A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia

Deng, Michelle; McAlonan, Gráinne; Cheung, CW; Chiu, Chaw-Chi; Law, C.W.; Cheung, Vincent C. K.; Sham, Pak C.; Chen, Eric; Chua, Siew E.

doi:10.1007/s00213-009-1619-z

Cited by 52 publications

(48 citation statements)

References 53 publications

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“…Auch Angaben zur Dauer der antipsychotischen Behandlungen bis zum Messzeitpunkt wurden nicht gemacht. In VBM-Longitudinalstudien an Ersterkrankten wurden nach 3 [46] …”

Section: Welche Schlussfolgerungen Erlauben Die Studien?unclassified

Frontale Hirnvolumenminderung durch Antipsychotika?

et al. 2014

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Zusammenfassung In dieser Übersicht werden die Ergebnisse longitudinaler Studien zur frontalen Hirnvolumenminderung bei Menschen mit einer Erkrankung aus dem Spektrum schizophrener Psychosen dargestellt und zur Behandlung mit Antipsychotika in Beziehung gesetzt. Nach einer systematischen Literaturrecherche wurden alle Studien ausgewertet, in denen an einer größeren Population Ergebnisse bildgebender Diagnostik zur Veränderung der Hirnstruktur im Langzeitverlauf mit Daten zur antipsychotischen Behandlung und zur Schwere der Erkrankung korreliert wurden. Die Ergebnisse zeigen, dass es eine Evidenz für eine Volumenminderung grauer und weißer Substanz des Frontalhirns gibt, die sich nicht alleine durch die Erkrankung selbst und ihre Krankheitsschwere erklären lässt, sondern mit hoher Wahrscheinlichkeit auch Ausdruck einer langfristigen Antipsychotikawirkung auf das Gehirn ist. Ob sog. „Second-generation“-Antipsychotika hier einen mittel- bis längerfristigen Vorteil gegenüber „First-generation“-Antipsychotika besitzen, ist derzeit unklar. Angesichts des Beitrags von Antipsychotika zu den hirnstrukturellen Veränderungen, die offenbar kumulativ dosisabhängig sind und negative Auswirkungen für die Neurokognition, die Positiv- und Negativsymptomatik und das soziale Anpassungsniveau mit sich bringen können, sollten die Empfehlungen zur antipsychotischen Langzeitbehandlung neu überdacht werden. Vor dem Hintergrund der neurobiologischen Befunde empfehlen wir und andere, möglichst niedrige antipsychotische Dosierungen zur Symptomkontrolle einzusetzen. Bei psychiatrischen Störungen außerhalb des Schizophreniespektrums sollten Antipsychotika ebenfalls nur mit Vorsicht und nach sorgfältiger Abwägung von Risiken und Nutzen angewandt werden. In diesem Kontext werden zunehmend auch Behandlungsansätze relevant, welche die antipsychotische Medikation minimieren oder sogar einen nur selektiven Einsatz erlauben.

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“…Auch Angaben zur Dauer der antipsychotischen Behandlungen bis zum Messzeitpunkt wurden nicht gemacht. In VBM-Longitudinalstudien an Ersterkrankten wurden nach 3 [46] …”

Section: Welche Schlussfolgerungen Erlauben Die Studien?unclassified

Frontale Hirnvolumenminderung durch Antipsychotika?

et al. 2014

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“…This study was limited by the crosssectional nature of the original studies contained therein. Clearly longitudinal studies are the optimal means to address progression of illness and medication effects directly, but follow-up studies in schizophrenia are extremely challenging (though see [18,19]). The ALE approach therefore serves as a practical substitute, allowing a synthesis of cross-sectional data at different stages of illness and results agree that schizophrenia involves progressive abnormalities within a limbic cortico-striato-thalamic loop system.…”

Section: Ale In Schizophreniamentioning

confidence: 99%

“…The impact of medication on morphology of cortico-striatal circuits is a critical issue in these studies. Anti-psychotic drugs appear to act to increase basal ganglia size [18,61]. This may represent a "normalising" effect, since prior to treatment first episode patients with schizo-phrenia tend to have smaller basal ganglia sizes [7,18,61].…”

Section: Limitationsmentioning

confidence: 99%

“…Anti-psychotic drugs appear to act to increase basal ganglia size [18,61]. This may represent a "normalising" effect, since prior to treatment first episode patients with schizo-phrenia tend to have smaller basal ganglia sizes [7,18,61]. However anti-psychotic drugs may also act to lower regional grey matter volumes in cortex, but the exact pattern and mechanism behind this observation is far from clear [18].…”

Section: Limitationsmentioning

confidence: 99%

“…This may represent a "normalising" effect, since prior to treatment first episode patients with schizo-phrenia tend to have smaller basal ganglia sizes [7,18,61]. However anti-psychotic drugs may also act to lower regional grey matter volumes in cortex, but the exact pattern and mechanism behind this observation is far from clear [18]. Mood stabilizing medications used to treat bipolar disorder are also considered to have a neuroprotective effect.…”

Section: Limitationsmentioning

confidence: 99%

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Is there an anatomical endophenotype for neurodevelopmental disorders? A review of dual disorder anatomical likelihood estimation (ALE) meta-analyses of grey matter volumes

McAlonan

Chan

et al. 2011

Chin. Sci. Bull.

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The term "neurodevelopmental disorder" broadly encompasses conditions thought to arise early in development and includes schizophrenia, bipolar disorder and autism among others. These conditions share a number of genetic and environmental risk factors postulated to lead to common difficulties in socio-emotional processing, communication and cognitive function. The alternative position is that, while the same traits are affected across these conditions, the nature or direction in which they are modified may be distinct. MRI studies provide a rapidly expanding and rich database which we propose can be used to contribute to this debate. Anatomical likelihood estimation (ALE) is a method of meta-analysis applied to voxel-based MRI studies. We have adapted this method to explore the extent to which schizophrenia and bipolar disorder and schizophrenia and autism share a common brain structural phenotype. We will review this work here and discuss whether there is sufficient other evidence to justify a common framework for further research into the inter-relatedness of such conditions. The endophenotype approach to schizophrenia and related disorders considers traits associated with the condition also observable in individuals who do not meet diagnostic criteria. The strategy relies upon assuming a dimensional perspective. It allows the size of samples studied to be greatly expanded as unaffected individuals or relatives who show similar traits to individuals with the illness can be included. In this way the impact of confounds such as medication and illness chronicity are reduced. In this paper we exploit the endophenotype approach in a rather different manner. Symptoms in psychiatry are never pathognomonic. Individuals with similar clusters of symptoms, response to treatment and outcome are categorized into discrete diagnostic groupings, but often the distinctions between diagnostic groups are blurred. This challenge in defining the target condition can be considered to be a disadvantage. However, an alternative is to examine similarities across different conditions from an intermediate or endophenotype perspective and determine whether common causal mechanisms may be at work across diagnostic categories.

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Striatal shape abnormalities as novel neurodevelopmental endophenotypes in schizophrenia: A longitudinal study

Chakravarty

Rapoport

Giedd

et al. 2014

Human Brain Mapping

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There are varying, often conflicting, reports with respect to altered striatal volume and morphometry in the major psychoses due to the influences of antipsychotic medications on striatal volume. Thus, disassociating disease effects from those of medication become exceedingly difficult. For the first time, using a longitudinally studied sample of structural magnetic resonance images from patients with childhood onset schizophrenia (COS; neurobiologically contiguous with the adult onset form of schizophrenia), their nonpsychotic siblings (COSSIBs), and novel shape mapping algorithms that are volume independent, we report the familial contribution of striatal morphology in schizophrenia. The results of our volumetric analyses demonstrate age-related increases in overall striatal volumes specific only to COS. However, both COS and COSSIBs showed overlapping shape differences in the striatal head, which normalized in COSSIBs by late adolescence. These results mirror previous studies from our group, demonstrating cortical thickness deficits in COS and COSSIBs as these deficits normalize in COSSIBs in the same age range as our striatal findings. Finally, there is a single region of nonoverlapping outward displacement in the dorsal aspect of the caudate body, potentially indicative of a response to medication. Striatal shape may be considered complimentary to volume as an endophenotype, and, in some cases may provide information that is not detectable using standard volumetric techniques. Our striatal shape findings demonstrate the striking localization of abnormalities in striatal the head. The neuroanatomical localization of these findings suggest the presence of abnormalities in the striatal-prefrontal circuits in schizophrenia and resilience mechanisms in COSSIBs with age dependent normalization.

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A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia

Abstract: Early increase in striatal volume change occurs as early as 3 weeks after anti-psychotic treatment, whilst thalamic volume increase is apparent later, by 8 weeks of treatment. We speculate that drug-mediated neuroplasticity may provide a biomarker for clinical recovery.

Cited by 52 publications

References 53 publications

Frontale Hirnvolumenminderung durch Antipsychotika?

Frontale Hirnvolumenminderung durch Antipsychotika?

Is there an anatomical endophenotype for neurodevelopmental disorders? A review of dual disorder anatomical likelihood estimation (ALE) meta-analyses of grey matter volumes

Striatal shape abnormalities as novel neurodevelopmental endophenotypes in schizophrenia: A longitudinal study

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