Andrew McKechanie

Synaptic scaffold evolution generated components of vertebrate cognitive complexity

The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2s role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.

Bridging the translational divide: identical cognitive touchscreen testing in mice and humans carrying mutations in a disease-relevant homologous gene.

Development of effective therapies for brain disorders has been hampered by a lack of translational cognitive testing methods. We present the first example of using the identical touchscreen-based cognitive test to assess mice and humans carrying disease-related genetic mutations. This new paradigm has significant implications for improving how we measure and model cognitive dysfunction in human disorders in animals, thus bridging the gap towards effective translation to the clinic.

Learning Disability Liaison Nursing Services in south-east Scotland: a mixed-methods impact and outcome study.

BACKGROUND There have been significant concerns about the care and treatment of people with intellectual disabilities (ID) when attending general hospitals, which have led to inquiries that highlight service and systems failures. One response has been the development of Learning Disability Liaison Nursing (LDLN) Services across the UK that aim to ensure that additional, specialist support is available for patients, their carers and general healthcare professionals. METHODS A mixed-methods study to investigate the impact of LDLN Services across four Scottish NHS boards was undertaken. In total, 323 referrals made over 18 months were analysed along with qualitative data drawn from interviews and focus groups with a sample of 85 participants including patients with ID (n = 5), carers (n = 16), primary care healthcare professionals (n = 39) and general hospital professionals (n = 19) and learning disability liaison nurses (n = 6). RESULTS The referral patterns to the four liaison nursing services closely matched the known health needs of adults with ID, with common admissions being due to neurological, respiratory and gastrointestinal issues. The LDLN role was seen to be complex and impacted on three key areas: (i) clinical patient care; (ii) education and practice development; and (iii) strategic organisational developments. Specific patient outcomes were linked to issues relating to capacity and consent to treatment, fostering person-centred adjustments to care, augmenting communication and the liaison nurses acting as positive role models and ambassadors for people with ID. CONCLUSIONS The LDLN Services were valued by stakeholders by achieving person-centred outcomes. With their expert knowledge and skills, the liaison nurses had an important role in developing effective systems and processes within general hospital settings. The outcomes highlight the importance of supporting and promoting LDLN Services and the challenges in delivering the multifaceted elements of the role. There is a need to take account of the complex and multidimensional nature of the LDLN role and the possible tensions between achieving clinical outcomes, education and practice developments and organisational strategic initiatives.

Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS:SFHS)

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.

Equality and access to general health care for people with learning disabilities: reality or rhetoric?

This paper contributes to the growing debate relating to meeting the health needs of people with learning disabilities when accessing general health services. It is set within the context of a population that has historically experienced poor care and treatment. This is despite legislation to protect vulnerable groups and clear government policies setting out the need to support people with learning disabilities to lead full and equal lives, providing additional support when needed. The evidence surrounding the health needs of people with learning disabilities is presented, along with the resultant implications for health services. This is set alongside emerging evidence that seeks to address the shortfalls and failings that, in some cases, are known to have contributed to premature and often needless death. Particular focus is given to a study that has evaluated the impact of learning disability liaison nursing services that have been developed to support the care of people with a learning disability to access hospital services. This paper stresses the need to further develop and evolve the research evidence base on what works to improve the health of people with learning disabilities, enhance their experience of care and minimise the risk of harm.

A Genome Wide Survey Supports the Involvement of Large Copy Number Variants in Schizophrenia With and Without Intellectual Disability

Copy number variants (CNVs) have been shown to play a role in schizophrenia and intellectual disability.

Links between Autism Spectrum Disorder Diagnostic Status and Family Quality of Life

Quality of life is often relatively lowered in families of children with additional needs, and this may be particularly the case where additional needs are accompanied by an autism spectrum disorder (ASD). Here we explore the effects of diagnostic status specifically, comparing families with children with an ASD diagnosis with others who a) have additional needs but no signs of ASD; and b) have additional needs and signs of ASD but no diagnosis. Mothers (n = 76) of children with additional needs completed standardised questionnaires about quality of life, stress, service provision, child behaviour and presence and severity of ASD traits. In addition, a group of mothers of typically developing young people (n = 17) completed standardised questionnaires on individual and family quality of life and on the behaviour of their son or daughter. Mothers of typically developing young people had significantly higher individual and family quality of life scores than each of the three other groups. Increased severity of ASD was associated with increased maternal stress, which in turn was associated with decreased family and maternal quality of life. The group reporting the lowest quality of life and the highest stress were the mothers of individuals with signs of ASD but no diagnosis. This pattern did not seem to be explained by lack of access to services, or rates of intellectual disability or challenging behaviour in this sub-group. The finding that poor quality of life and high stress was most apparent in the sub-group of mothers with children who had signs of ASD but did not have a diagnosis of ASD suggests that an interesting topic for further investigation is whether receipt of a diagnosis itself can positively influence quality of life and levels of maternal stress.

“Staying Well”: a psychoeducational group for people with an intellectual disability, co-morbid mental illness and offending behaviour

Purpose – UK best practice guidelines for the treatment for people with schizophrenia recommend the use of psychoeducational approaches. The purpose of this paper is to describe the introduction of psychoeducational groups for people with an intellectual disability and co-morbid mental illness within forensic settings. Design/methodology/approach – “Staying Well”, a psychoeducational programme for people with an intellectual disability and co-morbid mental illness was based in part on a group programme from Ashworth Hospital, but adapted and developed to be suitable for people with intellectual disability. Input from a very experienced speech and language therapist was of great importance. Five groups with a total of 20 participants (15 different individuals) with mild to moderate intellectual disability and co-morbid mental illness were run over a two-year period. At the end of each group, an individualised “Staying Well Plan” was devised, to reduce the risk of future relapses. Findings – The group was v...

Longitudinal gray matter change in young people who are at enhanced risk of schizophrenia due to intellectual impairment.

BACKGROUND Existing studies of brain structural changes before the onset of schizophrenia have considered individuals with either familial risk factors or prodromal symptomatology. We aimed to determine whether findings from these studies are also applicable to those at enhanced risk of developing schizophrenia for another reason-intellectual impairment. METHODS Participants with intellectual impairment (mean IQ: 78.2) received magnetic resonance imaging of the brain at baseline (mean age: 16 years old) and again 6 years later. The Positive and Negative Syndrome Scale was used to assess psychotic symptoms. Participants were dichotomized using their Positive and Negative Syndrome Scale scores at follow-up and gray matter changes were compared between the groups using tensor based morphometry and semiautomated region of interest analysis. RESULTS Forty-six individuals had scans of sufficient quality to be included in the study. The tensor based morphometry analyses revealed that those with psychotic symptoms at follow-up showed significantly greater gray matter reductions over 6 years in the medial temporal lobes bilaterally. Region of interest analyses revealed that those individuals with psychotic symptoms at follow-up showed a reduced right hippocampal volume at age 16 and reduced bilateral hippocampal volumes at follow-up. CONCLUSIONS This unique study of individuals vulnerable to schizophrenia due to intellectual impairment highlights aberrant development in the medial temporal lobe associated with the occurrence of psychotic symptoms. These developmental changes are also evident in populations at enhanced risk of schizophrenia for familial and symptomatic reasons, suggesting they are central to the development of the disorder regardless of the nature of the vulnerability state.

Psychosis in the British Army: a 2-year follow-up study.

BACKGROUND Recent research into mental illness in military populations has tended to focus on minor mental illness and the consequences of trauma. The literature contains very little on serious mental illness, including its occupational implications. AIMS To identify the incidence and factors associated with nonaffective psychosis in British Army personnel, to evaluate service quality in terms of duration of untreated psychosis, and to identify predictors of occupational outcome after 2 years, to inform future management of similar cases. METHODS A retrospective study of the case notes of all Army personnel admitted to the U.K. military psychiatric inpatient facility in Catterick Garrison with a nonaffective psychosis over a 4-year period between 1999 and 2002 was performed. RESULTS There were 48 cases of nonaffective psychosis and 14 cases of schizophrenia, corresponding to mean annual incidences of 0.11 cases per 1,000 and 0.03 cases per 1,000, respectively. The mean duration of untreated psychosis was 11 months, and 29 cases (60%) were diagnosed and treated in < 4 months. Officer status and longer duration of service predicted retention. Only eight patients (16.7%) were still in service at 2 years. CONCLUSIONS These findings indicate (1) there is a low incidence of nonaffective psychosis, (2) the military performs well in early detection and intervention in psychosis, and (3) a well-established military career and the premorbid psychological stability this implies predict a good occupational outcome.