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PubMed2000

Abnormalities of cAMP signaling in affective disorders: implication for pathophysiology and treatment.

OBJECTIVE: During the last decade, much attention has been given to the role of signal transduction pathways in affective disorders. This review describes the possible role of the cAMP signaling in such disorders. METHODS: Among the components of cAMP signaling, this review focuses on the cAMP-dependent phosphorylation system. We analyzed the basic components of the cAMP-dependent phosphorylation system and the preclinical evidence supporting their involvement in the biochemical action of antidepressants and mood stabilizers. The clinical data available until now, concerning the possible link between the cAMP-dependent phosphorylation system and the pathophysiology of affective disorders, are also reviewed. RESULTS: The studies herein presented demonstrated that the levels and the activity of cAMP-dependent protein kinase are altered by antidepressants and mood stabilizers. Furthermore. these medications are able to modify the phosphorylation state, as well as the levels of some of the cAMP-dependent protein kinase substrates. More recently, clinical studies have reported abnormalities in the cAMP-dependent phosphorylation system in both peripheral cells and the postmortem brain of patients with affective disorders. CONCLUSIONS: Overall, these studies support an involvement of cAMP signaling in affective disorders. The precise knowledge of the findings has the potential to improve the understanding of pharmacotherapy and to provide directions for the development of novel biochemical and genetic research strategies on the pathogenesis of affective disorders.

Antidepressive Agents↗
PubMed1999

Mother-infant affect synchrony as an antecedent of the emergence of self-control.

This study examined relations between mother-infant affect synchrony and the emergence of children's self-control. Mother-infant face-to-face play and infant difficult temperament were examined at 3 and 9 months. Maternal and infant affective states at play were coded in 0.25-s frames, and synchrony was computed with cross-correlation functions. Self-control, verbal IQ, and maternal warm discipline were assessed at 2 years. Maternal synchrony with infant affect at 3 months (infant-leads-mother-follows relation) and mutual synchrony at 9 months (cross-dependence between maternal and infant affect) were each related to self-control at 2 years when temperament, IQ, and maternal style were partialed. Infant temperament moderated the relations of synchrony and self-control, and closer associations were found between mutual synchrony and self-control for difficult infants. Shorter lags to maternal synchrony at 3 months were independently related to self-control. The mutual regulation of affect in infancy, as moderated by temperament, is proposed as an important contributor to the emergence of self-regulation.

Adult↗
PubMed1994

Affective and social-behavioral correlates of physical and social anhedonia in schizophrenia.

The association between scales measuring physical and social anhedonia, self-reports of affective response to emotion-eliciting films, and role play measures of social skill was evaluated in patients with schizophrenia, schizoaffective disorder, and bipolar affective disorder. We hypothesized that patients with schizophrenia would report significantly greater anhedonia than the bipolar patients and that higher scores on the anhedonia scales would be related to attenuated reports of the experience of positive affect and poorer social skill. Patients with schizophrenia and schizoaffective disorder did not differ in ratings of anhedonia, but both groups had higher physical and social anhedonia scores than did bipolar patients. Higher scores on the physical anhedonia scale, but not the social anhedonia scale, were related to attenuated reports of positive affect following viewing of affect-eliciting films in schizophrenia-schizoaffective disorder patients. Neither anhedonia scale was related to role play measures of social skill performance for any patient group.

Adolescent↗
PubMed1988

Development and validation of brief measures of positive and negative affect: the PANAS scales.

In recent studies of the structure of affect, positive and negative affect have consistently emerged as two dominant and relatively independent dimensions. A number of mood scales have been created to measure these factors; however, many existing measures are inadequate, showing low reliability or poor convergent or discriminant validity. To fill the need for reliable and valid Positive Affect and Negative Affect scales that are also brief and easy to administer, we developed two 10-item mood scales that comprise the Positive and Negative Affect Schedule (PANAS). The scales are shown to be highly internally consistent, largely uncorrelated, and stable at appropriate levels over a 2-month time period. Normative data and factorial and external evidence of convergent and discriminant validity for the scales are also presented.

Arousal↗
PubMed1997

Does unhappiness make you sick? The role of affect and neuroticism in the experience of common physical symptoms.

The relative strength of both affective state and the personality trait neuroticism in predicting common physical symptoms was tested. The authors used an event-sampling design to overcome methodological limitations of past research in the area. Contrary to much previous research, neuroticism was found to be unrelated to reports of physical symptoms, although it was found to be related to unpleasant affective state. Unpleasant affect bore a strong concurrent relation to the frequency of reported symptoms. Temporal relations between experiences of unpleasant affect and subsequent symptoms were found for some individuals, but wide individual variability was seen in both the strength and direction of this linkage. The findings suggest that when individuals are asked to report their subjective experiences of physical illness without the necessity to retrospect over significant periods of time, unpleasant affective state is more strongly related to experiences of symptoms than is the trait neuroticism.

Adaptation, Psychological↗
PubMed1986

Does attention affect visual feature integration?

Two questions are investigated in this work: first, whether the integration of color and shape information is affected by attending to the stimulus location, and second, whether attending to a stimulus location enhances the perceptual representation of the stimulus or merely affects decision processes. In three experiments, subjects were briefly presented with colored letters. On most trials, subjects were precued to the stimulus location (valid cue); on some trials, a nonstimulus location was cued (invalid cue). Subjects were less likely to incorrectly combine colors and letter shapes following a valid cue. The attentional facilitation afforded by the cue was not limited to feature integration but also affected the registration of features. However, when the amount of feature information was strictly controlled, attention still affected feature integration. The results indicate that orienting attention to the location of the cue affects the quality of the perceptual representation for features and their integration.

Adolescent↗
PubMed2001

Guilty pleasures and grim necessities: affective attitudes in dilemmas of self-control.

Do self-control situations pit controlled reason against impulsive emotion, or do some emotions support the controlled choice? A pilot study of self-control attitudes found ambivalence between hedonic affect associated with short-term perspectives and self-conscious affect associated with the long term. In Study 1, negative self-conscious affect accompanied higher self-control among delayed-cost dilemmas ("guilty pleasures") but not delayed-benefit dilemmas ("grim necessities"). Study 2 showed that hedonic affect was more accessible than was self-conscious affect, but this difference was less among high self-control dilemmas. In Study 3, unobtrusively primed self-conscious emotion words caused dieters to eat less if the emotions were negative, more if positive. Hedonic positive and negative emotion words had the opposite effect. Self-conscious emotional associations, then, can support self-control if brought to mind before the chance to act.

Analysis of Variance↗
PubMed2002

Self-focused attention and negative affect: a meta-analysis.

This meta-analysis synthesized 226 effect sizes reflecting the relation between self-focused attention and negative affect (depression, anxiety, negative mood). The results demonstrate the multifaceted nature of self-focused attention and elucidate major controversies in the field. Overall, self-focus was associated with negative affect. Several moderators qualified this relationship. Self-focus and negative affect were more strongly related in clinical and female-dominated samples. Rumination yielded stronger effect sizes than nonruminative self-focus. Self-focus on positive self-aspects and following a positive event were related to lower negative affect. Most important, an interaction between foci of self-attention and form of negative affect was found: Private self-focus was more strongly associated with depression and generalized anxiety, whereas public self-focus was more strongly associated with social anxiety.

Anxiety↗
PubMed1995

Stimulation in the human somatosensory thalamus can reproduce both the affective and sensory dimensions of previously experienced pain.

Thalamic structures involved in the unpleasant emotional or affective aspect of pain are poorly understood. We now describe studies of the region of the thalamic principal somatosensory nucleus (Vc) performed before thalamotomy for tremor in a patient who also had panic disorder. Microstimulation in the region posterior to Vc evoked chest pain, including a strong affective dimension, almost identical to that occurring during his panic attacks, as measured using a questionnaire. Results in our other patients indicate that stimulation-associated pain with a strong affective dimension occurred only in those patients who had previously experienced spontaneous pain with a strong affective component. These results are consistent with stimulation-evoked activation of limbic structures, which are connected through cortex with the region posterior to Vc and involved in the affective dimension of pain through conditioning by previous experience.

Adult↗
PubMed2006

Structural and functional affection of the heart in protein energy malnutrition patients on admission and after nutritional recovery.

BACKGROUND AND OBJECTIVES: The pathogenesis of different malnutrition diseases was suggested to affect the heart. This study was designed to detect cardiac affection in protein energy malnutrition (PEM) patients, whether clinically or by electrocardiogram (ECG) and echocardiogram, and to assess the value of the cardiac marker troponin I in patients at risk of myocardial injury with special emphasis on the effect of nutritional rehabilitation. PATIENTS AND METHODS: The present study was carried out on 30 PEM infants (16 nonedematous - 14 edematous) and 10 apparently healthy age and sex-matched infants acting as the control group. All studied infants were subjected to full history taking laying stress on dietetic history, thorough clinical and anthropometric measurements. Echocardiography and ECG were also performed. Laboratory investigations were performed including complete blood count, CRP, total proteins, albumin, liver and kidney functions as well as estimation of troponin-I in blood by immulite. Following initial evaluation, all malnourished infants were subjected to nutritional rehabilitation program for approximately 8 weeks, after which the patients were re-evaluated using the same preinterventional parameters. RESULTS: The results of the present study demonstrated that electrical properties of myocardium assessed by ECG showed significant decrease of R wave and QTc interval in patients compared to controls with significant improvement after nutritional rehabilitation. Echocardigraphic changes showed that cardiac mass index was significantly lower in both groups of malnourished cases compared to the controls with significant increase after nutritional rehabilitation. The study showed that the parameters of left ventricular (LV) systolic function which are the ejection fraction, fractional shortening and velocity of circumferential fiber shortening were not significantly reduced in patients compared to the controls. The diastolic function also showed no significant difference in the E wave/A wave (e/a) ratio between patients and controls. However, the systolic time interval showed significantly higher LV pre-ejection index in patients in comparison to controls. Edematous and nonedematous cases did not show any significant differences in ECG and echocardigraphic data before or after nutritional rehabilitation. The hearts of two severely affected patients uniquely demonstrated marked decrease of LV end diastolic diameter (LEVDd) together with the detection of troponin-I in their sera. CONCLUSION: We can conclude that malnutrition, regardless of its type, has a definite effect on cardiac volume, muscle mass, as well as the electrical properties of the myocardium. The systolic functions of the heart are affected more than the diastolic functions and this affection becomes manifest only in severe cases and may constitute a bad prognostic parameter thus necessitating more intense management and strict follow-up of such cases.

Child, Preschool↗
PubMed2006

Increased relative risk of subsequent affective disorders in patients with a hospital diagnosis of obesity.

OBJECTIVE: To investigate the risk of clinical affective disorders of patients who were hospitalized because of obesity in the study period 1 January 1977 to 31 December 1999. METHOD: Using data from Danish hospital registers, three study cohorts were identified by their diagnoses at discharge from hospital: one cohort comprising all patients with a first hospital admission with an index diagnosis of obesity, and two control cohorts comprising all patients with a first hospital admission with an index diagnosis of osteoarthritis or of non-toxic goiter, respectively. Later admissions to psychiatric hospital wards with discharge diagnoses of affective disorders were used as outcome events. Rates of readmission were estimated using competing risks models in survival analyses. Age, sex, abuse, and calendar time were included as covariables in the analyses. RESULTS: A study sample of 165,425 patients discharged with an index diagnosis was identified. In total, 1081 events occurred in the observation period. An index diagnosis of obesity was associated with an increased risk of affective-disorders hospitalization when compared with patients with osteoarthritis (Rate ratio: 1.35 (95% CI: 1.09-1.67)) and tended to be associated with an increased risk when compared to patients with non-toxic goiter (Rate ratio: 1.23 (95% CI: 0.99-1.53)). Patients with obesity diagnoses who did not have additional hospital diagnoses of substance- or alcohol abuse had a risk of affective disorders that was 1.55 (95% CI: 1.23-1.95) times greater than that of osteoarthritis patients without abuse diagnoses. CONCLUSIONS: Patients hospitalized with obesity may be prone to developing affective disorders that require in-hospital treatment, but the excess risk is modest. Severe obesity seems to be associated with other risk factors for mood disorders than those related to comorbid alcohol- or substance abuse.

Adolescent↗
PubMed2001

Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder.

Substantial evidence supports a role for dysfunction of brain serotonergic (5-HT) systems in the pathogenesis of major affective disorder, both unipolar (recurrent major depression) and bipolar.(1) Modification of serotonergic neurotransmission is pivotally implicated in the mechanism of action of antidepressant drugs(2) and also in the action of mood stabilizing agents, particularly lithium carbonate.(3) Accordingly, genes that code for the multiple subtypes of serotonin receptors that have been cloned and are expressed in brain,(4) are strong candidates for a role in the genetic etiology of affective illness. We examined a structural variant of the serotonin 2C (5-HT2C) receptor gene (HTR2C) that gives rise to a cysteine to serine substitution in the N terminal extracellular domain of the receptor protein (cys23ser),(5) in 513 patients with recurrent major depression (MDD-R), 649 patients with bipolar (BP) affective disorder and 901 normal controls. The subjects were drawn from nine European countries participating in the European Collaborative Project on Affective Disorders. There was significant variation in the frequency of the HT2CR ser23 allele among the 10 population groups included in the sample (from 24.6% in Greek control subjects to 9.2% in Scots, chi(2) = 20.9, df 9, P = 0.01). Logistic regression analysis demonstrated that over and above this inter-population variability, there was a significant excess of HT2CR ser23 allele carriers in patients compared to normal controls that was demonstrable for both the MDD (chi(2) = 7.34, df 1, P = 0.006) and BP (chi(2) = 5.45, df 1, P = 0.02) patients. These findings support a possible role for genetically based structural variation in 5-HT2C receptors in the pathogenesis of major affective disorder.

Amino Acid Substitution↗
PubMed2003

Affective disorders, antidepressant drugs and brain metabolism.

There is increasing evidence that affective disorders are associated with dysfunction of neurotransmitter postsynaptic transduction pathways and that chronic treatment with clinically active drugs results in adaptive modification of these pathways. Despite the close dependence of signal transduction on adenosine triphosphate (ATP) availability, the changes in energy metabolism in affective disorders are largely unknown. This question has been indirectly dealt with through functional imaging studies (PET, SPECT, MRS). Despite some inconsistencies, PET and SPECT studies suggest low activity in cortical (especially frontal) regions in depressed patients, both unipolar and bipolar, and normal or increased activity in the manic pole. Preliminary MRS studies indicate some alterations in brain metabolism, with reduced creatine phosphate and ATP levels in the brain of patients with affective disorders. However, the involvement of the energy metabolism in affective disorders is still debated. We propose direct neurochemical investigations on mitochondrial functional parameters of energy transduction, such as the activities of (a) the enzymatic systems of oxidative metabolic cycle (Kreb's cycle); (b) the electron transfer chain; (c) oxidative phosphorylation, and (d) the enzyme activities of ATP-requiring ATPases. These processes should be studied in affective disorders and in animals treated with antidepressant drugs or lithium.

Adaptation, Physiological↗
PubMed2006

Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes.

More than 80 mutations in the skeletal muscle ryanodine receptor gene have been found to be associated with autosomal dominant forms of malignant hyperthermia and central core disease, and with recessive forms of multi-minicore disease. Studies on the functional effects of pathogenic dominant mutations have shown that they mostly affect intracellular Ca2+ homoeostasis, either by rendering the channel hypersensitive to activation (malignant hyperthermia) or by altering the amount of Ca2+ released subsequent to physiological or pharmacological activation (central core disease). In the present paper, we show, for the first time, data on the functional effect of two recently identified recessive ryanodine receptor 1 amino acid substitutions, P3527S and V4849I, as well as that of R999H, another substitution that was identified in two siblings that were affected by multi-minicore disease. We studied the intracellular Ca2+ homoeostasis of EBV (Epstein-Barr virus)-transformed lymphoblastoid cells from the affected patients, their healthy relatives and control individuals. Our results show that the P3527S substitution in the homozygous state affected the amount of Ca2+ released after pharmacological activation with 4-chloro-m-cresol and caffeine, but did not affect the size of the thapsigargin-sensitive Ca2+ stores. The other substitutions had no effect on either the size of the intracellular Ca2+ stores, or on the amount of Ca2+ released after ryanodine receptor activation; however, both the P3527S and V4849I substitutions had a small but significant effect on the resting Ca2+ concentration.

Amino Acid Substitution↗
PubMed2003

Facilitation of iontophoretic drug delivery through intact and caries-affected dentine.

AIM: To investigate the facilitative role of iontophoresis in drug delivery through intact and caries-affected dentine into the pulp. METHODOLOGY: Forty-eight intact dentine or caries-affected dentine discs were prepared from freshly extracted human third molars. The hydraulic conductance was measured before and after the experiments. Drug diffusion with and without iontophoresis (0.05 mA, 10 min) was evaluated using a split-chamber device. The enamel side chamber was filled with metronidazole (MN), sodium salicylate (SS) or naproxen sodium (NA), while the pulpal side was circulated with phosphate buffered saline (PBS) and pressurized (15 cmH2O). Samples were collected after 1 h. Drug concentrations of the pulpal side solution were determined using a spectrophotometer. Then, electrical impedance of each dentine disc was measured. Finally, the dentine disc surfaces were observed by scanning electron microscopy. RESULTS: Drug diffusion was significantly influenced by iontophoresis, caries-induced changes in dentine and the drugs used (three-way anova, P < 0.05). The diffusion of all the drugs through caries-affected dentine was significantly less than that through intact dentine (independent t-test, P < 0.05). Also, iontophoresis facilitated the diffusion of all the drugs through intact and caries-affected dentine. The drug diffusion of SS was significantly higher than MN and NA (one-way anova, P < 0.05), independent of iontophoresis. CONCLUSIONS: Presence of dental caries may inhibit drug diffusion through dentine into the pulp. However, iontophoresis could enhance the delivery of ionized drugs through both intact and caries-affected dentine.

Adult↗
PubMed2002

Bond strength of five current adhesives to caries-affected dentin.

Five current dentin adhesives were evaluated for their ability to bond to caries-affected dentin. The materials were: total etch [Solid Bond (SB)], two self-etch [Clearfil SE Bond (CSE), Etch and Prime (EP)], two one bottle [Prime and Bond 2.1 (PB), One Coat Bond (OCB)]. Sixty extracted molar teeth with proximal caries (mesial or distal) extending into mid-dentin were used. By grinding normal and caries-affected proximal surfaces, flat dentin surfaces were obtained. The surfaces were then bonded with each adhesive system and composite resins were added to the surfaces by packing the material into a cylindrical-shaped plastic matrix with an internal diameter of 2.5 mm and height of 3 mm. Shear bond testing was performed following 10 days incubation of specimens in distilled water at 37 degrees C. Results were analysed by Kruskal-Wallis ANOVA, and Mann-Whitney U multiple comparison test and Wilcoxon rank tests. The results obtained with CSE, SB, and EP were similar in caries affected and normal dentin (P > 0.05). But bonds made to normal dentin with OCB and PB were lower (P < 0.05) than bonds to caries-affected dentin. Bonding to caries-affected dentin with CSE (24.49 +/- 5.38), SB (21.49 +/- 9.15), and EP (21.19 +/- 9.17) showed shear bond strengths higher than OCB (17.43 +/- 9.78) and PB (14.10 +/- 7.94) (P < 0.05). Bonding to normal dentin with CSE (29.91 +/- 8.95) was the highest (P < 0.05). SB (21.17 +/- 5.41) and EP (17.45 +/- 6.21) showed shear bond strengths higher than OCB (11.99 +/- 10.15) and PB (10.57 +/- 4.56) (P < 0.05).

Acetone↗
PubMed2001

Effects of 8-epi-PGF2alpha on isolated bronchial smooth muscle of healthy and heaves-affected horses.

8-Epi-PGF2alpha, a prostaglandin-like compound generated by oxidative stress, has been shown to be an in vitro bronchoconstrictor in airways from healthy laboratory animals and healthy humans, but it has never been studied in diseased airways. Here, the bronchoconstrictive capacity of 8-epi-PGF2alpha on isolated bronchial rings (BR) of healthy and heaves-affected horses was evaluated by comparing the maximal effect and the potency of 8-epi-PGF2alpha to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF2alpha and (3) its synthetic receptor agonist, U46619. Furthermore, the potential capacity of 8-epi-PGF2alpha to enhance the cholinergic (ACh) responsiveness of bronchial smooth muscle was investigated. 8-Epi-PGF2alpha contracted BR with a rank order of efficacy of Ach > U44619 > PGF2alpha > 8-epi-PGF2alpha in both healthy and heaves-affected horses. The contractile maximal response elicited by 8-epi-PGF2alpha was significantly smaller than that elicited by the other drugs, but was significantly higher in BR from heaves-affected horses than in those sampled in healthy horses, whilst pD2 values were similar. A subthreshold concentration of 8-epi-PGF2alpha (10-7 M) did not induce in vitro cholinergic hyper-responsiveness in BR of either healthy or heaves-affected horses. In conclusion, it has been demonstrated that 8-epi-PGF2alpha is an in vitro bronchoconstrictor of minor importance in healthy horses, but whose efficacy is significantly increased in heaves-affected horses.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear.

The human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with 15O-water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non-feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non-phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non-phobic startle vs. non-phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid-hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co-activation of these areas may reflect increased attention to fear-relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect.

Adult↗