1. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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2. |
- Wang, Li-San, et al.
(author)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Journal article (peer-reviewed)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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3. |
- Forsén Mantilla, Emma, et al.
(author)
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Factor analysis of the adolescent version of the Eating Disorders Examination Questionnaire (EDE-Q) : results from Swedish general population and clinical samples
- 2017
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In: Journal of Eating Disorders. - : BMC. - 2050-2974. ; 5
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Journal article (peer-reviewed)abstract
- Background: Although the Eating Disorder Examination Questionnaire (EDE-Q) is perhaps the single most widely used self-report measure of eating disorder (ED) symptoms, important questions remain about its validity and applicability in relation to particular groups of individuals, especially adolescents of both genders. Methods: The present study investigated the factor structure of the adolescent version of the Eating Disorder Examination Questionnaire (EDE-Q) in samples of Swedish girls and boys from the general population and girls with a diagnosed eating disorder. Girls (N = 239) and boys (N = 248) aged between 13 and 15 years who were attending school, and girls (N = 570) aged between 12 and 14 years who were in treatment for an eating disorder at a specialist eating disorder clinic were assessed on the adolescent version of the EDE-Q. Results: The adolescent version of the EDE-Q demonstrated satisfactory levels of internal consistency. However, confirmatory factor analysis (CFA) failed to support the four-factor model of the EDE-Q. Parallel analysis (PA) and subsequent exploratory factor analysis (EFA) suggested that the adolescent version of the EDE-Q comprises one underlying factor in young adolescent girls (both clinical and general population), centred on Dissatisfaction with Shape and Weight. In boys three factors were found: Weight-related Concerns, Body Discomfort and Restraint. Conclusions: The EDE-Q appears to measure different underlying aspects of eating disorder psychopathology in young teenagers compared to adults. The dimensions underlying disordered eating in young girls may become increasingly differentiated with time. There appear to be important gender-based differences in the dimensions underlying the EDE-Q in young teenagers. Therapists should be alert to beliefs that girls have about the importance of shape and weight, while in boys it may be more important to be attentive to how they feel about their bodies in relation to weight.
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4. |
- Forsén Mantilla, Emma, et al.
(author)
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Insidious : The relationship patients have with their eating disorders and its impact on symptoms, duration of illness, and self-image
- 2018
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In: Psychology and Psychotherapy. - : WILEY. - 1476-0835 .- 2044-8341. ; 91:3, s. 302-316
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Journal article (peer-reviewed)abstract
- ObjectivesIn published clinical and autobiographical accounts of eating disorders, patients often describe their disorder in personified ways, that is, relating to the disorder as if it were an entity, and treatment often involves techniques of externalization. By encouraging patients to think about their eating disorder as a relationship, this study aimed to examine how young female patients experience their eating disorder as acting towards them, how they react in response, and whether these interactions are associated with symptoms, illness duration, and self-image. DesignStructural Analysis of Social Behavior (SASB) was used to operationalize how patients experience the actions of their eating disorder and their own reactions to the disorder. MethodThe relationship between patients (N=150) and their eating disorders was examined with respect to symptoms, duration of illness, and self-image. Patients were also compared on their tendency to react with affiliation in relation to their disorder. ResultsPatients' responses on the SASB indicated that they tended to conceptualize their eating disorders as blaming and controlling, and they themselves as sulking and submitting in response. Greater experience of the eating disorder as being controlling was associated with higher levels of symptomatology. Patients reacting with more negative affiliation towards their disorder were less symptomatic. ConclusionsWhen encouraging patients to think about their eating disorder as a relationship, comprehensible relationship patterns between patients and their eating disorders emerged. The idea that this alleged relationship may resemble a real-life relationship could have theoretical implications, and its exploration may be of interest in treatment. Practitioner points Patients were able to conceptualize their eating disorder as a significant other to whom they relate when encouraged to do so. Patients tended to experience their disorder as controlling and domineering. Exploring the hypothetical patient-eating disorder relationship may prove helpful in understanding dysfunctional relational patterns. Helping patients to rebel against their eating disorder could potentially aid in symptom reduction.
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5. |
- Forsén Mantilla, Emma, et al.
(author)
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The unsafe haven : Eating disorders as attachment relationships
- 2019
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In: Psychology and Psychotherapy. - : WILEY. - 1476-0835 .- 2044-8341. ; 92:3, s. 379-393
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Journal article (peer-reviewed)abstract
- Objectives Some patients with eating disorders (EDs) seem to experience their illness as an entity, a symbolic other to whom they relate, and which may influence both symptom levels and self-image. Extending previous research, this study investigated whether the patient-ED relationship has attachment qualities. Design Structural Analysis of Social Behaviour was used to operationalize the patient-ED relationship, and the Attachment Style Questionnaire was used to measure attachment. Method We examined ED patients' (N = 148) relationship with their ED, attachment behaviour, symptoms, and self-image. Attachment dimensions of Confidence, Anxious/ambivalence, and Avoidance were found to be significantly correlated with aspects of the patient-ED relationship. Introjection (i.e., whether ED actions were incorporated into patients' self-image) was investigated by examining the match between self-image profiles and the actions of patients' EDs. A double mediation model was tested in which ED control/emancipation and patients' Self-blame mediated the effect of attachment security on ED symptoms. Results Attachment insecurity was associated with greater ED control and patient submission. In 28.5% of patients, there was a high degree of correlation between self-image and ED action profile. Data supported the mediation model. Conclusions Attachment processes appear to be associated with the manner in which ED patients relate to their disorder, at least in some cases. Attempts to maintain psychological proximity to the ED as an introjected attachment figure may help to explain treatment resistance and ambivalence about change. This perspective may be useful in treatment. Practitioner points Attachment behaviours are associated with the patient-ED relationship, in which attachment insecurity is correlated with greater eating disorder control and patient submission. Some patients seem to incorporate the actions of the ED in their self-image, suggesting the presence of introjection. The patient-ED relationship may help explain patients' anxiety and ambivalence about change, seen from an attachment perspective. In treatment, it may be important to explore alternative safe havens and secure bases to the ED, such as interpersonal relationships and activities.
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7. |
- Haig, David W., et al.
(author)
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Early Triassic (early Olenekian) life in the interior of East Gondwana : mixed marine-terrestrial biota from the Kockatea Shale, Western Australia
- 2015
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In: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 417, s. 511-533
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Journal article (peer-reviewed)abstract
- A new terrestrial marine assemblage from the lower beds of a thin outcrop section of the Kockatea Shale in the northern Perth Basin, Western Australia, contains a range of fossil groups, most of which are rare or poorly known from the Lower Triassic of the region. To date, the collection includes spinose acritarchs, organic-cemented agglutinated foraminifera, lingulids, minute bivalves and gastropods, ammonoids, spinicaudatans, insects, austriocaridid crustaceans, actinopterygians, a temnospondyl-like mandible, plant remains, and spores and pollen. Of these groups, the insects, crustaceans and macroplant remains are recorded for the first time from this unit. Palynomorphs permit correlation to nearby sections where conodonts indicate an early Olenekian (Smithian) age. The locality likely represents the margin of an Early Triassic shallow interior sea with variable estuarine-like water conditions, at the southwestern end of an elongate embayment within the East Gondwana interior rift sag system preserved along the Western Australian margin. Monospecific spinose acritarch assemblages intertwined with amorphous organic matter may represent phytoplankton blooms that accumulated as mats, and suggest potentially eutrophic surface waters. The assemblage represents a mixure of marine and terrestrial taxa, suggesting variations in water conditions or that fresh/brackish-water and terrestrial organisms were transported from adjacent biotopes. Some of the lower dark shaly beds are dominated by spinicaudatans, likely indicating periods when the depositional water body was ephemeral, isolated, or subjected to other difficult environmental conditions. The biota of the Kockatea Shale is insufficiently known to estimate biotic diversity and relationships of individual taxa to their Permian progenitors and Triassic successors, but provides a glimpse into a coastal-zone from the interior of eastern Gondwana. Specialist collecting is needed to clarify the taxonomy of many groups, and comparisons to other Lower Triassic sites are required to provide insights into the pattern of biotic decline and recovery at the end-Permian crisis. (C) 2014 Elsevier B.V. All rights reserved.
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8. |
- Headley, Alison, et al.
(author)
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Neurogranin as a predictor of memory and executive function decline in MCI patients.
- 2018
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In: Neurology. - 1526-632X. ; 90:10
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Journal article (peer-reviewed)abstract
- To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD).Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included.High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21,p< 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313,p= 0.0068 and β = -0.0346,p= 0.0169, respectively) independently of age, sex, education, andAPOEε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ42) were controlled for in these analyses.High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ42are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD.
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9. |
- Kern, Silke, et al.
(author)
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Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment.
- 2019
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 76:2, s. 187-193
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Journal article (peer-reviewed)abstract
- Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau).To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations.The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid.Risk of MCI.At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI.Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid.
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10. |
- Levallius, Johanna, et al.
(author)
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Take charge : Personality as predictor of recovery from eating disorder
- 2016
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In: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 246, s. 447-452
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Journal article (peer-reviewed)abstract
- Many treatments for eating disorders (ED) have demonstrated success. However, not all patients respond the same to interventions nor achieve full recovery, and obvious candidates like ED diagnosis and symptoms have generally failed to explain this variability. The current study investigated the predictive utility of personality for outcome in ED treatment. One hundred and thirty adult patients with bulimia nervosa or eating disorder not otherwise specified enrolled in an intensive multimodal treatment for 16 weeks. Personality was assessed with the NEO Personality Inventory Revised (NEO PI-R). Outcome was defined as recovered versus still ill and also as symptom score at termination with the Eating Disorder Inventory-2 (EDI-2). Personality significantly predicted both recovery (70% of patients) and symptom improvement. Patients who recovered reported significantly higher levels of Extraversion at baseline than the still ill, and Assertiveness emerged as the personality trait best predicting variance in outcome. This study indicates that personality might hold promise as predictor of recovery after treatment for ED. Future research might investigate if adding interventions to address personality features improves outcome for ED patients.
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