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Biomedical subjects

Timothy Dinan

Publications and source records attributed to Timothy Dinan.

5 recordsLinked to original sources

Therapeutic options: Addressing the current dilemma.

The main therapy for the symptomatic management of generalized anxiety disorder (GAD) is pharmacotherapy, although comprehensive management methods also include psychotherapeutic interventions. Traditionally, treatments including anxiolytics and antidepressants have been used in GAD management, but prescribing physicians have more recently moved towards using selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Indeed, newer medicines have been shown to be as effective as older treatments, but with improved safety and tolerability. Although the best way to treat GAD has yet to be established, these patients clearly need long-term supervision. Ideally, physicians should prescribe treatment with the purpose of ultimately eliminating symptoms and re-establishing normal function. To achieve this goal, physicians need a more effective, faster acting, safer, and better tolerated drug than the many existing GAD treatments.

Adrenergic Uptake Inhibitors↗

An overview of the central control of weight regulation and the effect of antipsychotic medication.

Weight regulation is a complex system necessary for maintaining health. Obesity and cachexia are consequences of dysregulation and cause significant physical morbidity and mortality. In the developed world, obesity is a growing epidemic. A greater understanding of the neuroanatomy of weight regulation has been gained through advances in imaging and neural mapping techniques. The neural connections between key hypothalamic and other central nuclei have been elucidated. Advances in molecular biology have led to the identification and cloning of important peripheral and central weight regulating peptides. Weight gain as a consequence of antipsychotic use is increasingly being recognized as a serious clinical issue. The weight regulation system provides a framework upon which antipsychotics exert their weight-inducing effects. Some studies have sought, with inconsistent results, to establish associations between antipsychotic use and levels of weight regulating mediators. The receptor pharmacology of antipsychotics known to increase weight can be studied with a view to establishing genetic variants contributing to the risk. To date, the 5-HT(2C) receptor 759C/T polymorphism shows most promise. Further studies are required to replicate previous findings and establish new associations.

Animals↗

Platelet surface glycoprotein expression in post-stroke depression: a preliminary study.

Depression is a significant risk factor for and consequence of both cardiovascular disease and stroke. The pathophysiological processes underlying this association are poorly understood. This study utilised a technique for measurement of whole blood platelet surface glycoproteins involved in early adhesion and aggregation in sample populations of patients with depression and stroke, and healthy controls. We analysed the platelet surface glycoproteins GPIb and GPIIbIIIa using flow cytometry in eight depressed subjects (Hamilton depression score >17), 14 post-stroke subjects (seven depressed and seven non-depressed), and in eight healthy control subjects. The number of GPIb receptors was significantly increased in subjects with depression and in post-stroke subjects compared to control subjects. The number of GPIb receptors from post-stroke subjects was not significantly different from that of depressed subjects. There were no differences between any groups in measures of GPIIbIIIa receptor numbers. No additive effect of co-morbid depression on the surface expression level of either marker could be detected in the post-stroke subjects. Platelet dysfunction may be involved in the pathophysiological process underlying the association between depression and cerebrovascular disease.

Adult↗

Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone.

Despite the importance of the 5HT1A receptor in regulating central serotonergic tone, there is a dearth of research examining its role in migraine. In this study, we examined the hypothesis that there would be altered neuroendocrine responses to a 5HT1A agonist challenge in different migraine subtypes. Prolactin (PRL) responses to the 5HT1A receptor agonist drug buspirone were compared in 30 female subjects with migraine (ten migraine with aura, MA; ten migraine without aura, MO and ten chronic/transformed migraine, CM), and ten healthy controls matched for age, gender and menstrual status. None of the subjects were taking psychotropic medication or migraine prophylactic treatment and those with formal psychiatric disorder were excluded. Endocrine responses were determined by measuring differences between baseline PRL and maximum increases post-buspirone (deltaPRL). There was no difference in baseline PRL between groups. MA subjects did not differ in their PRL responses to buspirone compared to healthy controls. The MO group had a four-fold increase in mean deltaPRL responses compared to healthy controls. Mean deltaPRL was also increased in the CM group compared to controls, but the difference was less exaggerated. This study indicates that there is supersensitive central amine receptor function in MO and CM, but not in MA. These findings support the hypothesis that central 5HT function differs among the migraine subtypes. The results also suggest that migrainous 'transformation' may be associated with adaptive changes in central 5HT receptor sensitivity. The relative contribution of 'state' and 'trait' receptor function to these findings as well as the possible role of dopamine receptors is discussed.

Adult↗

Elevated expression of integrin alpha(IIb) beta(IIIa) in drug-naïve, first-episode schizophrenic patients.

BACKGROUND: Patients with schizophrenia have an increased risk over the general public of developing cardiovascular illness. It is unknown if there are functional changes in platelet surface receptors in schizophrenia. We therefore analyzed the surface expression of glycoprotein (GP)Ib, the integrin receptor alpha(IIb)beta(IIIa), CD62 (P-selectin), and CD63, and investigated platelet function in schizophrenic patients compared with healthy volunteers. METHODS: Nineteen drug-naive, first-episode patients with a DSM IV diagnosis of paranoid schizophrenia were compared with matched healthy controls. Flow cytometry was used to assess platelet surface expression levels of GPIb, alpha(IIb)beta(IIIa), CD62, and CD63. Adenosine diphosphate-induced platelet aggregation was assayed. RESULTS: The schizophrenic patients had a significantly (p < .0001) increased number of 68,145 +/- 8,260.1 alpha(IIb)beta(IIIa) receptors, platelet compared with 56,235 +/- 8,079.4 receptors, platelet in healthy controls. CONCLUSIONS: Patients with schizophrenia have increased platelet expression of alpha(IIb)beta(IIIa), which may contribute to their increased risk of cardiovascular illness compared with the general population.

Adenosine Diphosphate↗