Predictors of psychotic symptoms among young people with special educational needs.

BACKGROUND: Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.AimsTo examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability. METHOD: Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54-1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3-9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6-50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97. CONCLUSIONS: Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.Declaration of interestNone.

Negative symptoms and longitudinal grey matter tissue loss in adolescents at risk of psychosis: preliminary findings from a 6-year follow-up study.

BACKGROUND: Negative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques. AIMS: To examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms. METHOD: A total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart. RESULTS: When comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus. CONCLUSIONS: Negative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.

Visual social attention in SYNGAP1-related intellectual disability.

SYNGAP1-ID is a neurodevelopmental disorder caused by a mutation of the SYNGAP1 gene. Characterized by moderate to severe developmental delay, it is associated with several physical and behavioral issues as well as additional diagnoses, including autism. However, it is not known whether social cognitive differences seen in SYNGAP1-ID are similar to those previously identified in idiopathic or other forms of autism. This study therefore investigated visual social attention in SYNGAP1-ID. Eye movements were recorded across three passive viewing tasks (face scanning, pop-out, and social preference) of differing social complexity in 24 individuals with SYNGAP1-ID and 12 typically developing controls. We found that SYNGAP1-ID participants looked at faces less than the controls, and when they did look at faces, they had less time looking at and fewer fixations to the eyes. For the pop-out task, where social and nonsocial objects (Phone, car, face, bird, and face-noise) were presented in an array, those with SYNGAP1-ID spent significantly less time looking at the phone stimulus as well as fewer fixations to the face compared with the typically developing controls. When looking at two naturalistic scenes side by side, one social in nature (e.g., with children present) and the other not, there were no differences between the SYNGAP1-ID group and typically developing controls on any of the examined eye tracking measures. This study provides novel findings on the social attention of those with SYNGAP1-ID and helps to provide further evidence for using eye tracking as an objective measure of the social phenotype in this population in future clinical trials.

The Behavioral Profile of SYNGAP1-Related Intellectual Disability.

This study aimed to describe the behavioral profile of individuals with SYNGAP1-ID. Parents/carers of 30 individuals aged 3-18 years old with a diagnosis of SYNGAP1-ID and 21 typically developing individuals completed the Vineland-3 Adaptive Behavior Scale and the Child Behavior Checklist. We found that those with SYNGAP1-ID showed fewer adaptive behaviors and higher levels of internalizing and externalizing behaviors across almost all domains compared to typically developing controls. There was some evidence that these differences were greatest in older children, and more apparent in those with co-occuring epilepsy. This characterization of the phenotype of SYNGAP1-ID significantly aids our understanding of the behavioral profile of this population and is a step towards the development of tailored interventions.

A genome wide survey supports the involvement of large copy number variants in schizophrenia with and without intellectual disability.

BACKGROUND: Copy number variants (CNVs) have been shown to play a role in schizophrenia and intellectual disability. METHODS: We compared the CNV burden in 66 patients with intellectual disability and no symptoms of psychosis (ID-only) with the burden in 64 patients with intellectual disability and schizophrenia (ID + SCZ). Samples were genotyped on three plates by the Broad Institute using the Affymetrix 6.0 array. RESULTS: For CNVs larger than 100 kb, there was no difference in the CNV burden of ID-only and ID + SCZ. In contrast, the number of duplications larger than 1 Mb was increased in ID + SCZ compared to ID-only. We detected seven large duplications and two large deletions at chromosome 15q11.2 (18.5-20.1 Mb) which were all present in patients with ID + SCZ. The involvement of this region in schizophrenia was confirmed in Scottish samples from the ISC study (N = 2,114; 1,130 cases and 984 controls). Finally, one of the patients with schizophrenia and low IQ carrying a duplication at 15q11.2, is a member of a previously described pedigree with multiple cases of mild intellectual disability, schizophrenia, hearing impairment, retinitis pigmentosa and cataracts. DNA samples were available for 11 members of this family and the duplication was present in all 10 affected individuals and was absent in an unaffected individual. CONCLUSIONS: Duplications at 15q11.2 (18.5-20.1 Mb) are highly prevalent in a severe group of patients characterized by intellectual disability and comorbid schizophrenia. It is also associated with a phenotype that includes schizophrenia, low IQ, hearing and visual impairments resembling the spectrum of symptoms described in "ciliopathies."

Profiling Autism and Attention Deficit Hyperactivity Disorder Traits in Children with SYNGAP1-Related Intellectual Disability.

SYNGAP1-related ID is a genetic condition characterised by global developmental delay and epilepsy. Individuals with SYNGAP1-related ID also commonly show differences in attention and social communication/interaction and frequently receive additional diagnoses of Autism Spectrum Disorder (ASD) or Attention Deficit Hyperactivity Disorder (ADHD). We thus set out to quantify ASD and ADHD symptoms in children with this syndrome. To assess ASD and ADHD, parents and caregivers of a child with SYNGAP1-related ID (N = 34) or a typically developing control (N = 21) completed the Social Responsiveness Scale-2, the Social Communication Questionnaire with a subset of these also completing the Conners-3. We found that those with SYNGAP1-related ID demonstrated higher levels of autistic traits on both the SRS and SCQ than typically developing controls. On the SRS, those with SYNGAP1-related ID scored highest for restricted repetitive behaviours, and were least impaired in social awareness. On the Conners-3, those with SYNGAP1-related ID also showed a high prevalence of ADHD traits, with scores demonstrating difficulties with peer relations but relatively low occurrence of symptoms for DSM-5 conduct disorder and DSM-5 oppositional defiant disorder. Hierarchical clustering analysis highlighted distinct SYNGAP1-related ID subgroups for both ASD and ADHD traits. These findings provide further characterisation of the SYNGAP1-related ID behavioural phenotype, guiding diagnosis, assessment and potential interventions.

Lived experiences of depression in autistic children and adolescents: A qualitative study on child and parent perspectives.

BACKGROUND: Depression is highly prevalent in autistic children and adolescents. Despite this, little is known about the nature of the autistic child's subjective experience of depression and the impact of depression on their lives. METHODS: We therefore conducted a qualitative study using thematic analysis with 7 autistic children and adolescents and their parents to identify common themes and individual differences. All children had previously experienced at least one depressive episode. RESULTS: Six main themes were identified: (1) Autism related experiences; (2) Difficulties with peer relationships; (3) Co-occurring relationships between anxiety and depression; (4) Impactful pessimism and anhedonia; (5) Impactful difficulties with focus and concentration and (6) Feelings of irritability, including aggressive behaviours. Parent's accounts of their children's experience of depression mirrored the child's perspective. Novel findings included reports of depression related restriction of diet variety and masking of mental health difficulties. Children and parents linked being autistic and developing depression, referring to the difficulties of being autistic in a complex, neurotypical world. CONCLUSIONS: These results highlight key challenges that autistic children and their families experience, calling for increased awareness of the impact of depression on autistic young people.

Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description.

BACKGROUND: SYNGAP1-related intellectual disability (ID) is a recently described neurodevelopmental disorder that is caused by pathogenic variation in the SYNGAP1 gene. To date, the behavioural characteristics of this disorder have mainly been highlighted via the prevalence of existing diagnoses in case series. We set out to detail the behavioural features of this disorder by undertaking interviews with those who have a child with SYNGAP1-related ID to allow them to describe their child's behaviour. METHODS: We conducted 27 semi-structured interviews with parents and caregivers which covered basic information (e.g., age, gender), family history, perinatal history, past medical history, developmental history, epilepsy, behavioural history, and a general description of their child's behaviour. RESULTS: Using a mixed quantitative and qualitative approach, the responses from the parents indicated that those with SYNGAP1-related ID showed high rates of autism spectrum disorder (52%), difficulties with fine and gross motor skills, delays in language development, and a high prevalence of epilepsy (70%). A qualitative analysis highlighted their general behaviour affected the themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences. Sensory features described involved auditory, visual, tactile, gustatory, and proprioceptive themes. CONCLUSIONS: Our findings and behavioural descriptions provide important insights as well as implications for the diagnosis and care of those with SYNGAP1-related ID.

A functional MRI facial emotion-processing study of autism in individuals with special educational needs.

This study aimed to investigate the functional imaging associations of autism in individuals with special educational needs and demonstrate the feasibility of such research. The study included 18 individuals (3 female,15 male; mean age 24.3; mean IQ 69.7) with special educational needs (SEN), of whom 9 met criteria for autism. The task examined the Blood-oxygen-level dependant response to fearful and neutral faces. Individuals in the autism group had 2 clusters of significantly reduced activity centred on the left superior frontal gyrus and left angular gyrus compared to those with SEN alone in response to the fearful faces. In the response to neutral faces, individuals in the autism group also had a cluster of significantly greater activity centred on the right precentral gyrus compared to those with SEN alone. We suggest that autistic characteristics in individuals with SEN are associated with changes in fearful facial emotion processing analogous to those previously reported in autistic individuals without SEN, and who are of average or above average cognitive ability. The finding of enhanced response to neutral facial stimuli needs further investigation, although we speculate this may relate to reports of the experience of 'hyper-mentalisation' in social situations as reported by some autistic individuals.

Autism in Fragile X Syndrome; A Functional MRI Study of Facial Emotion-Processing.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder, and among those with fragile X syndrome, approximately 1/3rd meet a threshold for an autism spectrum disorder (ASD) diagnosis. Previous functional imaging studies of fragile X syndrome have typically focused on those with fragile X syndrome compared to either neurotypical or autism spectrum disorder control groups. Further, the majority of previous studies have tended to focus on those who are more intellectually able than is typical for fragile X syndrome. In this study, we examine the impact of autistic traits in individuals with fragile X syndrome on a paradigm looking at facial emotion processing. The study included 17 individuals with fragile X syndrome, of whom 10 met criteria for autism as measured by the Autism Diagnostic Observation Schedule (ADOS). Prior to the scan, participants rehearsed on a mock scanner to help acclimatize to the scanner environment and thus allow more severely affected individuals to participate. The task examined the blood-oxygen-level-dependent (BOLD) response to fearful and neutral faces taken from the Ekman faces series. Individuals in the autism group had a region of significantly reduced activity centered on the left superior temporal gyrus, compared to those with FXS alone, in response to the fearful faces. We suggest that autism in individuals with fragile X syndrome is associated with similar changes in the neurobiology of facial emotion processing as seen in idiopathic autism.

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.

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.

Endocrine Dysfunction in Female FMR1 Premutation Carriers: Characteristics and Association with Ill Health.

Female FMR1 premutation carriers (PMC) have been suggested to be at greater risk of ill health, in particular endocrine dysfunction, compared to the general population. We set out to review the literature relating to endocrine dysfunction, including premature ovarian insufficiency (POI), in female PMCs, and then to consider whether endocrine dysfunction in itself may be predictive of other illnesses in female PMCs. A systematic review and pilot data from a semi-structured health questionnaire were used. Medline, Embase, and PsycInfo were searched for papers concerning PMCs and endocrine dysfunction. For the pilot study, self-reported diagnoses in females were compared between PMCs with endocrine dysfunction (n = 18), PMCs without endocrine dysfunction (n = 14), and individuals without the premutation (n = 15). Twenty-nine papers were identified in the review; the majority concerned POI and reduced fertility, which are consistently found to be more common in PMCs than controls. There was some evidence that thyroid dysfunction may occur more frequently in subgroups of PMCs and that those with endocrine difficulties have poorer health than those without. In the pilot study, PMCs with endocrine problems reported higher levels of fibromyalgia (p = 0.03), tremor (p = 0.03), headache (p = 0.01) and obsessive-compulsive disorder (p = 0.009) than either comparison group. Further larger scale research is warranted to determine whether female PMCs are at risk of endocrine disorders other than those associated with reproduction and whether endocrine dysfunction identifies a high-risk group for the presence of other health conditions.

Brief Report: The Association of Autistic Traits and Behavioural Patterns in Adolescents Receiving Special Educational Assistance.

INTRODUCTION: The study aim was to describe behaviours associated with autistic traits. METHODS: The Childhood Behaviour Checklist (CBCL) and Social Communication Questionnaire (SCQ) were used as measures of behaviour and autistic traits respectively in 331 adolescents receiving educational support. CBCL scores were compared between three groups defined by SCQ score: autism, pervasive developmental disorder (PDD) and non-PDD. RESULTS: The PDD and autism groups had significantly higher scores on the CBCL than the non-PDD group across all CBCL scales except Delinquent Behaviour. On seven of the eight scales, there was no difference between the autism and PDD groups. CONCLUSION: Those with PDD or autism display significantly higher levels of withdrawal, somatic complaints, anxiety/depression, social, thought and attention problems, and aggressive behaviour.

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.

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.

Can epigenetics help in the discovery of therapeutics for psychiatric disorders, especially schizophrenia?

Psychiatric disorders have a heterogeneous biological basis, where environmental factors interplay with non-mendelian genetics to produce complex cognitive/behavioural syndromes such as schizophrenia. Recent findings indicate a proportion of schizophrenia is associated with genomic copy number variation, suggesting that alteration of gene expression levels rather than direct mutation may play a role. Epigenetic mechanisms could be the crucial link between external stimuli and gene expression, influencing schizophrenia risk. These are dynamic reversible systems that offer much promise as targets for future therapies.

Acute military psychiatric casualties from the war in Iraq.

BACKGROUND: The view that most military personnel evacuated from war zones are suffering from combat stress reactions, or are otherwise traumatised by the horrors of war, has an impact on all aspects of military psychiatry. AIMS: To delineate the reasons for psychiatric aeromedical evacuation from Iraq from the start of build-up of UK forces in January 2003 until the end of October that year, 6 months after the end of formal hostilities. METHOD: A retrospective study was conducted of field and in-patient psychiatric assessments of 116 military personnel evacuated to the UK military psychiatric in-patient facility in Catterick Garrison. RESULTS: Evacuees were mainly non-combatants (69%). A significant proportion were in reserve service (21%) and had a history of contact with mental health services (37%). Only 3% had a combat stress reaction. In over 85% of cases evacuation was for low mood attributed to separation from friends or family, or difficulties adjusting to the environment. CONCLUSIONS: These findings have implications especially for screening for suitability for deployment, and for understanding any longer-term mental health problems arising in veterans from Iraq.