Effects of the 5-HT4 receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels

The 5-HT₄ receptor modulates activity of serotonergic neurons and is a new potential target for antidepressant treatment. This microdialysis study evaluated the effect of the 5-HT₄ receptor agonist, RS67333, on extracellular serotonin (5-hydroxytryptamine, 5-HT) and 5-HIAA levels in rat ventral hippocampus during chloral hydrate anaesthesia, and explored the ability of RS67333 to augment the effect of the selective serotonin reuptake inhibitor paroxetine. The effect of RS67333 was examined after acute and subchronic (3 days) administration. Acute RS67333 (1.5 mg/kg i.v.) had no effect on extracellular 5-HT or 5-HIAA levels, while acute paroxetine (0.5 mg/kg i.v.) increased 5-HT levels by 299 ± 16% and decreased 5-HIAA levels by 25 ± 4%. Administration of RS67333 80 min after paroxetine caused an additional transient increase in 5-HT levels (to 398 ± 52% of baseline). Subchronic RS67333 administration (1.5 mg/kg i.p.) increased basal 5-HT levels by 73 ± 15% and decreased 5-HIAA levels by 27 ± 13%. In conclusion, the 5-HT₄ receptor agonist RS67333 augmented the acute effect of paroxetine on extracellular 5-HT levels in the ventral hippocampus, and after 3 days increased basal hippocampal 5-HT levels.     

Temperature effects of reserpine injected into the cerebral ventricles of rabbits and cats

1. In unanaesthetized rabbits and cats reserpine was injected through a chronically implanted cannula in the left lateral cerebral ventricle, and rectal temperature was recorded.2. In rabbits the reserpine (0.5-0.6 mg) caused a rise in temperature, frequent defaecation and sedation. On repeating the intraventricular injections at 24 hr intervals the rise in temperature was not obtained with the second or third injection, but defaecation and sedation still occurred. When the hyperthermic response to intraventricular reserpine had disappeared the anterior hypothalamus still responded to intraventricular noradrenaline which produced a rise in temperature.3. In cats the reserpine (0.5-0.75 mg) caused a biphasic change in temperature, i.e. an initial fall followed by a rise, frequent defaecation, and catalepsy. On repeating the intraventricular injections at 24 hr intervals the initial hypothermic phase of the temperature response was not obtained with the second or third injection, but the late rise, defaecation and catalepsy were still produced. When the hypothermic phase had disappeared the hypothalamus still responded to intraventricular noradrenaline or adrenaline which produced a fall, and to intraventricular 5-hydroxytryptamine (5-HT) which produced a rise in temperature.4. It is concluded that the rise in temperature in rabbits and the initial fall produced in cats is not due to a direct action of reserpine on the cells of the anterior hypothalamus but to noradrenaline released from adrenergic fibres ending at these cells. When these fibres are depleted of their noradrenaline by one or two injections of reserpine, these effects are not obtained because noradrenaline is no longer available to be released in sufficient amounts to raise temperature in rabbits and to lower it in cats.     

FMRI brain activation in a finnish family with specific language impairment compared with a normal control group.

The aim of the present study was to investigate differences in brain activation in a family with SLI as compared to intact individuals with normally developed language during processing of language stimuli. Functional magnetic resonance imaging (fMRI) was used to monitor changes in neuronal activation in temporal and frontal lobe areas in 5 Finnish family members with specific language impairment (SLI) and 6 individuals in an intact control group. Magnetic resonance (MR) image acquisitions were made while the participants listened to series of isolated vowel sounds, pseudowords, and real words. The stimuli were digitized single Finnish vowel sounds, 3-phoneme pseudowords, and 3- and 4-phoneme real words. MR scanning was made with a 1.5 T Siemens Vision Plus scanner, and the auditory stimuli were presented according to an event-related fMRI design. The results showed significant differences between the family with SLI and the intact control group with regard to brain activation in areas in the temporal and frontal lobes. Temporal lobe activation differences were most pronounced in the middle temporal gyrus bordering the superior temporal sulcus. The control participants also activated an area in the inferior frontal lobe in BA 44. It is concluded that individuals with SLI showed reduced activation in brain areas that are critical for speech processing and phonological awareness. The present functional brain imaging data fit well with other recent imaging data that also showed structural abnormalities in the same and neighboring areas.     

Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT₄ receptor levels

Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for psychiatric disorder and has been linked to changes in the expression of certain 5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT expression on 5-HT? receptor levels in both 5-HTT knockout (KO) and overexpressing (OE) mice using autoradiography with the selective 5-HT? receptor radioligand, [3H]SB207145. Compared to wild-type (5-HTT?/?) controls, homozygous 5-HTT KO mice (5-HTT?/?) had reduced 5-HT? receptor binding site density in all brain regions examined (35-65% of 5-HTT?/?). In contrast, the density of 5-HT? receptor binding sites was not significantly different between heterozygous 5-HTT KO mice (5-HTT?/?) and 5-HTT?/? mice. The 5-HT synthesis inhibitor p-chlorophenylalanine (250 mg/kg twice daily for 3 d) abolished the difference in 5-HT? binding between 5-HTT?/? and 5-HTT?/? mice in all brain regions. Compared to wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT? binding density across all brain regions, except amygdala (118-164% of WT) and this difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20 mg/kg twice daily, 3 d). Together, these findings suggest that variation in 5-HTT expression causes adaptive changes in 5-HT? receptor levels which are directly linked to alterations in 5-HT availability.     

Health in All local Policies: Lessons learned on intersectoral collaboration in a community‐based health promotion network in Denmark

Health promotion increasingly involves collaboration with civil society organisations and the private sector rather than being implemented exclusively by public sector stakeholders. Health in All Policies (HiAP) is an approach that promotes health in policy‐making across public sectors. This study explored intersectoral integration and collaboration for health promotion at a local community level through a qualitative single case study of a local community network in Denmark: the Husum Health Network. The paper describes and discusses strengths, weaknesses, and challenges of HiAP‐inspired local efforts to build alliances and supportive environments for health within an inter‐organisational community‐based network. The data were generated from participant observations made at 11 meetings and events organised by the network partners and nine qualitative, semi‐structured interviews with Husum Health Network partners conducted from August 2014 to February 2015. The data were analysed using a theoretical framework introduced by Axelsson and Axelsson (2006) to characterise aspects of integration and differentiation between organisations. With high levels of structural and functional differentiation between the partners, the network provided an opportunity to exercise inter‐organisational integration at the local level. Integration was fostered by knowledge sharing, face‐to‐face interaction, and communal events. However, the loose structure of the network was a challenge to its sustainability and achievement. We argue that Health in All local Policies is a meaningful concept in the context of local community development only when referring to the polices and strategies of all stakeholder organisations involved in decision‐making and agenda setting, and not just local government institutions.     

Adherence to a Healthy Nordic Food Index Is Associated with a Lower Risk of Type-2 Diabetes—The Danish Diet,Cancer and Health Cohort Study

Background: Type-2 diabetes (T2D) prevalence is rapidly increasing worldwide. Lifestyle factors, in particular obesity, diet, and physical activity play a significant role in the etiology of the disease. Of dietary patterns, particularly the Mediterranean diet has been studied, and generally a protective association has been identified. However, other regional diets are less explored. Objective: The aim of the present study was to investigate the association between adherence to a healthy Nordic food index and the risk of T2D. The index consists of six food items: fish, cabbage, rye bread, oatmeal, apples and pears, and root vegetables. Methods: Data was obtained from a prospective cohort study of 57,053 Danish men and women aged 50–64 years, at baseline, of whom 7366 developed T2D (median follow-up: 15.3 years). The Cox proportional hazards model was used to assess the association between the healthy Nordic food index and risk of T2D, adjusted for potential confounders. Results: Greater adherence to the healthy Nordic food index was significantly associated with lower risk of T2D after adjusting for potential confounders. An index score of 5−6 points (high adherence) was associated with a statistically significantly 25% lower T2D risk in women (HR: 0.75, 95%CI: 0.61–0.92) and 38% in men (HR: 0.62; 95%CI: 0.53–0.71) compared to those with an index score of 0 points (poor adherence). Conclusion: Adherence to a healthy Nordic food index was found to be inversely associated with risk of T2D, suggesting that regional diets other than the Mediterranean may also be recommended for prevention of T2D.     

Levels of alcohol use and depression severity as predictors of missed therapy sessions in cognitive behavioural psycho-educational group treatment for depression

In this study, we investigate levels of depression and levels of alcohol use as predictors of unstable attendance in a therapeutic intervention. A sample of 154 patients scoring a mean of 26 on BDI-II attended a cognitive behavioural psycho-educational group treatment – ‘Coping and relapse prevention of depression’. We investigated the influence of alcohol use and depression on attendance using a model based on the count of missed therapy sessions as a function of AUDIT and BDI-II, as well as a multiplicative AUDIT?×?BDI-II interaction term. AUDIT-scores were statistically significantly associated with more unstable attendance in treatment. Level of depression (BDI-II) was not found to predict count of missed therapy sessions in the sample. Interaction effect between levels of depression and levels of alcohol use was not statistically significant in this sample. Demographic factors were not statistically associated with count of missed therapy sessions. Despite the statistically significant relation between AUDIT-score and count of missed therapy sessions, patients with risky alcohol patterns attended the intervention almost as stably as participants without risky alcohol use. The findings provide a basis for questioning the clinical usefulness of distinguishing between patients with and without comorbid alcohol problem before attending a psycho-educational group treatment addressing depression. Missed therapy sessions in patients with alcohol problems may be counteracted with general strategies to prevent dropout from treatment.     

Demand,Control and Support at Work Among Sick-Listed Patients with Neck or Back Pain: A Prospective Study

Purpose The main aim of this study was to assess changes in perceived demand, control and support at work of neck and back pain patients over 1 year. We also hypothesised that perceived changes in demand, control and support at work were associated with clinical improvement, reduced fear-avoidance beliefs and successful return to work. Methods Four hundred and five sick-listed patients referred to secondary care with neck or back pain were originally included in an interventional study. Of these, two hundred and twenty-six patients reported perceived psychosocial work factors at both baseline and 1-year follow-up, and they were later included in this prospective study. Changes in demand, control and support dimensions were measured by a total of nine variables. Results At the group level, no significant differences were found among the measured subscales. At the individual level, the regression analyses showed that decreases in fear-avoidance beliefs about work were consistently related to decreases in demand and increases in control, whereas decreases in disability, anxiety and depression were related to increases in support subscales. Conclusions The perception of demand, control and support appear to be stable over 1 year in patients with neck and back pain, despite marked improvement in pain and disability. Disability, anxiety, depression and fear-avoidance beliefs about work were significantly associated with the perception of the work environment, whereas neck and back pain were not.     

Consumption of Whole-Grain Bread and Risk of Colorectal Cancer among Norwegian Women (the NOWAC Study)

There is evidence that consumption of foods containing dietary fiber decreases the risk of colorectal cancer (CRC). Whole grains contain dietary fiber, as well as a range of micronutrients and bioactive compounds, but the association between the consumption of whole grains and the risk of CRC remains less studied. The aim of the present study was to investigate the association between whole-grain bread consumption and CRC incidence among Norwegian women, using data from a prospective cohort study (the Norwegian Women and Cancer Study). Dietary intake was estimated from the food-frequency questionnaires of 78,254 women in the cohort (median age: 55 years), and these women were then followed up for CRC incidence. During the 9 years of median follow-up, 795 women were diagnosed with CRC (316 proximal, 193 distal, 218 rectal). Associations between whole-grain bread consumption and the risk of CRC (including colorectal subsites) were investigated using Cox proportional hazards regression models. When compared to the low consumption group, the hazard ratio for CRC was 0.89 (95% confidence interval (CI): 0.72–1.09) for the high consumption group and 0.86 (95% CI: 0.72–1.02) for the medium consumption group in a multivariable model. Overall, no association between whole-grain bread consumption and CRC was found.