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      Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa : A Meta-Analysis and Qualitative Review

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          Abstract

          Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

          Hirnmorphologische Veränderungen in akut kranken und gewichtsrehabilitierten Patientinnen mit Anorexia nervosa – Meta-Analyse und qualitativer Review

          Fragestellung: Patientinnen mit Anorexia Nervosa (AN) zeigen eine Reduktion cerebraler grauer (GS) und weißer Substanz (WS), die sich bei Gewichtsrehabilitation wieder bessert. Sowohl das Ausmaß der Reduktion und ihre klinische Bedeutung, als auch der zeitliche Verlauf und die Vollständigkeit der Erholung wurden bisher noch nicht systematisch erforscht. Methodik: Wir führten eine Meta-Analyse und einen qualitativen Review von allen Bildgebungsstudien mit Magnetresonanztomographie zu Volumenänderungen bei akuten und gewichtsrehabilitierten Patienten mit AN durch. Ergebnisse: Es konnten Studien mit insgesamt 214 akuten und 177 gewichts-rehabilitierten Patientinnen in die Analyse eingeschlossen werden. Die GS der Patientinnen mit akuter AN war gegenüber gesunden Kontrollen um 5.6% reduziert, die WS um 3.8%. Eine kurzzeitige Gewichts-Normalisierung von 2–5 Monaten war mit einem Rückgang von etwa der Hälfte der GS-Reduktion verbunden, während die WS schon fast vollständig normalisiert erschien. 2–8 Jahre nach Remission waren GS und WS weitgehend rehabilitiert und nicht mehr signifikant gegenüber gesunden Kontrollen reduziert (GS: –1.0% bzw. WS: –0.7%). Kleine Residualveränderungen konnten damit aber nicht ausgeschlossen werden. Im qualitativen Review zeigten einige Studien, dass GS-Reduktion mit kognitiven Defiziten und schlechterer klinischer Prognose assoziiert war. Schlussfolgerungen: GS und WS waren bei Patientinnen mit akuter AN stark reduziert. Die Vollständigkeit der Erholung des Gehirns blieb weiter ungeklärt.

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          Most cited references42

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          Is impaired set-shifting an endophenotype of anorexia nervosa?

          Set-shifting difficulties have been reported in subjects with anorexia nervosa and appear to persist after recovery; therefore, they may be endophenotypic traits. The goals of this study were to investigate whether set-shifting difficulties are familial by examining discordant sister-pairs in comparison with healthy unrelated women and to replicate, with a broader battery, the lack of influence of an acute illness state on neuropsychological performance. Forty-seven pairs of sisters discordant for anorexia nervosa and 47 healthy unrelated women who were comparable in age and IQ completed neuropsychological tasks selected to assess set-shifting ability. Analyses of variance with standard errors that are robust against correlations within family clusters were used to compare the groups. Results were adjusted for obsessive-compulsive, anxiety, and depression symptoms. Subjects with acute (N=24) and fully remitted (N=23) anorexia nervosa were compared to assess state versus trait effects. Sisters with and without anorexia nervosa took significantly longer than unrelated healthy women to shift their cognitive set (CatBat task) and demonstrated greater perceptual rigidity (Haptic Illusion task) but did not differ significantly from each other. Women with anorexia nervosa were slower than other groups on Trail Making tasks. Women who had fully recovered from anorexia nervosa made significantly fewer errors than those with acute anorexia nervosa on the Trail Making alphabet task, but these subgroups did not differ on other measures. Both affected and unaffected sisters had more set-shifting difficulties than unrelated healthy women. This finding, together with the replicated finding that set-shifting difficulties persist after recovery, suggests that set-shifting difficulties are trait characteristics and may inform the search for the endophenotype in anorexia nervosa.
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            Adolescent-onset anorexia nervosa: 18-year outcome.

            The long-term outcome of anorexia nervosa is insufficiently researched. To study prospectively the long-term outcome and prognostic factors in a representative sample of people with teenage-onset anorexia nervosa. Fifty-one people with anorexia nervosa, recruited by community screening and with a mean age at onset of 14 years were compared with 51 matched comparison individuals at a mean age of 32 years (18 years after disorder onset). All participants had been examined at ages 16 years, 21 years and 24 years. They were interviewed for Axis I psychiatric disorders and overall outcome (Morgan-Russell assessment schedule and the Global Assessment of Functioning). There were no deaths. Twelve per cent (n=6) had a persisting eating disorder, including three with anorexia nervosa. Thirty-nine per cent of the anorexia nervosa group met the criteria for at least one psychiatric disorder. The general outcome was poor in 12%. One in four did not have paid employment owing to psychiatric problems. Poor outcome was predicted by premorbid obsessive-compulsive personality disorder, age at onset of anorexia nervosa and autistic traits. The 18-year outcome of teenage-onset anorexia nervosa is favourable in respect of mortality and persisting eating disorder.
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              Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa.

              The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. The authors used structural MR imaging to study gray and white matter volumes in women with current restricting-type anorexia nervosa (N=19), women recovered from restricting-type anorexia nervosa (N=24), women with bulimia nervosa (N=19), and healthy comparison women (N=24). All eating disorder groups exhibited increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manual tracing confirmed larger gyrus rectus volume, and volume predicted taste pleasantness ratings across all groups. Analyses also indicated other morphological differences between diagnostic categories. Antero-ventral insula gray matter volumes were increased on the right side in the anorexia nervosa and recovered anorexia nervosa groups and on the left side in the bulimia nervosa group relative to the healthy comparison group. Dorsal striatum volumes were reduced in the recovered anorexia nervosa and bulimia nervosa groups and predicted sensitivity to reward in all three eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas relative to the healthy comparison group. The results held when a range of covariates, such as age, depression, anxiety, and medications, were controlled for. Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value.
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                Author and article information

                Journal
                kij
                Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie
                Hogrefe AG, Bern
                1422-4917
                1664-2880
                January 2014
                : 42
                : 1
                : 7-18
                Affiliations
                [ 1 ] Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Germany
                [ 2 ] Department of Medical Statistics, University Hospital RWTH Aachen, Germany
                Author notes
                Jochen Seitz, MD, Department of Child and Adolescent Psychiatry,, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Neuenhofer Weg 21, 52074 Aachen, Germany Tel. +49 241-8088737 Fax +49 241-8082544 jseitz@ 123456ukaachen.de
                Article
                kij_42_1_7
                10.1024/1422-4917/a000265
                24365959
                e99c4d69-deec-475a-8942-15f6649ccc0e
                Copyright @ 2014
                History
                : July 1, 2013
                : September 24, 2013
                Categories
                Originalarbeiten/Original articles

                Pediatrics,Psychology,Family & Child studies,Development studies,Clinical Psychology & Psychiatry
                meta-analysis,Anorexia Nervosa,morphometric changes,Gehirnvolumen,Meta-Analyse,recovered,morphologische Veränderungen,gewichts-rehabilitiert,anorexia nervosa,brain volume

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