Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships.

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.

Anxiety, neuroticism and oxidative stress: cross-sectional study in non-smoking college students.

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.

[Results of experimental study of psychophysiological state and hematological characteristics in servicemen presenting with hyperuricemia].

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.

Personality characteristics and hypothalamic-pituitary-adrenal axis regulation in older persons.

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.

Neuroticism and morning cortisol secretion: both heritable, but no shared genetic influences.

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.

Neuroticism and introversion are associated with salivary cortisol patterns in adolescents.

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.

Resting brain metabolic correlates of neuroticism and extraversion in young men.

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.

Associations among central nervous system serotonergic function and neuroticism are moderated by gender.

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.

Association study between the serotonin 1A receptor (HTR1A) gene and neuroticism, major depression, and anxiety disorders.

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.

Effects of chronic neuroticization on the monoaminergic systems of different structures in the brains of rats with different typological characteristics.

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.

Correlation between striatal dopamine D2 receptor density and neuroticism in community volunteers.

The central dopaminergic system, as well as the central serotonergic system, has been reported to be correlated with higher neuroticism. The present study examined the relationship between striatal dopamine D(2) receptor density and neuroticism. Neuroticism was assessed with the Maudsley Personality Inventory, and psychiatric morbidity was evaluated with both the Mini International Neuropsychiatric Interview and the Hamilton Depression Rating Scale (HAM-D). Single photon emission computed tomography with [(123)I]iodo-benzamide was used to measure striatal dopamine D(2) receptor density. HAM-D scores and psychiatric morbidity in high-neuroticism individuals were higher than in low-neuroticism individuals. Moreover, striatal dopamine D(2) receptor densities were significantly correlated with the neuroticism score of the 41 subjects. The central dopaminergic system may play an important role in the neurobiological characteristics of neuroticism.

[The influence of chronic neurotization on the monoaminergic systems of various brain structures in rats with various typological characteristics].

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

Influence of neuroticism on oral absorption of diazepam.

The subjects were 24 healthy males, 19 to 21 yr old. Twelve subjects had high neuroticism (HN) levels determined by Maudsley Personality Inventory, and 12 had low neuroticism (LN) levels. Subjects took a single 5-mg dose of diazepam (DZP) after a standardized breakfast. The mean plasma concentration for DZP was significantly higher in HN subjects at 1.5 hr after drug than in LN subjects. No difference was found in the DZP plasma levels of these 2 groups after administering the drug directly into the duodenum through a tube. No clear relationship between plasma DZP concentrations and DZP-induced sedative effects determined by Choice Reaction Time Test (CRTT) was demonstrated in the study. The results suggest that the absorption rate of DZP from the gastrointestinal tract is faster in HN subjects than in LN subjects due to the faster gastric emptying time in HN subjects in our experimental situation, which might have induced mild stress.

Pleiotropy of the serotonin transporter gene for seasonality and neuroticism.

Pleiotropy refers to the ability of a single gene to influence multiple traits. A polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has previously been found to be associated both with the personality trait of neuroticism and with seasonal changes in mood and behavior, or seasonality. Hypothesizing that the contribution of the serotonin transporter gene to seasonality is specific, i.e. independent of neuroticism, we measured 5-HTTLPR genotypes and both psychological traits in 236 healthy volunteers. The results indicated that the 5-HTTLPR contributions to variation in the two traits are largely independent; approximately three-quarters of the effect of the gene on seasonality are not related to its effects on neuroticism. Moreover, the gene has a larger effect on the covariation between neuroticism and seasonality than it does on either trait alone. Sibling-pair analysis confirmed that the effects of the 5-HTTLPR are due to genetic pleiotropy rather than population stratification.

Biochemical assessment of thiamin status in patients with neurosis.

The thiamin status of 65 patients with neurosis was studied soon after their admission to the psychiatric department; 49 healthy persons were also studied. In comparison with the control group, the patients with neurosis had a twice as low thiamin excretion and a 22% lower erythrocyte transketolase (p less than 0.001), while their blood pyruvate and pyruvate excretions were 31-38% higher (p less than 0.001).

Ascorbic acid status of children with developmental disabilities.

Ascorbic acid status of thirty-nine white children with developmental disabilities, ages three to nineteen years, is reported. Mean daily ascorbic acid intakes were calculated from three-day food records. Biochemical assessment consisted of fasting serum levels and a 6-hr. load test. Nine children served as a control group for the load test only. Mean dietary intakes for the vitamin were 204 per cent of the allowance. The mean serum ascorbic acid value was 1.3 mg. per deciliter. Only two children had levels at the unacceptable deficient level. Following load tests, ten children were identified as low excretors (less than 17 per cent), nine were moderate excretors (17 to 23 per cent), and the rest were high excretors (above 23 per cent). All of the normal children were high excretors. Two of three children with low ascorbic acid intakes (below 66 per cent of the recommended allowance) were verified as deficient by their fasting serum levels and urinary recovery after a load.

[Changes in the rate of local cerebral blood flow and cytochrome concentration in several areas of the brain of the albino rat during neurotization]. / Izmenenie skorosti lokal'nogo mozgovogo krovotoka i soderzhaniia tsitokhromov v nekotorykh oblastiakh mozga belykh krys pri nevrotizatsii.

In several brain parts of rats with experimental neurosis local circulation rate (LCR) was measured by hydrogen clearence method, and cytochromes content was determined by differential spectrophotometry. In early period of neurotization (up to 15 days) reciprocal LCR changes were observed in the cortex and subcortical structures, and after 18 days were reduced in all the brain parts studied. The maximum reduction was observed after three weeks of neurotization. Neurotization during one week elicited significant decrease of cytochrome a level in the cortex. Its level in the cortex after 3 weeks of neurotization and in the hypothalamus and hippocampus after one and three weeks of neurotization did not differ from its normal content. Neurotization did not influence cytochromes c + c1 levels in the structures examined.

[Changes in energy metabolism in several brain regions and vegetative responses of white rats during neurotization]. / Izmenenie énergeticheskogo metabolizma v nekotorykh oblastiakh mozga i vegetativnykh reaktsii belykh krys nevrotizatsii.

Changes of vegetative reactions and cytochrome oxidase (CChO) activity in various brain structures were studied in rats during neurotization. One week neurotization led to an increase of arterial blood pressure, respiration rate, cardiac stroke volume and heart rate. In three weeks of neurotization there was a decrease of stroke volume accompanied by an increase of heart rate and some decrease or respiration rate leading to a reduction of oxygen consumption. Neurotization during one and especially three weeks elicited an enhancement of CChO activity in various brain areas, more pronounced in the cerebral cortex. A four week "rest" after neurotization during three weeks normalized the CChO activity. CChO activation during neurotization is supposed to be one of the mechanisms of adaptation to hypoxia accompanying neurosis.

[The nature of the neurohormonal reorganizations in patients with neuroses]. / Kharakter neirogormonal'nykh perestroek u bol'nykh nevrozami.

Neurohormonal balance was studied in patients suffering from neurasthenic, hysteric of obsessive-phobic neuroses. The peculiarities of functional restructuring in sympathoadrenal, opioid and pituitary-adrenal cortex systems were considered as related to clinical form or stage of the disease. Irrespective of the neurosis clinical form, a considerable rise in the endorphin blood levels with increasing sympathoadrenal and adrenocortical activities were typical of its initial stages. With long-lasting neuroses, the neurohormonal shifts characteristic of chronic emotional stress were detected.