| 1. |
- Hilbert, Kevin, et al.
(author)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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In: The American Journal of Psychiatry. - 1535-7228.
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Journal article (peer-reviewed)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 2. |
- Fokkens, Wytske J., et al.
(author)
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EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists
- 2012
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In: Rhinology. - 0300-0729. ; 50:1, s. 1-12
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Journal article (peer-reviewed)abstract
- The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also propose definitions for 'difficult to treat' rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between the upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists.
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| 3. |
- Bustin, Stephen A., et al.
(author)
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The need for transparency and good practices in the qPCR literature
- 2013
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 10:11, s. 1063-1067
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Journal article (other academic/artistic)abstract
- Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.
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| 4. |
- Desmet, Karel, et al.
(author)
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Associated factors of nurse-sensitive patient outcomes : A multicentred cross-sectional study in psychiatric inpatient hospitals
- 2023
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In: Journal of Psychiatric and Mental Health Nursing. - : Blackwell Publishing. - 1351-0126 .- 1365-2850. ; 30:6, s. 1231-1244
-
Journal article (peer-reviewed)abstract
- Introduction The lack of evidence on patient characteristics and relational-contextual factors influencing nurse-sensitive patient outcomes of a nurse-patient relationship is a possible threat to the quality and education of the nurse-patient relationship.Aim To measure nurse-sensitive patient outcomes of the nurse-patient relationship and to explore the associations between nurse-sensitive patient outcomes and a range of patient characteristics and relational-contextual factors.Method In a multicenter cross-sectional study, 340 inpatients from 30 units in five psychiatric hospitals completed the Mental Health Nurse-Sensitive Patient Outcome Scale. Descriptive, univariate and Linear Mixed Model analyses were conducted.Results Overall, patient-reported outcomes were moderate to good. Female participants, nurse availability when needed, more nurse contact and nurse stimulation were associated with higher outcomes. Age differences were observed for some of the outcomes. Outcomes also varied across hospitals but were not related to the number of times patients were hospitalized or to their current length of stay in the hospital.Discussion The results may help nurses to become more sensitive and responsive to factors associated with nurse-sensitive patient outcomes of the nurse-patient relationship.Implications The nurse-sensitive results can support nurses in designing future nurse-patient relationships.
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| 5. |
- Desmet, Karel, et al.
(author)
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Patient-reported outcomes of the nurse-patient relationship in psychiatric inpatients hospitals : a multicentred descriptive cross-sectional study
- 2023
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In: Journal of Psychiatric and Mental Health Nursing. - : Blackwell Publishing. - 1351-0126 .- 1365-2850. ; 30:3, s. 568-579
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Identifying patient-reported outcomes of the nurse-patient relationship is a priority in inpatient mental healthcare to guide clinical decision-making and quality improvement initiatives. Moreover, demonstrating nurse-sensitive patient outcomes can be a strategy to avoid further erosion of the specialism of psychiatric and/or mental health nursing.AIM/QUESTION: To measure nurse-sensitive patient outcomes of the nurse-patient relationship.METHOD: In a multicentred cross-sectional study, 296 inpatients admitted to five psychiatric hospitals completed the recently developed and validated Mental Health Nurse-Sensitive Patient Outcome-Scale (MH-NURSE-POS). The MH-NURSE-POS consists of 21 items (six-point Likert-scale) in four domains: 'growth', 'expression', 'control', and 'motivation'.RESULTS: Participants displayed moderate to good average scores for the MH-NURSE-POS total (4.42) and domain scores (≥4.09). Especially outcomes related to 'motivation' to follow and stay committed to the treatment received high average scores (≥4.60).DISCUSSION: The results demonstrate that patients perceive the nurse-patient relationship and the care given by psychiatric and/or mental health nurses as contributing to their treatment.IMPLICATIONS FOR PRACTICES: Patient-reported outcomes can guide nurses and managers to provide and organize nursing care and to build a nurse-patient relationship that has a positive impact on these outcomes. Additionally, outcomes can create nursing visibility as a profession in- and outside mental healthcare.
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| 6. |
- Desmet, Karel, et al.
(author)
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The development and psychometric evaluation of the Mental Health Nurse-Sensitive Patient Outcome-Scale (MH-NURSE-POS) for inpatient psychiatric hospital settings
- 2021
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In: International Journal of Mental Health Nursing. - : John Wiley & Sons. - 1445-8330 .- 1447-0349. ; 30:4, s. 988-1000
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Journal article (peer-reviewed)abstract
- Mental health nurses are struggling to describe their nursing identity as professional discipline in a changing mental health care. Measuring nurse-sensitive patient outcomes and demonstrating nursing's effect(s) experienced by patients contribute to (re)discover the specific nursing identity. However, a valid and reliable scale is currently lacking. The aim of this study was the development and psychometric evaluation of the Mental Health Nurse-Sensitive Patient Outcome Scale (MH-NURSE-POS) for inpatient psychiatric hospital settings. This three-staged study resulted in a scale capturing how inpatients experience the contribution of nurses in their treatment in psychiatric hospitals. First, a draft questionnaire was developed based on a literature review, an independent expert's advice, and an experts panel. Second, the content validity was tested in a two-round Delphi-procedure and focus groups with patients. A pilot test, based on cognitive interviews, confirmed the feasibility of the questionnaire. Third, the psychometric properties of the mental health nurse-sensitive patient outcomes were determined in a sample of 353 patients. The cross-sectional study included a convenience sample of five psychiatric hospitals (Belgium). The factor structure (Kaiser-Meyer-Olkin measure of sampling adequacy 0.924; Bartlett's test of sphericity χ2 = 4162.537; df = 231; P < 0.001), convergent validity by the Individualized Care Scale (Pearson correlation 0.660; P < 0.001), and reliability (Cronbach's Alpha 0.854) were evaluated. The factor analysis resulted in a four-factor solution representing growth, expression, control, and motivation. The Mental Health Nurse-Sensitive Patient Outcome Scale is a valid and reliable tool to measure the effectiveness of mental health nurses from the patient perspective.
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| 7. |
- Kronenberg, Linda M., et al.
(author)
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Burden and Expressed Emotion of Caregivers in Cases of Adult Substance Use Disorder with and Without Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder
- 2016
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In: International Journal of Mental Health and Addiction. - : Springer Science and Business Media LLC. - 1557-1874 .- 1557-1882. ; 14:1, s. 49-63
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Journal article (peer-reviewed)abstract
- Objective To identify and compare caregiver burden and expressed emotion (EE) in adult substance use disorder (SUD) patients with and without co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). To examine possible differences in correlations between caregiver burden and EE across patient groups. Design and Methods Cross-sectional study with measures of perceived burden (Involvement Evaluation Questionnaire: IEQ), subjective stress (General Health Questionnaire: GHQ) and perceptions of expressed emotion (Level of Expressed Emotion: LEE) in informal caregivers for patients with SUD, SUD+ADHD or SUD+ASD. Findings No differences in caregiver burden or expressed emotion when caregivers for patients with SUD were compared to caregivers for patients with SUD+ADHD. A moderate but non-significant difference for caregivers of patients with SUD versus SUD+ASD, which disappeared when the number of contact hours between patient and caregiver for the SUD only group was controlled for. The IEQ sum scores also substantially correlated with the LEE sum scores. Conclusion Informal caregivers for patients with only SUD show higher levels of burden and EE than informal caregivers for patients with SUD and a co-occurring ASD. This difference was largely explained by the higher number of contact hours between patient and caregiver in the SUD only group.
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| 8. |
- Kronenberg, Linda M., et al.
(author)
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Coping styles in substance use disorder (SUD) patients with and without co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD)
- 2015
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In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 15
-
Journal article (peer-reviewed)abstract
- Background: Patients with a substance use disorder (SUD) and co-occurring attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) often start using substances in an attempt to cope with the stress related to their ADHD or ASD. To improve treatment for these patient groups, it is important to identify and compare the various coping styles between SUD patients with and without ADHD or ASD and with subjects from a general population sample. Methods: Cross-sectional study using the Utrecht Coping List (UCL) in 50 SUD patients, 41 SUD + ADHD patients, 31 SUD + ASD patients and 1,200 railway employees. Results: Compared with the reference group, all three SUD groups showed a significant higher mean on the Palliative reaction, Avoidance, and Passive reaction subscales of the UCL. The scores for all UCL subscales of the SUD and the SUD + ADHD groups were very similar. However, the SUD + ASD group scored higher on Passive reaction and lower on Reassuring thoughts than the SUD and the SUD + ADHD groups and lower on Expression of emotions subscale in comparison with the SUD + ADHD group. Conclusions: Regardless of the presence of a co-occurring disorder, SUD patients reported more palliative, avoidant and passive coping when confronted than people in the general population. In addition, SUD patients with co-occurring ASD were different from other SUD patients in their coping and professionals should take this into account when working on more adaptive coping strategies with these patients.
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| 9. |
- Kronenberg, Linda M., et al.
(author)
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Everyday life consequences of substance use in adult patients with a substance use disorder (SUD) and co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) : a patient's perspective
- 2014
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In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 14, s. 264-
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Journal article (peer-reviewed)abstract
- Background: Although the prevalence of substance use disorder (SUD) with co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) is relatively high in adult patients, there is hardly any knowledge about these dual diagnoses. A recent study reported met-and unmet needs for several life domains regarding these patient groups. To improve treatment, it is necessary to identify the everyday life consequences of SUD and co-occurring ADHD or ASD in adult patients. Methods: Qualitative study using in-depth interviews. 11 SUD + ADHD and 12 SUD + ASD patients participated in the study. The interview transcripts were coded and analysed according to the seven steps for descriptive phenomenology by Colaizzi. Results: Both patients with ADHD and patients with ASD can get caught in a jumble of thoughts and emotions which can often lead to agitation and impulsivity in the case of ADHD or passivity and melancholia in the case of ASD with co-occurring SUD in both cases. Initially substance use ameliorates the symptoms and related problems, but both patient groups can later experience even greater problems: difficulties with the structuring of daily life due to a lack of planning (SUD + ADHD) or due to a lack of initiative (SUD + ASD). Both groups indicate that structure helps them function better. They also recognize that substance use disorganizes their lives and that an absence of structure contributes to substance use in what becomes a vicious circle which needs to be broken for effective treatment and care. Conclusions: This study provides insight into the daily life consequences of SUD with a co-occurring ADHD or ASD. Substance use is reported to solve some ADHD- or ASD-related problems in the short run but have negative consequences in the long run (i.e., contribute to already impaired cognitive functioning). Insight is provided into what clinicians can do to break this vicious circle and thus help ADHD patients to refrain from action and ASD patients to take action.
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| 10. |
- Kronenberg, Linda M., et al.
(author)
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Personal Recovery in Individuals Diagnosed with Substance use Disorder (SUD) and Co-Occurring Attention Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder (ASD)
- 2015
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In: Archives of Psychiatric Nursing. - : Elsevier BV. - 0883-9417 .- 1532-8228. ; 29:4, s. 242-248
-
Journal article (peer-reviewed)abstract
- The process of personal recovery in people diagnosed with substance use disorder and comorbid attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) was mapped. Four general themes representing four consecutive stages in the recovery process were identified in both client groups: (1) crisis and diagnosis; (2) dealing with agitation, symptoms, and burden; (3) reorganization of life; and (4) meaningful life. However, the personal recovery outcomes and the need for support were different for the two clients groups. Based on these findings, mental health nurses can offer recovery supporting care tailored to the challenging needs of these clients. For the SUD + ADHD group, overall, a coaching attitude is preferred. For the SUD + ASD group, overall, instructional, supportive and directive attitude is needed.
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| 11. |
- Voogt, L. Amar, et al.
(author)
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Development of the Psychiatric Nursing Intervention Providing Structure : An International Delphi Study
- 2016
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In: Journal of the American Psychiatric Nurses Association. - : SAGE Publications. - 1078-3903 .- 1532-5725. ; 22:2, s. 100-111
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Journal article (peer-reviewed)abstract
- BACKGROUND: Psychiatric nurses commonly refer to providing structure (PS) as a key intervention. But no consensus exists about what PS entails. PS can be understood as a complex intervention. In four previous studies, a definition, activities, and context variables were described that were presented to experts in a Delphi study. OBJECTIVE: To reach consensus about the definition of PS, its activities, and context variables. DESIGN: In a qualitative study, a Delphi study is used to gather the opinions of experts. The Delphi study consisted of three rounds with statements to score in each round. RESULTS: Experts reached consensus about a definition of PS, its activities, and context variables. Eleven statements related to the definition were accepted. Fourteen statements of a total of 17 statements related to the specific activities reached sufficient agreement, and 4 statements related to context variables were accepted. CONCLUSIONS: A definition could be given of PS with 4 general PS activities, 15 specific activities, and 3 context variables. Psychiatric nurses can use the information about PS to reflect on the use of PS activities within their own working environment, and these insights can help nurses develop their professional growth.
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| 12. |
- Agner, Tove, et al.
(author)
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Contact sensitisation in hand eczema patients-relation to subdiagnosis, severity and quality of life: a multi-centre study
- 2009
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In: Contact Dermatitis. - 0105-1873. ; 61:5, s. 291-296
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Journal article (peer-reviewed)abstract
- Background Contact sensitisation has been identified as a factor associated with poor prognosis for patients with hand eczema. Objectives To study implications of contact sensitisation with respect to severity, quality of life (QoL) and subdiagnosis of hand eczema. Methods The study was performed as a multi-centre, cross-sectional study from 10 European clinics. All patients were patch tested, and severity of hand eczema assessed by Hand Eczema Severity Index. A multi-variate analysis was performed to explore which factors influenced severity, QoL and sick leave. Results A total 416 patients were included, and 63% had contact sensitisation to one or more of the tested allergens. More women (66%) than men (51%) were sensitized. No significant association was found between sensitisation to specific allergens, disease severity, QoL or diagnostic subgroups. High age, male sex, atopic eczema and presence of contact sensitisation were independent risk factors for increased severity as measured by Hand Eczema Severity Index. Furthermore, the severity of hand eczema increased by the number of contact sensitisations detected (P = 0.023). High age and personal history of atopic eczema were independent risk factors for low QoL, as measured by Dermatology Life Quality Index, and atopic eczema as well as allergic contact dermatitis as subdiagnosis was associated with increased sick leave. Conclusion Diagnostic subgroups were not found to be related to specific allergens. Contact sensitisation was found to be a risk factor for increased severity of hand eczema, as did high age, male sex and atopic eczema.
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| 13. |
- Agner, Tove, et al.
(author)
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Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients
- 2008
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In: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 59:1, s. 43-47
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Journal article (peer-reviewed)abstract
- Background and Objectives: Hand eczema is a chronic disease with negative impact on quality of life (QoL). In this study, QoL in hand eczema patients is assessed and related to age, sex, severity, and diagnostic subgroups. Methods: A total of 416 patients with hand eczema from 10 European patch test clinics participated in the study. Data on QoL were obtained from a self-administered questionnaire using the Dermatology Life Quality Index (DLQI). Severity was assessed by a scoring system (Hand Eczema Severity Index, HECSI) as well as frequency of eruptions and sick leave due to hand eczema. Results: No significant difference was found between males and females with respect to QoL [DLQI median values and 25/75 percentiles for males and females being 7.0 (3-14) and 8.0 (3-13), respectively], although males were more severely affected than females (P < 0.025). A significant positive correlation was found for hand eczema severity and age (P < 0.001), while no significant correlation was found for QoL and age. QoL was found increasingly reduced when sick leave was getting higher (P < 0.001). A statistically significant correlation between QoL (as measured by DLQI) and hand eczema severity as measured by HECSI was found (P < 0.001). No significant difference in QoL was found between diagnostic subgroups. Conclusions: QoL was found markedly negatively affected in hand eczema patients and was significantly correlated to disease severity. No significant difference in QoL was found between males and females, in spite of significantly more severe eczema in males, indicating that QoL in female patients is more easily affected.
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| 14. |
- Biganzoli, L., et al.
(author)
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The requirements of a specialist breast centre
- 2020
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In: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 51, s. 65-84
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Journal article (peer-reviewed)abstract
- This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. The centrepiece of this article is the requirements section, comprising definitions; multidisciplinary structure; minimum case, procedure and staffing volumes; and detailed descriptions of the skills of, and resources needed by, members and specialisms in the multidisciplinary team in a breast centre. These requirements are positioned within narrative on European breast cancer epidemiology, the standard of care, challenges to delivering this standard, and supporting evidence, to enable a broad audience to appreciate the importance of establishing these requirements in specialist breast centres. (C) 2020 The Authors. Published by Elsevier Ltd.
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| 15. |
- Butler, Christopher C, et al.
(author)
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Treatment of acute cough/lower respiratory tract infection by antibiotic class and associated outcomes: a 13 European country observational study in primary care
- 2010
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In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 65:11, s. 2472-2478
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Journal article (peer-reviewed)abstract
- Acute cough/lower respiratory tract infection (LRTI) is one of the commonest reasons for consulting and antibiotic prescribing. There are theoretical reasons why treatment with particular antibiotic classes may aid recovery more than others, but empirical, pragmatic evidence is lacking. We investigated whether treatment with a particular antibiotic class (amoxicillin) was more strongly associated with symptom score resolution and time to patients reporting recovery than each of eight other antibiotic classes or no antibiotic treatment for acute cough/LRTI. Clinicians recorded history, examination findings, symptom severity and antibiotic treatment for 3402 patients in a 13 country prospective observational study of adults presenting in 14 primary care research networks with acute cough/LRTI. 2714 patients completed a symptom score daily for up to 28 days and recorded the day on which they felt recovered. A three-level autoregressive moving average model (1,1) model investigated logged daily symptom scores to analyse symptom resolution. A two-level survival model analysed time to reported recovery. Clinical presentation was controlled for using clinician-recorded symptoms, sputum colour, temperature, age, co-morbidities, smoking status and duration of illness prior to consultation. Compared with amoxicillin, no antibiotic class (and no antibiotic treatment) was associated with clinically relevant improved symptom resolution (all coefficients in the range -0.02 to 0.01 and all P values greater than 0.12). No antibiotic class (and no antibiotic treatment) was associated with faster time to recovery than amoxicillin. Treatment by antibiotic class was not associated with symptom resolution or time to recovery in adults presenting to primary care with acute cough/LRTI.
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| 16. |
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| 17. |
- Moens, Lotte N, et al.
(author)
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Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23450-
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Journal article (peer-reviewed)abstract
- In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence - both genetic and functional - indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that similar to 90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology.
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| 18. |
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| 19. |
- Van Den Bossche, Maarten J., et al.
(author)
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Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders
- 2012
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In: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 159B:4, s. 465-475
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Journal article (peer-reviewed)abstract
- The GWAS-based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage-dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient-control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7?kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 1726 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.
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| 20. |
- Van Den Bossche, Maarten J., et al.
(author)
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Rare copy number variants in neuropsychiatric disorders : Specific phenotype or not?
- 2012
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In: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 159B:7, s. 812-822
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Journal article (peer-reviewed)abstract
- From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on additional genetic and environmental factors. Our results also suggest that the neurodevelopmental component is larger in the etiology of schizophrenia and intellectual disability than in mood disorders. Finally, our data suggest that deletions are in general more pathogenic than duplications. Given the high frequency of the examined CNVs (12%) in patients of different neuropsychiatric disorders, screening of large cohorts with an affordable and feasible method like the MAQ assays used in this study is likely to result in important progress in unraveling the genetic factors leading to an increased susceptibility for several psychiatric disorders.
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