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3.
Mol Neurobiol ; 47(3): 1045-65, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23335160

ABSTRACT

Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer's disease, Parkinson's disease and Huntington's disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.


Subject(s)
Brain/metabolism , Brain/pathology , Insulin/metabolism , Nervous System Diseases/metabolism , Nervous System Diseases/pathology , Neurotic Disorders/metabolism , Neurotic Disorders/pathology , Animals , Humans , Nervous System Diseases/complications , Nervous System Diseases/physiopathology , Neurotic Disorders/complications , Neurotic Disorders/physiopathology
4.
Neuroreport ; 23(4): 246-50, 2012 Mar 07.
Article in English | MEDLINE | ID: mdl-22262089

ABSTRACT

The present study investigates for the first time the influence of the DRD2 C957T polymorphism on personality in persons who stutter. In a recent study, the CC genotype of this single nucleotide polymorphism has been associated with stuttering, which could not be replicated in a follow-up study. Here, we demonstrate, in N=105 persons who stutter, that carriers of the CC and the CT genotype significantly have the highest neuroticism scores. This shows that the inclusion of personality measures in the investigation of the biological underpinnings of stuttering represents an important new avenue. In healthy control persons, a sex by C+/- allele interaction effect could be demonstrated. Female but not male carriers of the C+ variant report the highest neuroticism scores. Because neuroticism has been reported to be associated with stuttering before, the present data support the idea that this personality trait acts as an endophenotype for stuttering, contributing towards bridging the gap from gene variation to the complex pathology. This idea is supported by an additional path model showing that the polymorphism DRD2 C957T influences the self-reported severity of stuttering mainly by its influence on neuroticism (independent of the variable sex).


Subject(s)
Neurotic Disorders/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Dopamine D2/genetics , Stuttering/genetics , Adult , Case-Control Studies , Female , Humans , Male , Middle Aged , Neurotic Disorders/metabolism , Neurotic Disorders/physiopathology , Personality/genetics , Stuttering/metabolism , Stuttering/physiopathology , Young Adult
5.
Curr Med Chem ; 18(18): 2783-90, 2011.
Article in English | MEDLINE | ID: mdl-21649582

ABSTRACT

The serotonin (5-HT) receptors of type 6 (5-HT6) are relatively new. They are quite different from all other 5-HT receptors, as they are characterized by a short third cytoplasmatic loop and a long C-terminal tail, and contain one intron located in the middle of the third cytoplasmatic loop. After some initial controversies, the available findings are now apparently more congruent. Nevertheless, discrepancies still exist, such as those in binding affinity, effects of 5-HT6 ligands on brain catecholamines and behavioral syndromes mediated by them. Much interest in 5-HT6 receptors was triggered by the evidence that some antipsychotics could bind to them. Subsequently, despite the lack of complete information on metabolic patterns of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic and anti-obese drugs. In any case, the available information on both the pharmacology of 5-HT6 receptors is still quite scant. Therefore, with the present paper we aimed at reporting a comprehensive review on the status of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.


Subject(s)
Neuropharmacology , Receptors, Serotonin/metabolism , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Animals , Cytoplasm/drug effects , Cytoplasm/metabolism , Humans , Neurotic Disorders/drug therapy , Neurotic Disorders/metabolism , Neurotic Disorders/pathology , Serotonin Antagonists/therapeutic use , Serotonin Receptor Agonists/therapeutic use
6.
Biol Psychol ; 87(3): 439-49, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21683756

ABSTRACT

The current study examined the singular and interactive effects of the 5-HTTLPR genotype and trait neuroticism on affective and physiological stress responses to an academic examination in healthy undergraduate students. From 771 students, 46 short/short (S/S)-allele carriers and 48 long/long (L/L)-allele carriers with the lowest and the highest neuroticism scores (80 females, 14 males; mean age±SD: 20.3±1.7 years) were selected. Salivary cortisol concentrations, mood and perceived stress were assessed before and after a 2-h written examination and compared with a control day. Negative mood, perceived stress and cortisol significantly increased during the examination compared to the control day. Negative stress effects on mood and perceived stress were significantly larger for S/S-allele carriers compared to L/L-allele carriers, regardless of trait neuroticism. Since vulnerability to real-life stressors is an important risk factor for depression pathogenesis, this may be a mediating factor making S/S-allele carriers more susceptible for depression symptoms.


Subject(s)
Affect , Anxiety/genetics , Hydrocortisone/metabolism , Neurotic Disorders/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Stress, Psychological/genetics , Alleles , Anxiety/metabolism , Anxiety/psychology , Female , Genotype , Humans , Male , Neurotic Disorders/metabolism , Neurotic Disorders/psychology , Personality , Polymorphism, Genetic , Psychiatric Status Rating Scales , Saliva/metabolism , Stress, Psychological/metabolism , Stress, Psychological/psychology , Young Adult
7.
Drug Alcohol Depend ; 116(1-3): 80-5, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21306838

ABSTRACT

BACKGROUND: Personality characteristics have been associated with cocaine use. However, little is known about the mechanisms through which personality could impact drug use. The present study investigated the cross-sectional and prospective relationships between personality dimensions (i.e., impulsivity, neuroticism) and problematic cocaine use. Reactivity to a pharmacological stressor as a potential mediator of the relationship between neuroticism and future cocaine use was also examined. METHODS: Participants were 53 cocaine-dependent individuals and 47 non-dependent controls. Subjects completed the Eysenck Personality Questionnaire (EPQ) at baseline and were administered i.v. corticotrophin releasing hormone (CRH; 1 µg/kg). Cocaine use in the 30 days following CRH administration was measured. RESULTS: Cocaine-dependent individuals had higher scores on the psychoticism (i.e., impulsivity, aggression; p=0.02) and neuroticism (p<0.01) scales of the EPQ than non-dependent controls. Cocaine-dependent individuals also had a greater subjective stress response to CRH than controls (p<0.01). Cocaine-dependent individuals with elevated psychoticism used significantly more cocaine over the follow-up period (p<0.05), whereas individuals with elevated neuroticism trended towards using cocaine more frequently over the follow-up (p=0.07). Finally, there was a trend for an indirect effect of neuroticism on frequency of cocaine use through subjective reactivity to CRH. CONCLUSIONS: The findings extend past research on the association between personality and cocaine use, and suggest that motives for cocaine use may systematically vary across personality characteristics. Moreover, tailoring therapeutic interventions to individuals' personalities may be an area that warrants further investigation.


Subject(s)
Cocaine-Related Disorders/epidemiology , Neurotic Disorders/epidemiology , Psychotic Disorders/epidemiology , Adult , Aggression/psychology , Central Nervous System Stimulants/adverse effects , Central Nervous System Stimulants/metabolism , Central Nervous System Stimulants/pharmacology , Cocaine/adverse effects , Cocaine/metabolism , Cocaine/pharmacology , Cocaine-Related Disorders/metabolism , Cocaine-Related Disorders/psychology , Cross-Sectional Studies , Female , Humans , Hydrocortisone/blood , Impulsive Behavior/epidemiology , Impulsive Behavior/metabolism , Impulsive Behavior/psychology , Male , Middle Aged , Neurotic Disorders/metabolism , Neurotic Disorders/psychology , Personality , Prospective Studies , Psychiatric Status Rating Scales , Psychotic Disorders/metabolism , Psychotic Disorders/psychology , Stress, Psychological/metabolism , Stress, Psychological/pathology , Time Factors
8.
Psychiatry Clin Neurosci ; 64(4): 435-41, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20653910

ABSTRACT

AIMS: Oxidative stress has gained attention recently in psychiatric medicine and has been reported to be associated with various diseases. However, the psychosocial factors involved in oxidative stress are still not well understood. Thus, the aim of this study was to examine whether anxiety levels and neuroticism were associated with serum oxidative and anti-oxidative status in healthy college students. METHODS: Participants in this cross-sectional study were 54 non-smoking college students. Their serum oxidative status was determined by reactive oxygen metabolites (ROM) and the biological anti-oxidant potential. Anxiety levels and neuroticism were assessed using the State-Trait Anxiety Inventory and the NEO Five-Factor Inventory, respectively. RESULTS: Correlation analysis showed an association of increased ROM concentration with elevated anxiety levels (State, rho = 0.39, P = 0.046; Trait, rho = 0.44, P = 0.024) and the personality trait of neuroticism (rho = 0.47, P = 0.016) in female students. However, the ROM concentration in male students was not associated with the anxiety level or any personality trait. CONCLUSION: Although these findings suggest that neurotic and anxious female students tend to be exposed to oxidative stress, these linkages should be confirmed by multivariate analysis in future research.


Subject(s)
Anxiety/metabolism , Neurotic Disorders/metabolism , Oxidative Stress , Anxiety/physiopathology , Chi-Square Distribution , Cross-Sectional Studies , Female , Humans , Male , Neurotic Disorders/physiopathology , Oxidative Stress/physiology , Personality/physiology , Personality Inventory , Reactive Oxygen Species/blood , Sex Factors , Statistics, Nonparametric , Students/psychology , Young Adult
9.
Brain Behav Immun ; 24(7): 1074-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20227485

ABSTRACT

Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases.


Subject(s)
Anxiety/metabolism , C-Reactive Protein/metabolism , Depression/metabolism , Hydrocortisone/metabolism , Interleukin-6/blood , Neurotic Disorders/metabolism , Adult , Anxiety/psychology , Depression/psychology , Female , Humans , Male , Neurotic Disorders/psychology , Personality Inventory , Saliva/metabolism , Surveys and Questionnaires
10.
Psychoneuroendocrinology ; 35(10): 1573-7, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20299157

ABSTRACT

A substantial body of research on the pathophysiology of negative health outcomes has focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Maladaptive and adaptive personality features have been discussed to be associated with health outcomes. In the current study, we investigated the association of neuroticism (N) and conscientiousness (C) with diurnal cortisol levels in 102 working parents (M age=37 years; 50% female). Further, we examined the impact of daily positive and negative affect on this association. During a 6-day time-sampling phase, cortisol was measured at awakening and after that within intervals of 3h. We found a positive association of N with cortisol levels throughout the measurement period, but no association of C with daily cortisol. When accounting for daily positive and negative affect, individuals with high scores on C displayed reductions in daily cortisol concentrations that were driven by positive affect compared to individuals with low C scores. No such association emerged for N. Our findings might further elucidate the role of personality in HPA axis regulation and improve our understanding of the association of endocrine states and health outcomes.


Subject(s)
Circadian Rhythm/physiology , Hydrocortisone/metabolism , Neurotic Disorders/metabolism , Neurotic Disorders/psychology , Adult , Affect/physiology , Area Under Curve , Female , Humans , Male , Personality/physiology , Personality Tests , Saliva/metabolism , Surveys and Questionnaires
11.
Vestn Ross Akad Med Nauk ; (12): 33-7, 2010.
Article in Russian | MEDLINE | ID: mdl-21395062

ABSTRACT

Laboratory, clinical, and pathophysiological methods were used to examine servicemen presenting with hyperuricemia. Pronounced hypersympaticotony was accompanied by stabilization of cardiac rhythm. Neurotic personality profile was identified in 48% of the subjects, psychotic in 17.3%, and undefined in 34.6%. The elevated plasma uric acid level was shown to be a factor associated with the neurotic psychotype. There was no correlation between other hematological characteristics and personality psychotype. The examined subjects exhibited high working capacity and level of ambition. Inability to take mind off the pressure of work creates psychosomatic predisposition for and risk of cardiovascular pathology strengthened by permanent hypersympaticotony. It is proposed to teach the subjects like those included in the study to reach neuromuscular relaxation in combination with cognitive-behavioural training as a means of preventing the development of cardiovascular pathology.


Subject(s)
Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/psychology , Hyperuricemia/complications , Hyperuricemia/physiopathology , Hyperuricemia/psychology , Uric Acid/blood , Adult , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cognitive Behavioral Therapy , Humans , Hyperuricemia/metabolism , Male , Middle Aged , Military Personnel , Neuropsychological Tests , Neurotic Disorders/etiology , Neurotic Disorders/metabolism , Neurotic Disorders/physiopathology , Neurotic Disorders/therapy , Personality Tests , Psychophysiology , Relaxation Therapy , Risk Factors , Type A Personality
12.
J Pers ; 77(5): 1561-75, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19678874

ABSTRACT

Neuroticism is widely used as an explanatory concept in etiological research of psychopathology. To clarify what neuroticism actually represents, we investigated the phenotypic and genetic relationship between neuroticism and the morning cortisol secretion. In the current classic twin study, 125 female twin pairs (74 monozygotic and 51 dizygotic pairs) participated. For each participant, 4 different neuroticism scores were available to calculate a neuroticism composite score that was used in the statistical analyses. The morning cortisol secretion was assessed by 4 salivary samples in the 1st hour after awakening. Significant genetic influences for the neuroticism composite score (55%), and each of the 4 cortisol samples (52%-69%) were found. There was no phenotypic or genotypic relationship between neuroticism and morning cortisol secretion. Although neuroticism and cortisol were both heritable traits, they did not share any genetic influences.


Subject(s)
Hydrocortisone/analysis , Neurotic Disorders/metabolism , Saliva/chemistry , Twins, Dizygotic/metabolism , Twins, Monozygotic/metabolism , Adult , Biomarkers/analysis , Circadian Rhythm/genetics , Female , Humans , Models, Genetic , Multivariate Analysis , Neurotic Disorders/genetics , Twins , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Young Adult
13.
Neuropsychopharmacology ; 34(8): 2019-27, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19242408

ABSTRACT

Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events. In a population sample (n=1269), we obtained questionnaire measures of personality (Big Five Inventory), depression and anxiety (Brief Symptom Inventory), and life events. The CNR1 gene was covered by 10 SNPs located throughout the gene to determine haplotypic association. Variations in the CNR1 gene were significantly associated with a high neuroticism and low agreeableness phenotype (explained variance 1.5 and 2.5%, respectively). Epistasis analysis of the SNPs showed that the previously reported functional 5' end of the CNR1 gene significantly interacts with the 3' end in these phenotypes. Furthermore, current depression scores significantly associated with CNR1 haplotypes but this effect diminished after covariation for recent life events, suggesting a gene x environment interaction. Indeed, rs7766029 showed highly significant interaction between recent negative life events and depression scores. The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression--and probably also for co-morbid psychiatric conditions such as substance use disorders--through a high neuroticism and low agreeableness phenotype. This study also suggests that the CNR1 gene influences vulnerability to recent psychosocial adversity to produce current symptoms of depression.


Subject(s)
Brain Chemistry/genetics , Depressive Disorder/genetics , Genetic Predisposition to Disease/genetics , Neurotic Disorders/genetics , Personality/genetics , Receptor, Cannabinoid, CB1/genetics , Adaptation, Psychological/physiology , Adolescent , Adult , Anxiety Disorders/genetics , Anxiety Disorders/metabolism , Anxiety Disorders/psychology , DNA Mutational Analysis , Depressive Disorder/metabolism , Depressive Disorder/psychology , Environment , Female , Genetic Testing , Haplotypes/genetics , Humans , Male , Middle Aged , Neurotic Disorders/metabolism , Neurotic Disorders/physiopathology , Phenotype , Polymorphism, Single Nucleotide/genetics , Surveys and Questionnaires , Young Adult
14.
Am J Geriatr Psychiatry ; 17(12): 1077-84, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20104064

ABSTRACT

OBJECTIVE: To investigate the cross-sectional association between personality characteristics and hypothalamic-pituitary-adrenal (HPA) axis regulation in older persons. METHODS: The study sample consisted of 1,150 participants (mean age 74.8 +/- 7.1 years, 48% male) from the population-based Longitudinal Aging Study Amsterdam. HPA axis activity was measured with salivary cortisol collected after awakening and late in the evening. Outcome measures were awakening and evening cortisol levels (natural log transformed) and the diurnal pattern of cortisol. Determinants were scores on questionnaires assessing neuroticism, mastery, and self-esteem. RESULTS: Multiple linear regression analyses adjusted for potential confounders did not show significant associations between any of the personality characteristics and any of the cortisol measures. On evening cortisol, a significant interaction was observed between neuroticism and age (B = -0.001; T = -2.50, df = 1,139; p value = 0.01). After stratification in two age groups, the authors observed that high levels of neuroticism were associated with elevated levels of evening cortisol in subjects aged <75 years (B = 0.02; 95% confidence interval: 0.01-0.03; T = 2.15, df = 630, p = 0.03) but not in subjects aged 75 years or older. CONCLUSIONS: The findings of this large population-based study of older persons suggest that the personality characteristics mastery and self-esteem are not associated with HPA axis regulation as measured with salivary awakening and evening cortisol. However, high neuroticism may be associated with elevated levels of evening cortisol in the younger old but not in the older old.


Subject(s)
Aged/physiology , Hypothalamo-Hypophyseal System/physiopathology , Personality , Pituitary-Adrenal System/physiopathology , Age Factors , Cohort Studies , Cross-Sectional Studies , Female , Geriatric Assessment/methods , Geriatric Assessment/statistics & numerical data , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Longitudinal Studies , Male , Netherlands , Neurotic Disorders/metabolism , Neurotic Disorders/physiopathology , Personality Inventory/statistics & numerical data , Pituitary-Adrenal System/metabolism , Saliva/metabolism , Self Concept , Surveys and Questionnaires
15.
Psychoneuroendocrinology ; 33(10): 1344-56, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18809259

ABSTRACT

Previous studies have yielded equivocal findings on the relationship between personality and cortisol activity. The present study examined associations between personality and cortisol activity in a large, diverse adolescent sample, while partialling the effects of relevant demographic and health-related covariates. A subsample of 230 participants (57% of whom reported elevated neuroticism) was selected from a larger sample of 16-18-year olds involved in a study on risk factors for emotional disorders. Subsample participants completed a battery of personality questionnaires, and saliva collection was requested several months later on three consecutive days at six time points per day, from wakeup to bedtime. Associations between personality and cortisol rhythms were examined using multilevel growth curve modeling. Neuroticism (N) and introversion (I) were significantly and differentially associated with features of diurnal cortisol patterns. Specifically, a significant N x gender interaction was observed, demonstrating flatter cortisol rhythms across the waking day among male participants with higher N. Elevated I, however, was associated with lower cortisol awakening responses for both male and female participants, and higher cortisol at the time of waking for male participants only. The present study supports personality as a significant predictor of diurnal cortisol patterns in late adolescence, after accounting for the effects of demographic and health covariates, and suggests that gender plays a role in moderating associations between personality and cortisol.


Subject(s)
Hydrocortisone/metabolism , Introversion, Psychological , Neurotic Disorders/metabolism , Psychology, Adolescent , Saliva/chemistry , Adolescent , Circadian Rhythm/physiology , Data Interpretation, Statistical , Female , Health , Humans , Inhibition, Psychological , Interpersonal Relations , Male , Personality Tests , Psychiatric Status Rating Scales , Surveys and Questionnaires
16.
Neuroreport ; 19(8): 883-6, 2008 May 28.
Article in English | MEDLINE | ID: mdl-18463506

ABSTRACT

Neuroticism and extraversion are two core dimensions of personality and are considered to be associated with emotional disorders. We investigated resting state brain metabolic correlates of neuroticism and extraversion using a positron emission tomography. Twenty healthy young men completed an F-flurodeoxyglucose-PET scan at rest and the Korean version of the revised Eysenck Personality Questionnaire. Neuroticism was negatively correlated with regional glucose metabolism in prefrontal regions including the medial prefrontal cortex. Extraversion was positively correlated with metabolism in the right putamen. These results suggest close associations between resting state brain activity in the prefrontal and striatal regions and specific personality traits and thus contribute to the understanding of the neurobiological bases of predisposition to psychiatric disorders.


Subject(s)
Energy Metabolism/physiology , Extraversion, Psychological , Neurotic Disorders/diagnostic imaging , Neurotic Disorders/metabolism , Prefrontal Cortex/diagnostic imaging , Putamen/diagnostic imaging , Adult , Fluorodeoxyglucose F18 , Glucose/metabolism , Humans , Male , Personality , Positron-Emission Tomography , Prefrontal Cortex/metabolism , Putamen/metabolism , Rest/physiology
17.
Biol Psychol ; 78(2): 200-3, 2008 May.
Article in English | MEDLINE | ID: mdl-18417268

ABSTRACT

Serotonergic dysregulation is associated with negative affect. Plasma prolactin responses to a tryptophan enhancement challenge are used as a measure of central nervous system serotonergic activity. We examined prolactin responses to a tryptophan challenge as they relate to the personality domains of neuroticism, extraversion, openness, agreeableness, and conscientiousness. Participants were 67 volunteers. Regression models assessed peak prolactin response to intravenous tryptophan infusion as a predictor of neuroticism, extraversion, openness, agreeableness, and conscientiousness. Prolactinxgender product terms were included to examine moderation by gender. Models were adjusted for baseline levels of prolactin, age, and race. Gender moderated the association between N and prolactin level (p<.03). Higher levels of N were associated with decreased levels of prolactin responses in females, whereas the opposite was true for males. Remaining personality domains were not related to prolactin levels. Findings add to literature suggesting the serotonin system functions differently, in important ways, in males and females.


Subject(s)
Central Nervous System/metabolism , Neurotic Disorders/metabolism , Neurotic Disorders/pathology , Serotonin/metabolism , Sex Characteristics , Adult , Extraversion, Psychological , Female , Humans , Male , Middle Aged , Personality , Personality Inventory , Prolactin/metabolism , Tryptophan/drug effects
18.
Am J Med Genet B Neuropsychiatr Genet ; 147B(5): 661-6, 2008 Jul 05.
Article in English | MEDLINE | ID: mdl-18163385

ABSTRACT

The serotonin neurotransmitter system in general, and the serotonin 1A receptor in particular, has been broadly implicated in the pathophysiology of mood and anxiety disorders, although the results of genetic association studies have been mixed. In this study, we examined the serotonin 1A receptor gene, HTR1A, for its association with shared genetic risk across a range of anxiety and depression-related phenotypes. Using multivariate structural equation modeling, we selected twin pairs from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders scoring at the extremes of a latent genetic risk factor that underlies susceptibility to neuroticism, major depression, and several anxiety disorders. One member from each selected pair was entered into a 2-stage, case-control association study for the HTR1A gene. In the resulting sample of 589 cases and 539 controls, four SNPs spanning the HTR1A locus, including the C(-1019)G functional promoter polymorphism (rs6295), were screened in stage 1, the positive results of which were tested for replication in stage 2. While one marker met threshold significance criteria in stage 1, this association was not replicated in stage 2. Post-hoc analyses did not reveal association to any of the specific psychiatric phenotypes. Our data suggests that the HTR1A gene may not play a major role in the genetic susceptibility underlying depressive and anxiety-related phenotypes.


Subject(s)
Anxiety Disorders/genetics , Depressive Disorder, Major/genetics , Diseases in Twins/genetics , Neurotic Disorders/genetics , Receptor, Serotonin, 5-HT1A/genetics , Adult , Anxiety Disorders/metabolism , Depressive Disorder, Major/metabolism , Diseases in Twins/metabolism , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Linkage Disequilibrium , Neurotic Disorders/metabolism
20.
Neurosci Behav Physiol ; 36(6): 605-11, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16783513

ABSTRACT

The levels of monoamines and their metabolites were studied by HPLC with electrochemical detection in homogenates of hypothalamus, hippocampus, prefrontal cortex, and amygdala in intact and neuroticized Wistar rats with different types of behavior in the open field and forced swimming tests. Intact rats with intermediate levels of activity and depressivity had higher serotonin concentrations in the hypothalamus and lower noradrenaline and hydroxyindoleacetic acid levels in the hippocampus than rats characterized by low activity and high depressivity. In neuroticization, the levels of study monoamines and their metabolites decreased in all the brain structures investigated with the exceptions of an increase in the dopamine concentration in the hippocampus and the dihydroxyphenylacetic acid concentration in the prefrontal cortex. The effect of neuroticization on the neurotransmitter systems in all study structures except the hypothalamus depended on the typological characteristics of the rats. This was most marked in rats with the extreme types of behavior--active and passive--in which changes in monoamine and metabolite contents were seen in all brain structures studied. Rats of the intermediate type showed no changes in any of the substances studied in the hippocampus.


Subject(s)
Behavior, Animal , Biogenic Monoamines/metabolism , Brain/metabolism , Neurotic Disorders/metabolism , Animals , Male , Neurotic Disorders/psychology , Rats , Rats, Wistar , Tissue Distribution
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