Shorter, E. & Tyrer, P. Separation of anxiety and depressive disorders: blind alley in psychopharmacology and classification of disease. BMJ 327, 158-160
ABSTRACT ne current division between anxiety and depression is increasingly recognised as inadequate. In the community, most mood disorders present as a combination of depression and anxiety. Yet the Food and Drug Administration in the United States, which has become the world bellwether of drug approval, indicates drugs either for major depression or for the various forms of anxiety recognised by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). As a result, the pharmaceutical industry is compelled to develop drugs for diagnoses that are of questionable clinical relevance. This is one reason for the big slowdown in drug discovery in psychiatric drugs. A return to the former unitary classification of mood and anxiety disorders as nervousness or cothymia might represent a way out of this blind alley.
Full-textDOI: · Available from: Edward Shorter, Oct 17, 2014
- SourceAvailable from: Nynke A Groenewold
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- "Heterogeneity in depression leads to decreased clinical specificity and a loss of statistical power. Dichotomizing results in the dismissal of valuable information, which may lead to biased results (Shorter and Tyrer, 2003). A dimensional model of psychopathology resolves both issues by assuming that symptom severity follows a continuum rather than a dichotomy. "
ABSTRACT: We examined the association of cognitive vulnerability to depression with changes in homogeneous measures of depressive symptoms. Baseline and 1-year follow-up data were obtained from 2981 participants of the Netherlands study of depression and anxiety. Multivariate regression analyses were carried out on cognitive reactivity, locus of control and implicit and explicit self-depressive associations in combination with negative life events. The purpose of this analysis was to predict changes on the mood/cognition and anxiety/arousal subscales of the inventory of depressive symptomatology - self report. Cognitive reactivity, locus of control and explicit self-depressive associations were independently associated with changes in depressive symptoms after adjustment for covariates and baseline severity (all p<0.01). Negative life-events interacted with cognitive vulnerability to depression to predict depressive symptoms. Locus of control (b1=0.16, SE=0.02, η(2)=0.01; b2=0.10, SE=0.02, η(2)=0.004, F=8.69, p<0.01) and explicit self-depressive associations (b1=0.10, SE=0.03, η(2)=0.02; b2=0.02, SE=0.04, F=7.50, p<0.01) were more strongly associated with the cognitive (b1) than the somatic (b2) symptom dimension of depression. The study sample is over-inclusive of depressed patients. Therefore it might be problematic generalizing the findings to the general population. Cognitive etiological factors may play a role in a "cognitive" subtype of depression. The findings strengthen the notion that homogeneous measures of depressive symptoms enable a greater degree of discrimination between subtypes than a multidimensional conception of depression.Journal of Affective Disorders 06/2013; 151(1). DOI:10.1016/j.jad.2013.05.057 · 3.71 Impact Factor
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- "This has led to much criticism of the models used. Likewise, there has been a growing discussion focused on whether anxiety and depression should be isolated from a drug development perspective (Shorter and Tyrer, 2003). Moreover, given the relative success of SSRIs, it is becoming clear that many pharmaceutical companies are compelled to develop a 'one pill fits all' approach to anxiety and mood disorders. "
ABSTRACT: Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.British Journal of Pharmacology 03/2011; 164(4):1129-61. DOI:10.1111/j.1476-5381.2011.01362.x · 4.99 Impact Factor
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- "Although the hypothesis elaborated in the present article suggests a molecular mechanism for psychological pain and physical pain in depression, it does not propose a molecular mechanism for other symptoms or common comorbidities of depression, such as anxiety (Shorter and Tyrer 2003), irritability (Snaith and Taylor 1985), guilt (American Psychiatric Association 2000), and worthlessness (American Psychiatric Association 2000), nor does it provide a mechanism by which inflammatory mediators in the brain induce the sickness symptoms that are common in depression, such as sleep and appetite disturbances (American Psychiatric Association 2000), fatigue (American Psychiatric Association 2000), nausea (Haug et al. 2002), diarrhea (Sugahara et al. 2004), or fever (Sugahara et al. 2004). In a separate manuscript in preparation (Wager-Smith 2010) we present a theoretical model whereby these symptoms respresent a family of behavioral defenses that are controlled by neuronal circuits for which the trigger threshold can be altered by inflammatory mediators. "
ABSTRACT: Depression is a major contributor to the global burden of disease and disability, yet it is poorly understood. Here we review data supporting a novel theoretical model for the biology of depression. In this model, a stressful life event leads to microdamage in the brain. This damage triggers an injury repair response consisting of a neuroinflammatory phase to clear cellular debris and a spontaneous tissue regeneration phase involving neurotrophins and neurogenesis. During healing, released inflammatory mediators trigger sickness behavior and psychological pain via mechanisms similar to those that produce physical pain during wound healing. The depression remits if the neuronal injury repair process resolves successfully. Importantly, however, the acute psychological pain and neuroinflammation often transition to chronicity and develop into pathological depressive states. This hypothesis for depression explains substantially more data than alternative models, including why emerging data show that analgesic, anti-inflammatory, pro-neurogenic and pro-neurotrophic treatments have antidepressant effects. Thus, an acute depressive episode can be conceptualized as a normally self-limiting but highly error-prone process of recuperation from stress-triggered neuronal microdamage.Neuroscience & Biobehavioral Reviews 09/2010; 35(3):742-64. DOI:10.1016/j.neubiorev.2010.09.010 · 10.28 Impact Factor