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Frontostriatal mechanisms of anhedonia in novel neurophysiological subtypes of depression

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Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates. Like other neuropsychiatric disorders, depression is not a unitary disease but rather a heterogeneous syndrome encompassing varied, co-occurring symptoms and diverging responses to treatment. Using functional magnetic resonance imaging (fMRI) in a large multisite sample (N=1,188), we showed that patients with depression can be subdivided into four neurophysiological subtypes defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks. Clustering patients on this basis enabled the development of biomarkers (statistical classifiers) for diagnosing depression subtypes with high (82-93%) sensitivity and specificity in multisite validation (N=711) and out-of-sample replication (N=477) datasets. These subtypes cannot be differentiated based solely on clinical features, but they are associated with differing clinical symptom profiles. They also predict differential improvements in anhedonia, anxiety, and other depressive symptoms in response to transcranial magnetic stimulation of the dorsomedial prefrontal cortex (N=154). To further understand the circuit mechanisms underlying one of these subtypes, we used optogenetic tools and two-photon calcium imaging to interrogate frontostriatal circuit function in a mouse model of chronic stress. Our results indicate that dysfunctional connectivity in frontostriatal circuits suppresses striatal responses to reward-related VTA signals, impairing the expression of reward-seeking behaviors. Together, these findings define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying individuals most likely to benefit from targeted neurostimulation therapies.

Targetgroup

open to public

Referent

Conor Liston (Weill Cornell Medical College)

Journey Description

Map

E - Main Entrance/Reception
1 - Managing Board; sections: Infection Biology Unit, Unit of Infection Models, Laboratory Animal Science Unit, Primate Genetics Laboratory, Behavioral Ecology and Sociobiology Unit, Cognitive Ethology Laboratory, Neurobiology Laboratory, Research Coordination, Public Relations, Information Technology, Administration, Technical Support, Library.
2 - Material Delivery/Purchase
3 - Platform Degenerative Diseases
4 - Cognitive Neuroscience Laboratory
5 - Animal Husbandry
6 - Imaging Center, Functional Imaging Laboratory


Arrival by car

Leave the interstate A7 at exit "Göttingen Nord". Follow the B27 straight ahead in the direction of "Braunlage". After the third traffic light intersection turn right towards "Kliniken". Afterwards turn left onto "Robert-Koch-Straße" direction "Universität Nordbereich/Polizei". At the end of "Robert-Koch-Straße" turn right onto "Otto-Hahn-Straße", direction "Nikolausberg". The first street on the left turn onto "Kellnerweg", follow the signs "Deutsches Primatenzentrum".


Arrival by bus

The footpath from the bus stop "Kellnerweg" to the Main Entrance/Reception: 
From Bus stop "Kellnerweg" (line 21/22 and 23) Cross the road, go in the direction of the bus. At the mailbox, turn left into the footpath and proceed to the end. Turn right into the Kellnerweg. The main entrance of the DPZ is on the left side.

Date and Time 20.11.17 - 16:00 - 17:30 Signup is not required

Location Seminar room E0.14, German Primate Center

Organiser

Leibniz ScienceCampus Primate Cognition

Contact Christian Schloegl
Phone: 0551-3851-480<br /><link cschloegl@dpz.eu>cschloegl@dpz.eu</link>

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