Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift... Show moreNeuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we built and validated supervised neuroanatomical machine learning models for individual-level inferences, using a case–control design and the largest known neuroimaging database on youth anxiety disorders: the ENIGMA-Anxiety Consortium (N = 3,343; age = 10–25 years; global sites = 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (panic disorder), but also transdiagnostically for all anxiety disorders when patients were subgrouped according to their sex, medication status and symptom severity (area under the receiver operating characteristic curve, 0.59–0.63). Classifications were driven by neuroanatomical features (cortical thickness, cortical surface area and subcortical volumes) in fronto-striato-limbic and temporoparietal regions. This benchmark study within a large, heterogeneous and multisite sample of youth with anxiety disorders reveals that only modest classification performances can be realistically achieved with machine learning using neuroanatomical data. Show less
Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies... Show moreBackground: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable. Show less
Does, F.H.S. van der; Nagamine, M.; Wee, N.J.A. van der; Chiba, T.; Edo, N.; Kitano, M.; ... ; Giltay, E.J. 2023
Background: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The... Show moreBackground: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The network approach to psychopathology suggests that symptoms may cause and exacerbate each other, resulting in the emergence and maintenance of disorders, including PTSD. It is therefore important to further explore the temporal interplay between symptoms. Most studies assessing the factor structure of the Impact of Event Scale-Revised [IES-R] have used cross-sectional designs. In this study, the structure of the IES-R was re-evaluated while incorporating the temporal interplay between symptoms.Methods: Using Dynamic Time Warping [DTW] the distances between PTSD symptoms on the IES-R were modelled in 1120 JGSDF personnel. Highly correlated symptoms were clustered at the group level using Distatis three-way principal component analyses of the distance matrices. The resulting clusters were compared to the original three subscales of the IES-R using a Confirmatory Factor Analysis (CFA).Results: The DTW analysis yielded four symptom clusters: Intrusion (five items), Hyperarousal (six items), Avoidance (six items), and Dissociation (five items). CFA yielded better fit estimates for this four-factor solution (RMSEA = 0.084, CFI = 0.918, TLI = 0.906), compared to the original three subscales of the IES-R (RMSEA = 0.103, CFI = 0.873, TLI = 0.858).Conclusions: DTW offers a new method of modelling the temporal relationships between symptoms. It yielded four IES-R symptom clusters, which may facilitate understanding of PTSD as a complex dynamic system. Show less
Major Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations... Show moreMajor Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations between enduring depression and brain functioning during regulation of negative and positive emotions using cognitive reappraisal.We used fMRI-data from the longitudinal Netherlands Study of Depression and Anxiety acquired during an emotion regulation task in 77 individuals with MDD. Task-related brain activity was related to disease load, calculated from presence and severity of depression in the preceding nine years. Additionally, we explored task related brain-connectivity. Brain functioning in individuals with MDD was further compared to 35 controls to explore overlap between load-effects and general effects related to MDD history/presence.Disease load was not associated with changes in affect or with brain activity, but with connectivity between areas essential for processing, integrating and regulating emotional information during downregulation of negative emotions. Results did not overlap with general MDD-effects. Instead, MDD was generally associated with lower parietal activity during downregulation of negative emotions. During upregulation of positive emotions, disease load was related to connectivity between limbic regions (although driven by symptomatic state), and connectivity between frontal, insular and thalamic regions was lower in MDD (vs controls).Results suggest that previous depressive load relates to brain connectivity in relevant networks during downregulation of negative emotions. These abnormalities do not overlap with disease-general abnormalities and could foster an incremental vulnerability to recurrence or chronicity of MDD. Therefore, optimizing emotion regulation is a promising therapeutic target for improving long-term MDD course. Show less
Major Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations... Show moreMajor Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations between enduring depression and brain functioning during regulation of negative and positive emotions using cognitive reappraisal.We used fMRI-data from the longitudinal Netherlands Study of Depression and Anxiety acquired during an emotion regulation task in 77 individuals with MDD. Task-related brain activity was related to disease load, calculated from presence and severity of depression in the preceding nine years. Additionally, we explored task related brain-connectivity. Brain functioning in individuals with MDD was further compared to 35 controls to explore overlap between load-effects and general effects related to MDD history/presence.Disease load was not associated with changes in affect or with brain activity, but with connectivity between areas essential for processing, integrating and regulating emotional information during downregulation of negative emotions. Results did not overlap with general MDD-effects. Instead, MDD was generally associated with lower parietal activity during downregulation of negative emotions. During upregulation of positive emotions, disease load was related to connectivity between limbic regions (although driven by symptomatic state), and connectivity between frontal, insular and thalamic regions was lower in MDD (vs controls).Results suggest that previous depressive load relates to brain connectivity in relevant networks during downregulation of negative emotions. These abnormalities do not overlap with disease-general abnormalities and could foster an incremental vulnerability to recurrence or chronicity of MDD. Therefore, optimizing emotion regulation is a promising therapeutic target for improving long-term MDD course. Show less
Early identification of individuals with Body dysmorphic disorder (BDD) is essential to direct them to appropriate care and to reduce the chance of developing or maintaining comorbid psychiatric... Show moreEarly identification of individuals with Body dysmorphic disorder (BDD) is essential to direct them to appropriate care and to reduce the chance of developing or maintaining comorbid psychiatric disorders (like an eating disorder (ED)). The present study aimed to develop a simple screener, the Body Dysmorphic Disorder Screener for DSM-5 (BDDS-5), to overcome existing screeners' limitations and test its psychometric properties.The BDDS-5 consists of 12 statements with dichotomous answer options. Specific attention is paid to the readability of the screener for those with lower reading skills. Additional eating disorder screening questions (S section) were added to investigate whether these questions are necessary for detecting potential BDD cases. Finally, the factor structure, internal consistency, and validity of the BDDS-5 were examined within populations with a high risk of screening positive for BDD or ED. Principal axis factor analysis showed that two factors accounted for 63.5% of the variance. The factor analysis was based on polychoric correlation. Based on the BDDS-5, 33 persons (14% of N = 235) were screened as likely BDD cases. Nineteen persons were excluded as potential BDD cases based on the eating disorder related question (question D). Based on the S-section, this turned out to be largely correct for the majority, however, in 8% (n = 4) of the cases BDD was probably missed. The convergent validity appeared to be high (r > 0.80) with three other BDD measures.The BDDS-5 is a valid and widely applicable screener for BDD that may help in the early detection of BDD. The BDDS-5 uses simple wording and is thus suitable for people 8 years and older. Show less
Leeuw, M. de; Verhoeve, S.I.; Wee, N.J.A. van der; Hemert, A.M. van; Vreugdenhil, E.; Coomans, C.P. 2023
Circadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily... Show moreCircadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily functions including appetite, sleep, activity and cortisol levels. The circadian clock synchronizes itself to the external world mainly by environmental light cues and can be disturbed by a variety of factors, including shift-work, jet-lag, stress, ageing and artificial light at night.Interestingly, mood has also been shown to follow a diurnal rhythm. Moreover, circadian disruption has been associated with various mood disorders and patients suffering from depression have irregular biological rhythms in sleep, appetite, activity and cortisol levels suggesting that circadian rhythmicity is crucially involved in the etiology and pathophysiology of depression.The aim of the present review is to give an overview and discuss recent findings in both humans and rodents linking a disturbed circadian rhythm to depression. Understanding the relation between a disturbed circadian rhythm and the etiology of depression may lead to novel therapeutic and preventative strategies. Show less
Bas, J.M.; Groenewold, N.A.; Amod, A.R.; Laansma, M.A.; Velzen, L.S. van; Aghajani, M.; ... ; Wee, N.J.A. van der 2023
Background: The short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral... Show moreBackground: The short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral centre for NPSLE to investigate the type of inflammatory NPSLE manifestations, type of immunosuppressive treatment prescribed for these manifestations and clinical outcomes. Methods: All patients with SLE visiting the Leiden University Medical Centre NPSLE clinic between 2007 and 2021 receiving immunosuppressive therapy for neuropsychiatric symptoms were included. Clinical, immunological and radiological information was collected in as standardised way during a 1-day multidisciplinary assessment. In a multidisciplinary consensus meeting, the presence of NPSLE and the type of NPSLE manifestations and treatment were determined. For this study, short-term (0-6 months) and long-term outcomes (7-24 months) of the NP symptoms were assessed by two independent readers and scored on a 7-point Likert scale, ranging from death to resolved. Results: In total, 95 out of 398 (24%) patients visiting the NPSLE clinic between 2007 and 2021 received any form of immunosuppressive treatment for 101 separate NPSLE events. The most common NP manifestation was cognitive dysfunction (50%) as identified by formal cognitive assessment, often present in combination with other NPSLE manifestations. Treatment modalities were induction (24%), induction and maintenance (73%) and other therapy (3%). The treatments mostly consisted of (combinations of) prednisone (97%), methylprednisolone (53%), azathioprine (generally 2 mg/kg daily) (49%) and cyclophosphamide (generally induction 750 mg/m(2) every 4 weeks for 24 weeks or 500mg biweekly for 12 weeks) (42%). Short-term outcome showed improvement on the Likert scale in 73% (improved: 22%, much improved: 29%, resolved: 22%), no change in 21% and worsening in 6% of patients. Long-term outcome was available for 78 out of 101 events and showed improvement in 70% (improved: 14%, much improved: 28%, resolved: 28%), no change in 17%, worsening in 10% and death in 3% of patients (none directly NPSLE-related). Conclusion: The outcome of inflammatory NPSLE after immunosuppressive treatment is generally good, with improvement of neuropsychiatric symptoms occuring in approximately 70% of events. Show less
Monahan, R.C.; Voorde, L.J.J. van de; Fronczek, R.; Bresser, J. de; Eikenboom, J.; Kloppenburg, M.; ... ; Steup-Beekman, G.M. 2023
Background The short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral... Show moreBackground The short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral centre for NPSLE to investigate the type of inflammatory NPSLE manifestations, type of immunosuppressive treatment prescribed for these manifestations and clinical outcomes.Methods All patients with SLE visiting the Leiden University Medical Centre NPSLE clinic between 2007 and 2021 receiving immunosuppressive therapy for neuropsychiatric symptoms were included. Clinical, immunological and radiological information was collected in as standardised way during a 1-day multidisciplinary assessment. In a multidisciplinary consensus meeting, the presence of NPSLE and the type of NPSLE manifestations and treatment were determined. For this study, short-term (0–6 months) and long-term outcomes (7–24 months) of the NP symptoms were assessed by two independent readers and scored on a 7-point Likert scale, ranging from death to resolved.Results In total, 95 out of 398 (24%) patients visiting the NPSLE clinic between 2007 and 2021 received any form of immunosuppressive treatment for 101 separate NPSLE events. The most common NP manifestation was cognitive dysfunction (50%) as identified by formal cognitive assessment, often present in combination with other NPSLE manifestations. Treatment modalities were induction (24%), induction and maintenance (73%) and other therapy (3%). The treatments mostly consisted of (combinations of) prednisone (97%), methylprednisolone (53%), azathioprine (generally 2 mg/kg daily) (49%) and cyclophosphamide (generally induction 750 mg/m2 every 4 weeks for 24 weeks or 500mg biweekly for 12 weeks) (42%). Short-term outcome showed improvement on the Likert scale in 73% (improved: 22%, much improved: 29%, resolved: 22%), no change in 21% and worsening in 6% of patients. Long-term outcome was available for 78 out of 101 events and showed improvement in 70% (improved: 14%, much improved: 28%, resolved: 28%), no change in 17%, worsening in 10% and death in 3% of patients (none directly NPSLE-related).Conclusion The outcome of inflammatory NPSLE after immunosuppressive treatment is generally good, with improvement of neuropsychiatric symptoms occuring in approximately 70% of events. Show less
Groenewold, N.A.; Bas, J.M.; Amod, A.R.; Laansma, M.A.; Velzen, L.S. van; Aghajani, M.; ... ; Wee, N.J.A. van der 2023
There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in... Show moreThere is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood. Show less
Groenewold, N.A.; Bas-Hoogendam, J.M.; Amod, A.R.; Laansma, M.A.; Velzen, L.S. van; Aghajani, M.; ... ; Wee, N.J.A. van der 2023
There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in... Show moreThere is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood. Show less
Tajioui, I.; Neerven, T. van; Tol, M.J. van; Bas, J. M.; Veltman, D.; Wee, N.J.A. van der; Leeuw, M. de 2023
Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention.... Show moreIdentifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk. Show less
Setroikromo, S.N.W.; Werff, S.J.A. van der; Smit, A.S.; Vermetten, E.; Wee, N.J.A. van der 2022
BackgroundInsights into the neurobiological basis of resilience can have important implications for the prevention and treatment of stress-related disorders, especially in populations that are... Show moreBackgroundInsights into the neurobiological basis of resilience can have important implications for the prevention and treatment of stress-related disorders, especially in populations that are subjected to high-stress environments. Evaluating large-scale resting-state networks (RSNs) can provide information regarding resilient specific brain function which may be useful in understanding resilience. This study aimed to explore functional connectivity patterns specific for (high) resilience in Dutch policemen after exposure to multiple work-related traumatic events. We investigated resting-state functional connectivity (RSFC) of the salience network (SN), limbic network, and the default-mode network (DMN). MethodsResting-state functional MRI scans were obtained from trauma-exposed executive personnel of the Dutch police force and non-trauma-exposed recruits from the police academy. Participants were divided into three groups: a resilient group (n = 31; trauma exposure; no psychopathology), a vulnerable group (n = 32; trauma exposure, psychopathology), and a control group (n = 19; no trauma exposure, no psychopathology). RSFC of the three networks of interest was compared between these groups, using an independent component analysis and a dual regression approach. ResultsWe found decreased resilience-specific positive RSFC of the salience network with several prefrontal regions. The DMN and limbic network RFSC did not show resilience-specific patterns. ConclusionThis study shows a differential RSFC specific for resilient police officers. This differential RSFC may be related to a greater capacity for internal-focused thought and interoceptive awareness, allowing more effective higher-order responses to stress in highly resilient individuals. Show less
Background: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of... Show moreBackground: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression. Method: Individuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed. Results: Depression severity was negatively associated with rostral ACC thickness (B = -0.55, pFDR = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, pFDR = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies. Conclusion: Overall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved. Show less
Nawijn, L.; Dinga, R.; Aghajani, M.; Tol, M.J. van; Wee, N.J.A. van der; Wunder, A.; ... ; Penninx, B.W.H.J. 2022
Background: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated... Show moreBackground: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD. Methods: We probed the relation between the DSM-5 ADS and task-related reactivity to emotional faces, as well as resting-state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS-, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated. Results: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS- patients (p = .015)-part of a larger striato-limbic cluster. MDD/ADS+ did not differ from MDD/ADS- or controls in resting-state functional connectivity of the salience or basal ganglia networks. Conclusions: Current findings suggest that amygdala and striato-limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research. Show less
Millard, S.K.; Bokelmann, K.; Schalbroeck, R.; Wee, N.J.A. van der; Loey, N.E.E. van; Laarhoven, A.I.M. van 2022
A large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot... Show moreA large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot study investigates whether altered cortical oscillatory processes are involved in chronic post-burn itch. Continuous electroencephalography (EEG) data were recorded during rest and stimulation of non-injured skin, inducing itch (histamine and electrical) and cold-pressor task pain for 15 adults with chronic post-burn itch and 15 matched healthy controls. Quantitative metrics comprised oscillatory power and peak frequencies in theta, alpha, and beta bands. No statistical differences between patients and healthy controls were found in oscillatory activity during rest or stimulation, with Bayesian analysis suggesting equivocal evidence. However, post-traumatic stress symptoms and duration of chronic itch may be associated with changes in oscillatory activity. A lack of differences in cortical oscillatory processing and itch levels at non-injured sites, suggests that itch symptoms have a localised character in this sample of patients with post-burn itch. For future studies, a biopsychological approach with integration of peripheral and central nervous system techniques, linear and non-linear EEG analysis, injured and non-injured stimulation sites, and incorporation of individual characteristics is recommended. Insight into pathophysiological mechanisms underlying chronic post-burn itch could improve diagnostics and treatments. Show less
