Precision medicine

• Panomic analysis

• System biology

• Computational Clinical Neuroscience

• Decision theory

Bipolar disorders as complex disorders:

insights for precision medicine

• Multimodal genomic inteception from association and linkage study to epigenomic variations

• Enviroment influence on disorder trajectory

• Multiple interacting Endophenotypes

• Disorder of neuronal plasticity and metaplasticity

Criteri per alterata plasticità

sinaptica nel disturbo bipolare• 1. Correlato anatomo-funzionale in vivo in pazienti Bipolari

• 2. Correlato/i cellulare/i delle alterazioni anatomo funzionalievidenziate in vivo

• 3. Dimostrato ruolo di tali modificazioni cellulari nella plasticitàsinaptica

• 4. Modificazioni cellulari e sinaptiche congrue con alterazionifisiopatologiche e neuotrasmettitoriali del disturbo

BrainAging: Accelerated Brain

Aging in Psychiatry disorders

included BP• Structural brain abnormalities are central to schizophrenia (SZ),

but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness.

• BrainAge: difference between chronological and the neuroanatomical age (brain age gap estimation)

• BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups.

Schizophrenia Bulletin Advanced Access published October 13, 2013

The theory of bipolar disorder as an illness of

accelerated aging: Implications for clinical care and

research

Bertolotto-Rizzo 2014 Neuroscience & Biobehavioral Reviews 4, 157–16

Date of download: 5/28/2014

Copyright © 2014 American Medical

Association. All rights reserved.

A Meta-analysis

JAMA Psychiatry. 2014;():. doi:10.1001/jamapsychiatry.2014.176

Identification of Pathways for Bipolar

Disorder:

The emerging role of dopamine-glutamate

interaction and postsynaptic density in bipolar

pathophysiology: implication for the treatment

de Bartolomeis et al., J of Neuropsychopharmacology, 2014, Vol. 28(6) 505–526

.

Postsynaptic

density

AdB Mol and Trasl Psy Lab Federico II

Smith et al., Neuron 84, 399–415, October 22, 2014 ª2014 Elsevier In

Common and rare variants in the ANK3 gene, encodingankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism. Here we demonstratethat ankyrin-G is integral to AMPAR-mediated synaptic transmission and maintenance of spine morphology

Microbiota and mood disorders

Sarchar et al., 2016 Trends in Neuroscience 716

The application of therapeutic

modulators of gut

microbiota to autism and mood disorders

has been experienced only in

experimental settings to date, with

few but promising results, that suggest

the microbiota modulation as a

therapeutic approach for autism and

mood disorders

Human study, the Behavioral Pattern

Monitor (BPM).

• Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM.

Mania-like exploratory

behavior• Animal study .The effects of amphetamine sulfate, the

selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM.

Striatal dopamine transporter

availability in unmedicated bipolar disorder

Anand et al., 2011, Bipolar Disorders : 13: 406–413

CAUDATE VENTRAL STRIATUM

11 unmedicated BPD patients in either the euthymic or depressed phase and 13 closely matched healthy subjects underwent PET imaging with the DAT- radiotracer [11C]CFT

DAT functional variant in Bipolar

Disorder patients

Horschitz eta al., 2005, Mol Psychiatry. Dec;10(12):1104-9.

• DA transport measurements and antagonist binding revealed that the A559V mutant protein is fully functional, whereas the E602G mutant is not.

• Confocal microscopy showed that the E602G protein is transcribed and translated but not delivered to the cell surface