Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major depressive disorder (MDD) is a severe psychiatric disorder with a lifetime prevalence of about 15%.1 The importance of the genetic component is well accepted,2 but the mode of inheritance is complex and non-Mendelian. A line of evidence suggests the involvement of serotonin and dopamine neurotransmitters in the pathophysiology of depression. In the present study, 102 unipolar MDD patients and 172 healthy controls were genotyped for polymorphisms in four serotonergic and three dopaminergic candidate genes [tryptophan hydroxylase (TPH), serotonin receptor 2A (HTR2A), serotonin receptor 2C (HTR2C), serotonin transporter promoter region (5-HTTLPR), dopamine receptor D4 (DRD4), dopamine transporter (DAT1) and catechol-O-methyl transferase (COMT)]. There were no statistical differences between MDD patients and healthy controls in the genotypic and allelic distribution of all polymorphisms investigated. Thus, our study does not support a major role for these polymorphisms in contributing to susceptibility to MDD, although it does not preclude minor effects.
 ...
PMID:Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. 1048 58

Previously, we reported an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, DRD4 variants accounted for only 2% of the phenotypic variance, indicating that contributions from other genes were probable. The serotonin transporter gene is a primary candidate in major psychoses, and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a number of psychopathological conditions. In the present study we investigated the original cohort of subjects to evaluate the 5-HTTLPR possible influence on the psychopathology of major psychoses in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the 5-HTTLPR and DRD4 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants did not significantly influence the previously reported association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The serotonin transporter gene does not, therefore, interact with DRD4 in determining the symptomatology of major psychoses.
 ...
PMID:No interaction between serotonin transporter gene and dopamine receptor D4 gene in symptomatology of major psychoses. 1049 Jul 3

We examined allelic polymorphisms of the serotonin transporter (5-HTT) gene and antidepressant response to 6 weeks' treatment with the selective serotonin reuptake inhibitor (SSRI) drugs fluoxetine or paroxetine. We genotyped 120 patients and 252 normal controls, using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene. Diagnosis of depression was not associated with 5-HTT polymorphisms. Patients homozygous l/l in intron 2 or homozygous s/s in the promoter region showed better responses than all others (p < 0.0001, p = 0.0074, respectively). Lack of the l/l allele form in intron 2 most powerfully predicted non-response (83.3%). Response to SSRI drugs is related to allelic variation in the 5-HTT gene in depressed Korean patients.
 ...
PMID:Serotonin transporter gene polymorphism and antidepressant response. 1068 61

A substance P antagonist has recently been reported to have clinical efficacy in the treatment of depression. We have therefore analysed sections from human pons, including the raphe region, with double in situ hybridization using riboprobes complementary to substance P and the 5-hydroxytryptamine transporter (5-HT-T mRNAs). A distinct overlap of cell bodies expressing these two markers was observed in the dorsal and median raphe nuclei. Analysis of double-labelled sections revealed that almost half of the 5-HT neurons in the dorsal raphe and around 25% in the median raphe nucleus expressed substance P mRNA. The highest percentage was observed in the ventrolateral dorsal raphe nucleus and the lowest in the caudal raphe nucleus. These results demonstrate that the phenotype of the raphe 5-HT neurons varies between species, since so far no 5-HT-substance P co-existence has been demonstrated in the dorsal raphe complex of rat. The question is raised whether the present results may be of significance for understanding a possible role of substance P in depression.
 ...
PMID:Serotonin and substance P co-exist in dorsal raphe neurons of the human brain. 1071 42

Several studies have attempted to confirm an association between a deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and Alzheimer's disease independent from the apolipoprotein E (APOE) varepsilon4 status. We examined this deletion/insertion polymorphism of the serotonin transporter gene in a sample of 222 consecutively recruited gerontopsychiatric patients which was divided into four different diagnostic groups: Alzheimer's disease (N=84), mild cognitive impairment (N=29), subjective cognitive complaints (N=49), depression/other psychiatric disorders (N=56) and 118 healthy, non-demented controls. The aim of this approach was to test whether the investigated polymorphism has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia, respectively. We could not detect any significant differences in the allelic distribution of the deletion/insertion polymorphism of the 5-HTT gene between the four patient subgroups and the control group. This finding indicates that the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of Alzheimer's disease and other psychogeriatric disorders.
 ...
PMID:Serotonin transporter (5-HTT) gene polymorphism in psychogeriatric patients. 1077 Nov 75

Cigarette smoking behavior is influenced by both personality traits and inherited factors. Previous research showed that neuroticism-a broad personality domain that includes anxiety, depression, impulsiveness and vulnerability-increases the risk of being a smoker, primarily because of difficulty in quitting. Neuroticism has also been associated with the 5-HTTLPR, a functional polymorphism in the promoter for the serotonin transporter gene. We used population and family-based methods to analyze the joint effects of the 5-HTTLPR and neuroticism on smoking behavior in a population of 759 never, current, and former smokers, all members of sib-pairs. Our main finding is that smoking behavior is influenced by an interaction between neuroticism and 5-HTTLPR genotype. Specifically, neuroticism was positively correlated with current smoking and negatively associated with smoking cessation in individuals and siblings with poorly transcribed 5-HTTLPR-S genotypes, but not in those with the more highly expressed 5-HTTLPR-L genotype. Individuals with both a 5-HTTLPR-S genotype and a high level of neuroticism had the greatest difficulty in quitting smoking. These data, if replicated, suggest that smoking behavior is more strongly influenced by the combination of the serotonin transporter gene and neuroticism than by either factor alone, and that personality scores and 5-HTTLPR genotype may predict the clinical efficacy of certain smoking cessation drugs.
 ...
PMID:Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior. 1082 46

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire and the neuroticism scale of the NEO-PI-R, in a sample of 148 Israeli subjects comprising 74 same-sex sibling pairs. We replicated the reported association between the short allele and higher scores on the TPQ harm avoidance scale (P = 0.03), including the subscale of shyness (P = 0.02), and also found association in the same direction between the short allele and the NEO-PI-R neuroticism subscales of anxiety (P = 0.03) and depression (P = 0.04). Sib-pair linkage analysis, using the regression method, further supported a role of the 5-HTTLPR in anxiety-related personality traits.
 ...
PMID:Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs. 1082 53

The serotonin transporter (5-HTT) regulates serotonergic neurotransmission and is thought to influence emotion. A 5-HTT-linked polymorphic region (5-HTTLPR) has two common variants, short (s) and long (l). We previously found population and within-family associations between the lower-expressing s allele and neuroticism, a trait related to anxiety, hostility, and depression, on a standard measure (the NEO Personality Inventory, Revised [NEO-PI-R]) in a primarily male population (n=505), and that the s allele was dominant. We investigated this association in a new sample (n=397, 84% female, primarily sib-pairs). The results robustly replicated the 5-HTTLPR neuroticism association, and the dominance of the s allele. Combined data from the two studies (n=902) showed a highly significant association between the s allele and higher NEO Neuroticism both across individuals and within families. Association between genotype and a related measure, Anxiety on the 16PF inventory, was replicated in the new population and within families in the combined sample. Association to another trait, estimated TPQ Harm Avoidance, was not replicated in the new sample but found only within the combined sibship group. Another association found in our original study, between the s allele and lower scores on NEO-PI-R Agreeableness, was also replicated and was more robust in the current and the combined samples. Associations between the functional 5-HTTLPR polymorphism were similar in women and men. These results help to define specific personality features reproducibly associated with 5-HTTLPR genotype. Such associations were strongest for traits defined by the NEO, enhancing the attractiveness of the five-factor personality model in genetic research on complex behavioral dimensions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:202-216, 2000. Published 2000 Wiley-Liss, Inc.
 ...
PMID:Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample. 1089 98

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.
 ...
PMID:Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. 1102 24

Reciprocal interactions between central 5-HT system and hypothalamo-pituitary-adrenal (HPA) axis are of particular relevance with regard to depression, in which alterations of both systems have been evidenced. In order to further explore these interactions, two models of mutant mice have been used. They consisted of knock-out mice lacking the 5-HT transporter (5-HTT-/-) and of transgenic mice with impaired glucocorticoid receptor (GR-i) expression. Under control conditions. the functional properties of 5-HT(1A) autoreceptors in GR-i mice were as in their paired wild-type. However, both chronic stress and long term treatment with fluoxetine induced abnormal adaptive changes in 5-HT(1A) autoreceptor functioning in GR-i mice. On the other hand, a marked desensitization of 5-HT(1A) autoreceptors was found in 5-HTT-/- mice as compared with paired wild-type animals, and this phenomenon was further enhanced by exposure to stressful conditions. These data show that alterations of HPA axis at the gene level has consequences on 5-HT neurotransmission, and reciprocally, that 5-HTT knock-out affects HPA-dependent responses to stress.
 ...
PMID:5-HT-HPA interactions in two models of transgenic mice relevant to major depression. 1105 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>