The size and burden of mental disorders and other disorders of the brain in Europe 2010

Aims

To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU.

Method

Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY).

Results

Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8 million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165 m vs. 2005: 82 m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (> 4%), ADHD (5%) in the young, and dementia (1–30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment.Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke.

Conclusion

In every year over a third of the total EU population suffers from mental disorders. The true size of “disorders of the brain” including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.     

The burden and cost of disorders of the brain in Europe with the inclusion of harmful alcohol use and nicotine addiction

Recent publications calculated an annual prevalence of 38% of the population within the European Union having a “disorder of the brain” including substance use disorders (SUD) (Wittchen et al., 2011). The overall economic burden was estimated at 789 billion € (Gustavsson et al., 2011). While these calculations included alcohol dependence, harmful use of alcohol, a common ICD-10 diagnosis, was not considered appropriately. Tobacco related figures were completely left out. We hence estimated burden and costs of these diagnoses for the European Union by extrapolating basic figures from Germany, which have average proportions of alcohol and tobacco related consumption and prevalence rates. Several German Data sets were used to estimate prevalence, disability adjusted life years (DALYs) and Cost-of-Illness for alcohol and tobacco use disorders in Germany. Results were obtained by focussing on the burden of SUD including well-known comorbidities. Results were then extrapolated to the European level. Compared with the earlier estimations DALYs increased from 2.8 million to over 6.6 million for SUDs. Costs augmented from 65.68 billion € PPP to about 350 billion € PPP. We discuss the robustness and validity of our findings under different assumptions and with regard to methodology. We further took into account that in the new DSM 5 alcohol abuse and alcohol dependence – and similar tobacco – will be collapsed into one category of “alcohol related disorder”. If added to the burden and cost calculations the substance use disorders rank on top of all disorders of the brain in Europe. Regardless of the calculation procedure our figures represent lower estimates and have to be regarded as conservative approaches.     

Pharmacology of epigenetics in brain disorders

Epigenetics is a rapidly growing field and holds great promise for a range of human diseases, including brain disorders such as Rett syndrome, anxiety and depressive disorders, schizophrenia, Alzheimer disease and Huntington disease. This review is concerned with the pharmacology of epigenetics to treat disorders of the epigenome whether induced developmentally or manifested/acquired later in life. In particular, we will focus on brain disorders and their treatment by drugs that modify the epigenome. While the use of DNA methyl transferase inhibitors and histone deacetylase inhibitors in in vitro and in vivo models have demonstrated improvements in disease-related deficits, clinical trials in humans have been less promising. We will address recent advances in our understanding of the complexity of the epigenome with its many molecular players, and discuss evidence for a compromised epigenome in the context of an ageing or diseased brain. We will also draw on examples of species differences that may exist between humans and model systems, emphasizing the need for more robust pre-clinical testing. Finally, we will discuss fundamental issues to be considered in study design when targeting the epigenome.     

Size and burden of depressive disorders in Europe.

We review epidemiological studies of depression in Europe. Community surveys are essential. Methodological differences in survey methods, instruments, nuances in language and translation limit comparability, but consistent findings are emerging. Western European countries show 1 year prevalence of major depression of around 5%, with two-fold variation, probably methodological, and higher prevalences in women, the middle-aged, less privileged groups, and those experiencing social adversity. There is high comorbidity with other psychiatric and physical disorders. Depression is a major cause of disability. Incidence has been less studied and lifetime incidence is not clear, with longitudinal studies required. There is pressing need for prevalence studies from Eastern Europe. The considerable differences in health care systems among European countries may impact on proportions of depressives receiving treatment and its adequacy, particularly in the key area of primary care, and require further study. There is a need for public health programmes aimed at improving treatment, reducing rates and consequences of depressive disorders.     

Targeting the endocannabinoid system in treating brain disorders

Recent cannabinoid research has a primary focus on developing therapeutics against human diseases. Many studies on cannabinoids indicate important progress for protection against several neurodegenerative disorders. Agonists of cannabinoid receptors activate signalling pathways in the brain that are linked to neuronal repair and cell maintenance, and endogenous ligands can also activate neuroprotective responses. These endocannabinoids are bioactive fatty acid amides and esters that are synthesised in the brain and include arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol. Endocannabinoids are released in response to pathogenic events, thus representing a potential compensatory repair mechanism. Enhancing this on-demand action of endocannabinoids is a strategy with which to promote endogenous repair signalling. For such enhancement, considerable work has gone into modulating the availability of endocannabinoids by blocking the processes of their deactivation. The targets include the anandamide-hydrolysing enzyme fatty acid amide hydrolase, the carrier-mediated anandamide transport system and 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase. The activity of endocannabinoids is terminated through transport and degradation and, accordingly, selective inhibitors of these processes effectively exploit the protective nature of cannabinergic responses. This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the CNS.     

Targeting the endocannabinoid system in treating brain disorders

Recent cannabinoid research has a primary focus on developing therapeutics against human diseases. Many studies on cannabinoids indicate important progress for protection against several neurodegenerative disorders. Agonists of cannabinoid receptors activate signalling pathways in the brain that are linked to neuronal repair and cell maintenance, and endogenous ligands can also activate neuroprotective responses. These endocannabinoids are bioactive fatty acid amides and esters that are synthesised in the brain and include arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol. Endocannabinoids are released in response to pathogenic events, thus representing a potential compensatory repair mechanism. Enhancing this on-demand action of endocannabinoids is a strategy with which to promote endogenous repair signalling. For such enhancement, considerable work has gone into modulating the availability of endocannabinoids by blocking the processes of their deactivation. The targets include the anandamide-hydrolysing enzyme fatty acid amide hydrolase, the carrier-mediated anandamide transport system and 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase. The activity of endocannabinoids is terminated through transport and degradation and, accordingly, selective inhibitors of these processes effectively exploit the protective nature of cannabinergic responses. This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the CNS.     

深部脑刺激技术在神经精神疾病中的应用

<正>神经精神疾病是神经系统在多种因素的影响下发生功能或器质性病变而引起的一类疾病,目前较为常见的神经精神疾病主要包括帕金森病(Parkinson’s Disease,PD)、癫痫(Epilepsy)、抑郁症(Depression)、强迫症(Obsessive-Compulsive Disorder,OCD)以及成瘾(Addiction)等。近年来,神经精神疾病的发病率呈现逐年上升的趋势,但大多数的发病机制尚不明确,给其治疗带来较大困难。目前神经精神疾病的治疗手段仍以药物治疗为主,且具有难治愈、易复发等特点,使得患者往往需要长期甚至终身服药以控制病情,同时,患者对药物耐受     

烟碱和大脑功能障碍(英文)

During the last decade, brain nicotinic acetylcholine receptors were extensively characterized from electrophys-iological and pharmacological points of view. These receptors play important roles in memory and cognition and participate in the pathogenesis of several brain disorders (Parkinson's and Alzheimer's diseases, Tourette's syndrome, schizophrenia, depression, attention deficit disorder) . In the same diseases, clinical studies showed that nicotine had beneficial effects, both as therapeutic and prophylactic agent. This review presents recent data concerning the structure and properties of neuronal nicotinic receptors, their involvement in the pathogenesis of various brain disorders and the beneficial effects of nicotine as therapeutic agent.     

Expression profiling in brain disorders and beyond.

Large scale expression profiling studies provide a wealth of data that even after stratification by sophisticated biostatistical procedures leave the researcher more or less puzzled and helpless. This report is meant to encourage molecular biologists facing compounding gene lists resulting from expression profiling studies to understand them as intellectual challenges that require the researchers' solid scientific experience plus a good deal of curiosity. Three examples from expression profiling investigations on distinct aspects of brain inflammation are covered here. They show that even without good software programs it is possible to come up with reasonable biological hypotheses to be evaluated in subsequent more detailed experiments.     

Neuropsychiatric disorders following vascular brain injury

Several neuropsychiatric disorders such as mood, anxiety and psychotic disorders occur following cerebrovascular lesions. Post-stroke depression is the most common of these disorders and, along with post-stroke anxiety, has been shown to inhibit physical and cognitive recovery. Antidepressants have been shown to effectively treat post-stroke depression and to have a positive impact on rehabilitation efforts in patients suffering from this disorder. Much less is known about the potential impact of psychiatric conditions on recovery after stroke. Controlled trials will be able to adequately determine the effectiveness of treatment for these disorders.     

Parvalbumin interneuron vulnerability and brain disorders

Parvalbumin-expressing interneurons (PV-INs) are highly vulnerable to stressors and have been implicated in many neuro-psychiatric diseases such as schizophrenia, Alzheimer’s disease, autism spectrum disorder, and bipolar disorder. We examined the literature about the current knowledge of the physiological properties of PV-INs and gathered results from diverse research areas to provide insight into their vulnerability to stressors. Among the factors that confer heightened vulnerability are the substantial energy requirements, a strong excitatory drive, and a unique developmental trajectory. Understanding these stressors and elaborating on their impact on PV-IN health is a step toward developing therapies to protect these neurons in various disease states and to retain critical brain functions.Subject terms: Cellular neuroscience, Diseases of the nervous system, Cell death in the nervous system, Stress and resilience     

脑深部电刺激在运动障碍性疾病中的临床应用

脑深部电刺激(DBS)作为神经调控的主要手段,目前已广泛应用于药物难治性帕金森病、特发性震颤、肌张力障碍、Meige综合征、躯干前曲症、不宁腿综合征、抽动秽语综合征等运动障碍性疾病治疗,为运动障碍性疾病提供了全新的治疗方法。本文综述DBS的临床应用进展。     

Functional genomics approaches to understanding brain disorders

The completed draft of the human genome sequence has facilitated a revolution in neuroscience research. This sequence information and the development of new technologies used to analyze gene expression on a genomic scale provides a new and powerful means to investigate brain disorders of unknown etiology and to isolate novel drug targets for these disorders. The term functional genomics broadly describes a set of technologies and strategies directed at the problem of determining the function of genes, and understanding how the genome works together to generate whole patterns of biological function. The most powerful of these functional genomics approaches, expression profiling or DNA microarrays, can be used to analyze the expression of thousands of genes simultaneously. The results to date from the application of DNA microarray methods to postmortem diseased human brain tissue, animal models and cell culture models of brain disorders provide an exciting glimpse into the future of this field.