Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Posttraumatic stress disorder (PTSD) is a prevalent disorder that adversely affects 2-5% of the general population. Little is known about PTSD in the primary care setting. The purpose of the present study was to evaluate the utility of a screening instrument for PTSD (the PCL-C) in primary care and to examine comorbidity, disability, and patterns of healthcare utilization among persons with PTSD in this setting. Adult, English-speaking patients attending for routine medical care (N=368) participated in a two-stage screening consisting of the administration of a self-report measure for posttraumatic stress disorder (the PCL-C) followed by a structured diagnostic interview. Current (1-month) prevalence of PTSD was determined, as were current comorbid disorders. Brief functional impairment and disability indices were administered, and healthcare utilization in the prior 6 months was ascertained. 11.8% (standard error 1.7%) of primary care attendees met diagnostic criteria for either full or partial PTSD. Comorbidity with major depression (61% of cases of PTSD) and generalized anxiety disorder (39%) was common, but less so with social phobia (17%) and panic disorder (6%). Substance use disorder comorbidity (22%) was also fairly common. Patients with PTSD reported significantly more functional impairment than patients without mental disorders. Patients with PTSD also made greater use of healthcare resources than not mentally ill patients. PTSD frequently is encountered in primary care, and is associated with considerable functional impairment and healthcare utilization. Comorbidity with other mood and anxiety disorders is extensive. It remains to be seen if greater awareness and more aggressive treatment of PTSD in primary care will lead to improved functioning and reduced (or more appropriate) healthcare utilization. These are topics for further study.
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PMID:Posttraumatic stress disorder in the primary care medical setting. 1093 33

The results of 2 validation studies for an assessment tool designed specifically for quality improvement and outcomes assessment efforts in mental healthcare are presented in this paper. The studies evaluated a new tool to assess the patient outcomes for major depressive disorder following treatment in routine clinical settings called the Depression-Arkansas Scale (D-ARK). Study 1 included 54 patients recruited from 3 hospital-based clinics (2 mental health clinics and 1 primary care clinic). Study 2 includes 827 patients from 5 clinical settings including a university based outpatient clinic, a VA based mental health clinic, and a managed-care program. These 2 very different studies provide preliminary evidence that the D-ARK may be a useful tool for quality improvement efforts in the mental healthcare setting. Specifically, they indicate that the D-ARK has strong validity when compared to 2 different research assessments, the Structured Clinical Interview for DSM-III-R, Patient Edition (SCID-P) and the Inventory to Diagnose Depression (IDD), and compared to clinical assessments using both the clinical diagnosis and a clinician checklist.
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PMID:Validity of the Depression-Arkansas (D-ARK) Scale: a tool for measuring major depressive disorder. 1238 69

Recent trends in mental-health care have increased the need for practical depression instruments. The Depression-Arkansas (D-ARK), a brief, economical, multipurpose instrument, has been validated for assessing major depressive disorder (MDD) and depressive-symptom severity. Psychometric properties of the D-ARK were compared with standard depression scales (Beck Depression Inventory and Geriatric Depression Scale) among 294 adult and 193 senior primary-care patients, respectively, and 163 patients enrolled in cognitive-behavioral depression classes. The severity scale displayed adequate internal reliability (coefficient alpha =.81-.86), high correlation with the BDI-2 (r =.78-.83) and GDS (r =.75), and similar factor structure to the BDI-2. The D-ARK was calibrated against the BDI-2 and GDS, providing familiar severity category cutpoints with the new instrument. This study yields further data supporting the reliability, validity, and practical utility of the D-ARK.
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PMID:The Depression-Arkansas scale: A validation study of a new brief depression scale in an HMO. 1265 38

Major depressive disorder is one of the most common and devastating psychiatric disorders. To identify candidate mechanisms for major depressive disorder, we compared gene expression in the temporal cortex from 12 patients with major depressive disorder and 14 matched controls using Affymetrix HgU95A microarrays. Significant expression changes were revealed in families of genes involved in neurodevelopment, signal transduction and cell communication. Among these, the expression of 17 genes related to oligodendrocyte function was significantly (P < 0.05, fold change > 1.4) decreased in patients with major depressive disorder. Eight of these 17 genes encode structural components of myelin (CNP, MAG, MAL, MOG, MOBP, PMP22, PLLP, PLP1). Five other genes encode enzymes involved in the synthesis of myelin constituents (ASPA, UGT8), or are essential in regulation of myelin formation (ENPP2, EDG2, TF, KLK6). One gene, that is, SOX10, encodes a transcription factor regulating other myelination-related genes. OLIG2 is a transcription factor present exclusively in oligodendrocytes and oligodendrocyte precursors. Another gene, ERBB3, is involved in oligodendrocyte differentiation. In addition to myelination-related genes, there were significant changes in multiple genes involved in axonal growth/synaptic function. These findings suggest that major depressive disorder may be associated with changes in cell communication and signal transduction mechanisms that contribute to abnormalities in oligodendroglia and synaptic function. Taken together with other studies, these findings indicate that major depressive disorder may share common oligodendroglial abnormalities with schizophrenia and bipolar disorder.
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PMID:Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. 1530 2

The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine. This study investigated whether the functionally relevant Val(108/158)Met gene variant is associated with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized clinical trial with both drugs. In patients treated with mirtazapine, but not paroxetine, allelic variations in the COMT gene were associated with differential response. COMT(VAL/VAL) and COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)-bearing patients in the mirtazapine group. Moreover, carriers of the COMT(VAL/VAL) or COMT(VAL/MET) genotype had significantly greater HAMD-17 (Hamilton Rating Scale for Depression 17 item version) score reductions than COMT(MET/MET) homozygotes from week 2 to 6, respectively, in the mirtazapine group. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the COMT gene.
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PMID:The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression. 1552 Aug 43

This study aimed at the identification of acute and post-traumatic stress responses, and comorbid mental disorders in breast cancer patients. Structured clinical interviews for DSM-IV (SCID) were conducted post-surgery with 127 patients (t1). Screening measures were used to assess post-traumatic stress responses, anxiety, and depression at t1 and at 6 months follow-up (t2). Based on the SCID, prevalence rates were 2.4% for both, cancer-related ASD and PTSD. Experiences most frequently described as traumatic were the cancer diagnosis itself and subsequent feelings of uncertainty. Patients with lifetime PTSD (8.7%) were more likely to meet the criteria for cancer-related ASD or PTSD (OR=14.1). Prevalence estimates were 7.1% for Adjustment Disorder, 4.7% for Major Depression, 3.1% for Dysthymic Disorder and 6.3% for Generalized Anxiety Disorder. Using the screening instruments, IES-R, PCL-C and HADS, we found PTSD in 18.5% at t1 and 11.2-16.3% at t2. The estimates of anxiety and depression reveal rates of 39.6% (t1) and 32.7% (t2) for anxiety, as well as 16.0% (t1) and 13.3% (t2) for depression (t1) (cut-off> or =8). The diagnosis of a life-threatening illness has been included as a potential trauma in the DSM-IV. However, it has to be critically evaluated whether subjective feelings of uncertainty like fears of treatment count among traumatic stressors, and thus, whether the diagnosis of PTSD is appropriate in this group of cancer patients. However, a large number of women with emotional distress illustrate the need for psychosocial counseling and support in this early treatment phase.
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PMID:Prevalence of acute and post-traumatic stress disorder and comorbid mental disorders in breast cancer patients during primary cancer care: a prospective study. 1685 47

Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and bipolar disorder. Although there are a number of patients with major depressive disorder (MDD) in the family members with the chromosome translocation, the possible association with MDD has not yet been studied. We therefore performed an association study of the DISC1 gene with MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single-nucleotide polymorphism (SNP) was associated with an increased risk of developing MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi-marker haplotype analysis containing this SNP (P=0.002). We also explored possible impact of Ser704Cys on brain morphology in healthy volunteers using MR imaging. We found a reduction in gray matter volume in cingulate cortex and a decreased fractional anisotropy in prefrontal white matter of individuals carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD.
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PMID:Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. 1695 94

The fibroblast growth factor (FGF) system has previously been found to be altered in post-mortem brains of individuals with major depressive disorder (MDD). The present study tested whether the FGF system is altered following acute social defeat. Rats were exposed to four consecutive days of either a social defeat paradigm or novel cages. Animals were sacrificed after the last social defeat session and gene expression was assessed in the hippocampus by mRNA in situ hybridization. Molecular components of the FGF system were significantly downregulated following social defeat. Specifically, FGF2 and FGFR1 mRNA expression was decreased in various subfields of the hippocampus. Decreased tone of the FGF system following an acute social stressor is congruent with human post-mortem results of FGF system downregulation in depression. These findings suggest that modulating the FGF system may have therapeutic value in the treatment of MDD.
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PMID:The fibroblast growth factor system is downregulated following social defeat. 1806 49

Genome-wide gene expression analysis using DNA microarray has a great advantage to identify the genes or specific molecular cascades involved in mental diseases, including major depression and suicide. In the present study, we conducted DNA microarray analysis of major depression using postmortem prefrontal cortices. The gene expression patterns were compared between the controls and subjects with major depression. As a result, 99 genes were listed as the differentially expressed genes in major depression, of which several genes such as FGFR1, NCAM1, and CAMK2A were of interest. Gene ontology analysis suggested an overrepresentation of genes implicated in the downregulation or inhibition of cell proliferation. The present results may support the hypothesis that major depression is associated with impaired cellular proliferation and plasticity. Comparison between the controls and suicide victims with major depression, bipolar disorder, or schizophrenia was also conducted in the present study. Two genes, CAD and ATP1A3, were differentially expressed in the three comparisons in the same direction. Interestingly, these two genes were also included in the differentially expressed 99 genes in major depression. It may be worth investigating the genes in relation to suicide or major depression.
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PMID:Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains. 1806 48

Unipolar major depressive disorder (MDD) is a prevalent, disabling condition with multiple genetic and environmental factors impacting disease risk. The diagnosis of MDD relies on a cumulative measure derived from multiple trait dimensions and alone is limited in elucidating MDD genetic determinants. We and others have proposed that MDD may be better dissected using paradigms that assess how specific genes associate with component features of MDD. This within-disease design requires both a well-phenotyped cohort and a robust statistical approach that retains power with multiple tests of genetic association. In the present study, common polymorphic variants of genes related to central monoaminergic and cholinergic pathways that previous studies align with functional change in vitro or depression associations in vivo were genotyped in 110 individuals with unipolar MDD. Subphenotypic characteristics were examined using responses to individual items assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM IV), the 17-item Hamilton Rating Scale for Depression (HAM-D) and the NEO Five Factor Inventory. Multivariate Permutation Testing (MPT) was used to infer genotype-phenotype relationships underlying dimensional findings within clinical categories. MPT analyses show significant associations of the norepinephrine transporter (NET, SLC6A2) -182 T/C (rs2242446) with recurrent depression [odds ratio, OR = 4.15 (1.91-9.02)], NET -3081 A/T (rs28386840) with increase in appetite [OR = 3.58 (1.53-8.39)] and the presynaptic choline transporter (CHT, SLC5A7) Ile89Val (rs1013940) with HAM-D-17 total score {i.e. overall depression severity [OR = 2.74 (1.05-7.18)]}. These relationships illustrate an approach to the elucidation of gene influences on trait components of MDD and with replication, may help identify MDD subpopulations that can benefit from more targeted pharmacotherapy.
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PMID:Multivariate permutation analysis associates multiple polymorphisms with subphenotypes of major depression. 1808 10


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