Abstract:
:Developing new pharmacotherapies for autism spectrum disorder (ASD) is a challenge. ASD has a complex genetic architecture, several neurobiological phenotypes and multiple symptom domains. However, new opportunities are emerging that could lead to the development of 'targeted' and individualized pharmacological interventions. Here, first we review these important new insights into the aetiology and neurobiology of ASD with particular focus on (i) genetic variants mediating synaptic structure and functioning and (ii) differences in brain anatomy, chemistry and connectivity in this condition. The characterization of the genotypic and phenotypic differences underlying ASD might in the future be invaluable for stratifying the large range of different individuals on the autism spectrum into genetically and/or biologically homogeneous subgroups that might respond to similar targeted interventions. Secondly, we propose a strategic framework for the development of targeted pharmacotherapies for ASD, which comprises several different stages in which research findings are translated into clinical applications. The establishment of animal models and cellular assays is important for developing and testing new pharmacological targets before initiating large-scale clinical trials. Finally, we present the European Autism Interventions - A Multicentre Study for Developing New Medications (EU-AIMS) Initiative, which was set up in the context of the EU Innovative Medicines Initiative as the first European platform for integrated translational research in ASD. The EU-AIMS Initiative consists of academic and industrial partners working in collaboration to deliver a more 'personalized' approach to diagnosing and treating ASD in the future.
journal_name
J Intern Medjournal_title
Journal of internal medicineauthors
Ecker C,Spooren W,Murphy Ddoi
10.1111/joim.12113subject
Has Abstractpub_date
2013-10-01 00:00:00pages
308-20issue
4eissn
0954-6820issn
1365-2796journal_volume
274pub_type
杂志文章,评审abstract::A young, apparently healthy, soldier developed acute muscle weakness and rhabdomyolysis following prolonged exercise. The resultant myoglobinuria caused severe acute renal failure. Further investigation revealed the presence of carnitine palmitoyltransferase deficiency as the cause of the rhabdomyolysis. Renal functio...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1993.tb00991.x
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVES:The clinical features of 80 patients with primary Sjögren's syndrome (PSS) were revised in order to evaluate the descriptive and analytical facilities of a newly proposed model for classification of the exocrine and nonexocrine disease manifestations in PSS. DESIGN:Retrospective, long-term (median 7.5 years...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1996.418817000.x
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:Addition of assessment of comorbid diseases ('D') and oxygen saturation ('S') to the CRB-65 score has been recommended to improve its accuracy for risk stratification in community-acquired pneumonia (CAP). The aim of this study was to validate the resulting DS-CRB-65 score in a large cohort of patients with ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/joim.12349
更新日期:2015-08-01 00:00:00
abstract::Six patients with acute renal failure, in five cases due to acute crescentic glomerulonephritis and in one case due to total bilateral renal cortical necrosis, were studied. All had serum erythropoietin (EPO) concentrations in the normal range, despite a relatively severe anaemia. Half-life and plasma clearance of int...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1991.tb00360.x
更新日期:1991-04-01 00:00:00
abstract:BACKGROUND:Structural remodelling of left ventricle is a common feature in the progression of congestive heart failure (CHF). Matrix metalloproteinases (MMPs) have been directly implicated as they degrade extracellular proteins. To test the hypothesis that MMP-and its inhibitor, tissue type inhibitor of matrix metallop...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2007.01823.x
更新日期:2007-09-01 00:00:00
abstract::This report describes the case of a male patient with progressive dysphagia, epigastric pain, odynophagia, generalized weakness and a mid-oesophagus ulceration in which biopsies showed acid-fast bacilli and histological evidence of tuberculosis. Culture of the biopsies and the sputum revealed mycobacterium tuberculosi...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1995.tb00902.x
更新日期:1995-07-01 00:00:00
abstract::Atherosclerosis is a chronic inflammatory disease characterized by accumulation of oxidized lipoproteins, increased cell death and hypertrophic degeneration of the arterial intima. The disease process is associated with local formation of modified self antigens that are targeted by both innate and adaptive immune resp...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2008.01945.x
更新日期:2008-05-01 00:00:00
abstract::The introduction of biologic therapies heralded a new era in the treatment for chronic inflammatory autoimmune diseases of which rheumatoid arthritis is one of the most prevalent. From a scientific point of view, these therapies demonstrated that the targeting of individual cytokines or cell-surface markers is a very ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2011.02355.x
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVES:The effect of a second and third generation oral contraceptive and of the progestagens used in these pills on lipid metabolism was studied in the absence or presence of the factor V Leiden mutation. DESIGN:A single centre, double blind randomized trial. SETTING:University Medical Centre. SUBJECTS:A total ...
journal_title:Journal of internal medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2796.2001.00906.x
更新日期:2001-11-01 00:00:00
abstract:AIM:To describe the mortality and mode of death over 5 years, and factors associated with death amongst patients with acute chest pain. PATIENTS:All patients who came to the emergency department at Sahlgrenska Hospital in Göteborg with acute chest pain or other symptoms raising suspicion of acute myocardial infarction...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1998.00244.x
更新日期:1998-01-01 00:00:00
abstract::The association of sex, age, relative weight, smoking and drinking habits, chronic obstructive pulmonary disease (COPD) and economic and marital status, with benign oesophageal disease (BOD) was investigated by means of a point-prevalence study of BOD in a Danish population. A total of 346 individuals, representing su...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1991.tb00399.x
更新日期:1991-07-01 00:00:00
abstract:OBJECTIVE:To evaluate the frequency of the common Finnish and Norwegian mutations in the low density lipoprotein (LDL) receptor gene in Swedish patients with familial hypercholesterolaemia (FH), and to start screening for other mutations in these patients. In contrast to the situation in Norway and Finland, where the f...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1998.00309.x
更新日期:1998-07-01 00:00:00
abstract::The syndrome defined as "idiopathic CD4 lymphocytopenia' (ICL) is a rare disease of unknown aetiology, often associated with severe depression of immune defences and the occurrence of opportunistic infections. A case is reported wherein a severe immunodeficiency syndrome with persistent idiopathic CD4+ lymphopenia dev...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1996.447785000.x
更新日期:1996-07-01 00:00:00
abstract:OBJECTIVES:To evaluate (i) the demineralizing effect of L-thyroxine (LT4) therapy at doses mildly inhibiting serum thyroid stimulating hormone (TSH) in patients with benign nodular goitre; (ii) the efficacy of treatment on nodule size. DESIGN:Cross-sectional study comparing euthyroid women with nodular goitre treated ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.2002.00977.x
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVES:To evaluate the predictive accuracy of the scoring system Rapid Acute Physiology score (RAPS) in nonsurgical patients attending the emergency department (ED) regarding in-hospital mortality and length of stay in hospital (LOS), and to investigate whether the predictive ability of RAPS could be improved by ex...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2004.01321.x
更新日期:2004-05-01 00:00:00
abstract::Multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system, is today a leading cause of unpredictable lifelong disability in young adults. The treatment of patients in progressive stages remains highly challenging, alluding to our limited understanding of ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.13045
更新日期:2020-07-01 00:00:00
abstract:OBJECTIVES:Cardiac sarcoidosis (CS) without clinically apparent extracardiac disease may escape detection because of the poor sensitivity of endomyocardial biopsy (EMB). We set out to analyse our experience of repeated and imaging-guided biopsies in clinically isolated CS. METHODS:We retrospectively reviewed the medic...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2011.02396.x
更新日期:2011-11-01 00:00:00
abstract:OBJECTIVES:to examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability. DESIGN:longitudinal cohort study of patients with CFS (Fukuda criteria). SETTING:specialist CFS clinical service. SUBJECTS:phase 1: 100 patients who participated in a study of...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2010.02306.x
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVES:To determine whether mutations in APOA1 affect levels of high-density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) and total mortality in the general population. BACKGROUND:Epidemiologically, risk of IHD is inversely related to HDL cholesterol levels. Mutations in apoli...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2011.02381.x
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVES:Few studies have simultaneously analysed the influence of elevated serum uric acid (UA) on acute myocardial infarction (AMI), ischaemic and haemorrhagic stroke (IS, HS) and congestive heart failure (CHF) in large healthy populations. We, here, examine UA as a risk factor for AMI, stroke and CHF by age and ge...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2009.02133.x
更新日期:2009-12-01 00:00:00
abstract::Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin-dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U k...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1989.tb01403.x
更新日期:1989-11-01 00:00:00
abstract:OBJECTIVES:To analyse whether there is an association between country of birth in first-generation immigrants and first hospitalization for or death from coronary heart disease (CHD) and to analyse whether this association remains in second-generation immigrants. DESIGN:In this follow-up study, the MigMed database at ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2006.01630.x
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Metabolomics is a versatile unbiased method to search for biomarkers of human disease. In particular, one approach in cancer therapy is to promote apoptosis in tumour cells; this could be improved with specific biomarkers of apoptosis for monitoring treatment. We recently observed specific metabolic patterns...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/joim.12117
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVES:Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at...
journal_title:Journal of internal medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1365-2796.2007.01808.x
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1999.00564.x
更新日期:1999-08-01 00:00:00
abstract::In the clinic, obesity and anorexia constitute prevalent problems whose manifestations are encountered in virtually every field of medicine. However, as the command centre for regulating food intake and energy metabolism is located in the brain, the basic neuroscientist sees in the same disorders malfunctions of a mod...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2005.01553.x
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:To describe the epidemiology, pathogenesis and clinical features of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP). DESIGN:A retrospective population-based mortality study. SUBJECTS:All inhabitants who died between 1978-1990 (2122) including 33 with AIP, in two municipali...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1996.21847000.x
更新日期:1996-10-01 00:00:00
abstract::Monitoring survival of cancer patients using data collected by population-based cancer registries is an important component of cancer control. In this setting, patient survival is often summarized using net survival, that is survival from cancer if there were no other possible causes of death. Although net survival is...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.13139
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:The RET proto-oncogene is known to be the susceptibility gene for various disease phenotypes, including multiple endocrine neoplasia type 2 (MEN 2). Recent studies have also suggested an involvement of RET in the development of the mammalian kidney. Although kidney agenesis or dysgenesis has been observed in ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.2001.00846.x
更新日期:2001-07-01 00:00:00
abstract::Previous studies in patients with peripheral arterial disease (PAD) have shown that the prognosis is relatively good when the distal systolic ankle index (ankle systolic pressure/arm systolic pressure) is above 50% and the distal toe systolic pressure is above 40 mmHg. In 132 patients suspected of PAD in the legs we i...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1989.tb01361.x
更新日期:1989-08-01 00:00:00