , Substância Branca , Humanos , Masculino , Adolescente , Feminino , Substância Branca/diagnóstico por imagem , Cortodoxona , Encéfalo/diagnóstico por imagem , Oxirredução , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Antioxidantes , Estresse PsicológicoRESUMO
We frequently need to change our current occupation, an operation requiring additional effortful cognitive demands. Switching from one task to another may involve two distinct processes: inhibition of the previously relevant task-set, and initiation of a new one. Here we tested whether these two processes are underpinned by separate neural substrates, and whether they differ depending on the nature of the task and the emotional content of stimuli. We used functional magnetic resonance imaging in healthy human volunteers who categorize emotional faces according to three different judgment rules (color, gender, or emotional expression). Our paradigm allowed us to separate neural activity associated with inhibition and switching based on the sequence of the tasks required on successive trials. We found that the bilateral medial superior parietal lobule and left intraparietal sulcus showed consistent activation during switching regardless of the task. On the other hand, no common region was activated (or suppressed) as a consequence of inhibition across all tasks. Rather, task-specific effects were observed in brain regions that were more activated when switching to a particular task but less activated after inhibition of the same task. In addition, compared to other conditions, the emotional task elicited a similar switching cost but lower inhibition cost, accompanied by selective decrease in the anterior cingulate cortex when returning to this task shortly after inhibiting it. These results demonstrate that switching relies on domain-general processes mediated by postero-medial parietal areas, engaged across all tasks, but also provide novel evidence that task inhibition produces domain-specific decreases as a function of particular task demands, with only the latter inhibition component being modulated by emotional information.
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Mapeamento Encefálico , Encéfalo/fisiologia , Cognição/fisiologia , Expressão Facial , Inibição Psicológica , Adulto , Emoções/fisiologia , Face , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa , Adulto JovemRESUMO
BACKGROUND: Bipolar disorder (BD) is a common affective disorder characterized by recurrent oscillations between mood states and associated with inflammatory diseases and chronic inflammation. However, data on MRI abnormalities in BD and their relationship with inflammation are heterogeneous and no review has recapitulated them. METHODS: In this pre-registered (PROSPERO: CRD42022308461) systematic review we searched Web of Science Core Collection and PubMed for articles correlating functional or structural MRI measures with immune-related markers in BD. RESULTS: We included 23 studies (6 on functional, 16 on structural MRI findings, 1 on both, including 1'233 BD patients). Overall, the quality of the studies included was fair, with a low risk of bias. LIMITATIONS: Heterogeneity in the methods and results of the studies and small sample sizes limit the generalizability of the conclusions. CONCLUSIONS: A qualitative synthesis suggests that the links between immune traits and functional or structural MRI alterations point toward brain areas involved in affective and somatomotor processing, with a trend toward a negative correlation between peripheral inflammatory markers and brain regions volume. We discuss how disentangling the complex relationship between the immune system and MRI alterations in BD may unveil mechanisms underlying symptoms pathophysiology, potentially with quickly translatable diagnostic, prognostic, and therapeutic implications.
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Transtorno Bipolar , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtornos do Humor , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Inflamação/diagnóstico por imagem , BiomarcadoresRESUMO
OBJECTIVES: Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. METHODS: We assessed hippocampus-based dFC coactivation patterns (CAPs) on resting-state fMRI data of 25 euthymic BD patients and 25 age- and sex-matched healthy controls (HC). RESULTS: Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo-insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default-like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. CONCLUSIONS: Overall, we observed alterations of large-scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self-centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow-up of BD patients and of disabling residual depressive symptoms in particular.
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Transtorno Bipolar , Humanos , Depressão/diagnóstico por imagem , Mapeamento Encefálico , Encéfalo , Hipocampo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. METHODS: We used a word processing paradigm to assess neural activations in adults with ADHD (N = 46) compared to controls (N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD (N = 18). RESULTS: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. CONCLUSION: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.