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4. Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls:Findings from the international multicentre EU-GEI study

Author

Heuschen, C. B.B.C.M., Bolhuis, K., Zantvoord, J. B., Bockting, C. L., Denys, D. A.J.P., Lok, A., Arango, C., Arrojo, M., Bernardo, M., Bobes, J., Del-Ben, C. M., Di Forti, M., Gayer-Anderson, C., Jones, P. B., Jongsma, H. E., Kirkbride, J. B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P. M., Menezes, P. R., Murray, R. M., Quattrone, D., Rutten, B. P., Sanjuán, J., Selten, J. P., Szöke, A., Tarricone, I., Tortelli, A., Velthorst, E., de Haan, L., Schirmbeck, F., Heuschen, C. B.B.C.M., Bolhuis, K., Zantvoord, J. B., Bockting, C. L., Denys, D. A.J.P., Lok, A., Arango, C., Arrojo, M., Bernardo, M., Bobes, J., Del-Ben, C. M., Di Forti, M., Gayer-Anderson, C., Jones, P. B., Jongsma, H. E., Kirkbride, J. B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P. M., Menezes, P. R., Murray, R. M., Quattrone, D., Rutten, B. P., Sanjuán, J., Selten, J. P., Szöke, A., Tarricone, I., Tortelli, A., Velthorst, E., de Haan, L., and Schirmbeck, F.

Abstract

Introduction: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. Methods: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. Results: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. Conclusions: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. Limitations: Cross-sectional study design, self-reported questionnaires.

Published
2024

6. Знаходження фізичних параметрів електродинамічного перетворювача методом використання параметра BL та методом доданої маси

Author

Denys D. Volkov

Subjects
електродинамічний перетворювач, параметр BL, додана маса, Electronics, TK7800-8360
Abstract

У даній статті представлені результати практичного порівняння двох методів знаходження фізичних параметрів електродинамічного перетворювача. Перший – класичний метод за допомогою доданої маси. Другий – запропонований метод оснований на використанні параметра BL. Розглянуті переваги та недоліки кожного з двох методів, а також похибки знайдених параметрів та їхня обґрунтованість.

Published
2019
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7. Neural effects of deep brain stimulation on reward and loss anticipation and food viewing in anorexia nervosa: a pilot study

Author

Oudijn, M.S., Linders, J.T.W., Lok, A., Schuurman, P.R., van den Munckhof, P., van Elburg, A.A., van Wingen, G.A., Mocking, R.J.T., Denys, D., Oudijn, M.S., Linders, J.T.W., Lok, A., Schuurman, P.R., van den Munckhof, P., van Elburg, A.A., van Wingen, G.A., Mocking, R.J.T., and Denys, D.

Abstract

Background: Anorexia nervosa (AN) is a severe and life-threatening psychiatric disorder. Initial studies on deep brain stimulation (DBS) in severe, treatment-refractory AN have shown clinical effects. However, the working mechanisms of DBS in AN remain largely unknown. Here, we used a task-based functional MRI approach to understand the pathophysiology of AN. Methods: We performed functional MRI on four AN patients that participated in a pilot study on the efficacy, safety, and functional effects of DBS targeted at the ventral limb of the capsula interna (vALIC). The patients and six gender-matched healthy controls (HC) were investigated at three different time points. We used an adapted version of the monetary incentive delay task to probe generic reward processing in patients and controls, and a food-specific task in patients only. Results: At baseline, no significant differences for reward anticipation were found between AN and HC. Significant group (AN and HC) by time (pre- and post-DBS) interactions were found in the right precuneus, right putamen, right ventral and medial orbitofrontal cortex (mOFC). No significant interactions were found in the food viewing task, neither between the conditions high-calorie and low-calorie food images nor between the different time points. This could possibly be due to the small sample size and the lack of a control group. Conclusion: The results showed a difference in the response of reward-related brain areas post-DBS. This supports the hypotheses that the reward circuitry is involved in the pathogenesis of AN and that DBS affects responsivity of reward-related brain areas. Trial registration Registered in the Netherlands Trial Register (https://www.trialregister.nl/trial/3322 ): NL3322 (NTR3469).

Published
2023

9. Neural effects of deep brain stimulation on reward and loss anticipation and food viewing in anorexia nervosa: a pilot study

Author

Leerstoel Engelhard, Experimental psychopathology, Oudijn, M.S., Linders, J.T.W., Lok, A., Schuurman, P.R., van den Munckhof, P., van Elburg, A.A., van Wingen, G.A., Mocking, R.J.T., Denys, D., Leerstoel Engelhard, Experimental psychopathology, Oudijn, M.S., Linders, J.T.W., Lok, A., Schuurman, P.R., van den Munckhof, P., van Elburg, A.A., van Wingen, G.A., Mocking, R.J.T., and Denys, D.

Published
2023

13. Psychopathological and Neurobiological Overlap Between Anorexia Nervosa and Self-Injurious Behavior

Author

Oudijn, M.S., Linders, J., Mocking, R., Lok, A., van Elburg, A.A., Denys, D., Leerstoel Engelhard, Experimental psychopathology, Leerstoel Engelhard, Experimental psychopathology, Graduate School, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Psychiatry and Mental health, self-destruction, neurobiology, eating disorders, non-suicidal self-injurious behavior, psychopathology, anorexia nervosa
Abstract

Empirical evidence and clinical observations suggest a strong -yet under acknowledged-link between anorexia nervosa (AN) and non-suicidal self-injurious behavior (NSSI). By reviewing the literature on the psychopathology and neurobiology of AN and NSSI, we shed light on their relationship. Both AN and NSSI are characterized by disturbances in affect regulation, dysregulation of the reward circuitry and the opioid system. By formulating a reward-centered hypothesis, we explain the overlap between AN and NSSI. We propose three approaches understanding the relationship between AN and NSSI, which integrate psychopathology and neurobiology from the perspective of self-destructiveness: (1) a nosographical approach, (2) a research domain (RDoC) approach and (3) a network analysis approach. These approaches will enhance our knowledge of the underlying neurobiological substrates and may provide groundwork for the development of new treatment options for disorders of self-destructiveness, like AN and NSSI. In conclusion, we hypothesize that self-destructiveness is a new, DSM-5-transcending concept or psychopathological entity that is reward-driven, and that both AN and NSSI could be conceptualized as disorders of self-destructiveness.

Published
2022

14. The role of gender in a large international OCD sample: A Report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) Network

Author

Benatti, B., Girone, N., Celebre, L., Vismara, M., Hollander, E., Fineberg, N.A., Stein, D.J., Nicolini, H., Lanzagorta, N., Marazziti, D., Pallanti, S., van Ameringen, M., Lochner, C., Karamustafalioglu, O., Hranov, L., Figee, M., Drummond, L.M., Grant, J.E., Denys, D., Fontenelle, L.F., Menchon, J.M., Zohar, J., Rodriguez, C.I., Dell'Osso, B., Adult Psychiatry, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention

Subjects
Adult, Male, Obsessive-Compulsive Disorder, Adolescent, OCD, Compulsive Personality Disorder, Neurosi obsessiva, Behavior disorders, Age at onset, Comorbidity, Education, Estudis de gènere, Obsessive-compulsive disorder, Educational Status, Humans, Gender differences, Female, Gender studies, Retrospective Studies, Settore MED/25 - Psichiatria, Trastorns de la conducta
Abstract

Introduction: Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD.& nbsp;Methods: Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed throughstructured clinical interviews, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS).& nbsp;Results: Among females, adult onset (> 18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 +/- 10.76 vs. 17.71 +/- 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 +/- 4.02 vs. 13.98 +/- 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender dif-ferences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity.& nbsp;Discussion/Conclusions.: Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD.

Published
2022

15. Psychopathological and Neurobiological Overlap Between Anorexia Nervosa and Self-Injurious Behavior: A Narrative Review and Conceptual Hypotheses

Author

Oudijn, M.S., Linders, J., Mocking, R., Lok, A., van Elburg, A.A., Denys, D., Oudijn, M.S., Linders, J., Mocking, R., Lok, A., van Elburg, A.A., and Denys, D.

Abstract

Empirical evidence and clinical observations suggest a strong -yet under acknowledged-link between anorexia nervosa (AN) and non-suicidal self-injurious behavior (NSSI). By reviewing the literature on the psychopathology and neurobiology of AN and NSSI, we shed light on their relationship. Both AN and NSSI are characterized by disturbances in affect regulation, dysregulation of the reward circuitry and the opioid system. By formulating a reward-centered hypothesis, we explain the overlap between AN and NSSI. We propose three approaches understanding the relationship between AN and NSSI, which integrate psychopathology and neurobiology from the perspective of self-destructiveness: (1) a nosographical approach, (2) a research domain (RDoC) approach and (3) a network analysis approach. These approaches will enhance our knowledge of the underlying neurobiological substrates and may provide groundwork for the development of new treatment options for disorders of self-destructiveness, like AN and NSSI. In conclusion, we hypothesize that self-destructiveness is a new, DSM-5-transcending concept or psychopathological entity that is reward-driven, and that both AN and NSSI could be conceptualized as disorders of self-destructiveness.

Published
2022

19. Deep brain stimulation of the ventral anterior limb of the capsula interna in patients with treatment-refractory anorexia nervosa

Author

Oudijn, M. S., Mocking, R. J.T., Wijnker, R. R., Lok, A., Schuurman, P. R., van den Munckhof, P., van Elburg, A. A., Denys, D. A.P.J., Leerstoel Engelhard, and Experimental psychopathology

Subjects
Clinical trial, Neuroscience(all), Treatment-refractory, Deep brain stimulation, Neurosurgery, Biophysics, Clinical Neurology, Anorexia nervosa, Body mass index
Published
2021

22. Genome-wide association study of obsessive-compulsive disorder

Author

Stewart, S E, Yu, D, Scharf, J M, Neale, B M, Fagerness, J A, Mathews, C A, Arnold, P D, Evans, P D, Gamazon, E R, Osiecki, L, McGrath, L, Haddad, S, Crane, J, Hezel, D, Illman, C, Mayerfeld, C, Konkashbaev, A, Liu, C, Pluzhnikov, A, Tikhomirov, A, Edlund, C K, Rauch, S L, Moessner, R, Falkai, P, Maier, W, Ruhrmann, S, Grabe, H-J, Lennertz, L, Wagner, M, Bellodi, L, Cavallini, M C, Richter, M A, Cook, Jr, E H, Kennedy, J L, Rosenberg, D, Stein, D J, Hemmings, S M J, Lochner, C, Azzam, A, Chavira, D A, Fournier, E, Garrido, H, Sheppard, B, Umaña, P, Murphy, D L, Wendland, J R, Veenstra-VanderWeele, J, Denys, D, Blom, R, Deforce, D, Van Nieuwerburgh, F, Westenberg, H G M, Walitza, S, Egberts, K, Renner, T, Miguel, E C, Cappi, C, Hounie, A G, Conceição do Rosário, M, Sampaio, A S, Vallada, H, Nicolini, H, Lanzagorta, N, Camarena, B, Delorme, R, Leboyer, M, Pato, C N, Pato, M T, Voyiaziakis, E, Heutink, P, Cath, D C, Posthuma, D, Smit, J H, Samuels, J, Bienvenu, O J, Cullen, B, Fyer, A J, Grados, M A, Greenberg, B D, McCracken, J T, Riddle, M A, Wang, Y, Coric, V, Leckman, J F, Bloch, M, Pittenger, C, Eapen, V, Black, D W, Ophoff, R A, Strengman, E, Cusi, D, Turiel, M, Frau, F, Macciardi, F, Gibbs, J R, Cookson, M R, Singleton, A, Hardy, J, Crenshaw, A T, Parkin, M A, Mirel, D B, Conti, D V, Purcell, S, Nestadt, G, Hanna, G L, Jenike, M A, Knowles, J A, Cox, N, and Pauls, D L

Published
2013
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23. Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder

Author

Burton, CL, Lemire, M, Xiao, B, Corfield, EC, Erdman, L, Bralten, J, Poelmans, G, Yu, D, Shaheen, SM, Goodale, T, Sinopoli, VM, Askland, KD, Barlassina, C, Bienvenu, OJ, Black, D, Bloch, M, Brentani, H, Camarena, B, Cappi, C, Cath, D, Cavallini, MC, Ciullo, V, Conti, D, Cook, EH, Coric, V, Cullen, BA, Cusi, D, Davis, LK, Delorme, R, Denys, D, Derks, E, Eapen, V, Edlund, C, Falkai, P, Fyer, AJ, Geller, DA, Goes, FS, Grabe, HJ, Grados, MA, Greenberg, BD, Grünblatt, E, Guo, W, Hounie, AG, Jenike, M, Keenan, CL, Kennedy, JL, Khramtsova, EA, Knowles, JA, Krasnow, J, Lange, C, Lanzagorta, N, Leboyer, M, Liang, KY, Lochner, C, Macciardi, F, Maher, B, Mathews, CA, Mattheisen, M, McCracken, JT, McGregor, N, McLaughlin, NCR, Miguel, EC, Neale, B, Nestadt, G, Nestadt, PS, Nicolini, H, Nurmi, EL, Osiecki, L, Piacentini, J, Pittenger, C, Posthuma, D, Pulver, AE, Rasmussen, SA, Rauch, S, Richter, MA, Riddle, MA, Ripke, S, Ruhrmann, S, Sampaio, AS, Samuels, JF, Scharf, JM, Shugart, YY, Smit, JH, Stein, DJ, Stewart, SE, Turiel, M, Vallada, H, Veenstra-VanderWeele, J, Vulink, N, Wagner, M, Walitza, S, Wang, Y, Wendland, J, Zai, G, Soreni, N, Hanna, GL, Fitzgerald, KD, Rosenberg, D, Paterson, AD, Burton, CL, Lemire, M, Xiao, B, Corfield, EC, Erdman, L, Bralten, J, Poelmans, G, Yu, D, Shaheen, SM, Goodale, T, Sinopoli, VM, Askland, KD, Barlassina, C, Bienvenu, OJ, Black, D, Bloch, M, Brentani, H, Camarena, B, Cappi, C, Cath, D, Cavallini, MC, Ciullo, V, Conti, D, Cook, EH, Coric, V, Cullen, BA, Cusi, D, Davis, LK, Delorme, R, Denys, D, Derks, E, Eapen, V, Edlund, C, Falkai, P, Fyer, AJ, Geller, DA, Goes, FS, Grabe, HJ, Grados, MA, Greenberg, BD, Grünblatt, E, Guo, W, Hounie, AG, Jenike, M, Keenan, CL, Kennedy, JL, Khramtsova, EA, Knowles, JA, Krasnow, J, Lange, C, Lanzagorta, N, Leboyer, M, Liang, KY, Lochner, C, Macciardi, F, Maher, B, Mathews, CA, Mattheisen, M, McCracken, JT, McGregor, N, McLaughlin, NCR, Miguel, EC, Neale, B, Nestadt, G, Nestadt, PS, Nicolini, H, Nurmi, EL, Osiecki, L, Piacentini, J, Pittenger, C, Posthuma, D, Pulver, AE, Rasmussen, SA, Rauch, S, Richter, MA, Riddle, MA, Ripke, S, Ruhrmann, S, Sampaio, AS, Samuels, JF, Scharf, JM, Shugart, YY, Smit, JH, Stein, DJ, Stewart, SE, Turiel, M, Vallada, H, Veenstra-VanderWeele, J, Vulink, N, Wagner, M, Walitza, S, Wang, Y, Wendland, J, Zai, G, Soreni, N, Hanna, GL, Fitzgerald, KD, Rosenberg, D, and Paterson, AD

Abstract

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10−8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p’s < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.

Published
2021

24. Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders

Author

Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abé, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargalló, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, Del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bülow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodríguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjó-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Silk, Timothy, Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abé, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargalló, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, Del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bülow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodríguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjó-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, and Silk, Timothy

Published
2021

25. Deep brain stimulation of the ventral anterior limb of the capsula interna in patients with treatment-refractory anorexia nervosa

Author

Leerstoel Engelhard, Experimental psychopathology, Oudijn, M. S., Mocking, R. J.T., Wijnker, R. R., Lok, A., Schuurman, P. R., van den Munckhof, P., van Elburg, A. A., Denys, D. A.P.J., Leerstoel Engelhard, Experimental psychopathology, Oudijn, M. S., Mocking, R. J.T., Wijnker, R. R., Lok, A., Schuurman, P. R., van den Munckhof, P., van Elburg, A. A., and Denys, D. A.P.J.

Published
2021

26. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S.I., Pozzi, E., Abe, Y., Abé, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S.H., Anagnostou, E., McIntosh, A.A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C.E., Baranov, A., Bargalló, N., Bau, C.H.D., Baumeister, S., Baune, B.T., Bellgrove, M.A., Benedetti, F., Bertolino, A., Boedhoe, P.S.W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B.P., Bruggemann, J.M., Bülow, R., Busatto, G.F., Calderoni, S., Calhoun, V.D., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carr, V.J., Cascella, N., Cercignani, M., Chaim-Avancini, T.M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A.I., Cullen, K.R., Cupertino, R.B., Daly, E., Dannlowski, U., Davey, C.G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E.W., Dima, D., Dohm, K., Ehrlich, S., Ely, B.A., Erwin-Grabner, T., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V., Fatjó-Vilas, M., Fedor, J.M., Fitzgerald, K.D., Ford, J.M., Frodl, T., Fu, C.H.Y., Fullerton, J.M., Gabel, M.C., Glahn, D.C., Roberts, G., Gogberashvili, T., Goikolea, J.M., Gotlib, I.H., Goya-Maldonado, R., Grabe, H.J., Green, M.J., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R.E., Gur, R.C., Haar, S., Haarman, B.C.M., Haavik, J., Hahn, T., Hajek, T., Harrison, B.J., Harrison, N.A., Hartman, C.A., Whalley, H.C., Heslenfeld, D.J., Hibar, D.P., Hilland, E., Hirano, Y., Ho, T.C., Hoekstra, P.J., Hoekstra, L., Hohmann, S., Hong, L.E., Höschl, C., Høvik, M.F., Howells, F.M., Nenadic, I., Jalbrzikowski, M., James, A.C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J.A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Krämer, B., Krug, A., Kuntsi, J., Kwon, J.S., Landén, M., Landrø, N.I., Lazaro, L., Lebedeva, I.S., Leehr, E.J., Lera-Miguel, S., Lesch, K.-P., Lochner, C., Louza, M.R., Luna, B., Lundervold, A.J., Macmaster, F.P., Maglanoc, L.A., Malpas, C.B., Portella, M.J., Marsh, R., Martyn, F.M., Mataix-Cols, D., Mathalon, D.H., McCarthy, H., McDonald, C., McPhilemy, G., Meinert, S., Menchón, J.M., Minuzzi, L., Mitchell, P.B., Moreno, C., Morgado, P., Muratori, F., Murphy, C.M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D.D., Nicolau, R., O'Gorman Tuura, R.L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R.A., Oranje, B., García De La Foz, V.O., Overs, B.J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Picó-Pérez, M., Picon, F.A., Piras, F., Plessen, K.J., Pomarol-Clotet, E., Preda, A., Puig, O., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P.G.P., Rubia, K.K., Hashimoto, R., Sacchet, M.D., Salvador, R., Santonja, J., Sarink, K., Sarró, S., Satterthwaite, T.D., Sawa, A., Schall, U., Schofield, P.R., Schrantee, A., Seitz, J., Serpa, M.H., Setién-Suero, E., Shaw, P., Shook, D., Silk, T.J., Sim, K., Simon, S., Simpson, H.B., Singh, A., Skoch, A., Skokauskas, N., Soares, J.C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S.M., Stern, E.R., Stewart, S.E., Takayanagi, Y., Temmingh, H.S., Tolin, D.F., Tomecek, D., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N.J.A., Van Der Werff, S.J.A., Van Haren, N.E.M., Van Wingen, G.A., Vance, A., Vázquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A.N., Völzke, H., Von Polier, G.G., Walton, E., Weickert, T.W., Weickert, C.S., Weideman, A.S., Wittfeld, K., Wolf, D.H., Wu, M.-J., Yang, T.T., Yang, K., Yoncheva, Y., Yun, J.-Y., Cheng, Y., Zanetti, M.V., Ziegler, G.C., Franke, B., Hoogman, M., Buitelaar, J.K., Van Rooij, D., Andreassen, O.A., Ching, C.R.K., Veltman, D.J., Schmaal, L., Stein, D.J., Van Den Heuvel, O.A., Turner, J.A., Van Erp, T.G.M., Pausova, Z., Thompson, P.M., Paus, T., Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S.I., Pozzi, E., Abe, Y., Abé, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S.H., Anagnostou, E., McIntosh, A.A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C.E., Baranov, A., Bargalló, N., Bau, C.H.D., Baumeister, S., Baune, B.T., Bellgrove, M.A., Benedetti, F., Bertolino, A., Boedhoe, P.S.W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B.P., Bruggemann, J.M., Bülow, R., Busatto, G.F., Calderoni, S., Calhoun, V.D., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carr, V.J., Cascella, N., Cercignani, M., Chaim-Avancini, T.M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A.I., Cullen, K.R., Cupertino, R.B., Daly, E., Dannlowski, U., Davey, C.G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E.W., Dima, D., Dohm, K., Ehrlich, S., Ely, B.A., Erwin-Grabner, T., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V., Fatjó-Vilas, M., Fedor, J.M., Fitzgerald, K.D., Ford, J.M., Frodl, T., Fu, C.H.Y., Fullerton, J.M., Gabel, M.C., Glahn, D.C., Roberts, G., Gogberashvili, T., Goikolea, J.M., Gotlib, I.H., Goya-Maldonado, R., Grabe, H.J., Green, M.J., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R.E., Gur, R.C., Haar, S., Haarman, B.C.M., Haavik, J., Hahn, T., Hajek, T., Harrison, B.J., Harrison, N.A., Hartman, C.A., Whalley, H.C., Heslenfeld, D.J., Hibar, D.P., Hilland, E., Hirano, Y., Ho, T.C., Hoekstra, P.J., Hoekstra, L., Hohmann, S., Hong, L.E., Höschl, C., Høvik, M.F., Howells, F.M., Nenadic, I., Jalbrzikowski, M., James, A.C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J.A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Krämer, B., Krug, A., Kuntsi, J., Kwon, J.S., Landén, M., Landrø, N.I., Lazaro, L., Lebedeva, I.S., Leehr, E.J., Lera-Miguel, S., Lesch, K.-P., Lochner, C., Louza, M.R., Luna, B., Lundervold, A.J., Macmaster, F.P., Maglanoc, L.A., Malpas, C.B., Portella, M.J., Marsh, R., Martyn, F.M., Mataix-Cols, D., Mathalon, D.H., McCarthy, H., McDonald, C., McPhilemy, G., Meinert, S., Menchón, J.M., Minuzzi, L., Mitchell, P.B., Moreno, C., Morgado, P., Muratori, F., Murphy, C.M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D.D., Nicolau, R., O'Gorman Tuura, R.L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R.A., Oranje, B., García De La Foz, V.O., Overs, B.J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Picó-Pérez, M., Picon, F.A., Piras, F., Plessen, K.J., Pomarol-Clotet, E., Preda, A., Puig, O., Quidé, Y., Radua, J., Ramos-Quiroga, J.A., Rasser, P.E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P.G.P., Rubia, K.K., Hashimoto, R., Sacchet, M.D., Salvador, R., Santonja, J., Sarink, K., Sarró, S., Satterthwaite, T.D., Sawa, A., Schall, U., Schofield, P.R., Schrantee, A., Seitz, J., Serpa, M.H., Setién-Suero, E., Shaw, P., Shook, D., Silk, T.J., Sim, K., Simon, S., Simpson, H.B., Singh, A., Skoch, A., Skokauskas, N., Soares, J.C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S.M., Stern, E.R., Stewart, S.E., Takayanagi, Y., Temmingh, H.S., Tolin, D.F., Tomecek, D., Tordesillas-Gutiérrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N.J.A., Van Der Werff, S.J.A., Van Haren, N.E.M., Van Wingen, G.A., Vance, A., Vázquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A.N., Völzke, H., Von Polier, G.G., Walton, E., Weickert, T.W., Weickert, C.S., Weideman, A.S., Wittfeld, K., Wolf, D.H., Wu, M.-J., Yang, T.T., Yang, K., Yoncheva, Y., Yun, J.-Y., Cheng, Y., Zanetti, M.V., Ziegler, G.C., Franke, B., Hoogman, M., Buitelaar, J.K., Van Rooij, D., Andreassen, O.A., Ching, C.R.K., Veltman, D.J., Schmaal, L., Stein, D.J., Van Den Heuvel, O.A., Turner, J.A., Van Erp, T.G.M., Pausova, Z., Thompson, P.M., and Paus, T.

Abstract

Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures Interregional profiles of group difference in cortical thickness between cases and controls. Results A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (exce

Published
2021
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29. Genes and environment both important in psychological suffering

Author

Abdellaoui, A., Treur, J. L., Michel Nivard, Smit, D. J. A., Veul, L., Vermeulen, J. M., Peyrot, W., Penninx, B. W. J. H., Boomsma, Dorret I., Den Brink, W., Denys, D., Verweij, K. J. H., Biological Psychology, APH - Mental Health, APH - Methodology, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Adult Psychiatry, and Amsterdam Reproduction & Development (AR&D)

Published
2020

30. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: Findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, P.S., Rooij, D. van, Hoogman, M., Twisk, J.W.R., Schmaal, L., Abe, Y., Alonso, P., Ameis, S.H., Anikin, A., Anticevic, A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Banaschewski, T., Baranov, A., Batistuzzo, M.C., Baumeister, S., Baur-Streubel, R., Behrmann, M., Bellgrove, M.A., Benedetti, F. De, Beucke, J.C., Biederman, J., Bollettini, I., Bose, A., Bralten, J., Bramati, I.E., Brandeis, D., Brem, S., Brennan, B.P., Busatto, G.F., Calderoni, S., Calvo, A., Calvo, R., Castellanos, F.X., Cercignani, M., Chaim-Avancini, T.M., Chantiluke, K.C., Cheng, Y., Cho, K.I.K., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A.I., Dale, A.M., Dallaspezia, S., Daly, E., Denys, D., Deruelle, C., Martino, A, Dinstein, I., Doyle, A.E., Durston, S., Earl, E.A., Ecker, C., Ehrlich, S., Ely, B.A., Epstein, J.N., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V, Fedor, J., Feng, X., Feusner, J.D., Fitzgerald, J., Fitzgerald, K.D., Fouche, J.P., Freitag, C.M., Fridgeirsson, E.A., Frodl, T., Gabel, M.C., Gallagher, L., Gogberashvili, T., Gori, I., Gruner, P., Gürsel, D.A., Haar, S., Haavik, J., Hall, G.B., Harrison, N.A., Hartman, Catharina A., Heslenfeld, D.J., Hirano, Y., Hoekstra, P.J., Hoexter, M.Q., Hohmann, S., Høvik, M.F., Hu, H., Huyser, C., Jahanshad, N., Jalbrzikowski, M., James, A., Janssen, J, Jaspers-Fayer, F., Jernigan, T.L., Kapilushniy, D., Kardatzki, B., Buitelaar, J.K., Franke, B., Heuvel, O.A. van den, Boedhoe, P.S., Rooij, D. van, Hoogman, M., Twisk, J.W.R., Schmaal, L., Abe, Y., Alonso, P., Ameis, S.H., Anikin, A., Anticevic, A., Arango, C., Arnold, P.D., Asherson, P., Assogna, F., Auzias, G., Banaschewski, T., Baranov, A., Batistuzzo, M.C., Baumeister, S., Baur-Streubel, R., Behrmann, M., Bellgrove, M.A., Benedetti, F. De, Beucke, J.C., Biederman, J., Bollettini, I., Bose, A., Bralten, J., Bramati, I.E., Brandeis, D., Brem, S., Brennan, B.P., Busatto, G.F., Calderoni, S., Calvo, A., Calvo, R., Castellanos, F.X., Cercignani, M., Chaim-Avancini, T.M., Chantiluke, K.C., Cheng, Y., Cho, K.I.K., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A.I., Dale, A.M., Dallaspezia, S., Daly, E., Denys, D., Deruelle, C., Martino, A, Dinstein, I., Doyle, A.E., Durston, S., Earl, E.A., Ecker, C., Ehrlich, S., Ely, B.A., Epstein, J.N., Ethofer, T., Fair, D.A., Fallgatter, A.J., Faraone, S.V, Fedor, J., Feng, X., Feusner, J.D., Fitzgerald, J., Fitzgerald, K.D., Fouche, J.P., Freitag, C.M., Fridgeirsson, E.A., Frodl, T., Gabel, M.C., Gallagher, L., Gogberashvili, T., Gori, I., Gruner, P., Gürsel, D.A., Haar, S., Haavik, J., Hall, G.B., Harrison, N.A., Hartman, Catharina A., Heslenfeld, D.J., Hirano, Y., Hoekstra, P.J., Hoexter, M.Q., Hohmann, S., Høvik, M.F., Hu, H., Huyser, C., Jahanshad, N., Jalbrzikowski, M., James, A., Janssen, J, Jaspers-Fayer, F., Jernigan, T.L., Kapilushniy, D., Kardatzki, B., Buitelaar, J.K., Franke, B., and Heuvel, O.A. van den

Abstract

Contains fulltext : 225388.pdf (Publisher’s version ) (Closed access), OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: Structural T(1)-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

32. Genen en omgeving beide belangrijk bij psychisch lijden

Author

Abdellaoui, A., Treur, J. L., Nivard, M. G., Smit, D. J.A., Veul, L., Vermeulen, J. M., Peyrot, W., Penninx, B. W.J.H., Boomsma, D. I., van Den Brink, W., Denys, D., Verweij, K. J.H., Abdellaoui, A., Treur, J. L., Nivard, M. G., Smit, D. J.A., Veul, L., Vermeulen, J. M., Peyrot, W., Penninx, B. W.J.H., Boomsma, D. I., van Den Brink, W., Denys, D., and Verweij, K. J.H.

Published
2020

33. Evidence for distinct forms of compulsivity in the SAPAP3 mutant-mouse model for obsessive-compulsive disorder

Author

Ehmer, I, Crown, L, van Leeuwen, W, Feenstra, M, Willuhn, I, Denys, D, Ehmer, I, Crown, L, van Leeuwen, W, Feenstra, M, Willuhn, I, and Denys, D

Abstract

The specific mechanisms underlying compulsive behavior in obsessive-compulsive disorder (OCD) are unknown. It has been suggested that such compulsivity may have its origin in cognitive dysfunction such as impaired processing of feedback information - received after the completion of goal-directed actions. The signal attenuation (SA) task models such a processing deficit in animals by attenuating the association strength between food reward and audiovisual feedback (signal) presented after performance of an operant response. The compulsive-like responding resulting from SA is well characterized in rats, but was so far not established in mice, a species for which powerful genetic OCD models exist. Thus, first, we demonstrate that the SA task can be implemented in mice and show that attenuation of reward-associated response feedback produces similar behavior in C57BL6 mice as previously reported in rats. Second, we tested the hypothesis that SAPAP3 knockout mice (SAPAP3-/-), prone to exhibit several OCD-like abnormalities including excessive grooming, show enhanced compulsive-like behavior in the SA task compared to their wild-type littermates (WT). However, task-related compulsivity measures in SAPAP3-/- and WT did not yield significant differences, neither following SA nor during "regular" extinction of operant behavior. Thus, compulsive-like instrumental behavior following feedback distortion was not potentiated in compulsively grooming mice, implicating specifically that a) a general deficit in feedback processing is not related to excessive grooming in SAPAP3-/-, and b) different manifestations of compulsivity may be driven by independent mechanisms.Significance Statement The signal attenuation (SA) task is a well-established behavioral paradigm for rats that promotes compulsivity. First, we demonstrate that the SA task can also be applied to test feedback processing in mice. Second, we investigated if SAPAP3 mutant mice, a highly validated genetic animal model

Published
2020

35. Instrumental learning in a mouse model for obsessive-compulsive disorder: Impaired habit formation in Sapap3 mutants

Author

Ehmer, I, Feenstra, M, Willuhn, I, Denys, D, Ehmer, I, Feenstra, M, Willuhn, I, and Denys, D

Abstract

It has been hypothesized that maladaptive habit formation contributes to compulsivity in psychiatric disorders such as obsessive-compulsive disorder (OCD). Here, we used an established animal model of OCD, Sapap3 knockout mice (SAPAP3-/-), to investigate the balance of goal-directed and habitual behavior in compulsive individuals and if altered habit formation is associated with compulsive-like behavior. We subjected 24 SAPAP3-/- and 24 wildtype littermates (WT) to two different schedules of reinforcement in a within-subjects design: a random-ratio (RR) schedule to promote goal-directedness, and a random-interval (RI) schedule, known to facilitate habitual responding. SAPAP3-/- acquired responding under both schedules, but showed lower response rates and fewer attempts to collect food pellets than WT, indicative of altered reward processing. As expected, WT were sensitive to sensory-specific satiety (outcome devaluation) following RR training, but not RI training, demonstrating schedule-specific acquisition of goal-directed and habitual responding, respectively. In contrast, SAPAP3-/- were sensitive to outcome devaluation after both RR and RI training, suggesting decreased engagement of a habitual response strategy. No linear relation was observed between increased grooming and behavior during the outcome devaluation test in SAPAP3-/-. Together, our findings demonstrate altered reward processing and impaired habit learning in SAPAP3-/-. We report a diminished propensity to form habits in these mice, which albeit inconsistent with the predominant idea of excessive habit formation in OCD, nonetheless points at dysregulation of behavioral automation in the context of compulsivity. Thus, the habit hypothesis of compulsivity should be updated to state that an imbalance of habitual and goal-directed responding in either direction can contribute to the development of compulsive behavior.

Published
2020

36. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, Francks, C, Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, and Francks, C

Abstract

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Published
2020

37. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, PSW, van Rooij, D, Hoogman, M, Twisk, JWR, Schmaal, L, Abe, Y, Alonso, P, Ameis, SH, Anikin, A, Anticevic, A, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Banaschewski, T, Baranov, A, Batistuzzo, MC, Baumeister, S, Baur-Streubel, R, Behrmann, M, Bellgrove, MA, Benedetti, F, Beucke, JC, Biederman, J, Bollettini, I, Bose, A, Bralten, J, Bramati, IE, Brandeis, D, Brem, S, Brennan, BP, Busatto, GF, Calderoni, S, Calvo, A, Calvo, R, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Cheng, Y, Cho, KIK, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, A, Dale, AM, Dallaspezia, S, Daly, E, Denys, D, Deruelle, C, Di Martino, A, Dinstein, I, Doyle, AE, Durston, S, Earl, EA, Ecker, C, Ehrlich, S, Ely, BA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, S, Fedor, J, Feng, X, Feusner, JD, Fitzgerald, J, Fitzgerald, KD, Fouche, J-P, Freitag, CM, Fridgeirsson, EA, Frodl, T, Gabel, MC, Gallagher, L, Gogberashvili, T, Gori, I, Gruner, P, Gursel, DA, Haar, S, Haavik, J, Hall, GB, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hirano, Y, Hoekstra, PJ, Hoexter, MQ, Hohmann, S, Hovik, MF, Hu, H, Huyser, C, Jahanshad, N, Jalbrzikowski, M, James, A, Janssen, J, Jaspers-Fayer, F, Jernigan, TL, Kapilushniy, D, Kardatzki, B, Karkashadze, G, Kathmann, N, Kaufmann, C, Kelly, C, Khadka, S, King, JA, Koch, K, Kohls, G, Konrad, K, Kuno, M, Kuntsi, J, Kvale, G, Kwon, JS, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Hoekstra, L, Liu, Y, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, Malpas, CB, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Mattos, P, McCarthy, H, McGrath, J, Mehta, MA, Menchon, JM, Mennes, M, Martinho, MM, Moreira, PS, Morer, A, Morgado, P, Muratori, F, Murphy, CM, Murphy, DGM, Nakagawa, A, Nakamae, T, Nakao, T, Namazova-Baranova, L, Narayanaswamy, JC, Nicolau, R, Nigg, JT, Novotny, SE, Nurmi, EL, Weiss, EO, Tuura, RLO, O'Hearn, K, O'Neill, J, Oosterlaan, J, Oranje, B, Paloyelis, Y, Parellada, M, Pauli, P, Perriello, C, Piacentini, J, Piras, F, Plessen, KJ, Puig, O, Ramos-Quiroga, JA, Reddy, YCJ, Reif, A, Reneman, L, Retico, A, Rosa, PGP, Rubia, K, Rus, OG, Sakai, Y, Schrantee, A, Schwarz, L, Schweren, LJS, Seitz, J, Shaw, P, Shook, D, Silk, TJ, Simpson, HB, Skokauskas, N, Vila, JCS, Solovieva, A, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Sudre, G, Szeszko, PR, Tamm, L, Taylor, MJ, Tolin, DF, Tosetti, M, Tovar-Moll, F, Tsuchiyagaito, A, van Erp, TGM, van Wingen, GA, Vance, A, Venkatasubramanian, G, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Wallace, GL, Wang, Z, Wolfers, T, Yoncheva, YN, Yun, J-Y, Zanetti, M, Zhou, F, Ziegler, GC, Zierhut, KC, Zwiers, MP, Thompson, PM, Stein, DJ, Buitelaar, J, Franke, B, van den Heuvel, OA, Boedhoe, PSW, van Rooij, D, Hoogman, M, Twisk, JWR, Schmaal, L, Abe, Y, Alonso, P, Ameis, SH, Anikin, A, Anticevic, A, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Banaschewski, T, Baranov, A, Batistuzzo, MC, Baumeister, S, Baur-Streubel, R, Behrmann, M, Bellgrove, MA, Benedetti, F, Beucke, JC, Biederman, J, Bollettini, I, Bose, A, Bralten, J, Bramati, IE, Brandeis, D, Brem, S, Brennan, BP, Busatto, GF, Calderoni, S, Calvo, A, Calvo, R, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Cheng, Y, Cho, KIK, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, A, Dale, AM, Dallaspezia, S, Daly, E, Denys, D, Deruelle, C, Di Martino, A, Dinstein, I, Doyle, AE, Durston, S, Earl, EA, Ecker, C, Ehrlich, S, Ely, BA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, S, Fedor, J, Feng, X, Feusner, JD, Fitzgerald, J, Fitzgerald, KD, Fouche, J-P, Freitag, CM, Fridgeirsson, EA, Frodl, T, Gabel, MC, Gallagher, L, Gogberashvili, T, Gori, I, Gruner, P, Gursel, DA, Haar, S, Haavik, J, Hall, GB, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hirano, Y, Hoekstra, PJ, Hoexter, MQ, Hohmann, S, Hovik, MF, Hu, H, Huyser, C, Jahanshad, N, Jalbrzikowski, M, James, A, Janssen, J, Jaspers-Fayer, F, Jernigan, TL, Kapilushniy, D, Kardatzki, B, Karkashadze, G, Kathmann, N, Kaufmann, C, Kelly, C, Khadka, S, King, JA, Koch, K, Kohls, G, Konrad, K, Kuno, M, Kuntsi, J, Kvale, G, Kwon, JS, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Hoekstra, L, Liu, Y, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, Malpas, CB, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Mattos, P, McCarthy, H, McGrath, J, Mehta, MA, Menchon, JM, Mennes, M, Martinho, MM, Moreira, PS, Morer, A, Morgado, P, Muratori, F, Murphy, CM, Murphy, DGM, Nakagawa, A, Nakamae, T, Nakao, T, Namazova-Baranova, L, Narayanaswamy, JC, Nicolau, R, Nigg, JT, Novotny, SE, Nurmi, EL, Weiss, EO, Tuura, RLO, O'Hearn, K, O'Neill, J, Oosterlaan, J, Oranje, B, Paloyelis, Y, Parellada, M, Pauli, P, Perriello, C, Piacentini, J, Piras, F, Plessen, KJ, Puig, O, Ramos-Quiroga, JA, Reddy, YCJ, Reif, A, Reneman, L, Retico, A, Rosa, PGP, Rubia, K, Rus, OG, Sakai, Y, Schrantee, A, Schwarz, L, Schweren, LJS, Seitz, J, Shaw, P, Shook, D, Silk, TJ, Simpson, HB, Skokauskas, N, Vila, JCS, Solovieva, A, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Sudre, G, Szeszko, PR, Tamm, L, Taylor, MJ, Tolin, DF, Tosetti, M, Tovar-Moll, F, Tsuchiyagaito, A, van Erp, TGM, van Wingen, GA, Vance, A, Venkatasubramanian, G, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Wallace, GL, Wang, Z, Wolfers, T, Yoncheva, YN, Yun, J-Y, Zanetti, M, Zhou, F, Ziegler, GC, Zierhut, KC, Zwiers, MP, Thompson, PM, Stein, DJ, Buitelaar, J, Franke, B, and van den Heuvel, OA

Abstract

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. Methods: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

38. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

Author

Bruin, WB, Taylor, L, Thomas, RM, Shock, JP, Zhutovsky, P, Abe, Y, Alonso, P, Ameis, SH, Anticevic, A, Arnold, PD, Assogna, F, Benedetti, F, Beucke, JC, Boedhoe, PSW, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, JK, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, JD, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Gruner, P, Guersel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, Ivanov, I, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Liu, Y, Lochner, C, Lazaro, L, Marques, P, Marsh, R, Martinez-Zalacain, Mataix-Cols, D, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Shimizu, E, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Venkatasubramanian, G, Wang, Z, Yun, J-Y, van Rooij, D, Thompson, PM, van den Heuvel, OA, Stein, DJ, van Wingen, GA, Bruin, WB, Taylor, L, Thomas, RM, Shock, JP, Zhutovsky, P, Abe, Y, Alonso, P, Ameis, SH, Anticevic, A, Arnold, PD, Assogna, F, Benedetti, F, Beucke, JC, Boedhoe, PSW, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, JK, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, JD, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Gruner, P, Guersel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, Ivanov, I, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Liu, Y, Lochner, C, Lazaro, L, Marques, P, Marsh, R, Martinez-Zalacain, Mataix-Cols, D, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Shimizu, E, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Venkatasubramanian, G, Wang, Z, Yun, J-Y, van Rooij, D, Thompson, PM, van den Heuvel, OA, Stein, DJ, and van Wingen, GA

Abstract

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.

Published
2020

39. Finding the physical parameters of the electrodynamic converter by the method of using the parameter BL and the method of mass added

Author

Denys D. Volkov

Subjects
Електроніка, Акустика, TK7800-8360, 534.134, параметр BL, електродинамічний перетворювач, додана маса, Electronics, electrodynamic converter, parameter BL, added mass, Electronics, Acoustics
Abstract

The task of finding the physical parameters of electrodynamic transducers is an integral part of the process of development and production of speakers [1,2]. The most popular method for this is the added mass method proposed by Neville Theel and Richard Small. This method is simple and reliable to use, does not require expensive technology and considerable computing power. But its biggest disadvantage is the direct addition of mass to the moving part of the converter, which can damage it and very often is practically impossible.The paper proposes a method of using the parameter BL (the product of the induction in the gap of the magnetic circuit and the inductance of the sound coil) is based on measuring the displacement of the moving part of the converter, as well as the current through the coil of the converter and the voltage at its terminals. These three characteristics make it possible to fully determine the parameters of the electrodynamic converter in the electrical and mechanical parts separately, ie to measure the total electrical impedance and the total mechanical impedance. Once the impedances have been determined, they can be handled individually, and different equivalent circuits can be applied to further determine directly the parameters of the converter model.To demonstrate the benefits of finding the physical parameters of the converter, using the BL parameter, an example of a typical three-inch wide-band electrodynamic converter was calculated. For detailed modeling of the electrical oscillation system, the model of John Vanderkoy was chosen, in which the complex resistance of the coil is the sum of the static resistance of the RDC, the frequency-dependent active resistance of the coil RVC (f) and the frequency-dependent inductance LVC (f). This allows the model to account for complex physical effects, such as eddy currents that occur in the metal parts of the magnetic system.A series of ten measurements were performed by each method and the mean for each physical parameter and the corresponding standard deviation were calculated.Simulation of the full electrical input impedance Ztot (f) using the BL parameter method shows that the results are closer to real measurements than the added mass method, especially at frequencies above resonance. Comparison using the BL optimization method and the Vanderkoy model for the magnetic system shows less error at high frequencies for both the full input impedance module and the phase. However, the parameters found by the classical method of added mass are close to those found by the method of the parameter BL, which proves its feasibility for rapid measurements in production.From a statistical point of view, the stability of the BL parameter utilization method, the high repeatability of the results, and the smaller statistical error compared to the added mass method were demonstrated. In addition, a significant advantage of the BL parameter method is the ability to use it for miniature converters or converters with very fragile membranes (RF converters). That is, in all cases where physical interference with the movable part (adding mass or volume) is practically impossible., У даній статті представлені результати практичного порівняння двох методів знаходження фізичних параметрів електродинамічного перетворювача. Перший – класичний метод за допомогою доданої маси. Другий – запропонований метод оснований на використанні параметра BL. Розглянуті переваги та недоліки кожного з двох методів, а також похибки знайдених параметрів та їхня обґрунтованість.

Published
2019

40. Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis

Author

nternational Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC), OCD Collaborative Genetics Association Studies (OCGAS): Arnold PD, Askland KD, Barlassina C, Bellodi L, Bienvenu OJ, Black D, Bloch M, Brentani H, Burton CL, Camarena B, Cappi C, Cath D, Cavallini M, Conti D, Cook E, Coric V, Cullen BA, Cusi D, Davis LK, Delorme R, Denys D, Derks E, Eapen V, Edlund C, Erdman L, Falkai P, Figee M, Fyer AJ, Geller DA, Goes FS, Grabe H, Grados MA, Greenberg BD, Grünblatt E, Guo W, Hanna GL, Hemmings S, Hounie AG, Jenicke M, Keenan C, Kennedy J, Khramtsova EA, Konkashbaev A, Knowles JA, Krasnow J, Lange C, Lanzagorta N, Leboyer M, Lennertz L, Li B, Liang KY, Lochner C, Macciardi F, Maher B, Maier W, Marconi M, Mathews CA, Matthesien M, McCracken JT, McLaughlin NC, Miguel EC, Moessner R, Murphy DL, Neale B, Nestadt G, Nestadt P, Nicolini H, Nurmi E, Osiecki L, Pauls DL, Piacentini J, Posthuma D, Pulver AE, Qin HD, Rasmussen SA, Rauch S, Richter MA, Riddle MA, Ripke S, Ruhrmann S, Sampaio AS, Samuels JF, Scharf JM, Shugart YY, Smit J, Stein D, Stewart SE, Turiel M, Vallada H, Veenstra-VanderWeele J, Wagner M, Walitza S, Wang Y, Wendland J, Vulink N, Yu D, Zai G., Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Reproduction & Development (AR&D), Human genetics, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, APH - Mental Health, Arnold, Paul D, Askland, Kathleen D, Barlassina, Cristina, Bellodi, Laura, Bienvenu, O. J, Black, Donald, Bloch, Michael, Brentani, Helena, Burton, Christie L, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Conti, David, Cook, Edwin, Coric, Vladimir, Cullen, Bernadette A, Cusi, Danielle, Davis, Lea K, Delorme, Richard, Denys, Damiaan, Derks, Eske, Eapen, Valsamma, Edlund, Christopher, Erdman, Lauren, Falkai, Peter, Figee, Martijn, Fyer, Abigail J, Geller, Daniel A, Goes, Fernando S, Grabe, Han, Grados, Marcos A, Greenberg, Benjamin D, Grünblatt, Edna, Guo, Wei, Hanna, Gregory L, Hemmings, Sian, Hounie, Ana G, Jenicke, Michael, Keenan, Clare, Kennedy, Jame, Khramtsova, Ekaterina A, Konkashbaev, Anuar, Knowles, James A, Krasnow, Janice, Lange, Cristophe, Lanzagorta, Nuria, Leboyer, Marion, Lennertz, Leonhard, Li, Bingbin, Liang, K. y, Lochner, Christine, Macciardi, Fabio, Maher, Brion, Maier, Wolfgang, Marconi, Maurizio, Mathews, Carol A, Matthesien, Manuel, Mccracken, James T, Mclaughlin, Nicole C, Miguel, Euripedes C, Moessner, Rainald, Murphy, Dennis L, Neale, Benjamin, Nestadt, Gerald, Nestadt, Paul, Nicolini, Humberto, Nurmi, Ericka, Osiecki, Lisa, Pauls, David L, Piacentini, John, Posthuma, Danielle, Pulver, Ann E, Qin, H. d, Rasmussen, Steven A, Rauch, Scott, Richter, Margaret A, Riddle, Mark A, Ripke, Stephan, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack F, Scharf, Jeremiah M, Shugart, Yin Yao, Smit, Jan, Stein, Daniel, Stewart, S. Evelyn, Turiel, Maurizio, Vallada, Homero, Veenstra vanderweele, Jeremy, Wagner, Michael, Walitza, Susanne, Wang, Y, Wendland, Jen, Vulink, Nienke, Yu, Dongmei, Zai, Gwyneth, and Netherlands Institute for Neuroscience (NIN)

Subjects
0301 basic medicine, Genetics, TRANSTORNO OBSESSIVO-COMPULSIVO, Single-nucleotide polymorphism, Odds ratio, Biology, Heritability, Confidence interval, Genetic architecture, Minor allele frequency, 03 medical and health sciences, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, Journal Article, SNP, SDG 2 - Zero Hunger, Molecular Biology, 030217 neurology & neurosurgery, Genetic association
Abstract

Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10(-7); odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10(-6); OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10(-6); OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.154.

Published
2018
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45. Integer Norm for Difference Assessment of the Frame Elements Considering the White Balance

Author

Lesya A. Lyushenko, Mykhailo V. Ivashchenko, and Denys D. Okhrymchuk

Subjects
Discrete mathematics, Computer science, Norm (mathematics), Color balance, Intelligent Information Technologies and Systems
Abstract

The proposed concept suggests a method, based on which a synthesis of an integer norm can be performed, which takes into account the white balance of the camera when performing the evaluation of the difference between the elements of an image. This idea is based on modifying the internal calculations of the camera, aimed at assessing the colour of the image element, using the process of colour model reduction that is embedded inside the camera, to the colour model of the classical representation. The use of this approach provides a number of advantages within the framework of systems in which there is a solution of computer vision problems in terms of using both graphical processing and artificial intelligence. Мета. Метою даної статті є дослідження запропонованого підходу, на основі якого можливо виконати синтез цілочислової норми, що враховує баланс білого камери при розрахуванні оцінки різниці між елементами зображення. Методи. Камера автоматично налаштовує баланс білого відповідно до одного з режимів, встановлених за замовчуванням. Оцінка різниці між двома точками зображення здійснюється за рахунок виконання нормалізації. Як метод розрахунку використовується евклідова норма. Результати. Запропоновано підхід до нормалізації, що враховує коефіцієнти корекції балансу білого. Розрахунки виконуються з точки зору здійснення операцій з цілими значеннями, що надає можливість їх використання для безпосереднього розгортання всередині апаратної логіки пристроїв. Цей факт дозволяє знизити як загальну вартість ресурсів для виконуваних операцій, по відношенню до існуючої арифметики з плаваючою крапкою, так і зниження вимог до конфігурації датчиків. Цель. Целью данной статьи является исследование подхода к синтезу целочисленной нормы, которая учитывает баланс белого камеры при расчете оценки разницы между элементами изображения. Методы. Камера автоматически настраивает баланс белого в соответствии с одним из режимов, установленных по умолчанию. Оценка разницы между двумя точками изображения осуществляется путем выполнения нормализации. В качестве метода расчета используется евклидова норма. Результаты. Предложен подход нормализации, учитывающий коэффициенты коррекции баланса белого. Расчеты выполняются исходя из операций с целыми значениями, что дает возможность использования их для непосредственного развертывания внутри аппаратной логики устройств. Это позволяет снизить как общую стоимость ресурсов для выполняемых операций, по отношению к существующей арифметике с плавающей точкой, так и упростить требования к конфигурации датчиков.

Published
2019

46. Elektroconvulsietherapie bij persisterende depressie in Nederland; zeer lage toepassingsgraad

Author

Scheepens, D S, van Waarde, J A, Lok, A, Zantvoord, J B, de Pont, B J H B, Ruhé, H G, Denys, D A J P, van Wingen, G A, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Adult Psychiatry, Nederlands Herseninstituut (NIN), and Spinoza Centre for Neuroimaging

Subjects
DBC information system, Electroconvulsive therapy, mental disorders, Persistent depressive episode, behavioral disciplines and activities
Abstract

BACKGROUND: Of all depressive disorders, 20% has a persistent course. For persistent depressive patients, electroconvulsive therapy (ect) is recommended for this patient population, since it is the most potent treatment for depression. The Dutch depression guideline advises the use of ect for persistent depressive disorder at approximately 12 months after inadequate efficacy of psychotherapy and/or pharmacological treatment. AIM: To quantify the use of electroconvulsive therapy in persistent depressive patients in the Netherlands. METHOD: Quantitative research using the Dutch registration system (diagnosis-treatment-combination; dbc) information system (dis) of the Dutch Healthcare Authority (nza). RESULTS: Of the patients within the dbc system (in 2014) with the main diagnosis of unipolar depression, 23,597 (26%) were registered for more than two years and could be classified as having a persistent depressive episode. Of these latter patients, only 278 (1.2%) received ect. CONCLUSION: In the Netherlands, only 1.2% of patients with a persistent depression received ect, whereas this treatment could have been considered for 26% of this group. The low application rate might be caused by professionals' inadequate knowledge about ect and the premature use of the handicap model.

Published
2019

48. Знаходження фізичних параметрів електродинамічного перетворювача методом використання параметра BL та методом доданої маси

Author

Volkov, Denys D.; Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського" and Volkov, Denys D.; Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського"

Abstract

У даній статті представлені результати практичного порівняння двох методів знаходження фізичних параметрів електродинамічного перетворювача. Перший – класичний метод за допомогою доданої маси. Другий – запропонований метод оснований на використанні параметра BL. Розглянуті переваги та недоліки кожного з двох методів, а також похибки знайдених параметрів та їхня обґрунтованість., The task of finding the physical parameters of electrodynamic transducers is an integral part of the process of development and production of speakers [1,2]. The most popular method for this is the added mass method proposed by Neville Theel and Richard Small. This method is simple and reliable to use, does not require expensive technology and considerable computing power. But its biggest disadvantage is the direct addition of mass to the moving part of the converter, which can damage it and very often is practically impossible.The paper proposes a method of using the parameter BL (the product of the induction in the gap of the magnetic circuit and the inductance of the sound coil) is based on measuring the displacement of the moving part of the converter, as well as the current through the coil of the converter and the voltage at its terminals. These three characteristics make it possible to fully determine the parameters of the electrodynamic converter in the electrical and mechanical parts separately, ie to measure the total electrical impedance and the total mechanical impedance. Once the impedances have been determined, they can be handled individually, and different equivalent circuits can be applied to further determine directly the parameters of the converter model.To demonstrate the benefits of finding the physical parameters of the converter, using the BL parameter, an example of a typical three-inch wide-band electrodynamic converter was calculated. For detailed modeling of the electrical oscillation system, the model of John Vanderkoy was chosen, in which the complex resistance of the coil is the sum of the static resistance of the RDC, the frequency-dependent active resistance of the coil RVC (f) and the frequency-dependent inductance LVC (f). This allows the model to account for complex physical effects, such as eddy currents that occur in the metal parts of the magnetic system.A series of ten measurements were performed by each method and the mean for

Published
2019

49. Monitoring Deep Brain Stimulation by measuring regional brain oxygen responses in freely moving mice

Author

Bazzu, G, Serra, P A, Hamelink, R, Feenstra, M G P, Willuhn, I, Denys, D, Bazzu, G, Serra, P A, Hamelink, R, Feenstra, M G P, Willuhn, I, and Denys, D

Abstract

BACKGROUND: Translational studies investigating the effects of deep brain stimulation (DBS) on brain function up to now mainly relied on BOLD responses measured with fMRI. However, fMRI studies in rodents face technical and practical limitations (e.g., immobilization, sedation or anesthesia, spatial and temporal resolution of data). Direct measurement of oxygen concentration in the brain using electrochemical sensors is a promising alternative to the use of fMRI. Here, we tested for the first time if such measurements can be combined with DBS. New Method We combined bilateral DBS in the internal capsule (IC-DBS) with simultaneous amperometric measurements of oxygen in the medial prefrontal cortex (prelimbic area) and striatum of freely moving mice. Using a two-day within-animal experimental design, we tested the effects of DBS on baseline oxygen concentrations, and on novelty- and restraint-induced increases in oxygen concentration.RESULTS: Basal oxygen levels were stable across the daily sampling periods. Exposure to novelty and immobilization reproducibly increased oxygen concentrations in both areas. IC-DBS did not significantly alter basal oxygen, but reduced the novelty-induced increase in the striatum. Comparison with Existing Method(s) Amperometric detection of brain oxygen concentration with high temporal and spatial resolution can be performed in a number of key brain areas to study the effects of DBS in animal models of disease. The method is easily implemented and does not require expensive equipment or complicated data analysis processes.CONCLUSIONS: Direct and simultaneous measurement of brain oxygen concentration in multiple brain areas can be used to study the effects of bilateral DBS neuromodulation on brain activity in freely moving mice.

Published
2019

50. Individual white matter bundle trajectories are associated with deep brain stimulation response in obsessive-compulsive disorder

Author

Liebrand, L C, Caan, M W A, Schuurman, P R, van den Munckhof, P, Figee, M, Denys, D, van Wingen, G A, Liebrand, L C, Caan, M W A, Schuurman, P R, van den Munckhof, P, Figee, M, Denys, D, and van Wingen, G A

Abstract

BACKGROUND: The ventral anterior limb of the internal capsule (vALIC) is a target for deep brain stimulation (DBS) in obsessive-compulsive disorder (OCD). Conventional surgical planning is based on anatomical landmarks.OBJECTIVE/HYPOTHESIS: We hypothesized that treatment response depends on the location of the active DBS contacts with respect to individual white matter bundle trajectories. This study thus aimed to elucidate whether vALIC DBS can benefit from bundle-specific targeting.METHODS: We performed tractography analysis of two fiber bundles, the anterior thalamic radiation (ATR) and the supero-lateral branch of the medial forebrain bundle (MFB), using diffusion-weighted magnetic resonance imaging (DWI) data. Twelve patients (10 females) who had received bilateral vALIC DBS for at least 12 months were included. We related the change in OCD symptom severity on the Yale-Brown obsessive-compulsive scale (Y-BOCS) between baseline and one-year follow-up with the distances from the active contacts to the ATR and MFB. We further analyzed the relation between treatment response and stimulation sites in standard anatomical space.RESULTS: We found that active stimulation of the vALIC closer to the MFB than the ATR was associated with better treatment outcome (p = 0.04; r2 = 0.34). In standard space, stimulation sites were largely overlapping between treatment (non)responders, suggesting response is independent of the anatomically defined electrode position.CONCLUSION: These findings suggest that vALIC DBS for OCD may benefit from MFB-specific implantation and highlight the importance of corticolimbic connections in OCD response to DBS. Prospective investigation is necessary to validate the clinical use of MFB targeting.

Published
2019

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