Mange psykiatriske lidelser har genetiske likheter

En del psykiske lidelser går igjen i familier, og er delvis arvelige. (Foto: Shutterstock / NTB Scanpix)

Flere psykiatriske diagnoser deler genetiske risikofaktorer leser vi i forskning.no.

Forskere har funnet genetiske markører fra 25 ulike psykiatriske og nevrologiske diagnoser, og funnet at mange lidelser har overlappende biologisk grunnlag. K.G.Jebsen Senter for nevropsykiatriske lidelser har bidratt med data om ADHD. Resultatene ble nylig publisert i Science.

– Fellestrekk ved psykiske lidelser som for eksempel ADHD og depresjon, gjør at man kan bruke de samme teknikkene for å behandle begge tilstandene, sier Lundervold.

Anttila, V.et al: Analysis of shared heritability in common disorders of the brain. Science. 22Jun2018

Event-Related-Potential (ERP) Correlates of Performance Monitoring in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

Introduction: Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in children and tends to persist into adulthood. Evidence from neuropsychological, neuroimaging, and electrophysiological studies indicates that alterations of error processing are core symptoms in children and adolescents with ADHD. To test whether adults with ADHD show persisting deficits and compensatory processes, we investigated performance monitoring during stimulus-evaluation and response-selection, with a focus on errors, as well as within-group correlations with symptom scores.

Methods: Fifty-five participants (27 ADHD and 28 controls) aged 19–55 years performed a modified flanker task during EEG recording with 64 electrodes, and the ADHD and control groups were compared on measures of behavioral task performance, event-related potentials of performance monitoring (N2, P3), and error processing (ERN, Pe). Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptom load.

Results: Adults with ADHD showed higher error rates in incompatible trials, and these error rates correlated positively with the ASRS scores. Also, we observed lower P3 amplitudes in incompatible trials, which were inversely correlated with symptom load in the ADHD group. Adults with ADHD also displayed reduced error-related ERN and Pe amplitudes. There were no significant differences in reaction time (RT) and RT variability between the two groups.

Conclusion: Our findings show deviations of electrophysiological measures, suggesting reduced effortful engagement of attentional and error-monitoring processes in adults with ADHD. Associations between ADHD symptom scores, event-related potential amplitudes, and poorer task performance in the ADHD group further support this notion.

Original Research ARTICLE:

Front. Psychol., 11 April 2018 |

https://doi.org/10.3389/fpsyg.2018.00485

 

Structure and function of the acidic amino acid decarboxylase GADL1

Elaheh Mahootchi, Arne Raasakka,‡ Ingeborg Winge,a,b Weisha Luan,c Petri Kursulaa,c* and Jan Haavika,b,d*

a Department of Biomedicine, University of Bergen, Bergen, Norway, b K. G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, c Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland, and d Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

‡ These authors made equal contributions

Aims:

Glutamic acid decarboxylase-like protein 1 (GADL1) is a recently discovered pyridoxal 5′-phosphate -dependent enzyme that has been associated with lithium response in bipolar disorder. The expression pattern and activity of GADL1 suggest a role in neurotransmitter and neuroprotectant metabolism, notably in the synthesis of beta-alanine and carnosine in the olfactory bulb. The catalytic properties and crystal structure of mouse GADL1 is described, together with a solution model based on small-angle X-ray scattering data.

Methods:

  • Construct preparation, protein expression and purification
  • Expression and purification of mouse GADL1 (MmGADL1)
  • Crystallization
  • Small-angle X-ray scattering

 

Results:

The substrate specificity and physiological functions of GADL1 are still unclear. While the overall fold and the conformation of the bound PLP are similar to those in other PLP-dependent decarboxylases, GADL1 adopts a more loose conformation in solution, which might have functional relevance in ligand binding and catalysis.

Conclusions:

The structure of MmGADL1 and its flexibility in solution, coupled to structural conservation with other PLP-dependent enzymes, point towards functional relevance of these features within the enzyme family. Future work will concentrate on high-resolution structural details of substrate and inhibitor binding by GADL1, as well as characterization of its metabolic role in mouse tissues.

https://www.ncbi.nlm.nih.gov/pubmed/29372909

 

Samarbeid med brukere av helsevesenet og medisinsk forskning

Brukermedvirkning er med å sikre kvaliteten på forskningen.

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Forskningen ved K.G. Jebsen senter for nevropsykiatriske lidelser (KGJN) tar utgangspunkt i sentrale kliniske problemer, som oftest er formidlet fra pasienter og deres pasientorganisasjoner.   Brukermedvirkning er viktig for senteret.  Brukermedvirkning i forskning er også framhevet fra myndighetene, blant annet i de to siste nasjonale helse- og omsorgsplanene:

Det er viktig at allmennheten oppfatter forskningen som nyttig. Pasientene, brukerorganisasjonene og helsepersonell (fagorganisasjonene) bør bidra med innspill for å sikre prioritering av relevante forskningstema og spille en viktig rolle i gjennomføringen av pasientnære studier. (Nasjonal helse- og omsorgsplan (2007-2010), i St.prp.nr.1 – (2006-2007) kapittel 6. )

Det må legges bedre til rette for økt brukermedvirkning i forskning og innovasjon. Brukermedvirkning sikrer at det forskes på relevante temaer for brukerne og at nye innovative løsninger er i tråd med brukernes behov. Med brukere menes både pasienter og personell. (Meld. St. 16 (2010–2011) Nasjonal helse- og omsorgsplan (2011–2015) og i Forskningsmeldingen – Meld. St.18 (2012-2013) Lange linjer – kunnskap gir muligheter.)

ADHD-forskere i senteret har samarbeidet med brukere gjennom flere brukerundersøkelser, blant annet for å kartlegge kvaliteten på helsetjenester. For å styrke samarbeidet, arrangerte KGJN i oktober et møte med et brukerpanel, bestående av fire representanter fra ADHD Norge, avdeling Hordaland.

På dette møtet ble det lagt planer for framtidig samarbeid. Brukerpanelet fikk komme med innspill om erfaringer og synspunkter, og det ble informert om hva ADHD-prosjektet forsker på, og hvordan brukerne kan bidra med innspill.

 

Brukerne fremhevet særlig behovet for mer kunnskap og tiltak innenfor følgende områder:

  • Det er for lite kunnskap i NAV-systemet og skolen om ADHD. Kan forskningen bidra med å øke kunnskapen om ADHD og formidle dette bedre?
  • Det er ønske om bedre oppfølging etter utredning fra Spesialisthelsetjenesten. Hvordan kan forskningen bidra med dette?
  • Formidling av forskningen. Hvordan nå ut til et bredere publikum, inkludert brukerne, gjennom nyhetsbrev, nettsider, sosiale medier.

Forskerne på sin side ønsket velkommen flere innspill til forskningstema. Forskerne ønsket også kontakt med flere pasienter og familiemedlemmer av ADHD-pasienter for å kunne studere arvelige faktorer. Her kan ADHD Norge med sitt nettverk gjøre en betydelig forskjell.

Disse temaene vil bli fulgt opp med nye samarbeidsmøter i 2018. Pasienter og familiemedlemmer som ønsker å bidra til ADHD-prosjektet kan kontakte Lisa Vårdal (telefon 55 58 68 48) eller via mail adhdprosjekt@psybp.uib.no.

Arc protein: a flexible hub for synaptic plasticity and cognition

arcprotein2

Highlights

•Arc is a multifunctional hub protein.
•Arc is flexible, modular and capable of reversible self-oligomerization.
•Arc localization and stability are regulated by post-translational modifications.
•Arc protein complexes are implicated in the genetics of human cognition.
•Arc is a master organizer of long-term synaptic plasticity.

Abstract

Mammalian excitatory synapses express diverse types of synaptic plasticity. A major challenge in neuroscience is to understand how a neuron utilizes different types of plasticity to sculpt brain development, function, and behavior. Neuronal activity-induced expression of the immediate early protein, Arc, is critical for long-term potentiation and depression of synaptic transmission, homeostatic synaptic scaling, and adaptive functions such as long-term memory formation. However, the molecular basis of Arc protein function as a regulator of synaptic plasticity and cognition remains a puzzle. Recent work on the biophysical and structural properties of Arc, its protein-protein interactions and post-translational modifications have shed light on the issue. Here, we present Arc protein as a flexible, multifunctional and interactive hub. Arc interacts with specific effector proteins in neuronal compartments (dendritic spines, nuclear domains) to bidirectionally regulate synaptic strength by distinct molecular mechanisms. Arc stability, subcellular localization, and interactions are dictated by synaptic activity and post-translational modification of Arc. This functional versatility and context-dependent signaling supports a view of Arc as a highly specialized master organizer of long-term synaptic plasticity, critical for information storage and cognition.

Fig. 1. Arc protein interaction network and signaling. A) Arc interactome connectivity according to STRING database, version 10.5. Nodes represent Arc binding partners, edges − protein-protein associations. The confidence score of each interaction is mapped to the edge thickness and opacity. B) Arc effector pathways. Main protein partners for each functional outcome are highlighted in bold. Detailed explanation is provided in text.
Fig. 1. Arc protein interaction network and signaling. A) Arc interactome connectivity according to STRING database, version 10.5. Nodes represent Arc binding partners, edges − protein-protein associations. The confidence score of each interaction is mapped to the edge thickness and opacity. B) Arc effector pathways. Main protein partners for each functional outcome are highlighted in bold. Detailed explanation is provided in text.

Our research has gained attention

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As we all struggle and work on our projects, let’s take a moment to congratulate ourselves on achieving high standards in our publications.

One of our studies on ADHD and immune system, published in Biological Psychiatry, was placed in the top 1% of the academic field of Neuroscience & Behavior based on highly cited threshold for the field and publication year, as of March/April 2017.

Bellow is the link for the article: “Attention Deficit Hyperactivity Disorder in Offspring of Mothers With Inflammatory and Immune System Diseases”

Our group was the first to perform a genome-wide association study on attention deficit hyperactivity disorder (ADHD) in Norway. The study became one of the top 25% most cited PLOS ONE articles in 2015.

Bellow you can find the link for the article: “Genome-Wide Analysis of Attention Deficit Hyperactivity Disorder in Norway”

So far, this article has been viewed 4,411 times and cited 16 times.

Congratulations!

Dette er min ADHD

Jeg har trodd at jeg er latere og dummere enn andre. De som klarer å lese bøker og alltid gjør ferdig leksene, og de som klarer å følge med og alltid har riktig svar, skriver kronikkforfatteren. (Illustrasjonsfoto) Foto: Scanpix / SCANPIX
Jeg har trodd at jeg er latere og dummere enn andre. De som klarer å lese bøker og alltid gjør ferdig leksene, og de som klarer å følge med og alltid har riktig svar, skriver kronikkforfatteren. (Illustrasjonsfoto)
Foto: Scanpix / SCANPIX

 

Jeg har aldri klart å slappe av. Jeg sliter med å følge samtaler fordi jeg ikke klarer å filtrere bort hverken intern eller ekstern støy. ADHD er ingen tullediagnose.

Det skriver Kamilla Paulsen i et innlegg på NRK Ytring.

 

Implication of the APP Gene in Intellectual Abilities

Craig Myruma,1, Oleksii Nikolaienkoa,1, Clive R. Bramhama, Jan Haavika,b and Tetyana Zayatsa,∗                   

aK.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen,Norway bDepartment of Psychiatry, Haukeland University Hospital, Bergen, Norway

Abstract

Background: Cognitive functions are highly heritable and polygenic, though the source of this genetic influence is unclear. On the neurobiological level, these functions rely on effective neuroplasticity, in which the activity-regulated cytoskeleton associated protein (ARC) plays an essential role.

Objectives: To examine whether the ARC gene complex may contribute to the genetic components of intellectual function given the crucial role of ARC in brain plasticity and memory formation.

Methods: The ARC complex was tested for association with intelligence (IQ) in children from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5,165). As Alzheimer’s disease (AD) shares genetics with cognitive functioning, the association was followed up in an AD sample (17,008 cases, 37,154 controls).

Results: The ARC complex revealed association with verbal and total IQ (empirical p = 0.027 and 0.041, respectively) in the ALSPAC. The strongest single variant signal (rs2830077; empirical p = 0.018), within the APP gene, was confirmed in the AD sample (p = 2.76E-03). Functional analyses of this variant showed its preferential binding to the transcription factor CP2.

Discussion: This study implicates APP in childhood IQ. While follow-up studies are needed, this observation could help elucidate the etiology of disorders associated with cognitive dysfunction, such as AD.

Read the article in IOSPress: Journal of Alzheimer`s Diseas

This article is also featured in Medical News Today.

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