The Early Diagnosis of Alzheimer's Disease: A Patient-Centred Conversation with the Care Team.

Alzheimer's disease (AD) is a neurodegenerative disorder which accounts for 60-80% of dementia cases, affecting approximately 10 million people in Europe. Neuroimaging techniques and cerebrospinal fluid biomarkers used in combination with cognitive assessment tools open the door to early diagnosis of AD. However, these tools present some challenges that need to be overcome, such as low sensitivity or specificity, high cost, limited availability or invasiveness. Thus, low-cost and non-invasive alternatives, such as plasma biomarkers, have the potential to drive changes in AD screening and diagnosis. In addition to the technical aspects, organisational challenges as well as ethical concerns need to be addressed. In many countries, there is an insufficient number of specialists to recognise, evaluate and diagnose dementia and the waiting times to see a specialist are long. Given that there is currently no cure for AD, it is important to consider the potential psychological impact of an early diagnosis. In addition, counselling before biomarker sampling and during diagnosis disclosure is vital to guarantee that the patients have all the information necessary and their queries are addressed in a sensitive manner. Here, we illustrate (using a clinical vignette) current challenges of diagnosis and discuss some of the benefits and challenges of early diagnosis in AD including the value of biomarkers in combination with clinical evaluation. Lastly, some guidelines for disclosing early diagnosis of AD are provided based on our experiences.

Creativity and mental disorder: family study of 300,000 people with severe mental disorder.

BACKGROUND: There is a long-standing belief that creativity is coupled with psychopathology. AIMS: To test this alleged association and to investigate whether any such association is the result of environmental or genetic factors. METHOD: We performed a nested case-control study based on Swedish registries. The likelihood of holding a creative occupation in individuals who had received in-patient treatment for schizophrenia, bipolar disorder or unipolar depression between 1973 and 2003 and their relatives without such a diagnosis was compared with that of controls. RESULTS: Individuals with bipolar disorder and healthy siblings of people with schizophrenia or bipolar disorder were overrepresented in creative professions. People with schizophrenia had no increased rate of overall creative professions compared with controls, but an increased rate in the subgroup of artistic occupations. Neither individuals with unipolar depression nor their siblings differed from controls regarding creative professions. CONCLUSIONS: A familial cosegregation of both schizophrenia and bipolar disorder with creativity is suggested.

Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents with Autism Spectrum Disorder: Design of Two Phase III Studies (SIGN Trials).

There are currently no approved pharmacological treatments to improve social reciprocity and limit repetitive and rigid behaviors in autism spectrum disorder (ASD). We describe the design of two Phase III studies evaluating the efficacy/safety of bumetanide oral liquid formulation in ASD. These are international, multicenter, randomized, double-blind, placebo-controlled studies in children and adolescents with ASD aged 7 to 17 years (n = 200; study 1), or younger children with ASD aged 2 to 6 years (n = 200; study 2). The primary endpoint of each is change in Childhood Autism Rating Scale 2 total raw score after 6 months. These studies could contribute to the first pharmacological treatment to improve social reciprocity and limit repetitive and rigid behaviors in children and adolescents with ASD.

Mental illness, suicide and creativity: 40-year prospective total population study.

We previously demonstrated that patients with schizophrenia or bipolar disorder and their relatives are overrepresented in creative occupations. Here, we use a new dataset with a considerably larger sample of patients (n = 1,173,763) to survey other psychiatric diagnoses and to validate previous findings. The specific aims of this study were to i) investigate if creativity is associated with all psychiatric disorders or restricted to those with psychotic features, and ii) to specifically investigate authors in relationship to psychopathology. We conducted a nested case-control study using longitudinal Swedish total population registries, where the occurrence of creative occupations in patients and their non-diagnosed relatives was compared to that of matched population controls. Diagnoses included were schizophrenia, schizoaffective disorder, bipolar disorder, unipolar depression, anxiety disorders, alcohol abuse, drug abuse, autism, ADHD, anorexia nervosa, and completed suicide. Creative professions were defined as scientific and artistic occupations. Data were analyzed using conditional logistic regression. Except for bipolar disorder, individuals with overall creative professions were not more likely to suffer from investigated psychiatric disorders than controls. However, being an author was specifically associated with increased likelihood of schizophrenia, bipolar disorder, unipolar depression, anxiety disorders, substance abuse, and suicide. In addition, we found an association between creative professions and first-degree relatives of patients with schizophrenia, bipolar disorder, anorexia nervosa, and for siblings of patients with autism. We discuss the findings in relationship to some of the major components of creativity.

Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings.

CONTEXT: It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants. OBJECTIVES: To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants. DESIGN: We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population. SETTING: Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register. PARTICIPANTS: In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden. MAIN OUTCOME MEASURES: Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status. RESULTS: Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals. CONCLUSIONS: Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.