| 1. |
- Brocki, Karin Cecilia, 1975-
(författare)
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Executive Control Processes: Dimensions, Development and ADHD
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Deficits in higher order cognitive processes such as inhibitory control and working memory (WM), grouped under the term of executive function (EF), have been shown to constitute one important component of the complex neuropsychology of Attention Deficit Hyperactivity Disorder (ADHD). The aim of the present thesis was to examine EF in relation to ADHD, with primary focus on structure (i.e., dimensions) and developmental change. Rooted in the developmental and dimensional perspectives of ADHD, which propose that the disorder represents the extreme of or quantitative delays in traits that are present throughout the general population, four studies (I-IV) based on non-clinical and clinical samples of children at different developmental levels were conducted.Together, the results from Study I-IV suggest that inhibitory control and WM are important components of EF in typically developing children as well as in relation to ADHD symptoms. Of particular interest are the findings from Study II, III, and IV, showing that inhibitory control and WM seem to be of different importance depending on the child’s age. More specifically, the non-clinical and clinical studies suggest that inhibitory control and WM are important in predicting ADHD symptoms, with deficits in inhibitory control primarily being associated with ADHD symptoms for preschool and younger elementary school-aged children, whereas deficits in WM are associated with ADHD symptoms for older elementary school-aged children. In conclusion, the results of the present thesis are consistent with Barkley’s (1997) developmental prediction concerning the relation between EF and ADHD, which suggests that impaired inhibitory control is an early developmental precursor to or a factor that “sets the stage” for deficits in more complex EFs such as WM. The home taking message from the present thesis is that age matters not only in the behavioral, but also in the neuropsychological manifestation of ADHD. To our knowledge, these findings are among the first to show that age is an important factor that should be taken into account in future ADHD research, theory, and treatment.
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| 2. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 3. |
- Frick, Matilda A, 1979-
(författare)
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Self-Regulation in Childhood : Developmental Mechanisms and Relations to ADHD Symptoms
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Self-regulation is a multi-faceted construct that concerns goal-directed behaviors, which aid individuals in everyday life and in achieving long-term goals. Self-regulation in believed to progress in a hierarchical fashion, in that simple cognitive functions are integrated into more complex functions across development. Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous childhood-onset disorder, characterized by deficits in various aspects of self-regulation, including core symptoms of inattention and hyperactivity/impulsivity, and comorbidity with externalizing disorders such as oppositional defiant disorder (ODD). The last decade has seen a shift from simple etiological models towards more complex ones, which stress multiple pathways to the disorder. In addition, there is an ongoing search for early markers of the condition, which will increase our understanding, enable early detection, intervention, and perhaps even prevention of the full disorder. Cognitive regulation, aspects of temperament (i.e. negative affect, surgency, and effortful control), and parenting are three areas of importance for self-regulation in general and of ADHD symptoms in particular. Grounded in these three constructs, informed by the hierarchical model of self-regulation development, and a multiple pathway perspective on ADHD, the present thesis aimed to map development of self-regulation, with a special focus on inattention and hyperactivity/impulsivity. Four studies were conducted based on three samples, ranging from infancy to 12 years, including both typically developing children and children diagnosed with ADHD. Study I found that early sustained attention predicted later cognitive regulation, providing support for the hierarchical model of self-regulation development. In addition, maternal sensitivity contributed to higher levels of emotion regulation whereas surgency contributed to lower levels of emotion regulation. Study II gained support for a multiple pathway perspective on ADHD, in that higher temperamental regulation and maternal sensitivity contributed to lower levels of inattention and hyperactivity/impulsivity, and higher surgency contributed to higher levels of hyperactivity/impulsivity. Study III replicated findings from Study II and confirmed early temperament markers of later inattention and hyperactivity/impulsivity, and that early cognitive regulation was a poor predictor of later symptoms. Study IV proposed contributions of multiple regulatory functions to ADHD symptoms and elevated negative affect in ODD. The latter was moderated by parental support, which seemed to be a protective factor for children with high levels of negative affect. In all, the findings point to the importance of both intrinsic and extrinsic factors in the development of self-regulation, which seems to progress in a hierarchical fashion. Aspects of temperament rather than cognitive regulation seem to be valid early markers of later inattention and hyperactivity/impulsivity. Multiple pathways to ADHD symptoms are proposed, with contributions of maternal sensitivity and temperament early in development and different regulatory functions in school-aged children. In addition, elevated negative affect in combination with low parental support seem to be characteristic of ODD rather than of core symptoms of ADHD. The thesis contributes to the complexity and heterogeneity of ADHD and that ADHD is best viewed as a developmental disorder, in that the influence of various regulatory factors change over time.
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| 4. |
- Frick, Matilda, 1979-, et al.
(författare)
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Pervasive versus situational childhood ADHD : latent classes and their clinical characteristics, based on parent and teacher ratings in a large longitudinal population sample
- 2024
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Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 33, s. 2253-2266
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Tidskriftsartikel (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) diagnoses require symptoms to be present in two settings. Low levels of concordance between symptoms rated at home and school raise questions regarding this approach. The aim was to examine whether there are sub-groups with context-specific expressions of ADHD symptoms (i.e., at home or school only) with clinically significant problems sufficient to support a new diagnostic formulation. We applied latent class transition analysis to parent and teacher data (N = 10,476) from the Avon Longitudinal Study of Parents and Children (ALSPAC), collected at ages 8, 10, and 20 years. We examined the short-term stability of emergent classes and their childhood and adult-associated risk profiles. In addition to an Unaffected class (similar to 45%), there was a Pervasive Combined class with elevated inattentive and hyperactive/impulsive symptoms at both home and school (similar to 11%) and three classes with situational expressions; School Combined (similar to 9%), Home Combined (similar to 18%), and School Inattentive (similar to 16%). Stability ranged from 0.27 to 0.78. The Pervasive Combined class was most symptomatic and impaired. School inattentive also displayed clinical symptom levels, whereas the School and Home Combined classes displayed subclinical levels. Different profiles regarding sex, cognition, conduct problems, and substance use emerged for the three situational classes. Distinct groupings of pervasive and situational ADHD expressions are identifiable in the general population. The isolation of a stable and burdensome Pervasive Combined class lends support to the current diagnostic approach. However, there are indications of situational expressions of ADHD with clinical symptom levels and associated difficulties.
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| 5. |
- Göran, Söderlund, et al.
(författare)
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The effects of background white noise on memory performance in inattentive school children
- 2010
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Ingår i: Behavioral and Brain Functions. - : Springer Science and Business Media LLC. - 1744-9081. ; 6:55
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Noise is typically conceived of as being detrimental for cognitive performance; however, a recent computational model based on the concepts of stochastic resonance and dopamine related internal noise postulates that a moderate amount of auditive noise benefit individuals in hypodopaminergic states. On the basis of this model we predicted that inattentive children would be enhanced by adding background white noise while attentive children’s performance would deteriorate. Methods: Fifty-one secondary school pupils carried out an episodic verbal free recall test in two noise conditions. In the high noise condition, verb-noun sentences were presented during auditory background noise (white noise, 78 dB), and in the low noise condition sentences were presented without noise. Results: Exposure to background noise improved performance for inattentive children and worsened performance for attentive children and eliminated episodic memory differences between attentive and inattentive school children. Conclusions: Consistent with the model, our data show that cognitive performance can be moderated by external background white noise stimulation in a non-clinical group of inattentive participants. This finding needs replicating in a larger sample using more noise levels but if replicated has great practical applications by offering a non-invasive way to improve school results in children with attentional problems.
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| 6. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 7. |
- Söderlund, Göran, 1955-
(författare)
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Noise improves cognitive performance in children with dysfunctional neurotransmission
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Research on children with Attention Deficit Hyperactivity Disorder (ADHD) has shown that they are extremely sensitive to distraction from external stimuli that lead to poor cognitive performance. This thesis shows that cognitive performance can be improved if this external stimulus is smooth and continuous (e.g. auditory white noise). Control children attenuate their performance under such conditions. The first Study proposes the moderate brain arousal model (MBA). This neurocomputational model predicts selective improvement from noise in ADHD children. Noise through a phenomenon called stochastic resonance (SR), can be beneficial in dopamine deprived neural systems. The statistical phenomenon of SR explains how the signal-to-noise ratio can be improved by noise in neural systems where the passing a threshold is required. The second Study provides experimental support for the MBA-model by showing that ADHD children improve performance in a free recall task while exposed to auditive noise. Control children declines in the same condition. The third Study generalizes this finding among low achieving children, which it is argued have low dopamine levels. Noise exposure improves performance in low achievers, but inhibits performance in high achievers. The conclusion is that external auditory noise can restore low dopamine levels and thus improve cognitive performance. It is also proposed that dopamine levels modulate the SR effect; this means that low dopamine persons require more noise to obtain an SR effect. Both excessive and insufficient dopamine is detrimental for cognitive performance. The MBA model can be used to explain several shortcomings where changes in the dopamine system have been identified. The MBA model can also help create appropriate and adaptive environments, especially in schools, for persons with a deficient dopamine function, such as ADHD children.
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