Andreas Warnke’s research while affiliated with University of Wuerzburg and other places

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Publications (415)


Schlafstörungen
  • Chapter

December 2023

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10 Reads

Christoph Wewetzer

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Andreas Warnke

Language and reading impairments are associated with increased prevalence of non-right-handedness
  • Article
  • Full-text available

February 2023

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267 Reads

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14 Citations

Child Development

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Silvia Paracchini

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

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Non-right handedness is associated with language and reading impairments

December 2022

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282 Reads

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3 Citations

Child Development

Worldwide, the majority of people prefer using the right hand for most motor tasks. Because of the link between handedness and language hemispheric dominance, handedness has been studied for association with language-related disorders. No clear pattern has emerged from these studies, and inconsistencies have been attributed to small sample sizes, publication bias, and heterogeneous criteria for the definition of handedness and disorders. Here, we assessed the frequency of non-right handedness (NRH) in 10 distinct cohorts not analysed before in this context. We identified N = 2,528 cases with reading and/or language impairment and N = 3,050 unique controls on the basis of a priori defined criteria. Overall, NRH was more frequent and more variable in the cases (8-24%) than in the controls (8-16%). Meta-analysis in the eight cohorts that met the inclusion criteria showed an increase of NRH in individuals with language/reading impairment compared to controls (OR = 1.21, CI = 1.03 - 1.44, p = 0.025). No moderator effects were detected for type of cohort (epidemiological versus clinical) and type of impairment (language versus reading). Our results support an association between NRH and reading and language impairments which could result from shared biological pathways underlying brain lateralization, handedness, and cognitive functions


Relationship between risperidone dose per day and the RISam (active moiety = RIS plus 9-OH-RIS) steady-state trough serum concentrations for n = 64 patients. The recommended therapeutic range of RISam concentrations (20–60 ng/ml) in adults is highlighted
Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone

June 2022

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153 Reads

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13 Citations

Journal of Neural Transmission

Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RISam) concentration was found (rs = 0.49, p = 0.001) with variation in dose explaining 24% (rs² = 0.240) of the variability in serum concentrations. While the RISam concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RISam concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RISam was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.


Non-right handedness is associated with language and reading impairments

March 2022

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334 Reads

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4 Citations

Worldwide, the majority of people prefer using the right hand for most motor tasks. Because of the link between handedness and language hemispheric dominance, handedness has been studied for association with language-related disorders. No clear pattern has emerged from these studies, and inconsistencies have been attributed to small sample sizes, publication bias, and heterogeneous criteria for the definition of handedness and disorders.Here, we assessed the frequency of non-right handedness (NRH) in 10 distinct cohorts not analysed before in this context. We identified N = 2,528 cases with reading and/or language impairment and N = 3,050 unique controls on the basis of a priori defined criteria. Overall, NRH was more frequent and more variable in the cases (8-24%) than in the controls (8-16%). Meta-analysis in the eight cohorts that met the inclusion criteria showed an increase of NRH in individuals with language/reading impairment compared to controls (OR = 1.21, CI = 1.03 - 1.44, p = 0.025). No moderator effects were detected for type of cohort (epidemiological versus clinical) and type of impairment (language versus reading). Our results support an association between NRH and reading and language impairments which could result from shared biological pathways underlying brain lateralization, handedness, and cognitive functions.


Correction to: Does helping mothers in multigenerational ADHD also help children in the long run? 2‑year follow‑up from baseline of the AIMAC randomized controlled multicentre trial

January 2021

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168 Reads

European Child & Adolescent Psychiatry

The original article was missing a statement regarding a shared first authorship. The authors Julia M. Geissler and Timo D. Vloet contributed equally to the manuscript.


A Novel Locus and Candidate Gene for Familial Developmental Dyslexia on Chromosome 4q

November 2020

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52 Reads

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4 Citations

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie

Objective: Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we investigated a four-generation pedigree where transmission of dyslexia is consistent with an autosomal dominant inheritance pattern. Methods: We performed genome wide array-based SNP genotyping and parametric linkage analysis and sequencing analysis of protein-coding exons, exon-intron boundaries and conserved extragenic regions within the haplotype cosegregating with dyslexia in DNA from one affected and one unaffected family member. Cosegregation was confirmed by sequencing all available family members. Additionally, we analyzed 96 dyslexic individuals who had previously shown positive LOD scores on chromosome 4q28 as well as an even larger sample ( n = 2591). Results: We found a single prominent linkage interval on chromosome 4q, where sequence analysis revealed a nucleotide variant in the 3’ UTR of brain expressed SPRY1 in the dyslexic family member that cosegregated with dyslexia. This sequence alteration might affect the binding efficiency of the IGF2BP1 RNA-binding protein and thus influence the expression level of the SPRY1 gene product. An analysis of 96 individuals from a cohort of dyslexic individuals revealed a second heterozygous variant in this gene, which was absent in the unaffected sister of the proband. An investigation of the region in a much larger sample further found a nominal p-value of 0.0016 for verbal short-term memory (digit span) in 2,591 individuals for a neighboring SNV. After correcting for the local number of analyzed SNVs, and after taking into account linkage disequilibrium, we found this corresponds to a p-value of 0.0678 for this phenotype. Conclusions: We describe a new locus for familial dyslexia and discuss the possibility that SPRY1 might play a role in the etiology of a monogenic form of dyslexia.


Trial flow for AIMAC study. ADHD attention-deficit/hyperactivity disorder, AIMAC ADHD in mothers and children, MPH methylphenidate
Child Outcome. ADHD/ODD criteria sum score; LMCF mean (T1–T4)/adjusted mean (T5) and 95% confidence interval per group. ADHD/ODD score = Attention deficit hyperactivity disorder (ADHD) section and oppositional defiant disorder (ODD) section of K-SADS-PL (= Kiddie Schedule for Affective Disorders and Schizophrenia—Present and Lifetime Version) assessed by blind observer. LMCF = Last mean carried forward [38]
Maternal Outcome. CAARS-O:L ADHD index; LMCF mean (T1–T4)/adjusted mean (T5) and 95% confidence interval per group. ADHD/ODD score = Attention deficit hyperactivity disorder (ADHD) section and oppositional defiant disorder (ODD) section of K-SADS-PL (= Kiddie Schedule for Affective Disorders and Schizophrenia—Present and Lifetime Version) assessed by blind observer. LMCF = Last mean carried forward [38]
Does helping mothers in multigenerational ADHD also help children in the long run? 2-year follow-up from baseline of the AIMAC randomized controlled multicentre trial

October 2020

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262 Reads

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3 Citations

European Child & Adolescent Psychiatry

ADHD often affects multiple generations in a family. Previous studies suggested that children with ADHD benefit less from therapy if parents are also affected, since ADHD symptoms interfere with treatment implementation. This two-group randomised controlled trial examined whether targeting maternal ADHD boosts the efficacy of parent–child training (PCT) for the child’s ADHD. Here, we report follow-up results 2 years from baseline. Mothers of 144 mother–child dyads (ADHD according to DSM-IV) were examined for eligibility (T1) and randomised to 12 weeks of intensive multimodal treatment comprising pharmacotherapy and DBT-based cognitive behavioural group psychotherapy (TG, n = 77) or clinical management comprising non-specific counselling (CG, n = 67) for Step 1 (concluded by T2). Subsequently, all dyads participated in 12 weekly PCT sessions for Step 2 (concluded by T3). In Step 3, participants received maintenance treatments for 6 months (concluded by T4). At 24 months after baseline (T5), we performed follow-up assessments. The primary endpoint was child ADHD/ODD score (observer blind rating). Outcomes at T5 were evaluated using ANCOVA. Assessments from 101 children and 95 mothers were available at T5. Adjusted means (m) of ADHD/ODD symptoms (range 0–26) in children did not differ between TG and CG (mean difference = 1.0; 95% CI 1.2–3.1). The maternal advantage of TG over CG on the CAARS-O:L ADHD index (range 0–36) disappeared at T5 (mean difference = 0.2; 95% CI − 2.3 to 2.6). Sensitivity analyses controlling for medication and significant predictors of follow-up participation showed unchanged outcomes. Within-group outcomes remained improved from baseline. At the 24-month follow-up, TG and CG converged. The superiority of intensive treatment regarding maternal symptoms disappeared. In general, cross-generational treatment seems to be effective in the long term. (BMBF grant 01GV0605; registration ISRCTN73911400).


FIGURE 1 | Gene loci of Neuropetide Y (NPY, A) and NPY-receptor (NPY1R, B).
Transmission Disequilibrium Test (TDT) results.
Meta-analysis results.
Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents

May 2019

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93 Reads

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2 Citations

Frontiers in Molecular Neuroscience

Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD.



Citations (50)


... Over the past years, the interest in studying laterality has increased considerably, driven by several findings that reveal a higher prevalence of non-right handedness (i.e., left-and mixed-handedness) among individuals with neurodevelopmental disorders. Atypical handedness (i.e., non-right handedness) has been associated with neurodevelopmental disorders such as developmental dyslexia (DD, for metaanalyses see Abbondanza et al., 2023;Eglinton & Annett, 1994;Packheiser et al., 2023), developmental coordination disorder (DCD, see for meta-analysis Darvik et al., 2018), intellectual disability (see for meta-analysis Papadatou-Pastou & Tomprou, 2015), and autism spectrum disorder (see for meta-analysis Markou et al., 2017). Furthermore, there is also evidence of atypical functional and structural lateralization among individuals with DD Bishop, 2013; and DCD (Biotteau et al., 2016;Hodgson & Hudson, 2017), among other disorders. ...

Reference:

Perinatal adversities as a common factor underlying the association between atypical laterality and neurodevelopmental disorders: A developmental perspective
Language and reading impairments are associated with increased prevalence of non-right-handedness

Child Development

... It is very helpful to provide learners with an overall speaking level assessment in computer-assisted language learning systems. There have been many studies in this direction [11][12][13]. In addition to the overall speaking level score of the speaker, providing more detailed and specific feedback on pronunciation errors is more helpful for learners' language learning [14][15]. ...

Non-right handedness is associated with language and reading impairments

Child Development

... Patient and medication data were derived from the multicentre pharmacovigilance trial (Phase IIIb) 'TDM-VIGIL', subproject 1, EudraCT number 2013-004881-33, which prospectively collected data from 710 children and adolescents with different psychiatric and behavioural disorders treated naturalistically between May 2014 and December 2018, described in detail elsewhere (Egberts et al. 2022). The samples were analysed at the specialized TDM laboratory of the centre of mental health of the university hospital Wuerzburg according to standardized and validated methods using HPLC separation and UV detection. ...

Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone

Journal of Neural Transmission

... There is a literature about non-right handedness (Abbondanza et al., 2022) and right hemisphere activation (Pugh et al., 2000) for language tasks in dyslexic populations that indicate an aberration in cerebral dominance. Also, a few studies have been published on the issue of structural planum temporale asymmetry as seen in in vivo imaging studies (for a review, see Shapleske et al., 1999). ...

Non-right handedness is associated with language and reading impairments
  • Citing Preprint
  • March 2022

... The combination of whole genome linkage (WGL) analyses in large families and WGS of the linkage regions has resulted in novel DD candidate genes. Examples are an intron variant with cis-regulatory effect on SEMA3C 21 and a missense variant in the gene SPY 22 . We have used a similar approach of WGL analyses of six large Danish DD families and analysed the linkage regions by WGS. ...

A Novel Locus and Candidate Gene for Familial Developmental Dyslexia on Chromosome 4q
  • Citing Article
  • November 2020

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie

... Considering these findings, despite being based on a limited number of studies, this suggests a non-specific effect on emotional-related comorbidities as comparisons with active control groups yielded negative results. On the other hand, another study found DBT and MPH to be more effective than supportive counselling , but the differences disappeared after 24 months (Geissler et al., 2020). ...

Does helping mothers in multigenerational ADHD also help children in the long run? 2-year follow-up from baseline of the AIMAC randomized controlled multicentre trial

European Child & Adolescent Psychiatry

... Additionally, several studies with mixed results showed genetic variants association of OCD with SAPAP3/DLGAP3 (Discs Large Homolog Associated Protein 3) Boardman et al., 2011;Crane et al., 2011;Mas et al., 2016;Züchner et al., 2009), a post-synaptic density component that forms a scaffolding complex with other proteins in the glutamatergic synapses (Scannevin and Huganir, 2000), and SLITRK1 (SLIT And NTRK Like Family Member 1) (Melo--Felippe et al., 2019; Ozomaro et al., 2013;Wendland et al., 2006), which plays a role in the growth and development of nerve cells (Beaubien et al., 2016). Moreover, the involvement of endogenous opioid (Urraca et al., 2004), endocannabinoid (Kayser et al., 2020), and NPY-system (Franke et al., 2019) was investigated in relation to OCD development, even though their role still remains poorly understood. ...

Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents

Frontiers in Molecular Neuroscience

... Initially put forward to counter collapsing of information across situations to enhance functional behaviour analyses, they listed 16 home situations and 12 school situations to focus on. Subsequent reports, however, appeared to undo the initial intention by suggesting from 1 to 4 factor solutions to summarize again (Breen & Altepeter, 1991;Breuer & Döpfner, 1997;DuPaul & Barkley, 1992), and several studies have simply used the total score (e.g., Hautmann et al., 2018;Naglieri et al., 2010). ...

Sequential treatment of ADHD in mother and child (AIMAC study): Importance of the treatment phases for intervention success in a randomized trial

BMC Psychiatry

... They are physically active and exercise obsessively. [3][4][5] No definite treatment of AN has been determined. Pharmacologic alternatives and seemingly effective psychotherapy and nutritional interventions may be applied. ...

A multicentre randomized controlled trial on trans-generational attention deficit/hyperactivity disorder (ADHD) in mothers and children (AIMAC): an exploratory analysis of predictors and moderators of treatment outcome
  • Citing Article
  • August 2018

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie

... In den vergangenen Jahren wurden verschiedene Artikel publiziert, die die derzeitige und zukünftige Situation des Fachgebietes Kinder-und Jugendpsychiatrie in Deutschland zum Thema haben [1][2][3]. ...

Wie bringen wir das Fach Kinder- und Jugendpsychiatrie und -psychotherapie besser ins Bewusstsein der Öffentlichkeit?
  • Citing Article
  • July 2018

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie