Depression and anxiety, an Indicated Prevention (DIP) protocol in homes for the elderly: feasibility and (cost) effectiveness of a stepped care programme

BACKGROUND: Depressive and anxiety disorders are a very common, serious and underdetected problem in homes for the elderly. Elderly persons in residential homes are at high risk for developing major depressive and anxiety disorders, and, therefore, deserve attention with regard to prevention. METHODS/DESIGN: This protocol describes a randomised trial on the feasibility and (cost) effectiveness of a stepped-care programme for prevention of depressive and anxiety disorders in homes for the elderly. The main outcome measure is the incidence of depressive and anxiety disorder in one year with a two years follow up. Secondary outcomes are symptoms of depression and anxiety, quality of life, direct health care costs and satisfaction with treatment. DISCUSSION: The number of studies examining the effects of preventive interventions on the incidence of mental disorders in the elderly population is very small. However, indicated prevention by means of a stepped-care programme seems to be an important option for decreasing the burden of illness for residents and their caregivers. This study contributes to the body of knowledge in this field. Positive effects may contribute to further use and development of tailored, (cost-) effective and easy to use interventions in a preventive stepped-care programme. TRIAL REGISTRATION: The Dutch Cochrane Centre, ISRCTN2754073

Serotonin synthesis, release and reuptake in terminals: a mathematical model

<p>Abstract</p> <p>Background</p> <p>Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system.</p> <p>Methods</p> <p>We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data.</p> <p>Results</p> <p>We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct <it>in silico </it>experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine.</p> <p>Conclusions</p> <p>Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.</p