Science 11 July 2008:Vol. 321. no. 5886, pp. 208 - 209
GENETICS:Insights into the Pathogenesis of Autism
Genetic analysis of inbred families reveals genes associated with susceptibility to autism.

Science 11 July 2008:Vol. 321. no. 5886, pp. 218 - 223
Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry
To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.

Science 11 July 2008:Vol. 321. no. 5886, p. 200
Comment on "Genetically Determined Differences in Learning from Errors"
Klein et al. (Reports, 7 December 2007, p. 1642) used individuals with a polymorphism adjacent to the dopamine receptor 2 gene as naturally occurring models for reduced brain dopamine receptor density in a probabilistic learning task. We raise the concern that this polymorphism resides in the gene for the kinase ANKK1, where it causes a nonconservative amino acid exchange.

Science 11 July 2008: Vol. 321. no. 5886, p. 200
Response to Comment on "Genetically Determined Differences in Learning from Errors"
Since the publication of our findings, further genetic and pharmacological studies have bolstered our conclusion that dopamine D2 receptors are essential for performance monitoring and learning. Although the functionally complex dopamine D2 receptor gene polymorphism DRD2-TAQ-IA may also affect cellular signaling components, the accumulated evidence supports the notion that our findings were mediated by differential D2 receptor density.

Nature 454, 137-138 (10 July 2008)
An unnecessary battle
Neuroscientists and geneticists don't need to be at loggerheads over the biology of mental disorders.
Mental disorders take a staggering health and economic toll. The World Health Organization has estimated that unipolar depressive disorder alone is one of the leading causes of disability worldwide. Schizophrenia, bipolar disorder, autism and the many other psychiatric disorders only add to the misery. Yet progress in understanding the underlying causes of these conditions seems to be moving at a crawl. Genes are surely involved, but decades of futile hunting have made it painfully clear that the contribution of any single gene to disease is probably minuscule.

Nature 454, 154-157 (2008)
Psychiatric genetics: The brains of the family
Does the difficulty in finding the genes responsible for mental illness reflect the complexity of the genetics or the poor definitions of psychiatric disorders? Alison Abbott reports. Every family has its foibles, but this one has more than most. The first member came to researchers' attention in 1968 as part of a genetic survey of juvenile delinquents who had been admitted to Scottish detention centres.

Nature 454, 167-168 (10 July 2008)
Behind the looking-glass
To understand how mirror neurons help to interpret actions, we must delve into the networks in which these cells sit, say Antonio Damasio and Kaspar Meyer.
A remarkable discovery was made more than ten years ago: some neurons in the brains of macaques are active both when a monkey moves and when it sees a person move in a comparable way. The lead researchers, Giacomo Rizzolatti and Vittorio Gallese, called the cells involved 'mirror neurons'.

JAMA Vol. 300 No. 2, July 9, 2008      
Homocysteine Levels, Paraoxonase 1 (PON1) Activity, and Cardiovascular Risk
To the Editor: Dr Bhattacharyya and colleagues1 described a strong link between genetic determinants and activity of paraoxonase 1 (PON1), oxidative stress, all-cause mortality, and major adverse coronary events. The authors suggested that their findings support the hypothesis that fewer oxidized lipids in the low-density lipoprotein cholesterol particle would be of clinical benefit, an idea for which I am not aware of any trial support.

JAMA Vol. 300 No. 2, July 9, 2008    
Homocysteine Levels, Paraoxonase 1 (PON1) Activity, and Cardiovascular Risk—Reply
In Reply: Mr Vos contends that there is no evidence that PON1 possesses antioxidant activity. Rather, he proposes that the homocysteine-thiolactonase activity of PON1 confers the established cardioprotective properties. As stated in our study, we agree that the true physiological function of PON1 remains to be fully elucidated. However, our report of a relationship between a functional PON1 Q192R polymorphism and decreased systemic levels of oxidative stress provides compelling evidence that a genetic determinant of PON1 (either the polymorphism Q192R or another in linkage disequilibrium with it) is associated with systemic indices of oxidant stress. The linkage disequilibrium bin in which the Q192R polymorphism resides lies entirely within the PON1 gene. Thus, the strong association between this polymorphism and systemic measures of oxidative stress argue strongly that PON1 is somehow linked to oxidant stress in vivo.

JAMA. 2008;300(2):157-158.
Practice Parameter: Simple Maneuver Is Best Therapy for Common Form of Vertigo
The most common form of vertigo is best treated with the easiest and quickest method, according to a new practice parameter issued on May 26 by the American Academy of Neurology. Posterior canal benign paroxysmal positional vertigo (BPPV) accounts for up to 30% of all vestibular presentations to dizziness clinics and also has a lifetime prevalence of 2.4% in the general population.

JAMA. 2008;300(2):161-163.
Primary Amebic Meningoencephalitis —Arizona, Florida, and Texas, 2007
Primary amebic meningoencephalitis (PAM) is a rare but nearly always fatal disease caused by infection with Naegleria fowleri, a thermophilic, free-living ameba found in freshwater environments. Infection results from water containing N. fowleri entering the nose, followed by migration of the amebae to the brain via the olfactory nerve. In 2007, six cases of PAM in the United States were reported to CDC; all six patients died. This report summarizes the investigations of the cases, which occurred in three southern tier states (Arizona, Florida, and Texas) during June-September and presents preliminary results from a review of PAM cases during 1937-2007. Because deaths from PAM often prompt heightened concern about the disease among the public, an updated and consistent approach to N. fowleri risk reduction messages, diagnosis and treatment, case reporting, and environmental sampling is needed.

Published 9 July 2008, doi:10.1136/bmj.a602
Cite this as: BMJ 2008;337:a602 Antipsychotics for people with dementia
More than 25 million people worldwide have dementia, with a new case developing every seven seconds. While putative disease modifying agents are being developed, we are limited to symptomatic treatments for cognitive and non-cognitive features. Non-cognitive symptoms—referred to as behavioural and psychological symptoms of dementia—including agitation, psychosis, depression, and aggression, occur in up to half of those with dementia in the community and an even higher proportion in residential care. Antipsychotics have been widely prescribed off licence for these symptoms, and 20-50% of people with dementia in institutional care receive them. What is the evidence for their efficacy?

Published 3 July 2008, doi:10.1136/bmj.a135 Cite this as: BMJ 2008;337:a135
Imported malaria in the UK
Malaria is endemic in more than 105 countries. With travel predicted to grow to nearly 1.6 billion international arrivals by 2020, travellers will be at increased risk of exposure. The linked observational study by Smith and colleagues substantiates the public health concerns regarding the prevention of malaria in migrant families in the United Kingdom. The authors report that cases of imported malaria significantly increased between 1987 and 2006, with an increasing proportion attributable to Plasmodium falciparum rather than Plasmodium vivax.

Published 8 July 2008, doi:10.1136/bmj.a734Cite this as: BMJ 2008;337:a734
NICE recommendations have had little effect on multiple sclerosis services five years on
Nearly two thirds of patients with multiple sclerosis in England and Wales are unable to access neurological rehabilitation services, an audit shows.
The Royal College of Physicians of London and the MS Trust surveyed 1300 people with the condition, 127 acute NHS hospital trusts, 140 primary care trusts and local health boards, and seven strategic health authorities and regional offices during January and February 2008. Questions were based on guidelines for managing the illness from the National Institute for Health and Clinical Excellence (NICE).

Published 3 July 2008, doi:10.1136/bmj.a120 Cite this as: BMJ 2008;337:a120
Research
Imported malaria and high risk groups: observational study using UK surveillance data 1987-2006
Objective To examine temporal, geographic, and sociodemographic trends in case reporting and case fatality of malaria in the United Kingdom.
Setting National malaria reference laboratory surveillance data in the UK.
Design Observational study using prospectively gathered surveillance data and data on destinations from the international passenger survey.
Participants 39 300 cases of proved malaria in the UK between 1987 and 2006.
Main outcome measures Plasmodium species; sociodemographic details (including age, sex, and country of birth and residence); mortality; destination, duration, and purpose of international travel; and use of chemoprophylaxis.

Results Reported cases of imported malaria increased significantly over the 20 years of the study; an increasing proportion was attributable to Plasmodium falciparum (P falciparum/P vivax reporting ratio 1.3:1 in 1987-91 and 5.4:1 in 2002-6). P vivax reports declined from 3954 in 1987-91 to 1244 in 2002-6. Case fatality of reported P falciparum malaria did not change over this period (7.4 deaths per 1000 reported cases). Travellers visiting friends and relatives, usually in a country in Africa or Asia from which members of their family migrated, accounted for 13 215/20 488 (64.5%) of all malaria reported, and reports were geographically concentrated in areas where migrants from Africa and South Asia to the UK have settled. People travelling for this purpose were at significantly higher risk of malaria than other travellers and were less likely to report the use of any chemoprophylaxis (odds ratio of reported chemoprophylaxis use 0.23, 95% confidence interval 0.21 to 0.25).
Conclusions Despite the availability of highly effective preventive measures, the preventable burden from falciparum malaria has steadily increased in the UK while vivax malaria has decreased. Provision of targeted and appropriately delivered preventive messages and services for travellers from migrant families visiting friends and relatives should be a priority.

Published 8 July 2008, doi:10.1136/bmj.a741 Cite this as: BMJ 2008;337:a741
The need for speed: the fast and furious marketing of amphetamines
Amphetamines were for years a "drug looking for a disease." Allen Shaughnessy considers a chronicle of their many uses in that time
Ask most doctors about methamphetamine and they will describe its ability to ruin many lives, causing a societal blight. Ask most doctors about methylphenidate and they will describe its valuable role in treating children and adults who can’t focus.
On Speed tracks "the many lives" of the amphetamines, from the discovery of amfetamine in 1929 to current use today as black market drugs of misuse and white market treatments for obesity and attention deficit hyperactivity disorder. Amfetamine started as a potent drug without a role—until one was created. The author characterises it as a "drug looking for a disease." On Speed also traces the development of the market for amphetamines and the evolution of drug companies into the potent marketing machines they have become.

NEJM Volume 359:166-176  July 10, 2008  Number 2
Initial Management of Epilepsy
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.
A 29-year-old woman presents for evaluation. The previous evening, her husband, who was in the next room, heard unusual sounds and found her lying on the bed looking dazed. She was confused for a few minutes but quickly returned to normal.