Ottawa ontario symptoms and conditions

There are studies like the one below that show a link between suicide and dysregulation in the brain. So we need to learn the relationship between the cysLT1 and cysLT2 receptors in the brain and those in the study.

The Journal of Neuroscience, February 11, 2004, 24(6):1478-1485; doi:10.1523/JNEUROSCI.4734-03.2004
Neurobiology of Disease
Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABAA Receptor Subunits in Frontal Cortical Brain Region

Zul Merali,1,2 Lisheng Du,1 Pavel Hrdina,1 Miklos Palkovits,3 Gabor Faludi,4 Michael O. Poulter,5 and Hymie Anisman1,5

1University of Ottawa Institute of Mental Health Research, and 2Departments of Psychology, Psychiatry, and Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada, 3Laboratory for Neuromorphology, Hungarian Academy of Sciences and Semmelweis University, 1094 Budapest, Hungary, 4Semmelweis University Hospital, 1125 Budapest, Hungary, and 5Institute of Neuroscience, Carleton University, Ottawa, Ontario, K1S 5B6 Canada

Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH1, and CRH2 receptors, as well as various GABAA receptor subunits (1, 2, 3, 4, 5, , and 2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH1, but not CRH2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the 1, 3, 4, and receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABAA receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABAA receptor subunit changes, or the disturbed coordination between these GABAA receptor subunits, contribute to depression and/or suicidally or are secondary to the illness/distress associated with it.

This testimony should help strengthen our case for warnings for Singulair.

Neurologist Sought Warning for Pfizer Drug
By JEREMY SINGER-VINE
June 20, 2008; Page B10

A British neurologist who analyzed effects of the drug Neurontin told a court hearing Thursday that he advised its maker -- now a unit of Pfizer Inc. -- to include a warning on the drug's label for potential side effects of depression and aggression, but his advice wasn't followed.

The University of London neurologist, Michael R. Trimble, was testifying at a hearing to decide whether civil cases brought against Pfizer alleging suicides linked to Neurontin can proceed. The hearing was jointly held by judges for U.S. District Court in Boston and a New York state court who are hearing similar cases. In various lawsuits consolidated in the federal court, plaintiffs allege more than 100 suicides were connected to Neurontin usage.

Dr. Trimble described what he said was a "plausible biological pathway" that could lead from the compound gabapentin -- the chemical name for Neurontin -- to suicidal behavior, hostility, and aggression. Dr. Trimble said that in 1995 and 1996, he was hired to write two confidential reports for Parke-Davis -- now a unit of Pfizer -- because the company "was concerned about psychosis in relation to their drug." Dr. Trimble said he was unable to find a link to psychosis, but noted effects of depression and aggression.

Lawyers for Pfizer argued at the hearing that the evidence linking the drug to suicidal side effects wasn't scientifically sound. Under cross-examination, they challenged his description of a pathway as a patchwork of studies that didn't prove a biological connection. Neurontin and generic forms of gabapentin are approved for treating epileptic convulsions, but have also been prescribed widely "off label" for other conditions.

In five of nine patient cases he analyzed in 1996, Dr. Trimble said he saw depression and aggression in patients who had no previous symptoms of the side effects, so he said he recommended to the company that the drug "should carry some kind of warning" for susceptible patients.

Thursday's proceedings were the initial phase of a hearing requested by Pfizer to challenge the opinions of the plaintiffs' experts. Under cross-examination and a subsequent examination by the plaintiffs' attorney, Dr. Trimble said the biological pathway between Pfizer's Neurontin and suicidal events were plausible and supported by a series of peer-reviewed neurology research.