Co-morbidity of adult attention-deficit/hyperactivity disorder with focus on personality traits and related disorders in a tertiary referral center

Jacob, Christian; Romanos, Jasmin; Dempfle, Astrid; Heine, Monika; Windemuth-Kieselbach, Christine; Kruse, Anja; Reif, Andreas; Walitza, Susanne; Romanos, Marcel; Strobel, Alexander; Brocke, Burkhard; Schäfer, Helmut; Schmidtke, Armin; Böning, Jobst; Lesch, Klaus‐Peter

doi:10.1007/s00406-007-0722-6

Cited by 197 publications

(202 citation statements)

References 43 publications

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“…Finally, allelic variation of TPH2 function appears to influence the risk of a variety of neuropsychiatric disorders such as ADHD and obsessive-compulsive disorder (OCD), clinical entities commonly associated with difficulties to control emotions and with a high co-morbidity of depression [39,40]. Transmission disequilibrium of potentially functional variants in the transcriptional control or in the coding region of TPH2 in ADHD [41 -43], and preferential transmission of a haplotype of TPH2 in early-onset OCD [44] were reported.…”

Section: Tph2 In Personality Traits Of Negative Emotionality and In Dmentioning

confidence: 99%

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

Lesch

Araragi

Waider

et al. 2012

Phil. Trans. R. Soc. B

Self Cite

128

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Aggression, which comprises multi-faceted traits ranging from negative emotionality to antisocial behaviour, is influenced by an interaction of biological, psychological and social variables. Failure in social adjustment, aggressiveness and violence represent the most detrimental long-term outcome of neurodevelopmental disorders. With the exception of brain-specific tryptophan hydroxylase-2 (Tph2), which generates serotonin (5-HT) in raphe neurons, the contribution of gene variation to aggression-related behaviour in genetically modified mouse models has been previously appraised (Lesch 2005 Novartis Found Symp. 268, 111 -140; Lesch & Merschdorf 2000 Behav. Sci. Law 18, 581 -604). Genetic inactivation of Tph2 function in mice led to the identification of phenotypic changes, ranging from growth retardation and late-onset obesity, to enhanced conditioned fear response, increased aggression and depression-like behaviour. This spectrum of consequences, which are amplified by stress-related epigenetic interactions, are attributable to deficient brain 5-HT synthesis during development and adulthood. Human data relating altered TPH2 function to personality traits of negative emotionality and neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation are based on genetic association and are therefore not as robust as the experimental mouse results. Mouse models in conjunction with approaches focusing on TPH2 variants in humans provide unexpected views of 5-HT's role in brain development and in disorders related to negative emotionality, aggression and antisocial behaviour.Keywords: tryptophan hydroxylase (TPH2); cognition; emotion; impulsivity; aggression; violence INTRODUCTIONNegative emotionality, aggression and antisociality are complex temperamental traits and social behaviours that arise out of multiple causes involving biological and psychological dynamisms and social forces, and different forms of emotional behaviour may each result from different biopsychosocial pathways. The societal implications of aggressiveness, which results in numerous facets of aggressive behaviour and ranges from the establishment of hierarchies and dominance to antisocial behaviour and delinquency, have been examined with preclinical and clinical frameworks.Developmentally inappropriate conduct, aggressiveness and failure in social adjustment represent the most detrimental and harmful long-term outcome of a wide spectrum of neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation.In both humans and animals, the term aggression comprises a variety of behaviours that are heterogeneous for clinical phenomenology and neurobiological features. While the impact of complex cultural variables on behaviour impedes simple extrapolation of animal phenotypes to human traits, clinical observation, experimental paradigms in the laboratory and cluster/ factor-analytic statistics have been used in attempts to subdivide aggression. On the basis of different approaches, hu...

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Section: Tph2 In Personality Traits Of Negative Emotionality and In Dmentioning

confidence: 99%

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

Lesch

Araragi

Waider

et al. 2012

Phil. Trans. R. Soc. B

Self Cite

128

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“…1 Moreover, the syndromal dimensions of hyperactivity and increased impulsivity are increasingly being recognized as highly persistent into adulthood and are associated with considerable risk for psychiatric comorbidity such as depression and substance use disorder as well as failure in psychosocial adaptation. 2 Although the substantial heritability of ADHD is documented in numerous family, twin and adoption studies, with estimates up to 80%, genome-wide linkage scans and candidate gene studies have failed to reliably identify ADHD-associated genes. 3 Hebebrand and co-workers 4 reported evidence for a risk haplotype at the dopamine transporter (DAT/SLC6A3) locus based on a linkage scan and subsequent finemapping of chromosome 5p13.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree

et al. 2010

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Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domaincontaining protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 a subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a B3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P = 0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome.

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“…The ADHD-ODD group showed histrionic, narcissistic, aggressive-sadistic and negativistic traits, whereas the ADHD-ODD-co-morbid group had a combination of avoidant, narcissistic, antisocial, aggressive-sadistic, negativistic and self-defeating traits. Jacob et al (2007) applied the Revised NEO Personality Inventory (NEO-PI-R) in 372 adults with ADHD and 454 adults without ADHD. Patients with ADHD had higher neuroticism and lower extraversion, openness to experience and conscientiousness.…”

Section: Introductionmentioning

confidence: 99%

Personality traits among ADHD adults: implications of late-onset and subthreshold diagnoses

et al. 2008

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Background-Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish onset prior to the DSM-IV criterion of age 7 or if the number of symptoms does not achieve the DSM threshold for diagnosis. Previous work has assessed the validity of such diagnoses based on psychiatric co-morbidity, family history and neuropsychological functions but none of these studies have used personality as a validation criterion.

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Co-morbidity of adult attention-deficit/hyperactivity disorder with focus on personality traits and related disorders in a tertiary referral center

Abstract: In a cohort of patients with AADHD referred to a single tertiary center co-morbidity with axis-I/II disorders was remarkably prevalent. In AADHD co-morbid mood, anxiety, and personality disorders as well as substance abuse/dependence is likely to be predictive of poor outcome.

Cited by 197 publications

References 43 publications

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree

Personality traits among ADHD adults: implications of late-onset and subthreshold diagnoses

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