Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats After Stroke.

Identification of new therapeutic targets by genome-wide analysis of gene expression in the ipsilateral cortex of aged rats after stroke.

Filed under: Depression Treatment

PLoS One. 2012; 7(12): e50985
Buga AM, Scholz CJ, Kumar S, Herndon JG, Alexandru D, Cojocaru GR, Dandekar T, Popa-Wagner A

Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions.We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc) may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups.We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.
HubMed – depression


Importance of Thinking Locally for Mental Health: Data from Cross-Sectional Surveys Representing South East London and England.

Filed under: Depression Treatment

PLoS One. 2012; 7(12): e48012
Hatch SL, Woodhead C, Frissa S, Fear NT, Verdecchia M, Stewart R, Reichenberg A, Morgan C, Bebbington P, McManus S, Brugha T, Kankulu B, Clark JL, Gazard B, Medcalf R, Hotopf M,

BACKGROUND: Reliance on national figures may be underestimating the extent of mental ill health in urban communities. This study demonstrates the necessity for local information on common mental disorder (CMD) and substance use by comparing data from the South East London Community Health (SELCoH) study with those from a national study, the 2007 English Adult Psychiatric Morbidity Study (APMS). METHODOLOGY/PRINCIPAL FINDINGS: Data were used from two cross-sectional surveys, 1698 men and women residing in south London and 7403 men and women in England. The main outcome, CMD, was indicated by a score of 12 or above on the Revised Clinical Interview Schedule. Secondary outcomes included hazardous alcohol use and illicit drug use. SELCoH sample prevalence estimates of CMD were nearly twice that of the APMS England sample estimates. There was a four-fold greater proportion of depressive episode in the SELCoH sample than the APMS sample. The prevalence of hazardous alcohol use was higher in the national sample. Illicit drug use in the past year was higher in the SELCoH sample, with cannabis and cocaine the illicit drugs reported most frequently in both samples. In comparisons of the SELCoH sample with the APMS England sample and the APMS sample from the Greater London area in combined datasets, these differences remained after adjusting for socio-demographic and socioeconomic indicators for all outcomes. CONCLUSIONS/SIGNIFICANCE: Local information for estimating the prevalence of CMD and substance use is essential for surveillance and service planning. There were similarities in the demographic and socioeconomic factors related to CMD and substance use across samples.
HubMed – depression


Orbito-frontal cortex volumes in panic disorder.

Filed under: Depression Treatment

Psychiatry Investig. 2012 Dec; 9(4): 408-12
Atmaca M, Yildirim H, Gurok MG, Akyol M

Given the association between the pathophysiology of panic disorder and prefrontal cortex function, we aimed to perform a volumetric MRI study in patients with panic disorder and healthy controls focusing on the in vivo neuroanatomy of the OFC.Twenty right-handed patients with panic disorder and 20 right-handed healthy control subjects were studied. The volumes of whole brain, total white and gray matters, and OFC were measured by using T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T. In addition, for psychological valuation, Hamilton Depression Rating (HDRS) and Panic Agoraphobia Scales (PAS) were administered.Unadjusted mean volumes of the whole brain volume, total white and gray matter were not different between the patients and healthy controls while the patient group had significantly smaller left (t=-6.70, p<0.0001) and right (t=-5.86, p<0.0001) OFC volumes compared with healthy controls.Our findings indicate an alteration of OFC morphology in the panic disorder and suggest that OFC abnormalities may be involved in the pathophysiology of panic disorder. HubMed – depression



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