Contribution of sleep research to the development of new antidepressants

Several sleep anomalies are known to accompany depression and other psychiatric disorders, and to be partially modified by drugs efficient on clinical symptoms. Many puzzling theoretical questions remain, even after 30 years of research, because these drugs do not act in a uniform way: some reduce slow-wave sleep while others increase it; some prolong rapid-eye movement sleep latency while others do not. The relationship between insomnia and depression is likely to be a close one, since a large majority of patients with depression suffer insomnia, and that insomnia can predate depression by a few years. However, questions remain here, too, since sleep deprivation is also an effective means to combat depression, and some patients present with hypersomnia rather than insomnia. This review details the action of all current classes of antidepressants on sleep. It examines the predictive value of baseline electronencephalographic sleep symptoms or early modifications due to treatment for eventual clinical efficiency. We will also discuss the two main theories on the relationship between sleep and depression. The action on sleep of all new drugs- and antidepressants in particular - is carefully examined during development, for insomnia is currently considered to be a major health concern in industrialized countries

Cognitive-behavioral factors associated with sleep quality in chronic pain patients

People with chronic pain commonly complain of sleep disturbance. This study reports the characteristics of the pain and sleep of a large sample of patients with chronic pain (n = 160). This study compared subgroups of good sleepers with pain (n = 48) and poor sleepers with pain (n = 108). Poor sleepers with pain were younger and reported more pain, pain-related disability, depression, pain-related anxiety, and dysfunctional beliefs about sleep. Using simultaneous regression analysis, this study examined the roles of pain, dysfunctional beliefs about sleep, pain-related disability, depression, and pain-related anxiety in predicting concurrent sleep quality. The findings are relevant to the development of models of sleep disturbance comorbid with chronic pain

Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis

Supporting people with depression and anxiety: a guide for practice nurses

This guide has been devleoped for GP practice nurses following a three year research study called ProCEED (Proactive care and its evaluation for enduring depression), conducted by Dr Marta Buszewicz and a research team at University College London

Connexin-dependent neuroglial networking as a new therapeutic target

Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial networking may emerge as new therapeutic targets in neurological and psychiatric disorders

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

The Recent History of Seasonal Affective Disorder (SAD)

Seminar TranscriptPsychiatric diagnosis is controversial and is regarded by some principally as a means of reinforcing the vested interests of medical professionals and pharmaceutical companies. On the other hand, the phenomena that are described in clinical psychiatric practice are real and clearly extend across time and between cultures. ‘In every culture there is some notion of emotional or psychological difference. Not all cultures identify these differences in the same way, nor do they use identical terms. Equally, however no culture is indifferent to those who are sad, frightened or unintelligible in their conduct.’ 1 The description and diagnosis of Seasonal Affective Disorder (SAD) or ‘winter depression’ is a comparatively recent development which provides an unrivalled opportunity to explore the construction of a psychopathological entity through the relevant peer-reviewed publications, as well as the professional and public reaction to these scientific discoveries. This Witness Seminar provides a riveting insight into the thinking of some key protagonists, both the scientists who developed the diagnosis of SAD as well as those for whom this new clinical entity resonated so clearly with their own experiences. What is the point of diagnosis? Ideally a diagnosis should point to a particular disease process, though even in general medicine this is often not the case. However, in a pragmatic sense the value of diagnosis is that it enables a group of people manifesting particular clinical phenomena to be identified as sharing a common prognosis and response to treatment – in the case of SAD a therapeutic response to artificial bright light. Indeed with SAD, it may be that increasing knowledge about the circadian effects of bright light stimulated a search for medical conditions in which it might be effective, that is, in some sense the availability of a treatment led to the identification of the condition. How truly recent is the identification of SAD as a diagnostic entity? In fact, seasonal variation in mood disorder has long been recognized and Rosenthal and colleagues (1984) quote the eminent nineteenth-century psychiatrist, Emil Kraepelin, as commenting in his standard textbook: ‘Repeatedly I saw in these cases moodiness set in in autumn and pass over in spring ... corresponding in a certain sense to the emotional changes which come over even healthy individuals at the changes of the seaso

Older patients' prescriptions screening in the community pharmacy: development of the Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3S) tool

Background: Ageing of the population often leads to polypharmacy. Consequently, potentially inappropriate prescribing (PIP) becomes more frequent. Systematic screening for PIP in older patients in primary care could yield a large improvement in health outcomes, possibly an important task for community pharmacists. In this article, we develop an explicit screening tool to detect relevant PIP that can be used in the typical community pharmacy practice, adapted to the European market. Methods: Eleven panellists participated in a two-round RAND/UCLA (Research and Development/University of California, Los Angeles) process, including a round zero meeting, a literature review, a first written evaluation round, a second face-to-face evaluation round and, finally, a selection of those items that are applicable in the contemporary community pharmacy. Results: Eighteen published lists of PIP for older patients were retrieved from the literature, mentioning 398 different items. After the two-round RAND/UCLA process, 99 clinically relevant items were considered suitable to screen for in a community pharmacy practice. A panel of seven community pharmacists selected 83 items, feasible in the contemporary community pharmacy practice, defining the final GheOP3S tool. Conclusion: A novel explicit screening tool (GheOP3S) was developed to be used for PIP screening in the typical community pharmacy practice