Implementation of the International Classification of Diseases 11th revision behavioural indicators for disorders of intellectual development with co-occurring autism spectrum disorder.

BACKGROUND: The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD-11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD-11 and the fidelity of its application in international clinical settings were also assessed. METHODS: A total of 116 children and adolescents (5-18 years old) with a suspected or established diagnosis of disorders of intellectual development were included across four sites [Italy (n = 18), Sri Lanka (n = 19) and two sites in India (n = 79)]. A principal component analysis was conducted to evaluate the application of the ICD-11 guidance for combining severity levels. RESULTS: Assessment using the BIs showed a higher proportion of individuals classified with mild severity, whereas the standardised measures indicated a higher proportion of severe ratings. Additionally, individuals with co-occurring ASD tended to have more severe impairments compared with those without ASD, as indicated by both BIs and standardised measures. Overall, the BIs were considered clinically useful, although more time and consideration were required when applying the guidelines for individuals with a co-occurring disorder of intellectual development and ASD. The principal component analysis revealed one principal component representing overall disorders of intellectual development severity levels. CONCLUSIONS: The ICD-11 BIs can be implemented as intended in international clinical settings for a broad range of presentations of individuals with neurodevelopmental disorders. Use of the BIs results in similar severity diagnoses to those made using standardised measures. The BIs are expected to improve the reliability of severity assessments in settings where appropriate standardised measures for intellectual and adaptive behaviours are not available or feasible.

Preliminary evaluation of serum zonulin in canine chronic enteropathies.

OBJECTIVES: In humans, serum zonulin, a biomarker of intestinal permeability, correlates with underlying enteropathies and has potential application as a therapeutic target. The aim of this study was to evaluate serum zonulin as a biomarker for canine chronic enteropathy. MATERIALS AND METHODS: Prospective enrolment of twenty-one client-owned dogs with at least 1 of the following gastrointestinal (GI) signs for at least 3 weeks duration: anorexia, hyporexia, dysrexia, vomiting, weight loss or diarrhea. 21 control dogs, age and breed matched, were also enrolled. Dogs with gastrointestinal signs were diagnosed with chronic enteropathy based on a complete blood count, serum chemistry, specific canine pancreatic lipase, cobalamin, resting cortisol, abdominal ultrasound and gastrointestinal endoscopy with histopathology. Enrolled control dogs had an unremarkable physical examination, complete blood count, serum chemistry and no clinical signs of gastrointestinal disease. Dogs were ineligible if antibiotics or immunosuppressive medications were administered within 1 month of enrolment. Blood samples were analysed using a commercial canine serum zonulin quantitative ELISA. RESULTS: Dogs with chronic enteropathies had median serum zonulin values of 0.28 ng/mL (interquartile range: 0.04-2.59), while control dogs of 0.27 ng/mL (0.05-3.67). There was no significant difference in canine serum zonulin levels between these populations. The estimated difference in the median concentrations was -0.01 ng/mL (95% CI: -0.23 to 0.89). CLINICAL SIGNIFICANCE: In this study, using a commercial canine zonulin ELISA, serum zonulin levels did not differentiate between dogs with chronic enteropathies and control dogs.

An international field study of the ICD-11 behavioural indicators for disorders of intellectual development.

BACKGROUND: The World Health Organization (WHO) has approved the 11th Revision of the International Classification of Diseases (ICD-11). A version of the ICD-11 for Mental, Behavioural and Neurodevelopmental Disorders for use in clinical settings, called the Clinical Descriptions and Diagnostic Requirements (CDDR), has also been developed. The CDDR includes behavioural indicators (BIs) for assessing the severity of disorders of intellectual development (DID) as part of the section on neurodevelopmental disorders. Reliable and valid diagnostic assessment measures are needed to improve identification and treatment of individuals with DID. Although appropriately normed, standardised intellectual and adaptive behaviour assessments are considered the optimal assessment approach in this area, they are unavailable in many parts of the world. This field study tested the BIs internationally to assess the inter-rater reliability, concurrent validity, and clinical utility of the BIs for the assessment of DID. METHODS: This international study recruited a total of 206 children and adolescents (5-18 years old) with a suspected or established diagnosis of DID from four sites across three countries [Sri-Lanka (n = 57), Italy (n = 60) and two sites in India (n = 89)]. Two clinicians assessed each participant using the BIs with one conducting the clinical interview and the other observing. Diagnostic formulations using the BIs and clinical utility ratings were collected and entered independently after each assessment. At a follow-up appointment, standardised measures (Leiter-3, Vineland Adaptive Behaviour Scales-II) were used to assess intellectual and adaptive abilities. RESULTS: The BIs had excellent inter-rater reliability (intra-class correlations ranging from 0.91 to 0.97) and good to excellent concurrent validity (intra-class correlations ranging from 0.66 to 0.82) across sites. Compared to standardised measures, the BIs had more diagnostic overlap between intellectual and adaptive functioning. The BIs were rated as quick and easy to use and applicable across severities; clear and understandable with adequate to too much level of detail and specificity to describe DID; and useful for treatment selection, prognosis assessments, communication with other health care professionals, and education efforts. CONCLUSION: The inclusion of newly developed BIs within the CDDR for ICD-11 Neurodevelopmental Disorders must be supported by information on their reliability, validity, and clinical utility prior to their widespread adoption for international use. BIs were found to have excellent inter-rater reliability, good to excellent concurrent validity, and good clinical utility. This supports use of the BIs within the ICD-11 CDDR to assist with the accurate identification of individuals with DID, particularly in settings where specialised services are unavailable.

Microbial and physicochemical assessment of irrigation water treatment methods.

AIMS: The presence of foodborne pathogens in preharvest agricultural water has been identified as a potential contamination source in outbreak investigations, driving markets and auditing bodies to begin requiring water treatment for high-risk produce. Therefore, it is essential that we identify water treatment methods which are effective as well as practical in their application on farm. METHODS AND RESULTS: In this work, we evaluated two sanitizers which are most prominent in preharvest agricultural water treatment (calcium hypochlorite (free chlorine: 3-5 ppm) and peracetic acid (PAA: 5 ppm)), an EPA registered antimicrobial device (ultraviolet light (UV)), in addition to a combination approach (chlorine + UV, PAA + UV). Treatments were evaluated for their ability to inactivate total coliforms and generic Escherichia coli and consistency in treatment efficacy over 1 h of operation. Physicochemical variables were measured along with microbial populations at 0, 5, 15, 30, 45 and 60 min of operation. Escherichia coli and coliform counts showed a significant (P < 0·05) reduction after treatment, with combination and singular treatments equally effective at inactivating E. coli and coliforms. A significant increase (P < 0·05) in oxidation-reduction potential was seen during water treatment (Chlorine; UV + Chlorine), and a significant reduction (P < 0·05) in pH was seen after PAA and PAA + UV treatments (60 min). CONCLUSION: Overall, the results indicate that all treatments evaluated are equally efficacious for inactivating E. coli and coliforms present in surface agricultural water. SIGNIFICANCE AND IMPACT OF THE STUDY: This information when paired with challenge studies targeting foodborne pathogens of interest can be used to support grower decisions when selecting and validating a preharvest agricultural water treatment programme.

Developing behavioural indicators for intellectual functioning and adaptive behaviour for ICD-11 disorders of intellectual development.

BACKGROUND: We present the work conducted to arrive at deriving behavioural indicators that could be used to guide clinical judgement in determining the presence and severity of deficits in intellectual functioning and adaptive behaviour for the purpose of making a diagnosis of disorders of intellectual development. METHODS: An interdisciplinary expert panel provided guidance in developing behavioural indicators for intellectual functioning. A national dataset of adaptive behaviour on a sample of individuals with a diagnosis of intellectual disability was used to develop the behavioural indicators for the adaptive behaviour. The adaptive behaviour data were analysed using a cluster analysis procedure to define the different severity groupings by chronological age groups. RESULTS: We present a series of tables containing behavioural indicators across the lifespan for intellectual functioning and adaptive behaviour, including conceptual, social and practical skills. These tables of behavioural indicators have been proposed for use in the clinical version of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) to be published by the World Health Organization. CONCLUSIONS: The proposed behavioural indicators for disorders of ID described in the present article and to be included in the ICD-11 Clinical Descriptions and Diagnostic Guidelines are put forth to assist professionals in making an informed clinical decision regarding an individual's level of intellectual functioning and adaptive behaviour for the purpose of making a determination about the presence and severity of disorders of ID.

Self Help Plus: study protocol for a cluster-randomised controlled trial of guided self-help with South Sudanese refugee women in Uganda.

BACKGROUND: Exposure to armed conflict and forced displacement constitute significant risks for mental health. Existing evidence-based psychological interventions have limitations for scaling-up in low-resource humanitarian settings. The WHO has developed a guided self-help intervention, Self Help Plus (SH+), which is brief, implemented by non-specialists, and designed to be delivered to people with and without specific mental disorders. This paper outlines the study protocol for an evaluation of the SH+ intervention in northern Uganda, with South Sudanese refugee women. METHODS: A two-arm, single-blind cluster-randomised controlled trial will be conducted in 14 villages in Rhino Camp refugee settlement, with at least 588 women experiencing psychological distress. Villages will be randomly assigned to receive either SH+ with enhanced usual care (EUC), or EUC alone. SH+ is a five-session guided self-help intervention delivered in workshops with audio-recorded materials and accompanying pictorial guide. The primary outcome is reduction in overall psychological distress over time, with 3 months post-treatment as the primary end-point. Secondary outcomes are self-defined psychosocial concerns, depression and post-traumatic stress disorder symptoms, hazardous alcohol use, feelings of anger, interethnic relations, psychological flexibility, functional impairment and subjective wellbeing. Psychological flexibility is a hypothesised mediator, and past trauma history and intervention attendance will be explored as potential moderators. DISCUSSION: This trial will provide important information on the effectiveness of a scalable, guided self-help intervention for improving psychological health and wellbeing among people affected by adversity. TRIAL REGISTRATION: ISRCTN50148022; registered 13/03/2017.

The classification of Obsessive-Compulsive and Related Disorders in the ICD-11.

BACKGROUND: To present the rationale for the new Obsessive-Compulsive and Related Disorders (OCRD) grouping in the Mental and Behavioural Disorders chapter of the Eleventh Revision of the World Health Organization's International Classification of Diseases and Related Health Problems (ICD-11), including the conceptualization and essential features of disorders in this grouping. METHODS: Review of the recommendations of the ICD-11 Working Group on the Classification for OCRD. These sought to maximize clinical utility, global applicability, and scientific validity. RESULTS: The rationale for the grouping is based on common clinical features of included disorders including repetitive unwanted thoughts and associated behaviours, and is supported by emerging evidence from imaging, neurochemical, and genetic studies. The proposed grouping includes obsessive-compulsive disorder, body dysmorphic disorder, hypochondriasis, olfactory reference disorder, and hoarding disorder. Body-focused repetitive behaviour disorders, including trichotillomania and excoriation disorder are also included. Tourette disorder, a neurological disorder in ICD-11, and personality disorder with anankastic features, a personality disorder in ICD-11, are recommended for cross-referencing. LIMITATIONS: Alternative nosological conceptualizations have been described in the literature and have some merit and empirical basis. Further work is needed to determine whether the proposed ICD-11 OCRD grouping and diagnostic guidelines are mostly likely to achieve the goals of maximizing clinical utility and global applicability. CONCLUSION: It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders.

A comparative study of the performance of individuals with fragile X syndrome and Fmr1 knockout mice on Hebb-Williams mazes.

Fragile X syndrome (FXS) is the most prevalent form of heritable mental retardation. It arises from a mutation in the FMR1 gene on the X chromosome that interferes with expression of fragile X mental retardation protein (FMRP) and leads to a wide range of behavioural and cognitive deficits. Previous studies have shown a deficit in basic visual perceptual processing as well as spatial abilities in FXS. How such a deficit may impact spatial navigation remains unknown. The current study extended previous research by evaluating spatial learning and memory using both virtual and physical versions of Hebb-Williams mazes, which allows for testing of humans and animals under comparable conditions. We compared the performance of individuals affected by FXS to typically developing individuals of equivalent mental age as well as the performance of Fmr1 knockout mice to wild-type control mice on the same maze problems. In human participants, performance of the comparison group improved across trials, showing expected significant decreases in both errors and latency. In contrast, the performance of the fragile X group remained at similar levels across trials. Although wild-type control mice made significantly fewer errors than the Fmr1 knockout mice, latencies were not statistically different between the groups. These findings suggest that affected humans and mice show similar spatial learning deficits attributable to the lack of FMRP. The implications of these data are discussed including the notion that Hebb-Williams mazes may represent a useful tool to examine the impact of pharmacological interventions on mitigating or reversing the symptoms associated with FXS.

A comparative neuropsychological test battery differentiates cognitive signatures of Fragile X and Down syndrome.

BACKGROUND: Standardised neuropsychological and cognitive measures present some limitations in their applicability and generalisability to individuals with intellectual disability (ID). Alternative approaches to defining the cognitive signatures of various forms of ID are needed to advance our understanding of the profiles of strengths and weaknesses as well as the affected brain areas. AIM: To evaluate the utility and feasibility of six non-verbal comparative neuropsychological (CN) tasks administered in a modified version of the Wisconsin General Test Apparatus (WGTA) to confirm and extend our knowledge of unique cognitive signatures of Fragile X syndrome (FXS) and Down syndrome (DS). METHOD: A test battery of CN tasks adapted from the animal literature was administered in a modified WGTA. Tasks were selected that have established or emerging brain-behaviour relationships in the domains of visual-perceptual, visual-spatial, working memory and inhibition. RESULTS: Despite the fact that these tasks revealed cognitive signatures for the two ID groups, only some hypotheses were supported. Results suggest that whereas individuals with DS were relatively impaired on visual-perceptual and visual-spatial reversal learning tasks they showed strengths in egocentric spatial learning and object discrimination tasks. Individuals with FXS were relatively impaired on object discrimination learning and reversal tasks, which was attributable to side preferences. In contrast, these same individuals exhibited strengths in egocentric spatial learning and reversal tasks as well as on an object recognition memory task. Both ID groups demonstrated relatively poor performance for a visual-spatial working memory task. CONCLUSION: Performance on the modified WGTA tasks differentiated cognitive signatures between two of the most common forms of ID. Results are discussed in the context of the literature on the cognitive and neurobiological features of FXS and DS.

Integrative cortical dysfunction and pervasive motion perception deficit in fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS) is associated with neurologic deficits recently attributed to the magnocellular pathway of the lateral geniculate nucleus. OBJECTIVE: To test the hypotheses that FXS individuals 1) have a pervasive visual motion perception impairment affecting neocortical circuits in the parietal lobe and 2) have deficits in integrative neocortical mechanisms necessary for perception of complex stimuli. METHODS: Psychophysical tests of visual motion and form perception defined by either first-order (luminance) or second-order (texture) attributes were used to probe early and later occipito-temporal and occipito-parietal functioning. RESULTS: When compared to developmental- and age-matched controls, FXS individuals displayed severe impairments in first- and second-order motion perception. This deficit was accompanied by near normal perception for first-order form stimuli but not second-order form stimuli. CONCLUSIONS: Impaired visual motion processing for first- and second-order stimuli suggests that both early- and later-level neurologic function of the parietal lobe are affected in Fragile X syndrome (FXS). Furthermore, this deficit likely stems from abnormal input from the magnocellular compartment of the lateral geniculate nucleus. Impaired visual form and motion processing for complex visual stimuli with normal processing for simple (i.e., first-order) form stimuli suggests that FXS individuals have normal early form processing accompanied by a generalized impairment in neurologic mechanisms necessary for integrating all early visual input.

Developmental profiles of SMI-32 immunoreactivity in monkey striate cortex.

A monoclonal antibody that recognizes a nonphosphorylated epitope on the medium and high molecular weight subunits of neurofilament (NF) proteins was used to investigate laminar and cell morphology changes in monkey striate cortex during post-natal development. Six cortices were obtained from monkeys of a variety of ages: five from developing animals with ages spanning the critical period and one adult. At post-natal day (PD) 0, immunohistochemistry with the SMI-32 antibody revealed immunoreactive (IR) cells in layer IVB and in infragranular layer VI. Early in the critical period (PD 7), these layers become more defined with an increase in the density of immunopositive cells. At the height of the critical period (PD 30 and 42), a drastic increase in the density of SMI-32 labelled pyramidal neurons in layers V and VI was observed. Similarly, layer IVC showed an abundance of dendritic fragments and dendrites that appeared to originate from the infragranular layers. At the end of the critical period (PD 103), a trend toward morphological maturation for individual neurons found within each layer was observed. During any developmental time point, neurons at first appearance tended to show an immature morphology with staining largely restricted to the cell bodies. As such, the characteristic arborizations common to mature pyramidal and multipolar cells was not evident. We propose that the staining pattern seen in this study is consistent with the idea that layers anatomically associated with the magnocellular (M) pathway develop earlier than their parvocellular (P) counterparts.

Psychiatric ethics and ethical psychiatry.

This paper critically examines the code of ethics that applies to practising psychiatrists. The code performs the functions for which it was designed admirably well. It does not, however, resolve moral dilemmas (i.e., complex situations in which any course of action compromises certain ethical principles). In these cases, the psychiatrist must turn to wider moral theory (i.e., psychiatric ethics) for guidance.

Effects of caffeine on behavior of schizophrenic inpatients.

The present study replicates that of De Freitas and Schwartz (1979), using more typical chronic patients (on open wards rather than locked wards), and monitoring coffee intake with serum caffeine levels. The serum caffeine levels observed indicate that caffeine can be effectively manipulated on an open ward by switching the type of coffee served. Contrary to our predictions, no significant improvements in patients' behavior occurred when decaffeinated coffee was first introduced, nor was there any deterioration when regular coffee was reinstated. Only after decaffeinated coffee was introduced for the second time did any of the predicted changes occur; however, the improvements were few in number and may be accounted for by the considerable effect of time per se across all time periods. Although the findings cannot be generalized to all psychiatric patients, the results do not support recent calls for a switch to decaffeinated coffee for this population of inpatients (i.e., chronic schizophrenic patients on high doses of neuroleptics who drink large amounts of coffee).

The relationship between neuroleptic dosage and cognitive functioning in chronic schizophrenic patients.

A review of the effects of phenothiazines on cognitive function suggests that phenothiazine derivatives facilitate performance on tests of cognitive function, at least in subjects who are thought disordered. Drug effects frequently depend on the dose administered, however, and the response to various doses of some drugs (e.g., antidepressants) is frequently nonlinear. In our study, 23 hospitalized males with chronic psychotic disorders, and stabilized on dosages of neuroleptics with chlorpromazine equivalents of from 50 to 7,200 milligrams daily, were tested in the morning and in the evening of the same day with the Mini-Mental State examination [1]. Cognitive functioning was positively correlated (+0.49) with dosage, but the relationship was curvilinear. Functioning improved with increasing dose up to a dose of about 2,000 milligrams daily; beyond that dosage (and up to 7,200 milligrams daily) functioning plateaued. Scores on same-day retest were essentially unchanged regardless of dose. The implication of these findings for the management of chronic psychotic patients is discussed.

Variables affecting the decision making of a review panel.

This study was designed to identify the variables that influence a review panel's decision to discharge or detain an involuntary patient. A group of fifty patients consecutively discharged by the review panel of a provincial mental hospital were compared according to thirty-five variables, with a group of forty-five patients consecutively detained by the panel. The variable set included information on the patient's psychiatric history, current hospitalization and treatment as well as ratings of dangerousness, insight and psychopathology, as reflected in the attending physician's case summary prepared for the review panel. The released and detained groups were found to be remarkably similar. They differed on ten of the thirty-five variables measured, but they did not differ on some variables that one would expect to form the basis of the panel's decision, including diagnosis and a history of suicide attempts. On the other hand, when the predictive value of the variable set as a whole was examined using discriminant analysis, the results indicated that there was a substantial amount of predictability to the review panel process. The group membership of 77.5% of the patients can be predicted from only nine variables that contribute to the discriminant function. The results will be of interest to clinicians who deal with review panels on a regular basis and the findings have implications for other practical issues including discharge planning and readiness for community living.