Do premorbid weight parameters predict BMI 30 years after adolescent-onset anorexia nervosa?

PURPOSE: To examine anthropometric predictors of BMI 30 years after the onset of adolescent AN. METHODS: A group of 51 individuals with adolescent-onset AN were identified in Sweden in 1985. Anthropometric data have been collected from birth records and school nurse charts. A group matched for gender, school and age constituted a healthy control group. Possible predictors of BMI 30 years after AN onset including ponderal index (a variable that estimates body proportionality and composition during the infancy period) and highest BMI Z score (highest BMI in childhood, adjusted for age and sex) were analyzed with linear regression and multivariate analysis. RESULTS: None of the five possible predictors were significantly correlated to BMI outcome 30 years after AN onset. In the control group, BMI at the 18- and 30-year follow-ups were statistically significantly predicted by ponderal index at birth (18-year follow-up: r = 0.36, p = .015; 30-year follow-up: r = 0.32, p = .034). CONCLUSIONS: We found no statistically significant premorbid anthropometric predictors of BMI 30 years after the onset of AN. Ponderal index at birth appears to normally predict BMI outcomes in the general adult population. Having had AN during adolescence may have caused a disruption of the expected long-term BMI trajectory, resulting in a lower weight status than expected. These findings may be implemented in clinical practice to address patients' fear of exponential weight gain after recovery.

Mental and physical health in children of women with a history of anorexia nervosa.

Few studies have investigated the offspring of women with anorexia nervosa (AN). The aim of this study was to examine perinatal status, mental and physical health in the offspring of mothers with a history of AN. Fifty-one individuals with adolescent-onset AN and 51 matched controls (COMP) have been followed prospectively. Presently, 30 years after AN onset, at a mean age of 44 years, female participants who had given birth (nAN = 40, nCOMP = 40) were interviewed regarding psychiatric health in their offspring using the Developmental and Well-Being Assessment and the MINI International Neuropsychiatric Interview. In addition, information on the offspring's perinatal status, psychiatric- and physical health was obtained from the Swedish Medical Birth Register and The Swedish National Patient Register. Data regarding mental and physical health were available for 83 and 86 offspring in the AN and COMP groups, respectively. At birth, all of weight, length, head circumference and ponderal index were significantly reduced in the offspring of mothers with a history of AN. In adolescence, parental interviews indicated an overrepresentation of current psychiatric diagnoses in the offspring of mothers with AN. Compared with the offspring in the COMP group, endocrinological, immune and metabolic disorders were much more common in the offspring of the AN group. In conclusion, a history of AN increases the risk of worse perinatal outcome of the offspring. Later on, in childhood and adolescence, psychiatric and physical morbidity may be overrepresented in the offspring of women with AN.

Neurodevelopmental and other psychiatric disorders in 22q11.2 deletion syndrome from childhood to adult age: Prospective longitudinal study of 100 individuals.

The 22q11.2 deletion syndrome (22q11.2DS), affects physical as well as cognitive and emotional functioning with increased risk for psychiatric and behavioral problems. This longitudinal study of 79 individuals (18-50 years) with 22q11.2DS investigated neurodevelopmental (NDD) and psychiatric disorders in adulthood, evaluated the stability of childhood diagnoses over time, and examined associations between clinical characteristics in childhood/adolescence and diagnostic outcome in adult age. Examination using validated instruments for cognitive, psychiatric, and global functional problems in the context of an in-depth clinical evaluation found adult age stability of NDD diagnoses made in childhood, however, rates increased at follow-up. Rates of anxiety, mood, and psychotic disorders were high, with a majority meeting diagnostic criteria for one or more psychiatric disorder. The rate of psychotic disorders was much lower compared to many other studies. Variability in functioning at follow-up was primarily associated with intellectual ability at T1. The findings obtained highlight the increased risk of NDD and psychiatric problems and of cognitive impairment and reduced levels of global functioning over time. Results emphasize the importance of clinical follow-up to enable appropriate support for the promotion of optimal health along with a need for future research on effective interventions and treatment strategies.

A randomized controlled trial of a new intervention in early symptomatic syndromes eliciting neurodevelopmental clinical examinations: PR-ESSENCE.

The need for effective intervention programs for youth with neurodevelopmental problems (ESSENCE) and challenging behaviour is great. This study examines Problem Resolution in ESSENCE (PR-ESSENCE), a newly developed model in which children and parents develop mutual problem resolution strategies. Ten-week randomized controlled trial of PR-ESSENCE for children and adolescents aged 5-18 years, compared to treatment as usual. Outcomes were assessed at baseline and randomized period endpoint. Primary outcome was the Clinical Global Impression-Improvement scale (CGI-I) rated by blinded assessors. Secondary outcomes were rated by parents-SNAP-IV, Eyberg Child Behavior Inventory (ECBI), Relationship Problems Questionnaire, Family Burden of Illness Module, and children-Beck Youth Inventories (BYI). ClinicalTrials.gov identifier: NCT03780413. The study enrolled 108 participants (active n = 72; controls n = 36, randomized 2:1), of whom 95 completed the randomized period. No clinically significant group differences were found in baseline characteristics. More than half had autism and 80% had ADD or ADHD. Large treatment effects were seen on CGI-I (ITT analysis, Effect Size 1.48). Treatment responders, much/very much improved on CGI-I, were 51.4% in active group and 5.6% of controls. Effect sizes were medium to large in parent ratings on SNAP-IV (ODD and ADHD symptoms), ECBI (behaviour problems), and in BYI child self-ratings of disruptive behaviour. PR-ESSENCE treatment improved global symptoms and functioning (CGI-I), behaviour problems, ADHD and ODD symptoms, and disruptive behaviour. Treatment effects were at least equivalent to those in previous studies of well-established Parent Management Training and Collaborative Problem Solving programs.

Effects of autism on 30-year outcome of anorexia nervosa.

BACKGROUND: Long-term consequences of comorbid autism spectrum disorder (ASD) in individuals with anorexia nervosa (AN) are inadequately investigated. METHODS: In the 1980s, 51 adolescent-onset AN cases (AN group) and 51 matched controls (COMP group) were recruited from the community. They have been examined on five occasions. The four last assessments included the Morgan-Russell Outcome Assessment Schedule (MROAS) to assess eating disorder outcomes (weight, dieting, menstruation), and related problems including psychiatric, psychosexual and socioeconomic state. In the present study, at age 44, when 30 years had elapsed, MROAS data were compared with previous results. At age 16, 21, 24 and 32 years, all individuals had been assessed regarding ASD. At the 30-year follow-up, the impact of the ASD on the MROAS data was analysed. RESULTS: In the AN group, all core anorectic symptoms (weight, dieting, menstruation) were on a par with the COMP group at the 30-year follow-up, but the positive outcomes were limited to those who had never had an ASD diagnosis. Psychiatric state was significantly worse in the AN group, particularly in the subgroup who had an ASD diagnosis assigned. The AN group-again particularly those with ASD-had a more negative attitude to sexual matters than the COMP group. The AN group had worse outcomes than the COMP group for 'personal contacts', 'social contacts,' and 'employment record' at the 30-year follow-up and the outcomes were worse the more often an ASD diagnosis had been assigned. LIMITATIONS: Rare data collection points throughout 30 years (only 5 assessments). ASD was assessed in the first four studies but was not assessed again at the 30-year follow-up. CONCLUSIONS: Mental health, psychosexual, and socioeconomic status were compromised up to 30 years after AN onset. Coexisting ASD contributed to the poor outcome. Core anorectic symptoms had "normalised" three decades after AN onset. Some individuals with anorexia nervosa (AN) also suffer from autism. In this study we have investigated outcome of AN 30 years after the onset of AN and whether the presence of autism affects the outcome. Since the 1980s we have followed 51 individuals with teenage-onset AN and 51 healthy controls. They have been examined on five occasions, and an instrument that measures symptoms of AN (weight, dieting, body image), psychiatric symptoms, ability to work, and relationships with partner, family, and friends has been used to assess outcome. Autism was assessed in the first four studies. Symptoms of AN had normalised at 30-year follow-up, but only among those without autism. Psychiatric symptoms, ability to work, and relationships were issues that persisted after 30 years in the AN group, and those who had both autism and a history of AN had even more pronounced problems in these areas. The AN group had a more negative attitude to sexual matters than the control group, the outcome was worse the more often an autism diagnosis had been assigned. CONCLUSIONS: Mental health, psychosexual, and socioeconomic status are affected up to 30 years after AN onset, particularly among those with autism.

Thirty years after anorexia nervosa onset, serum neurofilament light chain protein concentration indicates neuronal injury.

Little is known about the long-term consequences of anorexia nervosa (AN) in terms of possible brain neuronal injury. We aimed at investigating whether women with adolescent-onset AN exhibit increased serum levels of neurofilament light chain protein (NfL), a biomarker for neuronal injury, compared with matched controls at 30-year follow-up. Blood samples were collected from 34 women with adolescent-onset AN and 38 matched healthy comparison women (COMP), at a mean age of 44 years (range 38-48 years). NfL was measured in serum using the in-house single molecule array (Simoa) method. The individuals were asked whether they or their parents had been diagnosed with dementia. The Swedish National Patient Register was searched for diagnoses related to dementia. Serum NfL concentrations were significantly higher in the AN group (AN 27.7 pg/ml; COMP 19.0 pg/ml; p = 0.041). When individuals with medical/neurological disorders in the AN and COMP groups were excluded, there was a statistically non-significant trend towards higher concentrations in the AN group (AN 27.4 pg/ml; COMP 18.8 pg/ml; p = 0.060). None of the participants had been diagnosed with dementia. There was no significant correlation between serum NfL and AN duration (r = 0.15). There was a moderate negative correlation between the serum NfL concentration and the current BMI in the AN group (r = 0.44). This is the first time that serum NfL has been assessed in middle-aged women with a history of adolescent-onset AN. The results suggest that there might be increased axonal degeneration as a sequel of AN. Individuals remaining underweight had higher serum NfL concentrations than those with a normal/high BMI. Additional studies are needed to confirm increased serum NfL concentrations in individuals recovered from AN. There is a need for further study of axonal degeneration as a consequence of AN.

Anorexia nervosa: 30-year outcome.

BACKGROUND: Little is known about the long-term outcome of anorexia nervosa. AIMS: To study the 30-year outcome of adolescent-onset anorexia nervosa. METHOD: All 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971-1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed. RESULTS: At the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism. CONCLUSIONS: This long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.

Social scene perception in autism spectrum disorder: An eye-tracking and pupillometric study.

Typically, developing humans innately place subjective value on social information and orient attention to it. This can be shown through tracking of gaze patterns and pupil size, the latter of which taps into an individual's cognitive engagement and affective arousal. People with Autism Spectrum Disorder (ASD) present with atypical social, communicative and behavioral patterns, but underlying substrates of these behavioral differences remain unclear. Moreover, due to high comorbidity with other neurodevelopmental disorders, it is often difficult to distinguish which differences are distinctive to ASD. In this study, a group of 35 adolescents and young adults with neurodevelopmental disorders were tested to investigate the processing of social and non-social scenes in individuals who meet the diagnostic criteria for autism and those who do not. Eye tracking and pupillometry measures were collected while participants observed images of tightly controlled natural scenes with or without a human being. Contrary to individuals without autism diagnosis, participants with autism did not show greater pupillary response to images with a human. Participants with autism were slower to fixate on social elements in the social scenes, and this latency metric correlated with clinical measures of poor social functioning. The results confirm the clinical relevance of eye-tracking and pupillometric indices in the field of ASD. We discuss the clinical implications of the results and propose that analysis of changes in visual attention and physiological level to social stimuli might be an integral part of a neurodevelopmental assessment.

Paediatric acute-onset neuropsychiatric syndrome in children and adolescents: an observational cohort study.

BACKGROUND: Paediatric acute-onset neuropsychiatric syndrome (PANS) is a newly defined symptom-based condition that mainly occurs in children and adolescents. Few studies have described the clinical characteristics of the syndrome. METHODS: We clinically assessed and reviewed the medical histories of children and adolescents (aged 4-14 years) with suspected PANS who were referred to a specialist clinic in Gothenburg, Sweden, by local paediatricians and child psychiatrists. We scored severity of symptoms and impairment retrospectively for the timepoint with the most severe symptoms using the PANS scale. FINDINGS: Of 41 patients (37 referred and four visited upon parents' request), 23 (ten girls and 13 boys) met PANS diagnostic criteria. Mean age at PANS onset was 8·5 years (SD 3·37). 11 (48%) patients had a family history of developmental or neuropsychiatric disorders in a first-degree relative and 11 (48%) had a family history of autoimmune or inflammatory diseases in a first-degree relative. 17 (74%) patients had been previously diagnosed with a developmental disorder (n=5) or had symptoms indicative of developmental problems (n=12). A verified or suspected infection was temporally related to PANS onset in all patients; the infection was bacterial in ten (43%) patients (eight had streptococcal infection and two an infection caused by other bacteria) and viral in 13 (57%) patients. All patients had a relapsing-remitting course of illness. The mean PANS scale symptom score was 46 (SD 3·67) and the mean impairment score was 45 (2·74). Antibiotic treatment was reported as beneficial by the parents of 12 (63%) of the 19 children who received antibiotics. INTERPRETATION: Our PANS cohort had severe, acute-onset, complex neuropsychiatric symptoms, a relapsing-remitting symptom course, and possible infectious triggers. Further research into the cause of, and appropriate treatment for, PANS is warranted. FUNDING: Swedish Brain Foundation.

The role of general anesthesia on traits of neurodevelopmental disorders in a Swedish cohort of twins.

BACKGROUND: The role of general anesthetics as a risk factor for possible neurodevelopmental disorders (NDDs) in humans is unresolved. The investigation of the role of anesthetics in the development of postgeneral anesthesia (anesthesia onward) NDDs has proven to be complicated, partly because of the inherent confounding in clinical cohort studies, and partly by the fact that anesthetics are only one part in the complex process of anesthesia-surgery. METHODS: Utilizing the Swedish databases Child and Adolescent Twins Study in Sweden (CATSS) and National Patient Register (NPR), we investigated twins discordant for anesthesia, born between 1997 and 2004 for traits of NDDs. We identified 68 twin pairs discordant for anesthesia and explored traits of Attention-Deficit/Hyperactivity Disorder (ADHD), Learning Disability (LD), and Autism Spectrum Disorder (ASD) in them while simultaneously taking congenital abnormalities and systemic disorders (CSDs) into account. We analyzed the possible effect of anesthesia on neurodevelopmental problems, and we analyzed the within-pair differences using conditional linear regression. RESULTS: Twins with a recorded episode of anesthesia had higher traits of NDDs than twins without; similarly twins with CSDs had higher mean scores on all traits than twins without CSDs. The within-pair analyses suggested that exposure to anesthesia was associated with higher scores of ADHD (regression coefficient 1.02 and 95% confidence intervals: 0.27-1.78) in monozygotic (MZ) twins discordant for anesthesia. This effect remained when adjusting for congenital abnormalities. DISCUSSION: Our finding that traits of ADHD were slightly associated with anesthesia in a genetically sensitive design is in need of replication and warrants further investigation. Future studies should aim to elucidate mechanisms behind this possible association (e.g. anesthetics doses, age at exposure, exposure duration).

Anxiety and depression in adolescents with ADHD and autism spectrum disorders; correlation between parent- and self-reports and with attention and adaptive functioning.

BACKGROUND: Adolescents with attention-deficit/hyperactive disorder (ADHD) or autism spectrum disorder (ASD) are at high risk of anxiety and depression. This is important to identify in the clinical assessment to understand its impact. AIMS: The aim of this study is to investigate the correlation between parent- and self-reports of anxiety and depression in adolescents with ADHD or ASD, as well as the correlation with adaptive functioning and performance on an attention test. METHOD: A total of 65 adolescents with an ADHD diagnosis (n = 24) or an ASD diagnosis (n = 41) filled out Beck Youth Inventories of Emotional and Social Impairment (BYI) to assess depression and anxiety and completed a Continuous Performance Test (QbTest) measuring ADHD symptoms. Parents of the participants completed the internalizing domain in the Five to Fifteen questionnaire (FTF), measuring symptoms of anxiety and depression, and the Vineland Adaptive Behavior Scales (VABS) about the adolescent's adaptive functioning. RESULTS: Approximately a third of the study group self-reported substantial internalizing mental symptoms not always recognized by parents, and not always obvious in adaptive function or performance at ADHD test. Correlations between BYI and FTF were low. The BYI depression inventory correlated negatively with VABS and positively with activity level in a subgroup medicated for ADHD. There was a stronger correlation between girls BYI and FTF results as compared with boys. CONCLUSIONS: The results highlight the need for identification of anxiety and depression, using both self- and parent report. Present anxiety and depression symptoms do not seem to affect the clinical assessment of ASD and ADHD.

Gender differences in autism spectrum disorders: Divergence among specific core symptoms.

Community-based studies have consistently shown a sex ratio heavily skewed towards males in autism spectrum disorders (ASD). The factors underlying this predominance of males are largely unknown, but the way girls score on standardized categorical diagnostic tools might account for the underrecognition of ASD in girls. Despite the existence of different norms for boys and girls with ASD on several major screening tests, the algorithm of the Autism Diagnosis Interview-Revised (ADI-R) has not been reformulated. The aim of our study was to investigate which ADI-R items discriminate between males and females, and to evaluate their weighting in the final diagnosis of autism. We then conducted discriminant analysis (DA) on a sample of 594 probands including 129 females with ASD, recruited by the Paris Autism Research International Sibpair (PARIS) Study. A replication analysis was run on an independent sample of 1716 probands including 338 females with ASD, recruited through the Autism Genetics Resource Exchange (AGRE) program. Entering the raw scores for all ADI-R items as independent variables, the DA correctly classified 78.9% of males and 72.9% of females (P < 0.001) in the PARIS cohort, and 72.2% of males and 68.3% of females (P < 0.0001) in the AGRE cohort. Among the items extracted by the stepwise DA, four belonged to the ADI-R algorithm used for the final diagnosis of ASD. In conclusion, several items of the ADI-R that are taken into account in the diagnosis of autism significantly differentiates between males and females. The potential gender bias thus induced may participate in the underestimation of the prevalence of ASD in females. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 680-689. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Aspects of Sexuality in Adolescents and Adults Diagnosed with Autism Spectrum Disorders in Childhood.

The literature concerning sexuality in autism spectrum disorders (ASDs) is limited regarding inappropriate sexual behaviours and paraphilias and its relation to age, verbal ability, symptom severity, intellectual ability, or adaptive functioning. A cohort of 184 adolescents and young adults (ages 15-39 years) with ASD diagnosed in childhood, including both low and high functioning individuals, was examined. The large majority were found to have a sexual interest and showed interest towards the opposite sex. Inappropriate sexual behaviours and paraphilias were reported for about a fourth of the individuals. No relationships were found between inappropriate sexual behaviours and any of the background variables listed above. However, associations were found between paraphilias and ASD symptom severity, intellectual ability, and adaptive functioning.

Effects of autism spectrum disorders on outcome in teenage-onset anorexia nervosa evaluated by the Morgan-Russell outcome assessment schedule: a controlled community-based study.

BACKGROUND: The purpose of the study was to evaluate time trends and effects of co-existing autism spectrum disorders (ASD) on outcome in an ongoing long-term follow-up study of anorexia nervosa (AN). METHODS: The Morgan-Russell Outcome Assessment Schedule (MROAS) was used at 6-, 10- and 18-year follow-up of a representative sample of 51 individuals with teenage-onset AN and a matched group of 51 healthy comparison cases. The full multinomial distribution of responses for the full scale and each of the subscales was evaluated using exact nonparametric statistical methods. The impact of diagnostic stability of ASD on outcome in AN was evaluated in a dose-response model. RESULTS: There were no deaths in either group. Food intake and menstrual pattern were initially poor in the AN group but normalised over time. MROAS 'mental state' was much poorer in the AN group and did not improve over time. The psychosexual MROAS domains 'attitudes' and 'aims' showed persistent problems in the AN group. In the MROAS socioeconomic domain, the subscales 'personal contacts', 'social activities' and 'employment record' all showed highly significant between-group differences at all three follow-ups. A statistically significant negative dose-response relationship was found between a stable diagnosis of ASD over time and the results on the subscales 'mental state', 'psychosexual state' and 'socio-economic state'. CONCLUSIONS: Outcome of teenage-onset AN is favourable with respect to mortality and persisting eating disorder, but serious problems remain in the domains 'mental state', 'psychosexual function' and 'socioeconomic state'. Outcome is considerably worse if ASD is present. Treatment programmes for AN need to be modified so as to accommodate co-existing ASD.

Asperger syndrome in males over two decades: stability and predictors of diagnosis.

OBJECTIVE: To examine the diagnostic stability of a childhood diagnosis of Asperger Syndrome (AS) into adulthood in a prospective longitudinal study, and identify the predictors of stability. METHODS: One hundred males with AS diagnosed in childhood (T0) according to Gillberg's AS criteria, were followed up prospectively into adulthood over an average of 19 years (range 13-26 years). Fifty males (mean age 30 years) participated in this second follow-up (T2) of the cohort. Seventy-six had participated in a previous follow-up (T1) at mean age 22 years (47 participated in both follow-ups). Diagnosis at T2 was assessed using three sets of diagnostic criteria (Gillberg's AS criteria, DSM-IV Pervasive Developmental Disorder (PDD) and DSM-5 Autism Spectrum Disorder (ASD) criteria) and compared to previous assessments. Background predictors of diagnostic stability were analyzed. General functioning at T2 was assessed and compared to T1. RESULTS: There was a decline in the stability of AS diagnosis over time, the rate dropping from 82% at T1 to 44% at T2, when using the Gillberg criteria. There was also a significant decrease in the rate of cases fulfilling any PDD diagnosis according to the DSM-IV, from 91% at T1 to 76% at T2 in the 47 cases followed up twice. Severity of autism spectrum symptoms at T1 was the main predictor of diagnostic stability at T2. Twenty percent of those meeting criteria for a PDD diagnosis according to DSM-IV, did not meet DSM-5 ASD criteria although they had marked difficulties in everyday life. CONCLUSION: Asperger Syndrome, when considered as an ASD/PDD diagnosis, was fairly stable into adulthood, but there was a significant increase over time in cases no longer meeting criteria for an ASD diagnosis according to the DSM-IV, or AS according to the Gillberg criteria. Cases with a stable diagnosis showed significantly more core ASD symptoms in adolescence/young adulthood.

Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.

The Autism--Tics, AD/HD and other Comorbidities (A-TAC) telephone interview: convergence with the Child Behavior Checklist (CBCL).

OBJECTIVE: To compare telephone interview screening for child psychiatric/neuropsychiatric disorders using the inventory of Autism-Tics, Attention deficit/hyperactivity disorder (AD/HD) and other Comorbidities (A-TAC) with results from the Child Behavior Checklist (CBCL). BACKGROUND: The A-TAC is a parent telephone interview focusing on autism spectrum disorders (ASDs) and co-existing problems, developed for lay interviewers. SUBJECTS AND METHODS: A-TAC telephone interviews and CBCL questionnaires were obtained from parents of 106 Swedish twin pairs aged 9 and 12 years. RESULTS: Correlations between A-TAC modules and CBCL scales aimed at measuring similar concepts were generally significant albeit modest, with correlation coefficients ranging from 0.30 through 0.55. CONCLUSION: The A-TAC has convergent validity with the CBCL in several problem areas, but the A-TAC also provides more detailed and specific assessments of ASD symptoms and related neuropsychiatric problems.

The autism--tics, AD/HD and other comorbidities inventory (A-TAC): further validation of a telephone interview for epidemiological research.

BACKGROUND: Reliable, valid, and easy-to-administer instruments to identify possible caseness and to provide proxies for clinical diagnoses are needed in epidemiological research on child and adolescent mental health.The aim of this study is to provide further validity data for a parent telephone interview focused on Autism--Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC), for which reliability and preliminary validation data have been previously reported. METHODS: Parents of 91 children clinically diagnosed at a specialized Child Neuropsychiatric Clinic, 366 control children and 319 children for whom clinical diagnoses had been previously assigned were interviewed by the A-TAC over the phone. Interviewers were blind to clinical information. Different scores from the A-TAC were compared to the diagnostic outcome. RESULTS: Areas under ROC curves for interview scores as predictors of clinical diagnoses were around 0.95 for most disorders, including autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (AD/HD), tic disorders, developmental coordination disorders (DCD) and learning disorders, indicating excellent screening properties. Screening cut-off scores with sensitivities above 0.90 (0.95 for ASD and AD/HD) were established for most conditions, as well as cut-off scores to identify proxies to clinical diagnoses with specificities above 0.90 (0.95 for ASD and AD/HD). CONCLUSIONS: The previously reported validity of the A-TAC was supported by this larger replication study using broader scales from the A-TAC-items and a larger number of diagnostic categories. Short versions of algorithms worked as well as larger. Different cut-off levels for screening versus identifying proxies for clinical diagnoses are warranted. Data on the validity for mood problems and oppositional defiant/conduct problems are still lacking. Although the A-TAC is principally intended for epidemiological research and general investigations, the instrument may be useful as a tool to collect information in clinical practice as well.