Pleiotropic effects on psychopathology (Lancet 2013)

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
Lancet. 2013 Apr 20;381(9875):1371-9.
http://www.ncbi.nlm.nih.gov/pubmed/23453885
Cross-Disorder Group of the Psychiatric Genomics Consortium.
Erratum in: Lancet. 2013 Apr 20;381(9875):1360.

BACKGROUND:
Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories.
We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.

METHODS:
We analyzed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders

FINDINGS:
SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2.
Model selection analysis supported effects of these loci for several disorders.
Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity.
Pathway analysis supported a role for calcium channel signalling genes for all five disorders.

INTERPRETATION:
Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology.
These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.

cited by:
Genes and the Human Condition (From Behavior to Biotechnology)
Coursera 2014
https://www.coursera.org/course/genes

Cognition in Major Depressive Disorder (Feb. 2014)

What’s New in Cognition in Major Depressive Disorder: Latest Clinical Findings
Guy M. Goodwin, FMedSci; Roger S. McIntyre, MD
CME Released: 02/07/2014
http://www.medscape.org/viewarticle/819551

Potential Additive Approaches Used in Depression:

  • Psychostimulants (eg, methylphenidate and lisdexamfetamine) [a-c]
  • Immune-inflammatory-based therapies and metabolic interventions [b]
  • Manual-based psychotherapies (eg, cognitive behavioral therapy) [b]
  • Neurostimulation strategies, electroconvulsive therapy, and repetitive transcraneal magnetic stimulation [d, e]

a. Lavretsky H, et al. Neuropsychopharmacology. 2013;38(Suppl 2):S90
b. McIntyre RS, et al. J Affect Disord. 2013 Nov 15.
c. Trivedi MH, et al. J Clin Psychiatry. 2013;74(8):802-809.
d. Schulze-Rauschenbach SC, et al. Br J Psychiatry. 2005;186:410-416.
e. Rasmussen KG. J ECT. 2011;27(1):51-54.

Trigeminal Nerve Stimulator in Depression, Epilepsy

Trigeminal Nerve Stimulation an Option for ADHD?
May 20, 2013
http://www.medscape.com/viewarticle/804440
Currently, the system has no approvals in the United States from the US Food and Drug Administration (FDA).
Leon Ekchian, president and   CEO of NeuroSigma, Inc, said the company plans first to apply for the epilepsy indication in the United States, with depression next and ADHD   indications probably further down the road.

EU Approval for Nerve Stimulator in Depression, Epilepsy
Emma Hitt, PhD
Sep 07, 2012
http://www.medscape.com/viewarticle/770512

An external trigeminal nerve stimulation (eTNS) system (Monarch, NeuroSigma, Inc) has received European Union (EU) CE Certification for the adjunctive treatment of epilepsy and major depressive disorder for adults and children aged 9 years and older.

The device has been evaluated in clinical trials conducted at the University of California, Los Angeles (UCLA) and the University of Southern California. It consists of an external pulse generator and disposable electric patches placed on the forehead that are replaced daily and are worn primarily during sleep.

NeuroSigma, Inc.
http://www.neurosigma.com