Differential effects of the 5-HT2 receptor antagonist on the anti-immobility effects of noradrenaline and serotonin reuptake inhibitors in the forced swimming test

The effects of the 5-HT(2) receptor antagonist, LY 53857 on the effects of noradrenaline and serotonin reuptake inhibitors were investigated using the forced swimming test. LY 53857 enhanced anti-immobility effects of clomipramine and maprotiline, which can inhibit reuptake of noradrenaline. However, LY 53857 did not affect the immobility time of mice treated with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine. These results suggest that antagonism of the 5-HT(2) receptor leads to potentiation of the antidepressant effects of noradrenaline reuptake inhibitors but not SSRIs and that LY 53857 may modify the activity of noradrenergic neurons.     

Distribution and quantification of 5-HT nerve cell bodies in the nucleus raphe dorsalis area of C57BL and BALBc mice. Relationship between anatomy and biochemistry

BALBc and C57BL mice have been shown to have a different 5-HT metabolism. The present study compares the number and the distribution of 5-HT cell bodies in the nucleus raphe dorsalis area (B7 + B6) of these strains. By using 5-HT immunohistochemistry, we found a higher number of 5-HT neurons in the most caudal part of NRD (B6) of BALBc mice compared to C57BL. This difference may be correlated with a higher level of endogenous 5-HT, a higher uptake capacity toward exogenous [³H]5-HT, and a lower release of the amine in this same area of BALBc mice compared to C57BL. It could also imply a significant participation of the nerve cell bodies in the regulation of 5-HT transmission inside 5-HT nuclei.     

Ethical questions in the treatment of subjects with dementia. Part I. Respecting autonomy: awareness, competence and behavioural disorders

The document deals with some ethical issues raised by the treatment of demented people. In particular the conceptual and empirical aspects of the assessment of awareness and competence of these patients are analysed, as well as the dilemmas related to the treatment of behavioral disorders.     

利培酮治疗偏执型精神分裂症患者的外周血5羟色胺3A受体基因表达水平与精神阳性症状的相关性研究

目的 探讨利培酮治疗偏执型精神分裂症患者的精神阳性症状与外周血5-HT3A mRNA受体基因表达水平之间的关系,为新型抗精神药物治疗精神分裂症提供疗效依据.方法 对36例首发未服抗精神病药治疗的偏执型精神分裂症患者口服利培酮治疗8周,于治疗前基线期及治疗后8周抽静脉血并评定PANSS及外周血5-HT3A mRNA相对表...     

Lack of association between suicidal ideation and enhanced platelet 5-HT2A receptor-mediated calcium mobilization in cancer patients with depression.

BACKGROUND: Increased density of 5-HT2A receptors was observed in the platelets of depressive patients with suicidal ideation. Enhanced 5-HT2A receptor-mediated platelet calcium mobilization has been proposed as a biological marker for the pathophysiology of major depression in cancer patients as well as in physically healthy patients. To examine whether depressive cancer patients with suicidal ideation have enhanced 5-HT2A receptor-mediated platelet response compared with those without suicidal ideation, we compared 5-HT-induced platelet calcium mobilization in depressive cancer patients with and without suicidal ideation. METHODS: 5-HT-induced platelet calcium mobilization was examined in 24 cancer patients diagnosed as having major depression according to the DSM-IV criteria. Suicidal ideation was evaluated by the Hamilton Depression Rating Scale and Zung's Self Depression Scale, as well as by the DSM-IV criteria. RESULTS: There was no significant differences in 5-HT-induced platelet calcium response between the depressive cancer patients with (n = 8) and without suicidal ideation (n = 16). 5-HT-induced platelet calcium response was also not significantly associated with the severity of suicidal ideation or with the severity of depression assessed by Hamilton Depression Rating Scale and Zung's Self Depression Scale. CONCLUSIONS: These findings suggest that enhanced 5-HT2A receptor-mediated response was not associated with suicidal ideation in cancer patients with depression.     

Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain

Summary. The effects of 3-week treatment with a typical antipsychotic drug chlorpromazine and three atypical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to dopamine D₂ and serotonin 5-HT_2A receptors were examined in the rat stratum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased D₂ receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.25, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg) and olanzapine (1, 2 mg/kg) significantly decreased 5-HT_2A receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occupation for D₂ and 5-HT_2A receptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HT_2A receptors with lower D₂ receptor occupancy might be involved in the absence of up-regulation of D₂ receptors after subchronic treatment with some atypical antipsychotic drugs. Received September 24, 1999; accepted December 1, 1999     

Functional antagonism between nociceptin/orphanin FQ and corticotropin-releasing factor in rat anxiety-related behaviors: Involvement of the serotonergic system

Nociceptin/orphanin FQ (N/OFQ) acts as an anxiolytic-like agent in the rat and behaves as a functional antagonist of corticotropin-releasing factor (CRF) due to its ability to oppose CRF biological actions. In response to stress, CRF triggers changes in neurotransmitter systems including serotonin (5-HT). The role of 5-HT_1A receptor in anxiety has been supported by preclinical and clinical studies.     

Epidemiology of disorders of gut-brain interaction in Belgium and differences between two language groups: Results from the Rome foundation global epidemiology study

Background

The Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described.

Methods

We analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups.

Key Results

DGBI prevalence was similar in the French-speaking and Dutch-speaking population. Having one or more DGBI was negatively associated with psychosocial well-being. The scores for depression were lower in the Dutch-speaking participants with one or more DGBI compared to the French-speaking participants. Interestingly, we also found significantly lower scores in the general Dutch-speaking versus the French-speaking population for depression and non-gastrointesinal somatic symptoms, and higher global physical health and mental health quality-of-life component scores. In the Dutch-speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non-prescribed pain medication was higher in the French-speaking group. Anxiety and sleep medication use was also higher in the latter group.

Conclusions & Interferences

The results of this first in-depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French-speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI.     

5-Hydroxytryptamine-sensitive [H]imipramine binding of protein nature in the human brain.: II. Effect of normal aging and dementia disorders

Recently, a high-affinity [³H]imipramine binding site of protein nature that appeared related to the 5-hydroxytryptamine (5-HT, serotonin) uptake mechanism was demonstrated in the rat brain. In a preceding paper a similar [³H]imipramine binding site of protein nature and displaceable by 5-HT was demonstrated in the human brain. Most previous [³H]imipramine binding studies of the human brain have used desipramine-sensitive binding, which appears to contain a significant amount of additional binding not related to 5-HT neurons. Therefore this study of the human brain in the normal aging, in Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) and in multiinfarction dementia (MID) presents data on 5-HT-sensitive [³H]imipramine binding. The influence of normal aging (17–100 years) was studied in the frontal and cingulate cortices, in the putamen, caudate nucleus, amygdala and in the hippocampus. An age-related change in 5-HT-sensitive [^{3H]imipramine binding was only noted in the cingulate cortex with a 50% loss in B_max over the adult age range. In contrast, desipramine-sensitive [3H]imipramine binding studied in the frontal cortex and in the putamen showed marked increases in B_max with age which correlated with increases in K_d}. It is suggested that these increases are related to an increased binding to lipophilic membrane components not related to 5-HT neurons. The 5-HT-sensitive [³H]imipramine binding ( B_max) was reduced to 60% of control in the cingulate cortex and to 50% in the putamen in AD/SDAT. In MID there was a 50% loss of [³H]imipramine binding sites ( B_max) in the putamen, but a 30% loss in the cingulate cortex did not reach statistical significance. It is concluded that the losses of 5-HT-sensitive [³H]imipramine binding sites reflect a corresponding loss of 5-HT neurites.     

Personality disorders in the community: results from the Australian National Survey of Mental Health and Wellbeing Part II. Relationships between personality disorder,Axis I mental disorders and physical conditions with disability and health consultations

Background The aims of this study were threefold. First, to ascertain whether personality disorder (PD) was a significant predictor of disability (as measured in a variety of ways) over and above that contributed by Axis I mental disorders and physical conditions. Second, whether the number of PD diagnoses given to an individual resulted in increasing severity of disability, and third, whether PD was a significant predictor of health and mental health consultations with GPs, psychiatrists, and psychologists, respectively, over the last 12 months. Method Data were obtained from the National Survey of Mental Health and Wellbeing, conducted between May and August 1997. A stratified random sample of households was generated, from which all those aged 18 and over were considered potential interviewees. There were 10641 respondents to the survey, and this represented a response rate of 78 %. Each interviewee was asked questions indexing specific ICD-10 PD criteria. Results Five measures of disability were examined. It was found that PD was a significant predictor of disability once Axis I and physical conditions were taken into account for four of the five disability measures. For three of the dichotomously-scored disability measures, odds ratios ranged from 1.88 to 6.32 for PD, whilst for the dimensionally-scored Mental Summary Subscale of the SF-12, a beta weight of −0.17 was recorded for PD. As regards number of PDs having a quasi-linear relationship to disability, there was some indication of this on the SF-12 Mental Summary Subscale and the two role functioning measures, and less so on the other two measures. As regards mental consultations, PD was a predictor of visits to GPs, psychiatrists and psychologists, over and above Axis I disorders and physical conditions. Conclusion The study reports findings from a nationwide survey conducted within Australia and as such the data are less influenced by the selection and setting bias inherent in other germane studies. However, it does support previous findings that PD is a significant predictor of disability and mental health consultations independent of Axis I disorders and physical conditions. Accepted: 13 January 2002     

Interaction between the serotonergic system and HPA and HPT axes in patients with major depression: implications for pathogenesis of suicidal behavior

Disturbances in the serotonin (5-hydroxytryptamine, 5-HT) system constitute the neurobiological abnormality most consistently associated with suicide. This abnormality could be a marker of vulnerability predisposing individuals to auto-aggressive and impulsive behavior. However, other abnormalities, such as hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, have also been described in suicide victims. While inhibitory effects of adrenocorticosteroids on 5-HT(1A) receptor function have been shown in animals, HPA axis hyperactivity does not seem to be responsible for the reduced 5-HT activity found in depressed patients with a history of suicidal behavior. On the other hand, hypothalamic-pituitarythyroid (HPT) axis dysfunction, frequently observed in depression, may represent a compensatory response to reduced central 5-HT neurotransmission. Moreover, in depressed patients with a history of suicidal behavior, the absence of a functional link between HPT and dopamine activity at the hypothalamic level may be implicated in the pathophysiology of suicidal behavior. Future research is needed to determine why compensatory mechanisms are not efficient in patients with suicidal behavior.     

Genetic epistasis between the brain-derived neurotrophic factor Val66Met polymorphism and the 5-HTT promoter polymorphism moderates the susceptibility to depressive disorders after childhood abuse

Background

Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene–gene–environment interaction moderating the interaction between the s/l- promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms.

Methods

2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms.

Results

Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p = 0.02). Emotional abuse carried the main effect of the interaction (p = 0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles.

Conclusions

Our results point to a gene–gene–environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms.     

Evidence for the involvement of the serotonergic 5-HT2A/C and 5-HT3 receptors in the antidepressant-like effect caused by oral administration of bis selenide in mice

The present study investigated a possible antidepressant-like activity of bis selenide using two predictive tests for antidepressant effect on rodents: the forced swimming test (FST) and the tail suspension test (TST). Bis selenide (0.5–5 mg/kg, p.o.) decreased the immobility time in the mouse FST and TST. The anti-immobility effect of bis selenide (1 mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis), ketanserin (1 mg/kg, i.p., a 5-HT_2A/2C receptor antagonist), and ondasentron (1 mg/kg, i.p., a 5-HT₃ receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an α₁-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α₂-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D₁ receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D₂ receptor antagonist), or WAY 100635 (0.1 mg/kg, s.c., a selective 5-HT_1A receptor antagonist) did not block the antidepressant-like effect of bis selenide (1 mg/kg, p.o.) in the TST. Administration of bis selenide (0.1 mg/kg, p.o.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. Bis selenide did not alter Na⁺ K⁺ ATPase, MAO-A and MAO-B activities in whole brains of mice. Bis selenide produced an antidepressant-like effect in the mouse TST and FST, which may be related to the serotonergic system (5-HT_2A/2C and 5-HT₃ receptors).     

Relationship between speaking English as a second language and agitation in people with dementia living in care homes: Results from the MARQUE (Managing Agitation and Raising Quality of life) English national care home survey

Objective

As not speaking English as a first language may lead to increased difficulties in communication with staff and other residents, we (1) tested our primary hypotheses that care home residents with dementia speaking English as a second language experience more agitation and overall neuropsychiatric symptoms, and (2) explored qualitatively how staff consider that residents' language, ethnicity, and culture might impact on how they manage agitation.

Methods

We interviewed staff, residents with dementia, and their family carers from 86 care homes (2014–2015) about resident's neuropsychiatric symptoms, agitation, life quality, and dementia severity. We qualitatively interviewed 25 staff.

Results

Seventy‐one out of 1420 (5%) of care home residents with dementia interviewed spoke English as a second language. After controlling for dementia severity, age, and sex, and accounting for care home and staff proxy clustering, speaking English as a second language compared with as a first language was associated with significantly higher Cohen‐Mansfield Agitation Inventory (adjusted difference in means 8.3, 95% confidence interval 4.1 to 12.5) and Neuropsychiatric inventory scores (4.1, 0.65 to 7.5). Staff narratives described how linguistic and culturally isolating being in a care home where no residents or staff share your culture or language could be for people with dementia, and how this sometimes caused or worsened agitation.

Conclusions

Considering a person with dementia's need to be understood when selecting a care home and developing technology resources to enable dementia‐friendly translation services could be important strategies for reducing distress of people with dementia from minority ethnic groups who live in care homes.     

Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.     

Electroconvulsive therapy,depression, the immune system and inflammation: A systematic review

Background

The management and treatment of major depressive disorder are major public health challenges, the lifetime prevalence of this illness being 4.4%–20% in the general population. Major depressive disorder and treatment resistant depression appear to be, in part, related to a dysfunction of the immune response. Among the treatments for depression ECT occupies an important place. The underlying cerebral mechanisms of ECT remain unclear.