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  • 1
    Online Resource
    Online Resource
    Knockdown of the ADHD Candidate Gene Diras2 in Murine Hippocampal Primary Cells
    SAGE Publications ; 2021
    In:  Journal of Attention Disorders Vol. 25, No. 4 ( 2021-02), p. 572-583
    Details
    In: Journal of Attention Disorders, SAGE Publications, Vol. 25, No. 4 ( 2021-02), p. 572-583
    Abstract: Objective: The DIRAS2 gene is associated with ADHD, but its function is largely unknown. Thus, we aimed to explore the genes and molecular pathways affected by DIRAS2. Method: Using short hairpin RNAs, we downregulated Diras2 in murine hippocampal primary cells. Gene expression was analyzed by microarray and affected pathways were identified. We used quantitative real-time polymerase chain reaction (qPCR) to confirm expression changes and analyzed enrichment of differentially expressed genes in an ADHD GWAS (genome-wide association studies) sample. Results: Diras2 knockdown altered expression of 1,612 genes, which were enriched for biological processes involved in neurodevelopment. Expression changes were confirmed for 33 out of 88 selected genes. These 33 genes showed significant enrichment in ADHD patients in a gene-set-based analysis. Conclusion: Our findings show that Diras2 affects numerous genes and thus molecular pathways that are relevant for neurodevelopmental processes. These findings may further support the hypothesis that DIRAS2 is linked to etiological processes underlying ADHD.
    Type of Medium: Online Resource
    ISSN: 1087-0547 , 1557-1246
    URL: Article
    DOI: 10.1177/1087054718822129
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Multi-level biomarker analysis of nitric oxide synthase isoforms in bipolar disorder and adult ADHD
    SAGE Publications ; 2015
    In:  Journal of Psychopharmacology Vol. 29, No. 1 ( 2015-01), p. 31-38
    Details
    In: Journal of Psychopharmacology, SAGE Publications, Vol. 29, No. 1 ( 2015-01), p. 31-38
    Abstract: Several studies have shown altered levels of nitric oxide (NO) and its stable metabolites (NO x - ) in blood and cerebrospinal fluid of psychiatric patients. The aim of our study was to replicate previous findings and investigate the influence of the nitrinergic system in bipolar disorder and adult attention-deficit/hyperactivity disorder (aADHD) in particular. Methods: The concentrations of NO 2 - and NO 3 - in peripheral blood in a sample of aADHD, bipolar disorder (BPD) and controls were analysed. The sample was genotyped for a three marker haplotype in the NOS3 gene (rs2070744, rs1799983 and Intron 4 VNTR) and for genetic variants of the NOS1 gene ( NOS1 ex 1c, NOS1 ex 1f). Finally, qRT PCR was performed. Results: We found significantly lower NO x - levels in BPD ( p 〈 0.001). rs2070744 T/T-carriers of the whole sample showed increased mRNA expression of NOS3 ( p=0.05). Only in BPD an influence of rs2070744 was seen regarding NO metabolite levels; C/C carriers displayed lower NO x - levels ( p=0.05). Conclusion: We could replicate and extend previous findings showing altered NO x - levels in BPD and an influence of NOS3 rs2070744 on NOS3 expression and NO x - concentration. Together, these data point to a role of the nitrinergic pathway in BPD.
    Type of Medium: Online Resource
    ISSN: 0269-8811 , 1461-7285
    URL: Article
    DOI: 10.1177/0269881114555251
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2028926-1
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  • 3
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    Online Resource
    Further evidence for the association of the NPSR1 gene A/T polymorphism (Asn 107 Ile) with impulsivity and hyperactivity
    SAGE Publications ; 2015
    In:  Journal of Psychopharmacology Vol. 29, No. 8 ( 2015-08), p. 878-883
    Details
    In: Journal of Psychopharmacology, SAGE Publications, Vol. 29, No. 8 ( 2015-08), p. 878-883
    Abstract: Administration of neuropeptide S (NPS) elicits anxiolysis, arousal and higher activity in rodents. In humans, the NPS receptor ( NPSR1) gene rs324981 A/T (Asn 107 Ile) polymorphism is associated with fear responses and anxiety. We have recently revealed an association of NPSR1 with impulsivity-related traits and psychopathology. In the present study the association of the NPSR1 genotype with impulsivity and attention-deficit/hyperactivity disorder (ADHD)-related symptoms was re-examined in two independent non-clinical cohorts. We used self-reports of two population-derived samples of the Estonian Psychobiological Study of Traffic Behaviour (EPSTB): a community car driving sample ( n=491, M Age =37) and a driving school student sample ( n=773, M Age =24). Impulsivity was measured with the Adaptive and Maladaptive Impulsivity Scale (AMIS) in both samples, and with the Barratt Impulsivity Scale (BIS) in driving schools only. For the latter sample, also measurement of ADHD symptoms was carried out with the Adult ADHD Self-Report Scale (ASRS). NPSR1 T-allele carriers had higher scores of impulsivity, motor restlessness and total ADHD scores. The effect on impulsivity originated from male participants but for ADHD symptoms the association was independent of sex. Thus we have confirmed in two additional population-derived samples that the T-allele of the NPSR1 rs324981 polymorphism is associated with increased impulsivity and ADHD-related traits.
    Type of Medium: Online Resource
    ISSN: 0269-8811 , 1461-7285
    URL: Article
    DOI: 10.1177/0269881115573803
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
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  • 4
    Online Resource
    Online Resource
    A functional NPSR1 gene variant and environment shape personality and impulsive action: A longitudinal study
    SAGE Publications ; 2014
    In:  Journal of Psychopharmacology Vol. 28, No. 3 ( 2014-03), p. 227-236
    Details
    In: Journal of Psychopharmacology, SAGE Publications, Vol. 28, No. 3 ( 2014-03), p. 227-236
    Abstract: Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety. We examined whether the NPSR1 gene functional polymorphism Asn 107 Ile (rs324981, A 〉 T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE). We used self-reports or teachers’ ratings for both the younger ( n=593) and older ( n=583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Males with the TT genotype displayed more ADHD-related symptoms. Adaptive impulsivity and Extraversion increased the most from age 18 to 25. While highest increases were observed in AA men, TT women exhibited the largest decreases. For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity. High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects. We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity- and anxiety-mediating role of NPSR1. Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.
    Type of Medium: Online Resource
    ISSN: 0269-8811 , 1461-7285
    URL: Article
    DOI: 10.1177/0269881112472562
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 5
    Online Resource
    Online Resource
    Influence of a Multimodal and Multimodal-Aerobic Therapy Concept on Health-Related Quality of Life in Breast Cancer Survivors
    SAGE Publications ; 2019
    In:  Integrative Cancer Therapies Vol. 18 ( 2019-01), p. 153473541882044-
    Details
    In: Integrative Cancer Therapies, SAGE Publications, Vol. 18 ( 2019-01), p. 153473541882044-
    Abstract: Context: Cancer-related fatigue (CRF) is one of the most burdensome symptoms in breast cancer survivors (BCSs), accompanied by reduced health-related quality of life (HRQOL). Objectives: This study investigated the influence of a multimodal therapy (MT; psychoeducation, eurythmy therapy, painting therapy, and sleep education/restriction), or a combination therapy (CT; MT plus aerobic training [AT]) on HRQOL in BCS with chronic CRF in comparison with AT alone. Methods: One hundred and twenty-six BCSs with CRF were included in a pragmatic comprehensive cohort study and allocated either per randomization or by preference to MT, CT, or AT. The EORTC QLQ-C30 core questionnaire was used to measure HRQOL. All analyses on HRQOL parameters were done in an explorative intention. Results: Patients were assigned to MT (n = 44), CT (n = 54), or AT (n = 28). CT was significantly superior to AT after 10 weeks of intervention (T1) in improving physical function. MT was found to have significant superiority over AT at T1 and T2 for physical functioning, emotional functioning, insomnia, and financial problems as well as role functioning, cognitive, social functioning, and fatigue 6 months later (T2). Conclusion: A multimodal approach appears to be a suitable concept for BCS with chronic CRF. A confirmatory study with larger samples should demonstrate the superiority of MT and adapted CT in HRQOL compared with the current treatment AT found in these explorative analyses.
    Type of Medium: Online Resource
    ISSN: 1534-7354 , 1552-695X
    URL: Article
    DOI: 10.1177/1534735418820447
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2101248-9
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  • 6
    Online Resource
    Online Resource
    Comedication and Polypharmacy With ADHD Medications in Adults: A Swedish Nationwide Study
    SAGE Publications ; 2021
    In:  Journal of Attention Disorders Vol. 25, No. 11 ( 2021-09), p. 1519-1528
    Details
    In: Journal of Attention Disorders, SAGE Publications, Vol. 25, No. 11 ( 2021-09), p. 1519-1528
    Abstract: Objective: Evidence regarding comedication among individuals with ADHD is lacking, especially in adults. This study investigated comedication and polypharmacy with ADHD medications in adults. Method: We identified adults dispensed with ADHD medications during 2013 in Sweden and matched them to controls. Logistic regression was used to calculate odds ratios (ORs) of receiving other medications. Results: Individuals receiving ADHD medications had higher risk of receiving any major classes of somatic medications (ORs ranged from 4.1, 95% confidence interval [CI] = [4.0, 4.3] , to 7.4, 95% CI = [6.5, 8.5] across age groups). They were more likely to receive respiratory system, alimentary tract and metabolic system, and cardiovascular system medications. In addition, they had higher risk of receiving any other psychotropic medications. The proportion of polypharmacy with five or more medication classes increased from 10.1% to 60.4% from 18 to 64 years. Conclusion: Comedication was more common in adults receiving ADHD medications. Potential benefits and harms of comedication and polypharmacy require further research. (J. of Att. Dis. XXXX; XX[ X] XX-XX)
    Type of Medium: Online Resource
    ISSN: 1087-0547 , 1557-1246
    URL: Article
    DOI: 10.1177/1087054720923725
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 7
    Online Resource
    Online Resource
    Sex- and Subtype-Related Differences in the Comorbidity of Adult ADHDs
    SAGE Publications ; 2016
    In:  Journal of Attention Disorders Vol. 20, No. 10 ( 2016-10), p. 855-866
    Details
    In: Journal of Attention Disorders, SAGE Publications, Vol. 20, No. 10 ( 2016-10), p. 855-866
    Abstract: Objective: Comorbidity in adult ADHD (aADHD) has been investigated in a large number of studies using varying research approaches with divergent results. In contrast, there is limited information about sex- or subtype-related differences from studies with small sample size. Method: A large sample of 910 individuals (458 males, 452 females) affected with aADHD was recruited at a tertiary referral center. All probands underwent a four-step procedure for diagnosing aADHD, including the Structured Clinical Interview of Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) Axis I disorders to assess comorbidity. This study will provide additional information regarding the co-morbidity of Axis I disorders in the currently largest clinical referral sample. However, the main objective of this study is to gain information about sex- or subtype-related differences. Results: Affected females show higher rates of mood (61% vs. 49%), anxiety (32% vs. 22%), and eating disorders (16% vs. 1%) than affected males, while substance use disorders were more frequent in affected males (45% vs. 29%), which mirrors sex differences in prevalence in the general population. There were hardly any relevant differences in comorbidities between subtypes, with the exception of the inattentive subtype having an especially low prevalence of panic disorder. Comorbidity in general and substance use disorders in particular, but not sex or subtype, were highly predictive of lower psychosocial status. Conclusion: Sex-related differences in the comorbidity of aADHD are more pronounced than subtype-related differences.
    Type of Medium: Online Resource
    ISSN: 1087-0547 , 1557-1246
    URL: Article
    DOI: 10.1177/1087054713510353
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2188086-4
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  • 8
    Online Resource
    Online Resource
    The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder
    SAGE Publications ; 2006
    In:  Journal of Psychopharmacology Vol. 20, No. 4 ( 2006-07), p. 547-552
    Details
    In: Journal of Psychopharmacology, SAGE Publications, Vol. 20, No. 4 ( 2006-07), p. 547-552
    Abstract: Panic disorder is a common psychiatric disorder characterized by recurrent anxiety attacks and anticipatory anxiety. Due to the severity of the symptoms of the panic attacks and the frequent additional occurrence of agoraphobia, panic disorder is an often debilitating disease. Elevation of central serotonin levels by drugs such as clomipramine represents one of the most effective treatment options for panic disorder. This points to an important role of dysregulation of the serotonergic system in the genetic etiology of panic disorder. The novel brain-specific 5-HT synthesizing enzyme, tryptophan hydroxylase-2 (TPH2), which represents the rate-limiting enzyme of 5-HT production in the brain, may therefore be of particular importance in panic disorder. We focused on the putative transcriptional control region of TPH2 and identified two novel common single nucleotide polymorphisms (SNPs) of TPH2 in and close to this region. Moreover, a recently described loss-of-function mutation of TPH2 which results in an 80% reduction of serotonin production, was assessed. In an analysis of the putative transcriptional control region SNPs in a sample of panic disorder patients and controls no association of the disorder with the TPH2 SNPs or haplotypes was found. Moreover, the loss-of-function R441H mutation of TPH2 was not present in the panic disorder patients. The results of this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder with or without agoraphobia.
    Type of Medium: Online Resource
    ISSN: 0269-8811 , 1461-7285
    URL: Article
    DOI: 10.1177/0269881106059704
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
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  • 9
    Online Resource
    Online Resource
    Sex- and Subtype-Related Differences of Personality Disorders (Axis II) and Personality Traits in Persistent ADHD
    SAGE Publications ; 2016
    In:  Journal of Attention Disorders Vol. 20, No. 12 ( 2016-12), p. 1056-1065
    Details
    In: Journal of Attention Disorders, SAGE Publications, Vol. 20, No. 12 ( 2016-12), p. 1056-1065
    Abstract: Objective: Despite growing awareness of adult ADHD and its comorbidity with personality disorders (PDs), little is known about sex- and subtype-related differences. Method: In all, 910 patients (452 females, 458 males) affected with persistent adult ADHD were assessed for comorbid PDs with the Structured Clinical Interview of DSM-IV and for personality traits with the revised NEO personality inventory, and the Tridimensional Personality Questionnaire. Results: The most prevalent PDs were narcissistic PD in males and histrionic PD in females. Affected females showed higher Neuroticism, Openness to Experience, and Agreeableness scores as well as Harm Avoidance and Reward Dependence scores. Narcissistic PD and antisocial PD have the highest prevalence in the H-type, while Borderline PD is more frequent in the C-type. Conclusion: Sex- and subtype-related differences in Axis II disorder comorbidity as well as impairment-modifying personality traits have to be taken into account in epidemiological studies of persistent ADHD.
    Type of Medium: Online Resource
    ISSN: 1087-0547 , 1557-1246
    URL: Article
    DOI: 10.1177/1087054714521293
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2188086-4
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  • 10
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    Online Resource
    Nitric Oxide Synthase Modulates CFA-Induced Thermal Hyperalgesia through Cytokine Regulation in Mice
    SAGE Publications ; 2010
    In:  Molecular Pain Vol. 6 ( 2010-01-01), p. 1744-8069-6-13-
    Details
    In: Molecular Pain, SAGE Publications, Vol. 6 ( 2010-01-01), p. 1744-8069-6-13-
    Abstract: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-10), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1β. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-10, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.
    Type of Medium: Online Resource
    ISSN: 1744-8069 , 1744-8069
    URL: Article
    DOI: 10.1186/1744-8069-6-13
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2174252-2
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