| 1. |
- Landén, Mikael, 1966, et al.
(author)
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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
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Journal article (peer-reviewed)abstract
- Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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| 2. |
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| 3. |
- van Dongen, J, et al.
(author)
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DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
- 2021
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:6, s. 2148-2162
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Journal article (peer-reviewed)abstract
- DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
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| 4. |
- Bartels, M., et al.
(author)
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Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
- 2018
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In: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
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Journal article (peer-reviewed)abstract
- Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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| 5. |
- Ferrari-Souza, J. P., et al.
(author)
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APOEε4 potentiates amyloid β effects on longitudinal tau pathology
- 2023
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In: Nature Aging. - 2662-8465. ; 3:10
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Journal article (peer-reviewed)abstract
- The mechanisms by which the apolipoprotein E epsilon 4 (APOE epsilon 4) allele influences the pathophysiological progression of Alzheimer's disease (AD) are poorly understood. Here we tested the association of APOE epsilon 4 carriership and amyloid-beta (A beta) burden with longitudinal tau pathology. We longitudinally assessed 94 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for A beta ([F-18]AZD4694) and tau ([F-18]MK-6240) at baseline, as well as a 2-year follow-up tau-PET scan. We found that APOE epsilon 4 carriership potentiates A beta effects on longitudinal tau accumulation over 2 years. The APOE epsilon 4-potentiated A beta effects on tau-PET burden were mediated by longitudinal plasma phosphorylated tau at threonine 217 (p-tau217(+)) increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results suggest that the APOE epsilon 4 allele plays a key role in A beta downstream effects on the aggregation of phosphorylated tau in the living human brain.
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| 6. |
- Bellaver, B., et al.
(author)
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Blood-brain barrier integrity impacts the use of plasma amyloid-beta as a proxy of brain amyloid-beta pathology
- 2023
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:9, s. 3815-3825
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Journal article (peer-reviewed)abstract
- INTRODUCTION Amyloid-beta (A beta) and tau can be quantified in blood. However, biological factors can influence the levels of brain-derived proteins in the blood. The blood-brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers.METHODS We assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography A beta, p-tau, and albumin measures.RESULTS Plasma A beta(42/40) better identified CSF A beta(42/40) and A beta-PET positivity in individuals with high BBB permeability. An interaction between plasma A beta(42/40) and BBB permeability on CSF A beta(42/40) was observed. Voxel-wise models estimated that the association of positron emission tomography (PET), with plasma A beta was most affected by BBB permeability in AD-related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p-tau levels.DISCUSSION These findings suggest that BBB integrity may influence the performance of plasma A beta, but not p-tau, biomarkers in research and clinical settings.
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| 7. |
- Ferreira, P. C. L., et al.
(author)
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Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals
- 2023
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In: Alzheimers & Dementia. - 1552-5260. ; 19:10, s. 4463-4474
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Journal article (peer-reviewed)abstract
- INTRODUCTIONPhosphorylated tau (p-tau) biomarkers have been recently proposed to represent brain amyloid-& beta; (A & beta;) pathology. Here, we evaluated the plasma biomarkers' contribution beyond the information provided by demographics (age and sex) to identify A & beta; and tau pathologies in individuals segregated as cognitively unimpaired (CU) and impaired (CI). METHODSWe assessed 138 CU and 87 CI with available plasma p-tau231, 217(+), and 181, A & beta;42/40, GFAP and A & beta;- and tau-PET. RESULTSIn CU, only plasma p-tau231 and p-tau217(+) significantly improved the performance of the demographics in detecting A & beta;-PET positivity, while no plasma biomarker provided additional information to identify tau-PET positivity. In CI, p-tau217(+) and GFAP significantly contributed to demographics to identify both A & beta;-PET and tau-PET positivity, while p-tau231 only provided additional information to identify tau-PET positivity. DISCUSSIONOur results support plasma p-tau231 and p-tau217(+) as state markers of early A & beta; deposition, but in later disease stages they inform on tau tangle accumulation. HighlightsIt is still unclear how much plasma biomarkers contribute to identification of AD pathology across the AD spectrum beyond the information already provided by demographics (age + sex).Plasma p-tau231 and p-tau217(+) contribute to demographic information to identify brain A & beta; pathology in preclinical AD.In CI individuals, plasma p-tau231 contributes to age and sex to inform on the accumulation of tau tangles, while p-tau217(+) and GFAP inform on both A & beta; deposition and tau pathology.
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| 8. |
- Aghajani, Moji, et al.
(author)
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Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders
- 2016
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In: Human Brain Mapping. - Hoboken, USA : Wiley-Blackwell. - 1065-9471 .- 1097-0193. ; 37:11, s. 4017-4033
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Journal article (peer-reviewed)abstract
- Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile.
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| 9. |
- Hoeve, Machteld, et al.
(author)
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The association between childhood maltreatment, mental health problems, and aggression in justice-involved boys
- 2015
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In: Aggressive Behavior. - Hoboken, USA : Wiley-Blackwell. - 0096-140X .- 1098-2337. ; 41:5, s. 488-501
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Journal article (peer-reviewed)abstract
- The link between childhood maltreatment and adolescent aggression is well documented; yet, studies examining potential mechanisms that explain this association are limited. In the present study, we tested the association between childhood maltreatment and adolescent aggression in boys in juvenile justice facilities (N = 767) and examined the contribution of mental health problems to this relationship. Data on childhood maltreatment, mental health problems, and aggression were collected by means of self-report measures and structural equation models were used to test mediation models. We found that mental health problems mediated the link between maltreatment and aggression. Results demonstrated different pathways depending on the type of aggression examined. The association between childhood maltreatment and reactive aggression was fully mediated by a variety of mental health problems and for proactive aggression the association was partially mediated by mental health problems. We also found that reactive and proactive aggression partially mediated the association between maltreatment and mental health problems. These findings suggest that a transactional model may best explain the negative effects of childhood trauma on mental health problems and (in particular reactive) aggression. In addition, our findings add to the existing evidence that reactive and proactive aggression have different etiological pathways.
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| 10. |
- Roetman, P. J., et al.
(author)
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Children With Early-Onset Disruptive Behavior: Parental Mental Disorders Predict Poor Psychosocial Functioning in Adolescence
- 2019
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 58:8, s. 806-817
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Journal article (peer-reviewed)abstract
- Objective: Parental mental disorders (MD) and child early-onset disruptive behavior (DB) are well-established risk factors for poor outcomes in adolescence. However, it is not clear whether parental MD increases risk of future maladjustment among children who already display DB. Method: Parents of 9-year-old children reported on child DB, whereas a patient registry was used to determine parental MD. At follow-ups at ages 15 (n = 6,319) and 18 (n = 3,068) years, information about various problems were collected via registries, parent-, and self-reports. Results: In the total sample, child DB was related to all outcomes (mean odds ratio [OR] = 1.18; range = 1.07−1.51; p values <.01), paternal MD to criminality, aggression, truancy, poor school performance, and a cumulative risk index of poor functioning, and maternal MD to peer problems, rule breaking, and truancy (mean OR = 1.67; range = 1.19−2.71; p values <.05). In the subsample of children with DB, paternal MD predicted criminality, consequences of antisocial behavior, truancy, poor school performance, and cumulative risk, whereas maternal MD predicted peer problems (mean OR = 1.94; range = 1.30−2.40; p values <.05). Conclusion: This study provides novel evidence that parental MD places 9-year-olds with DB at risk for negative outcomes in adolescence. In addition, paternal MD is a better predictor than maternal MD, regardless of child DB at age 9, suggesting that fathers should be given increased attention in future research. Treatment-as-usual of children with DB could be augmented with additional screening and, if necessary, treatment of mental health problems in their parents. © 2019 American Academy of Child and Adolescent Psychiatry
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| 11. |
- Aghajani, Moji, et al.
(author)
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Neural processing of socioemotional content in conduct-disordered offenders with limited prosocial emotions
- 2021
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In: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 105
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Journal article (peer-reviewed)abstract
- BACKGROUND: Reflecting evidence on Callous-Unemotional (CU) traits (e.g., lack of empathy and guilt, shallow affect), the DSM-5 added a categorical CU-based specifier for Conduct Disorder (CD), labeled 'with Limited Prosocial Emotions' (LPE). Theory and prior work suggest that CD youths with and without LPE will likely differ in neural processing of negative socioemotional content. This proposition, however, is mainly derived from studies employing related, yet distinct, operationalizations of CU traits (e.g., dimensional measure/median split/top quartile), thus precluding direct examination of LPE-specific neurocognitive deficits.METHODS: Employing a DSM-5 informed LPE proxy, neural processing of recognizing and resonating negative socioemotional content (angry and fearful faces) was therefore examined here among CD offenders with LPE (CD/LPE+; N = 19), relative to CD offenders without LPE (CD/LPE-; N = 31) and healthy controls (HC; N = 31).RESULTS: Relative to HC and CD/LPE- youths and according to a linearly increasing trend (CD/LPE- < HC < CD/LPE+), CD/LPE+ youths exhibited hyperactivity within dorsolateral, dorsomedial, and ventromedial prefrontal regions during both emotion recognition and resonance. During emotion resonance, CD/LPE+ youths additionally showed increased activity within the posterior cingulate and precuneal cortices in comparison to HC and CD/LPE- youths, which again followed a linearly increasing trend (CD/LPE- < HC < CD/LPE+). These effects moreover seemed specific to the LPE specifier, when compared to a commonly employed method for CU-based grouping in CD (i.e., median split on CU scores).CONCLUSIONS: These data cautiously suggest that CD/LPE+ youths may exhibit an over-reliance on cortical neurocognitive systems when explicitly processing negative socioemotional information, which could have adverse downstream effects on relevant socioemotional functions. The findings thus seem to provide novel, yet preliminary, clues on the neurocognitive profile of CD/LPE+, and additionally highlight the potential scientific utility of the LPE specifier.
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| 12. |
- Colins, Olivier F, 1978-, et al.
(author)
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Mental health problems and recidivism among detained male adolescents from various ethnic origins
- 2013
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In: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 22:8, s. 481-490
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Journal article (peer-reviewed)abstract
- This study examines differences in self-reported mental health problems between detained youths from Dutch, Moroccan, and Surinamese origin and the usefulness of mental health problems to predict violent and property recidivism in these juveniles. A sample of 296 detained boys aged between 12 and 18 years were assessed by means of the Strengths and Difficulties Questionnaire (SDQ). Official information regarding criminal history and recidivism was collected 3-6 years later. In general, Dutch youths and Surinamese youths reported more conduct problems than Moroccan youths, while Dutch youths also reported more hyperactivity than Surinamese youths. Mental health problems were not predictive of violent recidivism in any of the ethnic groups, while being related with property recidivism in Dutch and Surinamese youths. The current study showed that Moroccan youths present themselves on the SDQ as a less seriously disturbed group of youths than their Dutch and Surinamese counterparts. Our results also clearly showed that SDQ self-report scores are not predictive of future violent crimes in any of the three ethnic groups. Implications of the findings and limitations of the current study are discussed.
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| 13. |
- Colins, Olivier F., et al.
(author)
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Psychometric Properties and Prognostic Usefulness of the Youth Psychopathic Traits Inventory (YPI) as a Component of a Clinical Protocol for Detained Youth : A Multiethnic Examination
- 2017
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In: Psychological Assessment. - : American Psychological Association (APA). - 1040-3590 .- 1939-134X. ; 29:6, s. 740-753
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Journal article (peer-reviewed)abstract
- Prior studies have shown that the Youth Psychopathic Traits Inventory (YPI) holds promise as a self-report tool for assessing psychopathic traits in detained adolescents. However, these studies have been conducted in a research context where anonymity and confidentiality are provided. Few studies have examined the usefulness of the YPI in clinical settings. To address this research gap, the present study examined data from 1,559 detained boys who completed the YPI as part of a clinical protocol. Official criminal records were available for a subsample (n = 848), allowing us to test the prognostic usefulness of the YPI. Results of confirmatory factor analyses, overall, support the proposed 3-factor structure, though model fit indices were not as good in Dutch boys compared to boys from other ethnic groups. Measurement invariance tests showed that the YPI scores are manifested in the same way across all 4 ethnic groups and suggest that means scores between the 4 ethnic groups are comparable. The YPI scores were internally consistent, and correlations with external variables, including aggression and conduct problems, support the convergent validity of the interpretation of YPI scores. Finally, results demonstrated that YPI scores were not significantly positively related to future criminality. In conclusion, this study suggests that the YPI may hold promise as a self-report tool for assessing psychopathic traits in detained male adolescents during a clinical protocol. However, the finding that the YPI did not predict future offending suggests that this tool should not yet be used for risk assessment purposes in forensic settings.
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| 14. |
- Krabbendam, Anne A, et al.
(author)
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Personality disorders in previously detained adolescent females : a prospective study
- 2015
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In: American Journal of Orthopsychiatry. - : American Psychological Association (APA). - 0002-9432 .- 1939-0025. ; 85:1, s. 63-71
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Journal article (peer-reviewed)abstract
- This longitudinal study investigated the predictive value of trauma and mental health problems for the development of antisocial personality disorder (ASPD) and borderline personality disorder (BPD) in previously detained women. The participants were 229 detained adolescent females who were assessed for traumatic experiences and mental health problems (mean age = 15.5 years). Three to 6 years later (M = 4.5; SD = 0.6), ASPD and BPD were diagnosed with a semistructured interview. Forty percent of the women had a personality disorder (i.e., ASPD 15.8%, BPD 9.2%, or both ASPD and BPD 15.2%). Posttraumatic stress, depressive symptoms, and dissociation during detention increased the risk for BPD in adulthood. Surprisingly, neither conduct problems nor substance dependence predicted ASPD; these findings require further study because they add to the controversy surrounding ASPD in females. The high prevalence rates of personality disorders indicate the need for intervention programs that target these unwanted outcomes.
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| 15. |
- Vahl, Pauline, et al.
(author)
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Psychopathic-like traits in detained adolescents : clinical usefulness of self-report
- 2014
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In: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 23:8, s. 691-699
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Journal article (peer-reviewed)abstract
- Studies have demonstrated that self-report tools can be used to reliably and validly examine psychopathic-like traits in adolescents. However, it is unclear if self-report instruments are still reliable and valid when confidentiality cannot be guaranteed, such as during routine assessments in juvenile detention centres. To address this issue, the current study used data from the routine mental health screening of 365 detained male adolescents (12-18 years) in two juvenile detention centres. With the intention of gaining insight in the clinical usefulness of self-reported psychopathic-like traits, we examined relations known from literature with emotional and behavioural features. Self-reported psychopathic-like traits, measured by the Youth Psychopathic Traits Inventory-Short version (YPI-S), were uniquely associated with substance abuse, anger/irritability, conduct problems and hyperactivity, but not with internalizing problems. YPI-S-dimensions showed several specific relationships with variables of interest. For example, only the callous unemotional dimension was negatively related with prosocial behaviour and only the behavioural dimension was positively related with hyperactivity. In conclusion, self-reported psychopathic-like traits showed expected relations with relevant variables. These findings suggest that self-report can be used to identify detained youths with high levels of psychopathic-like traits outside a research context, thus, even when anonymity and confidentiality are not guaranteed.
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| 16. |
- Vermeiren, Angelique P. A., et al.
(author)
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The Association Between APOE epsilon 4 and Alzheimer-type Dementia Among Memory Clinic Patients is Confined to those with a Higher Education. The DESCRIPA Study
- 2013
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 35:2, s. 241-246
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Journal article (peer-reviewed)abstract
- We assessed the interaction between the APOE epsilon 4 allele and education level in the etiology of Alzheimer's disease (AD) among memory clinic patients from the multicenter DESCRIPA study. Subjects (n = 544) were followed for 1 to 5 years. We used Cox's stratified survival modeling, adjusted for age, gender, and center. APOE epsilon 4 predicted the onset of AD-type dementia in middle (HR 3.45 95% CI 1.79-6.65, n = 222) and high (HR 3.67 95% CI 1.36-9.89, n = 139) but not in low educated subjects (HR 0.81, 95% CI 0.38-1.72, n = 183). This suggests that mechanisms in developing Alzheimer-type dementia may differ between educational groups that raises questions related to Alzheimer-type dementia prevention.
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