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BACKGROUND: Limited research exists on mother-infant interaction in women at-risk-of postpartum psychosis (PP). This study aimed to investigate potential predictors of mother-infant interaction quality in women at-risk-of-PP during the first postnatal year. Potential predictors investigated were: maternal ability to recognize emotions, childhood maltreatment, parenting stress, and infant social-interactive behaviour at birth. METHODS: 98 women (and their offspring) were included, 40 at-risk-of-PP because of a diagnosis of Bipolar Disorder, Schizoaffective Disorder or previous PP, and 58 with no current/previous mental illness or family history of PP. Mother-infant interaction was assessed using the CARE-Index at 8â¯weeks and 12â¯months postpartum. Maternal ability to recognize emotions was assessed with the VERT-K, maternal experience of childhood maltreatment with the CECA-Q, maternal parenting stress with the PSI-SF and infant social-interactive behaviour with the NBAS. RESULTS: Women at-risk-of-PP were less able to recognize fear than healthy controls and this predicted the quality of the mother-infant interaction at 8â¯weeks' and 12â¯months' postpartum, over and above the effect of maternal Group (respectively, ßâ¯=â¯0.33, pâ¯=â¯.015; ßâ¯=â¯0.40, pâ¯=â¯.006). Infant social-interactive behaviour at birth was a significant predictor for mother-infant interaction at 12â¯months (ßâ¯=â¯0.32, pâ¯=â¯.031), although this did not differ significantly between the groups. LIMITATIONS: A relatively small sample size precluded a more in-depth investigation of indirect pathways and other potential predictors. CONCLUSIONS: These results are important as they suggest that preventive interventions targeting emotion recognition may be implemented in women at-risk-of-PP, with the aim of improving mother-infant interaction and potentially also the infant long-term development.
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PURPOSE: While neuropsychological deficits are commonly observed in affective and psychotic disorders, this remains unexplored in these disorders when they occur during pregnancy and the postpartum period. METHODS: A neuropsychological test battery was administered to women defined at risk of postpartum depression (PD, N = 53) because having either a current or past diagnosis of major depressive disorder, women at risk of postpartum psychosis (PP, N = 43) because of a diagnosis of bipolar disorder or schizoaffective disorder and/or a previous episode of PP and women not at risk (NR, N = 48) in the third trimester of pregnancy. Generalized and specific cognitive abilities were compared between groups. RESULTS: Women at risk of PP presented worse executive functions and processing speed compared to NR and worse performance compared to women at risk of PD across all cognitive domains. In addition, women at risk of PP who developed a psychiatric relapse in the first four weeks post-partum showed worse verbal learning and memory, visual memory, executive functions and processing speed in pregnancy compared to NR, whereas women at risk of PP who remained well presented neuropsychological performance that was intermediate between that of the women NR and those at risk of PP who developed symptoms. There were no differences in performance between women at risk of PD and the NR women, even if 31 women at risk of PD presented depressive symptoms at the time of cognitive assessment. CONCLUSIONS: Our findings in women at risk of PP align with neuropsychological findings in individuals with, or at risk of psychosis unrelated to pregnancy. In addition, initial evidence that women at risk of PP who develop a psychiatric relapse in the postpartum show a particularly poor neuropsychological performance in pregnancy suggests that this could be considered part of a phenotype for the disease and help guiding future preventive strategies in this clinical population. In women at risk of PD, the presence of depressive symptoms did not influence cognitive performance.
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INTRODUCTION: Advances have been made in understanding the aetiology of functional neurological disorder (FND); however, its pathophysiological mechanisms have not been definitively demonstrated. Evidence suggests interacting roles for altered emotional processing and interoception, elevated autonomic arousal, and dissociation, but there is limited evidence demonstrating their causal influence on specific FND symptoms. Our superordinate aim is to elucidate potentially shared and distinct aetiological factors and mechanisms in two common FND subtypes, functional seizures (FS) and functional motor symptoms (FMS). METHODS: This study has a multimodal, mixed between- and within-groups design. The target sample is 50 individuals with FS, 50 with FMS, 50 clinical controls (anxiety/depression), and 50 healthy controls. Potential aetiological factors (e.g., adverse life events, physical/mental health symptoms, dissociative tendencies, interoceptive insight/sensibility) will be assessed with a detailed medical history interview and self-report questionnaires. A laboratory session will include a neurocognitive battery, psychophysiological testing, cardiac interoception and time estimation tasks and an isometric handgrip task. A subsample will undergo magnetic resonance imaging, including structural, resting-state and task-based scans combined with psychophysiological recording. Remote monitoring with ecological momentary assessment and wearables will measure variability in FND symptoms and their potential predictors/correlates for ≥2 weeks in patients' daily lives. Longitudinal follow-ups at 3, 6, and 12-months will monitor longer-term outcomes in the clinical groups. DISCUSSION: This study employs multimodal research methods to rigorously examine several putative mechanisms in FND, at subjective/experiential, behavioural, and physiological levels. The study will test causal hypotheses about the role of altered emotional processing, autonomic arousal, dissociation and interoception in the initiation or exacerbation of FND symptoms, directly comparing these processes in FS and FMS to healthy and clinical controls. This is the first study of its kind, with potential to reveal important targets for prevention and treatment of FND in future.
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Convulsiones , Humanos , Convulsiones/fisiopatología , Convulsiones/psicología , Adulto , Masculino , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética , Adulto Joven , Interocepción/fisiología , Adolescente , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action. METHODS: A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment. DISCUSSION: This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD. TRIAL REGISTRATION: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .
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Trastorno por Déficit de Atención con Hiperactividad , Nervio Trigémino , Adolescente , Niño , Femenino , Humanos , Masculino , Trastorno por Déficit de Atención con Hiperactividad/terapia , Método Doble Ciego , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functional symptoms, quality of life, and general functioning). METHODS: Seventeen participants with FMS or FS and 17 healthy control participants underwent an in-depth clinical interview and completed questionnaires assessing adverse life events, psychological and physical symptoms, alexithymia, autistic traits, illness perceptions, health-related quality of life (HRQoL), and work and social functioning. RESULTS: Participants with FMS or FS perceived various causes of the disorder, including physical symptoms (65%), emotional problems (53%), adverse life events (47%), and work-related factors (29%). Triggers of FMS and FS included physical activity or exertion (59%), stress and emotions (59%), sensory experiences (47%), and fatigue (41%). Compared with healthy control participants, participants with FMS or FS reported more adverse events during adolescence and higher levels of alexithymia, somatoform dissociation, psychological dissociation (disengagement, depersonalization, and derealization), anxiety, depression, and physical symptoms. Participants with FMS or FS had worse HRQoL than healthy control participants and impaired work and social functioning. There were inverse associations between HRQoL scores and somatoform dissociation, anxiety, and adverse life events. CONCLUSIONS: Participants with FMS or FS reported diverse biopsychosocial etiological factors and symptom triggers. Ongoing psychological symptoms and lifetime adverse experiences were associated with worse HRQoL. Future studies will examine these factors in larger samples of individuals with FMS or FS to better understand their shared and distinct etiological underpinnings.
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This case report describes a rare incident of fluid exhibiting retrograde flow from the nasopharynx through the nasolacrimal duct and accumulating within the eye guard while under general anesthesia. The patient was in a steep Trendelenburg position for several hours and received multiple liters of intravenous fluid. The patient did not have a history of sinusitis, sinus surgery, cocaine use, dacryostenosis and dacryocystitis, or nasolacrimal duct irrigation and probing. This case provides insight into the potential ophthalmic implications of surgical and anesthetic management. While the patient fortunately had no complications, this case also underscores the importance of intraoperative vigilance.
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Conducto Nasolagrimal , Humanos , Conducto Nasolagrimal/cirugía , Anestesia General , Cara , Inclinación de Cabeza , VigiliaRESUMEN
BACKGROUND: This study aimed to investigate mother-infant interaction and infant development in women at-risk of postpartum psychosis (PP), with and without a postpartum relapse. METHODS: 103 women (and their offspring) were included, 43 at-risk-of-PP because of a diagnosis of bipolar disorder, schizoaffective disorder or previous PP, and 60 with no current/previous mental illness or family history of PP. Of the at-risk women, 18 developed a psychiatric relapse within 4 weeks after delivery (AR-unwell), while 25 remained symptom-free (AR-well). Mother-infant interaction was assessed using the CARE-Index at 8 weeks' and 12 months' postpartum and infant development using the Bayley-III at 12 months' postpartum. RESULTS: Women at-risk-of-PP as a group, regardless of whether they developed a psychiatric relapse within 4 weeks after delivery, had less synchronous mother-infant interactions and had infants with less optimal cognitive, language, motor and socio-emotional development than healthy controls. In particular, boys of at-risk women had the lowest scores in cognitive, language and motor development and in mother-infant interaction, while girls of the at-risk women had the lowest scores in socio-emotional development. The synchrony in the dyad predicted infant cognitive and language development. There was no evidence for a difference in mother-infant interaction nor in infant development between the AR-unwell and AR-well groups. CONCLUSIONS: These results suggest that, while there is a lack of evidence that an early postpartum relapse in women at-risk-of-PP could represent a risk for the infant per se, maternal risk for PP may be associated with less optimal mother-infant interaction and infant development.
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Trastornos Psicóticos , Trastornos Puerperales , Lactante , Masculino , Niño , Femenino , Humanos , Desarrollo Infantil , Trastornos Psicóticos/psicología , Periodo Posparto/psicología , Relaciones Madre-Hijo/psicología , RecurrenciaRESUMEN
BACKGROUND: Differences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the hypotheses that highly arousing affective stimulation would result in elevated subjective functional neurological symptoms (FNS), and this would be associated with elevated autonomic reactivity. The possible influence of cognitive detachment was also explored. METHOD: Individuals diagnosed with FND (motor symptoms/seizures; n=14) and healthy controls (n=14) viewed Positive, Negative and Neutral images in blocks, while passively observing the stimuli ('Watch') or detaching themselves ('Distance'). The FND group rated their primary FNS, and all participants rated subjective physical (arousal, pain, fatigue) and psychological states (positive/negative affect, dissociation), immediately after each block. Skin conductance (SC) and heart rate (HR) were monitored continuously. RESULTS: FNS ratings were higher after Negative compared with Positive and Neutral blocks in the FND group (p=0.002, ηp 2=0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, ηp 2=0.267). SC and/or HR correlated with FNS ratings in the Negative-Watch and Neutral-Distance conditions (r values=0.527-0.672, p values=0.006-0.035). The groups did not differ in subjective affect or perceived arousal (p values=0.541-0.919, ηp 2=<0.001-0.015). CONCLUSIONS: Emotionally significant events may exert an influence on FNS which is related to autonomic activation rather than altered subjective affect or perceived arousal. This influence may be modulated by cognitive detachment. Further work is needed to determine the relevance and neural bases of these processes in specific FND phenotypes.
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Trastornos de Conversión , Humanos , Trastornos Disociativos , Nivel de Alerta/fisiología , ConvulsionesRESUMEN
Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine's effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous ketamine vs. placebo in patients with treatment resistant depression (TRD) vs. healthy volunteers (HV), we used seed-based resting-state functional connectivity (rsFC) analyses to determine differential changes in subgenual ACC (sgACC), perigenual ACC (pgACC) and dorsal ACC (dACC) rsFC two days post-infusion. Across cingulate subregions, ketamine differentially modulated rsFC to the right insula and anterior ventromedial prefrontal cortex, compared to placebo, in TRD vs. HV; changes to pgACC-insula connectivity correlated with improvements in depression scores. Post-hoc analysis of each cingulate subregion separately revealed differential modulation of sgACC-hippocampal, sgACC-vmPFC, pgACC-posterior cingulate, and dACC-supramarginal gyrus connectivity. By comparing rsFC changes following ketamine vs. placebo in the TRD group alone, we found that sgACC rsFC was most substantially modulated by ketamine vs. placebo. Changes to sgACC-pgACC, sgACC-ventral striatal, and sgACC-dACC connectivity correlated with improvements in anhedonia symptoms. This preliminary evidence suggests that accurate segmentation of the ACC is needed to understand the precise effects of ketamine's antidepressant and anti-anhedonic action.
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Ketamina , Humanos , Ketamina/farmacología , Ketamina/uso terapéutico , Giro del Cíngulo , Corteza Prefrontal , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Imagen por Resonancia MagnéticaRESUMEN
Opioid receptors are widely expressed in the brain, and the opioid system has a key role in modulating mood, reward processing and stress responsivity. There is mounting evidence that the endogenous opioid system may be dysregulated in depression and that drug treatments targeting mu, delta and kappa opioid receptors may show antidepressant potential. The mechanisms underlying the therapeutic effects of opioid system engagement are complex and likely multi-factorial. This chapter explores various pathways through which the modulation of the opioid system may influence depression. These include impacts on monoaminergic systems, the regulation of stress and the hypothalamic-pituitary-adrenal axis, the immune system and inflammation, brain-derived neurotrophic factors, neurogenesis and neuroplasticity, social pain and social reward, as well as expectancy and placebo effects. A greater understanding of the diverse mechanisms through which opioid system modulation may improve depressive symptoms could ultimately aid in the development of safe and effective alternative treatments for individuals with difficult-to-treat depression.
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Studies report that the microstructural integrity of the uncinate fasciculus (UF; connecting the anterior temporal lobe to the orbitofrontal cortex) is abnormal in adults with psychopathy and children with conduct problems (CP), especially those with high callous-unemotional (CU) traits. However, it is unknown if these abnormalities are 'fixed' or 'reversible'. Therefore, we tested the hypothesis that a reduction in CP symptoms, following a parenting intervention, would be associated with altered microstructural integrity in the UF. Using diffusion tensor imaging tractography we studied microstructural differences (mean diffusivity (MD) and radial diffusivity (RD)) in the UF of 43 typically developing (TD) and 67 boys with CP before and after a 14-week parenting intervention. We also assessed whether clinical response in CP symptoms or CU traits explained changes in microstructure following the intervention. Prior to intervention, measures of MD and RD in the UF were increased in CP compared to TD boys. Following intervention, we found that the CP group had a significant reduction in RD and MD. Further, these microstructural changes were driven by the group of children whose CU traits improved (but not CP symptoms as hypothesized). No significant microstructural changes were observed in the TD group. Our findings suggest, for the first time, that microstructural abnormalities in the brains of children with CP may be reversible following parenting intervention.
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Trastorno de la Conducta , Sustancia Blanca , Masculino , Adulto , Humanos , Niño , Imagen de Difusión Tensora/métodos , Sustancia Blanca/diagnóstico por imagen , Responsabilidad Parental , Trastorno de la Conducta/diagnóstico por imagen , Trastorno de la Conducta/terapia , Trastorno de Personalidad Antisocial/psicologíaRESUMEN
The Hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of mood disorders, and preliminary data suggests that glucocorticoid receptor (GR) antagonism may be an important therapeutic mechanism. The effects of modulating HPA axis function on emotional processing related brain activity, which may be abnormal in depressed mood, is poorly understood. This study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine the effects of the GR and progesterone receptor antagonist mifepristone on emotional faces processing task related brain activations in 19 right-handed healthy male participants. Each participant received 600 mg mifepristone or placebo on two separate imaging days and then performed an emotional processing fMRI task four hours later. The effect of mifepristone on task related brain activations was determined using Region-of-Interest (ROI) analyses and an exploratory whole brain voxel-wise analyses. No significant changes were observed in the defined ROIs (amygdala, anterior cingulate cortex, insula) or in the exploratory whole brain analyses that was associated with mifepristone administration in either the angry vs happy faces or angry and happy faces vs implicit baseline contrasts. Task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our study failed to show significant evidence of modulation of emotional processing related brain activity associated with acute mifepristone administration. Future research should use fMRI to investigate the longer-term administration effects of mifepristone on mood in healthy participants and people with mood disorders to provide a deeper understanding of the potential effects on depressive symptoms.
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Sistema Hipotálamo-Hipofisario , Mifepristona , Humanos , Masculino , Mifepristona/farmacología , Sistema Hipófiso-Suprarrenal , Emociones/fisiología , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Expresión FacialRESUMEN
INTRODUCTION: This study aimed to provide a preliminary assessment of objective and subjective neurocognitive functioning in individuals with functional motor symptoms (FMS) and/or functional seizures (FS). We tested the hypotheses that the FMS/FS group would display poorer objective attentional and executive functioning, altered social cognition, and reduced metacognitive accuracy. METHOD: Individuals with FMS/FS (n = 16) and healthy controls (HCs, n = 17) completed an abbreviated CANTAB battery, and measures of intellectual functioning, subjective cognitive complaints, performance validity, and comorbid symptoms. Subjective performance ratings were obtained to assess local metacognitive accuracy. RESULTS: The groups were comparable in age (p = 0.45), sex (p = 0.62), IQ (p = 0.57), and performance validity (p-values = 0.10-0.91). We observed no impairment on any CANTAB test in this FMS/FS sample compared to HCs, although the FMS/FS group displayed shorter reaction times on the Emotional Bias task (anger) (p = 0.01, np2 = 0.20). The groups did not differ in subjective performance ratings (p-values 0.15). Whilst CANTAB attentional set-shifting performance (total trials/errors) correlated with subjective performance ratings in HCs (p-values<0.005, rs = -0.85), these correlations were non-significant in the FMS/FS sample (p-values = 0.10-0.13, rs-values = -0.46-0.50). The FMS/FS group reported more daily cognitive complaints than HCs (p = 0.006, g = 0.92), which were associated with subjective performance ratings on CANTAB sustained attention (p = 0.001, rs = -0.74) and working memory tests (p < 0.001, rs = -0.75), and with depression (p = 0.003, rs = 0.70), and somatoform (p = 0.003, rs = 0.70) and psychological dissociation (p-values<0.005, rs-values = 0.67-0.85). CONCLUSIONS: These results suggest a discordance between objective and subjective neurocognitive functioning in this FMS/FS sample, reflecting intact test performance alongside poorer subjective cognitive functioning. Further investigation of neurocognitive functioning in FND subgroups is necessary.
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Key Clinical Message: Prompt diagnosis and treatment of GCA are crucial to preserve vision. Because of this, new-onset ptosis or diplopia in elderly patients should warrant consideration of GCA, even in the absence of "classic" features, systemic symptoms or elevated inflammatory markers. Abstract: Giant cell arteritis (GCA) is a vision-threatening, ophthalmic emergency that classically presents with new-onset headaches, scalp tenderness, systemic symptoms, visual disturbances, and elevated inflammatory markers. We describe an atypical presentation of GCA in an 87-year-old patient with fatigable ptosis and diplopia, with subsequent anterior ischemic optic neuropathy and choroidal infarction.
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BACKGROUND: The rate of cytomegalovirus (CMV) retinitis is increasing, likely secondary to aggressive immunosuppressive regimens for a variety of diseases. Transplant and rheumatological literature show growing evidence suggesting a unique relationship between CMV infection and mycophenolate in particular. This study reports two cases of CMV retinitis infection in patients on mycophenolate immunosuppression. CASE PRESENTATION: Case A was a 39-year-old African American woman with systemic lupus erythematosus (SLE) with stage IV lupus nephritis who presented for bilateral retinal detachments with areas of moth-eaten and thin retina concerning for prior viral retinitis. Case B was a 53-year-old man who presented with floaters in the right eye status-post heart transplant since 2008 on immunosuppressive therapy. Fundoscopic examination of the right eye showed frosted branch angiitis with intraretinal hemorrhage and inner retinal thickening and disorganization, consistent with CMV retinitis infection. Both patients were on mycophenolate immunosuppression with the recommendation to reduce or discontinue mycophenolate. CONCLUSION: Patients on mycophenolate immunosuppression may be more vulnerable to cytomegalovirus infection, including CMV retinitis. Ophthalmologists should be aware of this increased risk and consider reducing or discontinuing mycophenolate to promote viral clearance in these susceptible patients, in conjunction with the patient's transplant or rheumatology teams.
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Receptor-enriched analysis of functional connectivity by targets (REACT) is a strategy to enrich functional MRI (fMRI) data with molecular information on the neurotransmitter distribution density in the human brain, providing a biological basis to the functional connectivity (FC) analysis. Although this approach has been used in BOLD fMRI studies only so far, extending its use to ASL imaging would provide many advantages, including the more direct link of ASL with neuronal activity compared to BOLD and its suitability for pharmacological MRI studies assessing drug effects on baseline brain function. Here, we applied REACT to simultaneous ASL/BOLD resting-state fMRI data of 29 healthy subjects and estimated the ASL and BOLD FC maps related to six molecular systems. We then compared the ASL and BOLD FC maps in terms of spatial similarity, and evaluated and compared the test-retest reproducibility of each modality. We found robust spatial patterns of molecular-enriched FC for both modalities, moderate similarity between BOLD and ASL FC maps and comparable reproducibility for all but one molecular-enriched functional networks. Our findings showed that ASL is as informative as BOLD in detecting functional circuits associated with specific molecular pathways, and that the two modalities may provide complementary information related to these circuits.
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Circulación Cerebrovascular , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Circulación Cerebrovascular/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico/métodosRESUMEN
Altered interoception may be a pathophysiological mechanism in functional neurological disorder (FND). However, findings have been inconsistent across interoceptive dimensions in FND including functional motor symptoms (FMS) and seizures (FS). Here, individuals with FMS/FS (n = 17) and healthy controls (HC, n = 17) completed measures of interoceptive accuracy and insight (adapted heartbeat tracking task [HTT] with confidence ratings), a time estimation control task (TET) and the Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2) to assess interoceptive sensibility. The groups did not differ in interoceptive accuracy (p = 1.00, g = 0.00) or confidence (p = .99, g = 0.004), although the FMS/FS group displayed lower scores on the "Not-Distracting" (p < .001, g = 1.42) and "Trusting" (p = .005, g = 1.17) MAIA-2 subscales, relative to HCs. The groups did not differ in TET performance (p = .82, g = 0.08). There was a positive relationship between HTT accuracy and confidence (insight) in HCs (r = .61, p = .016) but not in FMS/FS (r = 0.11, p = .69). HTT confidence was positively correlated with MAIA-2 "Self-Regulation" (r = 0.77, p = .002) and negatively correlated with FND symptom severity (r = -0.84, p < .001) and impact (r = -0.86, p < .001) in FMS/FS. Impaired interoceptive accuracy may not be a core feature in FMS/FS, but reduced insight and altered sensibility may be relevant. Reduced certainty in self-evaluations of bodily experiences may contribute to the pathogenesis of FND symptoms.
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Concienciación , Interocepción , Humanos , Concienciación/fisiología , Interocepción/fisiología , Convulsiones , Autoevaluación (Psicología) , Frecuencia Cardíaca/fisiologíaRESUMEN
BACKGROUND: Resting state connectivity studies link ketamine's antidepressant effects with normalisation of the brain connectivity changes that are observed in depression. These changes, however, usually co-occur with improvement in depressive symptoms, making it difficult to attribute these changes to ketamine's effects per se. AIMS: Our aim is to examine the effects of ketamine in brain connectivity, 2 h after its administration in a cohort of volunteers with remitted depression. Any significant changes observed in this study could provide insight of ketamine's antidepressant mechanism as they are not accompanied by symptom changes. METHODS: In total, 35 participants with remitted depression (21 females, mean age = 28.5 years) participated in a double-blind, placebo-controlled study of ketamine (0.5 mg/kg) or saline. Resting state scans were acquired approximately 2 h after the ketamine infusion. Brain connectivity was examined using a seed-based approach (ventral striatum, amygdala, hippocampus, posterior cingulate cortex and subgenual anterior cingulate cortex (sgACC)) and a brain network analysis (independent component analysis). RESULTS: Decreased connectivity between the sgACC and the amygdala was observed approximately 2 h after the ketamine infusion, compared to placebo (pFWE < 0.05). The executive network presented with altered connectivity with different cortical and subcortical regions. Within the network, the left hippocampus and right amygdala had decreased connectivity (pFWE < 0.05). CONCLUSIONS: Our findings support a model whereby ketamine would change the connectivity of brain areas and networks that are important for cognitive processing and emotional regulation. These changes could also be an indirect indicator of the plasticity changes induced by the drug.
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Ketamina , Femenino , Humanos , Adulto , Depresión/tratamiento farmacológico , Imagen por Resonancia Magnética , Encéfalo , Antidepresivos/farmacología , Antidepresivos/uso terapéuticoRESUMEN
OBJECTIVE: Neuropharmacological changes in visual snow syndrome (VSS) are poorly understood. We aimed to use receptor target maps combined with resting functional magnetic resonance imaging (fMRI) data to identify which neurotransmitters might modulate brain circuits involved in VSS. METHODS: We used Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) to estimate and compare the molecular-enriched functional networks related to 5 neurotransmitter systems of patients with VSS (n = 24), healthy controls (HCs; n = 24), and migraine patients ([MIG], n = 25, 15 of whom had migraine with aura [MwA]). For REACT we used receptor density templates for the transporters of noradrenaline, dopamine, and serotonin, GABA-A and NMDA receptors, as well as 5HT1B and 5HT2A receptors, and estimated the subject-specific voxel-wise maps of functional connectivity (FC). We then performed voxel-wise comparisons of these maps among HCs, MIG, and VSS. RESULTS: Patients with VSS had reduced FC in glutamatergic networks localized in the anterior cingulate cortex (ACC) compared to HCs and patients with migraine, and reduced FC in serotoninergic networks localized in the insula, temporal pole, and orbitofrontal cortex compared to controls, similar to patients with migraine with aura. Patients with VSS also showed reduced FC in 5HT2A -enriched networks, largely localized in occipito-temporo-parietal association cortices. As revealed by subgroup analyses, these changes were independent of, and analogous to, those found in patients with migraine with aura. INTERPRETATION: Our results show that glutamate and serotonin are involved in brain connectivity alterations in areas of the visual, salience, and limbic systems in VSS. Importantly, altered serotonergic connectivity is independent of migraine in VSS, and simultaneously comparable to that of migraine with aura, highlighting a shared biology between the disorders. ANN NEUROL 2023;94:873-884.