Scientists Create Genetically Accurate Mouse Model for Autism

Marlene Busko

May 28, 2008 (London, United Kingdom) — Mice containing a mutation in a gene encoding neuroligin-3, which is implicated in human autism, may represent the first genetically accurate model of autism that is not confounded by other neurological diseases, researchers report.

The study, by Craig M. Powell, MD, and colleagues, from the University of Texas Southwestern Medical Center, in Dallas, Texas, showed that mice with a neuroligin-3

R451C substitution exhibited impaired social interaction but also showed superior spacial learning skills.

Dr. Powell presented these findings in an oral presentation at the 7th Annual International Meeting for Autism Research. Part of this work was recently published (Tabuchi K et al. Science. 2007;318:71-76).

"We've created the first animal model that’s a genetically accurate model of autism that’s not associated with other neuropsychiatric syndromes like fragile X syndrome, Rett's syndrome, or tuberous sclerosis," Dr. Powell told Medscape Psychiatry.

Their data suggest that this mouse model may be useful to better understand the molecular mechanism of autism and ultimately to design and test new therapeutic approaches, he added.

What Is Happening in the Autistic Brain?

During the past several years, scientists have been attempting to develop an appropriate animal model for autism, the group writes.

A small percentage of patients with autism spectrum disorder (ASD) carry mutations in genes encoding neuroligin-3 and -4, which are postsynaptic cell-adhesion molecules, they note. In addition, mutations in neuroligin binding partners, neurexin-1 and shank-3, have also been found in patients with ASD.

The team aimed to create and characterize a genetically accurate mouse model of autism by introducing a mutation linked with autism — the R451C substitution in neuroligin-3 — into mice.

The researchers examined the performance of 19 "knock-in" mice with this mutation vs 19 wild-type littermate controls in a variety of behavioral tests relevant to autism. They also performed various tests to measure synaptic protein activity.

Compared with the control mice, the R451C-mutant knock-in mice showed impaired social interaction, but they had normal anxiety, coordination, and sensitivity to pain. Interestingly, the mice with the mutated gene performed better in the Morris water maze, which showed that they had enhanced spatial learning ability.

Unexpectedly, these behavioral changes in the mutant mice were accompanied by an increase in inhibitory synaptic transmission in the cortex.

Encouraging Early Results

"These are very encouraging preliminary data," said Dr. Powell.

"What we are trying to do now is target the changes in synaptic function in these mice — the increase in inhibitory synaptic function in the cortex," he said. "We're using drugs that might reduce the level of inhibition that's abnormally elevated in the knock-in mice," he added, noting that it is hoped that this will treat the behavioral symptoms in the mice.

By looking at more mouse models and gaining a better understanding of what is wrong with the brain in autism, researchers hope to find common pathways that would some day be potential drug targets for patients, he said.

7th Annual International Meeting for Autism Research: Oral Presentation 132.1. May 15-17, 2008

taken from medscape.com

Better Care Need For Lone Asylum Seeking Children

Lone asylum seeking children are more likely to have experienced high levels of war trauma, combat and torture than those who arrive in a country with adult carers, according to a new study looking at the mental health of asylum seeking children in the UK.

The authors of the research, which is published online this week in the Journal of Child Psychology and Psychiatry, are calling on governments to ensure that children who arrive in a country on their own are offered appropriate support.

The study reveals that lone asylum seeking children are at much greater risk of mental health problems, such as post traumatic stress symptoms, than their accompanied peers. Such children are sent away from their families, or flee their communities, because of persecution, organised violence or war.

There are an estimated 5,500 unaccompanied asylum seeking children in the UK. According to the new research, placing such children in foster care greatly helps their mental health. In the UK, unaccompanied asylum seekers aged between 16 and 18 are often placed in bed and breakfast accommodation, receiving a lower level of support than children who come into the care system at an earlier age. Foster care and high support living arrangements can prove costly for local authorities.

The study showed that unaccompanied asylum seekers living independently had higher levels of post traumatic symptoms, such as preoccupation with the war events, flashbacks and nightmares, than those living in foster care.

Overall, more than half of the male (61%) and nearly three quarters of the female unaccompanied asylum seekers (73%) were assessed as having a high risk of post traumatic stress disorder, far more than the accompanied male and female refugee children (14% and 35% respectively).

Those who were unaccompanied had much greater personal experience of war, including combat, torture and detention, than those who were accompanied. Many more of the lone asylum seeking children in the new study (45%) had been involved in combat, compared with the accompanied children (12%). Nearly half had experienced torture of some kind (38%), whereas very few had been subjected to torture in the accompanied group (3%). In the lone group nearly one in five reported that they had been imprisoned or in detention of some kind (18%), compared with only one in twenty in the accompanied group (6%).

Dr Matthew Hodes, lead author of the new study from the Division of Neurosciences and Mental Health at Imperial College London, said: "Ours is the first study from the UK to directly investigate the war trauma that unaccompanied asylum seeking children have experienced and see how this relates to their psychological state. It shows that there is a close relationship between the levels of distress that these children experience and their living arrangements.

"These children often arrive in the UK after experiencing terrible things in their home country, and we would like to see foster care or special children's homes offered to them in order to reduce their suffering. Living with a foster family reduces a child's sense of isolation, provides them with someone who can care for them, and helps them to integrate with other children and adults. All of these factors can help lower their post traumatic stress symptoms and other studies show that many of the children much prefer this kind of care," added Dr Hodes.

The study compared the experiences of 78 unaccompanied asylum seeking children aged 18 and under, predominantly from the Balkans and Horn of Africa, who were supported by the City of Westminster local authority in London, with 35 accompanied refugee children living with family members. The children were interviewed about their experiences prior to reaching the UK and their current living arrangements, and completed questionnaires designed to reveal the state of their mental health, including post traumatic and depression symptoms.

taken from medicalnewstoday

Female Sex Offenders Often Have Mental Problems

Women who commit sexual offences are just as likely to have mental problems or drug addictions as other violent female criminals. This according to the largest study ever conducted of women convicted of sexual offences in Sweden.

Between 1988 and 2000, 93 women and 8,500 men were convicted of sexual offences in Sweden. Given that previous research has focused on male perpetrators, knowledge of the factors specific to female sex offenders has been scant.

A group of researchers at the Swedish medical university Karolinska Institutet have now looked into incidences of mental illness and drug abuse in these 93 convicted women, and compared them with over 20,000 randomly selected women in the normal population and with the 13,000-plus women who were convicted of non-sexual crimes over the same period.

Thirty-seven per cent of the women convicted of sex offences had undergone treatment at a psychiatric clinic during the period, and eight per cent had been diagnosed as having a psychosis. There was no difference in incidences of mental illness and drug abuse between these women and women who had committed other kinds of violent crime.

"This is interesting as men who commit sexual offences usually have fewer psychiatric problems than men who commit other violent crimes," says Niklas Långström, Associate Professor at Karolinska Institutet's Centre for Violence Prevention and one of the authors of the study. "So it seems as if female sex offenders, more so than male, suffer from mental illness or have drug problems."

However, the figures differ widely from the control group. Incidences of psychosis were 16 times higher amongst the sex offenders than the control group, drug abuse 23 times higher. According to the research team, the results indicate that women suspected or convicted of sexual offences should undergo routine psychiatric examination, something which, at present, is not done.

By sexual offence in this study is meant rape, non-consensual sex, sexual abuse and sexual molestation. The group has earlier published a similar study on male sexual offenders.

Publication:

'Sexual Offending in Women and Psychiatric Disorder: A National Case-Control Study'
Seena Fazel, Gabrielle Sjöstedt, Martin Grann & Niklas Långström
Archives of Sexual Behavior, online Maj 2008, DOI 10.1007/s10508-008-9375-4.

Karolinska Institutet is one of the leading medical universities in Europe. Through research, education and information, Karolinska Institutet contributes to improving human health. Each year, the Nobel Assembly at Karolinska Institutet awards the Nobel Prize in Physiology or Medicine

taken from medicalnewstoday

'Quichua' Healers Of The Andes Diagnose Mental Illnesses

Yachactaitas (the Quichua healers of the Andes) may be identifying general psychiatric disorders in their communities, according to a study published in the May 2008 issue of the British Journal of Psychiatry.

Traditional healers' practices are widespread around the world, yet their diagnostic skills have rarely been investigated.

This exploratory study was carried out in Otavalo, in the province of Imbabura in the highlands of Ecuador. For over 18 months, 10 yachactaitas from three rural villages drew patients from the surrounding areas.

They identified 50 of these as having a condition known as llaqui. Each was referred to a Quichua-speaking physician trained in western transcultural psychiatry, and underwent the following investigations:

• A structured interview, using a Quichua questionnaire on the nature of llaqui


• A medical evaluation, including personal and medical history, and a physical examination


• Laboratory tests, including blood, faecal and urine analysis, and an X-ray


• Psychiatric evaluation and diagnosis, using established western diagnostic criteria


• An adapted Quichua version of a self-rating depression scale

94% of the people studied lived in the rural villages of the Otavalo area. Most were peasant farmers, artisans or homemakers. 56% were illiterate, and an additional 34% had not completed elementary school education. 54% were male, and 65% married.

The Quichuas themselves (and the yachactaitas in particular) identify llaqui as a cluster of four illness sub-categories comprising a symptom (sadness), the name of an illness, life events and a causal factor of illness.

The first two sub-categories are merged into one, which can be translated as 'victim of malignant spirits.' The person is under attack by natural spirits or spirits under human control that will damage the person's body or soul.

The third sub-category ('heart pain or shattered heart') results from life events and sorcery. Among the Quichuas, land disputes, family conflicts and the death of a relative are the most stressful life events. This condition also resembles the symptoms of typical anxiety or depression.

The fourth sub-category ('victim of sorcery') is believed to result from the aggression of malignant spirits under human control (usually a healer), or by a physical or visual contact with materials used in the treatment of sorcery. People can have symptoms from more than one illness sub-category at the same time.

The western clinical diagnoses of the 50 participants with llaqui showed that 82% had a depressive disorder; 44% medically unexplained symptoms (somatoform disorders); and 40% anxiety disorders. Over 80% of them also had infectious or parasitic diseases.

The researchers comment that it is surprising that the Quichua healers, using supernatural and life events notions, seem to identify people who are psychiatrically ill. Since participants were identified as ill by both the yachactaita and by the biomedically trained doctor, a remarkable overlap is apparent in the diagnostic work of both practitioners.

The findings of this study are in line with those of previous studies in different and remote parts of the world. The results highlight the contribution of yachactaitas in the provision of mental healthcare for Quichua people living in the Andes, for whom government-funded psychiatric services are non-existent, say the researchers.

The yachactaitas' diagnostic abilities could be useful in the screening of patients in psychiatric epidemiological and public health research.

"Efficacy of Quichua healers as psychiatric diagnosticians"
Incayawar M (2008)
British Journal of Psychiatry 192, 5, pages 390-391
Click here to view Abstract online

Taken from Medical News Today

Mental Illnesses Under-treated Compared With Physical Illnesses In High-, Low- And Middle-income Countries

Despite often higher disability, mental illnesses are under-treated compared with physical illnesses in high-, low- and middle-income countries, a World Health Organisation study has found.

The aims of this 15-country study, published in the May issue of the British Journal of Psychiatry, were to establish the degree and type of disability, and level of treatment, of specific mental and physical disorders.

The World Health Organisation's World Mental Health Surveys were carried out in six countries classified by the World Bank as low- and middle-income (Colombia, Lebanon, People's Republic of China, South Africa, Ukraine) and nine as high-income (Belgium, France, The Netherlands, Germany, Italy, Spain, Japan, the USA and New Zealand).

The total sample size was 73,441, with individual country samples ranging from 2372 (The Netherlands) to 12,992 (New Zealand). The average response rate was 70.3%, with country-specific rates varying from 45.9% (France) to 87.7% (Colombia).

The commonly occurring physical disorders included in the surveys included asthma, cancer, heart disease, hypertension, diabetes, arthritis, back and neck pain, chronic headaches, other chronic pain disorders and stomach ulcers.

The mental disorders studied included anxiety disorders, such as panic disorder, social phobia and post-traumatic stress disorder; mood disorders, such as depression and bipolar disorder; and impulse-control disorders, such as adult attention deficit hyperactivity disorder and intermittent explosive disorder.

The researchers measured treatment sought and received for both types of disorder, and assessed the level and type of disability attributed to them by respondents. The four disability areas explored were home management, ability to work, social life and close personal relationships.

Four key findings emerged from the analyses:

1. Respondents generally attributed more disability to their mental than to their physical disorder



2. The higher disability of mental compared with physical disorders held as strongly in low- and middle-income countries as in high-income countries



3. The higher level of disability associated with mental disorder compared with physical disorder was much more pronounced for disability in social and personal relationships than in productive roles, such as work and housework



4. The proportion of people receiving treatment at the time of interview was much lower for mental than for physical disorders in high-income countries, and even more so in low- and middle-income countries. This finding applied both to the total sample and also to participants rated as having a severely disabling disorder.

These results are consistent with previous comparative burden-of-illness studies in suggesting that musculoskeletal disorders and major depression are the most disabling disorders across the socioeconomic spectrum. Previous studies have documented this pattern only for the USA, although World Mental Health Surveys have also highlighted the importance of depression.

The researchers comment that these new results imply that mental disorders are disabling more because they create psychological barriers rather than physical barriers to functioning. Among these barriers are limitations in cognitive and motivational capacity, regulation of feelings, embarrassment and stigma.

Disability in productive role functioning, such as work and home management, was generally comparable for mental and physical disorders.

Given this greater disability of mental than physical disorders, it is disturbing to find that only a minority of people with severe mental disorders receive treatment, and that treatment is substantially more common for severe physical disorders, the researchers say.

Combined with the burden of disability that mental disorders produce, the low treatment rates call for more attention to be paid to mental disorders, they believe. Treatment effectiveness trials show that common anxiety and mood disorders can often be successfully treated, although long-term outcomes are more uncertain and further research is needed.

Despite this uncertainty, the findings of this study strongly imply that more attention should be given to the treatment of mental disorders, particularly in middle- and low- income countries.

"Disability and treatment of specific mental and physical disorders across the world."
Kessler R. C. et al (2008)
British Journal of Psychiatry 192, 5, pages 368-375
Click here to view Abstract online

Taken from Medical News Today