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3. The Mood and Resilience in Offspring (MARIO) project: a longitudinal cohort study among offspring of parents with and without a mood disorder

Author

Onderzoek, Brain, Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., Hillegers, Manon H.J., Onderzoek, Brain, Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., and Hillegers, Manon H.J.

Published
2024

4. The Mood and Resilience in Offspring (MARIO) project:a longitudinal cohort study among offspring of parents with and without a mood disorder

Author

Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., Hillegers, Manon H.J., Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., and Hillegers, Manon H.J.

Abstract

Background:One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. Methods: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected.Discussion: The MARIO cohort s

Published
2024

5. 5.4 Demographics and Clinical Diagnoses in the Mood and Resilience in Offspring Study: A Longitudinal Cohort Study in Offspring of Parents With a Mood Disorder

Author

Vreeker, Annabel, primary, Horsfall, Melany, additional, Beerthuizen, Annemerle, additional, Bergink, Veerle, additional, Boks, Marco, additional, Eikelenboom, Merijn, additional, Hartman, Catharina A., additional, de Leeuw, Max, additional, Penninx, Brenda, additional, and Hillegers, Manon, additional

Published
2023
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15. Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Author

AIOS Psychiatrie, Risico & Preventie Ond., Onderzoeksgroep 8, Brain, Onderzoeksgroep 3, Onderzoek, de Leeuw, Max, Bohlken, Marc M., Mandl, René CW, Hillegers, Manon HJ, Kahn, René S., Vink, Matthijs, AIOS Psychiatrie, Risico & Preventie Ond., Onderzoeksgroep 8, Brain, Onderzoeksgroep 3, Onderzoek, de Leeuw, Max, Bohlken, Marc M., Mandl, René CW, Hillegers, Manon HJ, Kahn, René S., and Vink, Matthijs

Published
2017

18. The effect of aging on fronto-striatal reactive and proactive inhibitory control

Author

Leerstoel Kemner, Afd ontwikkelings psychologie, Helmholtz Institute, Afd Psychologische functieleer, Social and personality development: A transactional approach, Experimental Psychology (onderzoeksprogramma PF), Kleerekooper, Iris, van Rooij, Sanne J H, van den Wildenberg, Wery P M, de Leeuw, Max, Kahn, Rene S, Vink, Matthijs, Leerstoel Kemner, Afd ontwikkelings psychologie, Helmholtz Institute, Afd Psychologische functieleer, Social and personality development: A transactional approach, Experimental Psychology (onderzoeksprogramma PF), Kleerekooper, Iris, van Rooij, Sanne J H, van den Wildenberg, Wery P M, de Leeuw, Max, Kahn, Rene S, and Vink, Matthijs

Published
2016

19. Diminishing striatal activation across adolescent development during reward anticipation in offspring of schizophrenia patients

Author

Afd ontwikkelings psychologie, Social and personality development: A transactional approach, Helmholtz Institute, Afd Psychologische functieleer, Experimental Psychology (onderzoeksprogramma PF), Vink, Matthijs, de Leeuw, Max, Pouwels, Ruby, van den Munkhof, Hanna E, Kahn, René S, Hillegers, Manon, Afd ontwikkelings psychologie, Social and personality development: A transactional approach, Helmholtz Institute, Afd Psychologische functieleer, Experimental Psychology (onderzoeksprogramma PF), Vink, Matthijs, de Leeuw, Max, Pouwels, Ruby, van den Munkhof, Hanna E, Kahn, René S, and Hillegers, Manon

Published
2016

21. The effect of aging on fronto-striatal reactive and proactive inhibitory control

Author

AIOS Psychiatrie, Brain, Onderzoeksgroep 4, UMC Utrecht, Onderzoek, Kleerekooper, Iris, van Rooij, Sanne J H, van den Wildenberg, Wery P M, de Leeuw, Max, Kahn, Rene S., Vink, Matthijs, AIOS Psychiatrie, Brain, Onderzoeksgroep 4, UMC Utrecht, Onderzoek, Kleerekooper, Iris, van Rooij, Sanne J H, van den Wildenberg, Wery P M, de Leeuw, Max, Kahn, Rene S., and Vink, Matthijs

Published
2016

22. DRD2 schizophrenia-risk allele is associated with impaired striatal functioning in unaffected siblings of schizophrenia patients

Author

UMC Utrecht, Onderzoek, Brain, AIOS Psychiatrie, Onderzoeksgroep 4, Neurogenetica, Vink, Matthijs, de Leeuw, Max, Luykx, Jurjen J., Van Eijk, Kristel R., Van Den Munkhof, Hanna E., Van Buuren, Mariët, Kahn, René S., UMC Utrecht, Onderzoek, Brain, AIOS Psychiatrie, Onderzoeksgroep 4, Neurogenetica, Vink, Matthijs, de Leeuw, Max, Luykx, Jurjen J., Van Eijk, Kristel R., Van Den Munkhof, Hanna E., Van Buuren, Mariët, and Kahn, René S.

Published
2016

23. Diminishing striatal activation across adolescent development during reward anticipation in offspring of schizophrenia patients

Author

Onderzoeksgroep 5, Brain, AIOS Psychiatrie, Onderzoek, Onderzoeksgroep 3, Vink, Matthijs, de Leeuw, Max, Pouwels, Ruby, Van Den Munkhof, Hanna E., Kahn, René S., Hillegers, Manon, Onderzoeksgroep 5, Brain, AIOS Psychiatrie, Onderzoek, Onderzoeksgroep 3, Vink, Matthijs, de Leeuw, Max, Pouwels, Ruby, Van Den Munkhof, Hanna E., Kahn, René S., and Hillegers, Manon

Published
2016

30. Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Author

de Leeuw, Max, Bohlken, Marc M, Mandl, René CW, Hillegers, Manon HJ, Kahn, René S, and Vink, Matthijs

Abstract

Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10–18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

Published
2017
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31. Anger and cluster B personality traits and the conversion from unipolar depression to bipolar disorder.

Author

Mesbah R, de Bles N, Rius-Ottenheim N, van der Does AJW, Penninx BWJH, van Hemert AM, de Leeuw M, Giltay EJ, and Koenders M

Subjects
Anger, Humans, Netherlands epidemiology, Personality, Prospective Studies, Bipolar Disorder epidemiology, Depressive Disorder epidemiology
Abstract

Introduction: Feelings of anger and irritability are prominent symptoms of bipolar disorder (BD) that may occur during hypomanic, depressive and, especially, during mixed mood states. We aimed to determine whether such constructs are associated with the conversion to BD in subjects with a history of unipolar depression., Methods: Data were derived from the depressed participants of Netherlands Study of Depression and Anxiety with 9 years of follow-up. Hypomania was ascertained using the Composite International Diagnostic Interview at 2, 4, 6, and 9 years follow-up. Cross-sectionally, we studied the association between prevalent hypomania and anger related constructs with the "Spielberger Trait Anger subscale," the "Anger Attacks" questionnaire, the cluster B personality traits part of the "Personality Disorder Questionnaire," and "aggression reactivity." Prospectively, we studied whether aggression reactivity predicted incident hypomania using Cox regression analyses., Results: Cross-sectionally, the bipolar conversion group (n = 77) had significantly higher scores of trait anger and aggression reactivity, as well as a higher prevalence on "anger attacks," "antisocial traits," and "borderline traits" compared to current (n = 349) as well as remitted (n = 1159) depressive patients. In prospective analyses in 1744 participants, aggression reactivity predicted incident hypomania (n = 28), with a multivariate-adjusted hazard ratio of 1.4 (95% confidence interval: 1.02-1.93; p = .037)., Conclusion: Anger is a risk factor for conversion from unipolar depression to BD. In addition, patients who converted to BD showed on average more anger, agitation and irritability than people with a history of unipolar depression who had not converted., (© 2021 The Authors. Depression and Anxiety published by Wiley Periodicals LLC.)

Published
2021
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32. DRD2 Schizophrenia-Risk Allele Is Associated With Impaired Striatal Functioning in Unaffected Siblings of Schizophrenia Patients.

Author

Vink M, de Leeuw M, Luykx JJ, van Eijk KR, van den Munkhof HE, van Buuren M, and Kahn RS

Subjects
Adult, Alleles, Female, Humans, Magnetic Resonance Imaging, Male, Risk, Executive Function physiology, Inhibition, Psychological, Neostriatum physiopathology, Receptors, Dopamine D2 genetics, Schizophrenia genetics, Schizophrenia physiopathology, Siblings
Abstract

A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n= 21) and noncarriers (n= 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2016
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