Search

The histaminergic involvement in selective processes underlying its role in human sensori-motor performance is largely unknown. Recently, selective effects of central H₁-inverse agonism on sensory visual processes were observed in electrophysiological--but not behavioral data; a discrepancy suggested to result from speeded response-choice related processes. This study attempts to establish the effects on visual processes and identify putative compensatory mechanisms related to increased visual and response-choice task demands by assessing H₁-inverse agonism induced changes in blood oxygenation level dependent (BOLD) response. Twelve participants received oral doses of dexchlorpheniramine 4 mg, lorazepam 1 mg, and placebo in a three-way crossover designed study. Brain activity was assessed for choice reaction time task performance in a 3 T magnetic resonance scanner 2 h after drug administration. Participants responded with their left or right hand and index or middle finger as indicated by the laterality of stimulus presentation and identity of the stimulus, respectively. Stimuli were intact or visually degraded and responses were compatible or incompatible with the laterality of stimulus presentation. Both dexchlorpheniramine and lorazepam affected the BOLD response in the occipital cortex indicating affected visual information processing. Dexchlorpheniramine decreased BOLD response in the dorsal precuneus and left precentral gyrus as part of a motor network, which however might not be interpreted as a compensatory mechanism, but may be the upstream consequence of impaired visual processing.

The neurotransmitter histamine has been suggested to be involved in cognitive functioning. Generally, studies in animals have shown a decrease in performance after decreasing histamine neurotransmission and improved performance after increasing histamine neurotransmission. It is unclear, however, what role histamine plays in cognition in humans. Up until now, most data are derived from studies and reviews that aimed to assess the sedative potential of H(1)-antagonists and not the effects on cognition in particular. The objective of this paper is specifically to review which cognitive domains are affected by H(1)-antagonists. Taken together, 90 experimental studies on the performance effects of sedative H(1)-antagonists published between 1973 and 2009 were reviewed. Results showed that psychomotor skills and attention are most frequently impaired and memory the least. Tasks assessing memory that were affected usually required rapid responses. It was concluded that both the complexity of the task as well as the demand for information processing speed determines the sensitivity to the effects of central H(1)-antagonism. The importance of the sensitive cognitive domains to histaminergic dysfunction, as well as the relation between histamine related decrease in arousal and task performance deserve further research.

Background and purpose: Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia. Experimental approach: Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three-way, double-blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event-related potentials. Key results: Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event-related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times. Conclusions and implications: The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target.

Results from recent animal studies suggest an important role for histamine in memory functioning. Histaminergic drugs might prove beneficial for people suffering from memory impairment. To determine if histamine is involved in memory functioning this study evaluates the effects of histaminergic dysfunction on memory performance by administrating a H1-antagonist to humans. The study was conducted according to a 4-way, double-blind, crossover design in 20 healthy female volunteers, aged 18—45 years. On each test day subjects completed three test sessions: before and around 2 and 4 h after administration of single oral doses of dexchlorpheniramine 2 mg or 4 mg, scopolamine 1 mg or placebo. Drug effects were assessed using tests of memory, psychomotor and attention performance, and subjective alertness. Results showed that dexchlorpheniramine impaired performance in tests of spatial learning, reaction time, tracking and divided attention but showed no effects on working memory, visual memory, word learning or memory scanning. Scopolamine induced a similar pattern of effects. In addition, both drugs decreased subjective alertness. In conclusion results show that dexchlorpheniramine and scopolamine clearly impaired performance on psychomotor and attention tasks but do not suggest a specific role of the histaminergic system in learning and memory in humans.

Serotonin (5-HT) is an important neurotransmitter involved in the brain–gut axis. It is possible to lower the 5-HT level in the body by means of a nutritional intervention using an amino acid mixture; the acute tryptophan depletion (ATD) method. We studied the effect of ATD on gastric emptying in healthy females, who received both ATD and placebo in a random order. Gastric emptying was measured using the [13C]octanoic acid breath test. The present data demonstrate significant differences in both gastric emptying and lag phase (Tlag) between the ATD and placebo experiment. Eight out of ten subjects showed a delayed gastric emptying in the ATD experiment. Both the gastric half-emptying time (T1/2) and the Tlag were significantly higher in the ATD experiment. T1/2 in the ATD experiment was 137·2 (range 76·2–634·8) min; T1/2 for the placebo experiment was 98·5 (range 63·7–168·8) min (P=0·028). Tlag in the ATD experiment was 83·7 (range 45·1–356·2) min; Tlag for the placebo experiment was 56·9 (range 23·2–101·2) min (P=0·007). We conclude that lowering the 5-HT level in the body using the ATD method leads to a significantly delayed gastric emptying of a solid meal. Nutritional manipulation of the serotonergic system in healthy volunteers may lead to alterations in gastrointestinal motility.

Background. Lower serum high-density lipoprotein cholesterol and increased ratio of omega-6/omega-3 fatty acids have been reported in unipolar and bipolar depressed patients. Changes in cholesterol and fatty acids have been suggested to affect membrane viscosity and consequently serotonergic neurotransmitter expression.The goal of this study was to investigate whether lower baseline cholesterol and increased omega-6 and lower omega-3 fatty acids are present in healthy first-degree relatives of bipolar patients compared with controls and whether these changes were associated with neuroendocrine responses to an i.v. tryptophan challenge or mood.Method. Baseline cholesterol, fatty acids and mood were determined in healthy first-degree relatives of patients with bipolar disorders (N=30) and healthy matched controls (N=15) (parallel-group design). Prolactin and cortisol were measured following tryptophan infusion.Results. First-degree relatives showed significantly lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids. Lower total omega-3 and higher total omega-6 fatty acids in phospholipids were positively correlated with peak prolactin response to tryptophan. Lower total omega-3 fatty acids in phospholipids and cholesteryl esters were associated with lower mood.Conclusions. Abnormalities of lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids in these subjects are in agreement with findings in bipolar and major depressed patients. Changes in fatty acids show an association with central serotonergic parameters. It is suggested that these abnormalities in cholesterol and fatty acids may constitute a trait marker for bipolar disorders.

Cognitive impairment has repeatedly been described in bipolar disorders (BD). Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of BD patients. We investigated the effects of an intravenous (i.v.) tryptophan (Trp) challenge and placebo on cognitive performance in 30 healthy first-degree relatives of bipolar patients (FH) and 15 matched controls in a double-blind crossover design. A distinction was made between relatives of type I BD patients (FH I) and type II BD patients (FH II). Performances on planning, memory, attention, and psychomotor tasks were assessed 3 h after Trp infusion. After Trp, planning and attention were impaired in FH subjects but not in controls. Independent of Trp, FH subjects showed cognitive deficits on memory, focused and divided attention, and psychomotor performance. FH I subjects showed more pronounced cognitive impairments then FH II and controls. In all groups, Trp impaired memory and psychomotor performance significantly. In conclusions, cognitive deficits in FH following Trp may reflect a central 5-HT vulnerability in frontal brain areas. Independent of Trp, cognitive deficits in FH provide evidence for a trait marker for BD.

Biological vulnerability for bipolar disorders (BD) in relatives of BD patients has not as yet been established. Serotonergic vulnerability was studied, using acute tryptophan depletion (ATD), in healthy first-degree relatives of BD patients and healthy controls. The effects of ATD on mood and cortisol release in 30 healthy adult, lifetime symptom free, unaffected first-degree relatives of BD patients (Family History; FH) were compared with effects in 15 healthy matched controls in a placebo-controlled, double-blind, crossover design. During ATD and placebo, salivary cortisol response was also assessed during a stress-inducing speech task (SIST). First-degree relatives of type II BD patients (FH II) showed an elevation of mood, whereas control subjects and relatives of type I BD patients (FH I) showed a lowering of mood after ATD. ATD was followed by a decrease in cortisol level in both FH subgroups, but not in the controls. The results suggest serotonergic vulnerability that affected mood in FH II subjects and cortisol release in both FH I and FH II subjects.

Central serotonergic vulnerability indicated by altered mood and neuroendocrine responses to an intravenous (i.v.) tryptophan (Trp) challenge was assessed in healthy adult unaffected first-degree relatives of bipolar disorder (BD) patients ( n = 30) (family history; FH). The effects of a single dose of 7.0 g Trp on mood, cortisol and prolactin (Prl) in FH subjects were compared with healthy matched controls ( n = 15) in a placebo-controlled, double blind cross-over design. Prl and cortisol responses increased following Trp. Overall, Trp lowered mood. Hormonal and mood effects did not differ between FH and controls. Results show some evidence for differences in serotonergic vulnerability between relatives of type I BD patients and relatives of type II BD patients.

Our knowledge about the influence of nutritional supplements on human cognition, especially in the elderly, rests largely on animal behavioural research and neurochemical experiments in vitro, while only a few epidemiological studies and even fewer controlled experiments in humans are reported. This is an inherent problem, due partly to the difficulty of conducting controlled nutritional experiments in humans, but may also partly be due to the gap between the research disciplines of nutritional and neurobehavioral experimental science. Learning objectives —The aim of this paper is to discuss some new findings in this line of research, and to stress the importance of the need to start bridging the gap between disciplines by identifying possible human experimental models of altered cognitive function, which can elucidate the specific mechanisms of action through which nutritional supplements may enhance cognitive performance in humans in vivo. These experimental models are important because the research in this field is mostly based on epidemiological studies, which describe associations between nutrients and cognitive functions. Contrary to epidemiological studies, experimental models mimic associations between nutrients and cognition by manipulating their presumed mechanisms of action and can eventually explain the causal nature of found associations.

An infrared diode laser spectrometer for fibre component characterization was set up. IR fluoride glass fibre samples with well-defined angles at the fibre ends were prepared and preliminary coupling experiments were performed with special attention paid to minimize residual back reflexion by the fibres as a prerequisite for fibre application in infrared diode laser trace gas analyzers.