RESUMEN
BACKGROUND: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS), is a short self-report tool used to aid in the assessment of obsessive-compulsive symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used throughout child, adolescent and adult psychiatry settings in Sweden but has not been validated up to date. AIM: The aim of the current study was to examine the psychometric properties of the BOCS amongst a psychiatric outpatient population. METHOD: The BOCS consists of a 15-item Symptom Checklist including three items (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category "Obsessive-compulsive related disorders", accompanied by a single six-item Severity Scale for obsessions and compulsions combined. It encompasses the revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive free intervals, extent of avoidance and excluding the resistance item. 402 adult psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder, autism spectrum disorder and other psychiatric disorders completed the BOCS. RESULTS: Principal component factor analysis produced five subscales titled "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic groups in all subscales (P < 0.001). Sensitivities, specificities and internal consistency for both the Symptom Checklist and the Severity Scale emerged high (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's α = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's α = 0.94). CONCLUSIONS: The BOCS has the ability to discriminate OCD from other non-OCD related psychiatric disorders. The current study provides strong support for the utility of the BOCS in the assessment of obsessive-compulsive symptoms in clinical psychiatry.
Asunto(s)
Trastorno Obsesivo Compulsivo/diagnóstico , Escalas de Valoración Psiquiátrica/normas , Psicometría/instrumentación , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Suecia , Adulto JovenRESUMEN
Background: There are contradictory research findings regarding whether individuals with Autism Spectrum Disorders (ASDs) are more or less likely to commit crimes. The aims of the current study were to: (1) Describe psychiatric and crime-related characteristics of a large group of offenders with ASD who had undergone a Forensic Psychiatric Investigation (FPI). (2) Identify clinical subgroups among this group of offenders. (3) Investigate associations between the identified clinical subgroups and (a) psychiatric comorbidity (b) types of crimes and (c) criminal responsibility. Methods: The study cohort consists of all subjects (n = 831) who received an ASD-diagnosis at an FPI between 2002 and 2018 in Sweden. Descriptive and clinical, as well as crime related variables were obtained from the FPIs. Non-parametric (Pearson χ2, Fisher's exact and Mann-Whitney U-test) inferential statistics were used for analyses of between-group differences and effect sizes were reported. A Latent Class Analysis was used to identify homogeneous subgroups (or classes) from categorical characteristics. Results: The cohort consisted of 708 men and 123 women, aged 18 to 74 yrs. Two-thirds (66.7%) of the cohort had at least one other psychiatric diagnosis, the most prevalent was substance use disorder (SUD). A severe mental disorder, equivalent to lack of criminal responsibility, was most often reported among offenders with a comorbid diagnosis of schizophrenia spectrum disorder. The most common type of crime was violent crime. Three person-oriented clinical subgroups were identified; (1) ASD with few other diagnoses; (2) ASD and very high levels of SUDs, plus moderate levels of other externalizing disorders and psychotic psychopathology and (3) ASD and moderate to high levels of personality disorders (other than ASPD) and SUDs. Conclusion: Our results highlight the importance of all parts of the CJS to be prepared to handle offenders with ASD, often with high levels of additional psychiatric problems. Traditional approaches in treatment or other psychosocial interventions for ASD may need to be adapted to at least three general clinical profiles- one with mainly neurodevelopmental problems, one with a spectrum of externalizing problems and one with complex personality related difficulties.
RESUMEN
Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Variación Genética/genética , Melatonina/genética , Acetilserotonina O-Metiltransferasa/genética , N-Acetiltransferasa de Arilalquilamina/genética , Femenino , Humanos , Masculino , Proteínas del Tejido Nervioso/genética , Receptor de Melatonina MT1/genética , Receptores Acoplados a Proteínas G/genéticaRESUMEN
The prevention of aggressive behaviours is a core priority for psychiatric clinical work, but the association between the diagnostic concepts used in psychiatry and aggression remains largely unknown. Outpatients referred for psychiatric evaluations of childhood-onset neuropsychiatric disorders (n=178) and perpetrators of violent crimes referred to pre-trial forensic psychiatric investigations (n=92) had comprehensive, instrument-based, psychiatric assessments, including the Life History of Aggression (LHA) scales. Total and subscale LHA scores were compared to the categorical and dimensional diagnoses of childhood and adult DSM-IV axis I and II mental disorders, general intelligence (IQ), Global Assessment of Functioning (GAF), and personality traits according to the Temperament and Character Inventory (TCI). Overall, the two groups had similar LHA scores, but the offender group scored higher on the Antisocial subscale. Higher total LHA scores were independently associated with the hyperactivity facet of attention-deficit/hyperactivity disorder (AD/HD), childhood conduct disorder, substance-related disorders, and low scores on the Cooperativeness character dimension according to the TCI. IQ and GAF-scores were negatively correlated with the LHA subscale Self-directed aggression. Autistic traits were inversely correlated with aggression among outpatients, while the opposite pattern was noted in the forensic group. The findings call for assessments of aggression-related behaviours in all psychiatric settings.
Asunto(s)
Agresión/psicología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno de la Conducta/diagnóstico , Conducta Cooperativa , Trastornos Mentales/complicaciones , Trastornos Relacionados con Sustancias/diagnóstico , Adulto , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno de la Conducta/epidemiología , Trastorno de la Conducta/etiología , Femenino , Psiquiatría Forense , Humanos , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Estadísticas no Paramétricas , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicología , Adulto JovenRESUMEN
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.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Entrevistas como Asunto/normas , Encuestas y Cuestionarios , Trastornos de Tic/diagnóstico , Adolescente , Algoritmos , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno Autístico/diagnóstico , Trastorno Autístico/epidemiología , Niño , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Comorbilidad , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Estudios Epidemiológicos , Femenino , Humanos , Entrevistas como Asunto/métodos , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Padres/psicología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Psicometría , Curva ROC , Reproducibilidad de los Resultados , Suecia/epidemiología , Trastornos de Tic/epidemiologíaRESUMEN
Many international studies show that adolescents in coercive institutional care display high prevalences of mental disorders, especially in the form of disruptive behavior disorders [including attention-deficit/hyperactivity disorder (AD/HD), oppositional defiant disorder, and conduct disorder], anxiety disorders, and mood disorders. High degrees of overlap across mental disorders have also been reported. In addition, institutionalized adolescents are often traumatized. Despite this well-documented psychiatric morbidity, the mental health care needs of detained adolescents are often overlooked. The main objective of this study is to assess prevalences of psychiatric disorders, results of intelligence tests, and previous contacts with child and adolescent psychiatric services among adolescents in institutional care. DSM-IV diagnoses, mental health contacts, substance abuse, neurocognitive abilities, and school performance were registered in 100 adolescents (92 boys, 8 girls) aged 12-19 years (mean age 16.0; SD ± 1.5) consecutively committed to Swedish juvenile institutions between 2004 and 2007. At least one psychiatric disorder was diagnosed in 73% of the subjects: 48% met DSM-IV diagnostic criteria for AD/HD, 17% for an autism spectrum disorder, and 10% for a mental retardation. The collapsed prevalence for psychiatric disorders requiring specialist attention was 63%. Our data indicate that systematic diagnostic procedures are crucial in the treatment planning for institutionalized adolescents. Adequate treatment strategies need to be designed and implemented to meet the extensive mental health care needs of this vulnerable population.
Asunto(s)
Adolescente Institucionalizado , Necesidades y Demandas de Servicios de Salud , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Adolescente , Niño , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Salud Mental , Prevalencia , Encuestas y Cuestionarios , Suecia , Adulto JovenRESUMEN
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.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastornos de la Conducta Infantil/diagnóstico , Trastornos de la Conducta Infantil/epidemiología , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Entrevistas como Asunto , Determinación de la Personalidad/estadística & datos numéricos , Trastornos de Tic/diagnóstico , Trastornos de Tic/epidemiología , Factores de Edad , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Trastornos de la Conducta Infantil/genética , Trastornos de la Conducta Infantil/psicología , Trastornos Generalizados del Desarrollo Infantil/genética , Trastornos Generalizados del Desarrollo Infantil/psicología , Comorbilidad , Estudios Transversales , Enfermedades en Gemelos/diagnóstico , Enfermedades en Gemelos/epidemiología , Enfermedades en Gemelos/genética , Enfermedades en Gemelos/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Trastornos Mentales/genética , Trastornos Mentales/psicología , Proyectos Piloto , Psicometría/estadística & datos numéricos , Reproducibilidad de los Resultados , Factores Sexuales , Suecia , Trastornos de Tic/genética , Trastornos de Tic/psicologíaRESUMEN
To evaluate the psychometric characteristics of the Swedish version of the Junior Temperament and Character Inventory (J-TCI), it was sent to parents of 9- and 12-yr.-old twins in Sweden. The final number of responders was 196 parents who rated 92 female and 104 male twin pairs. The inventory of one twin, randomly chosen from each pair, was included in the analyses. Reward Dependence, Persistence, and Cooperativeness were scored higher in girls; Novelty Seeking was higher in the 9-yr.-olds and Persistence in the 12-yr.-olds. Pearson's correlations showed that some dimensions were not statistically independent from each other, even if the covariance was moderate. Internal consistency (Cronbach's alpha) was satisfactory for Harm Avoidance, Novelty Seeking, Self-Directedness, and Cooperativeness (.68-.81), while it was lower in those dimensions that had fewer items. The Swedish parent version of the J-TCI shared about the same psychometric characteristics as found in international samples.
Asunto(s)
Carácter , Inventario de Personalidad/estadística & datos numéricos , Temperamento , Análisis de Varianza , Niño , Femenino , Humanos , Masculino , Psicometría/estadística & datos numéricos , Sistema de Registros , Encuestas y Cuestionarios , Suecia , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Individuals with autism spectrum disorders (ASDs) often display symptoms from other diagnostic categories. Studies of clinical and psychosocial outcome in adult patients with ASDs without concomitant intellectual disability are few. The objective of this paper is to describe the clinical psychiatric presentation and important outcome measures of a large group of normal-intelligence adult patients with ASDs. METHODS: Autistic symptomatology according to the DSM-IV-criteria and the Gillberg & Gillberg research criteria, patterns of comorbid psychopathology and psychosocial outcome were assessed in 122 consecutively referred adults with normal intelligence ASDs. The subjects consisted of 5 patients with autistic disorder (AD), 67 with Asperger's disorder (AS) and 50 with pervasive developmental disorder not otherwise specified (PDD NOS). This study group consists of subjects pooled from two studies with highly similar protocols, all seen on an outpatient basis by one of three clinicians. RESULTS: Core autistic symptoms were highly prevalent in all ASD subgroups. Though AD subjects had the most pervasive problems, restrictions in non-verbal communication were common across all three subgroups and, contrary to current DSM criteria, so were verbal communication deficits. Lifetime psychiatric axis I comorbidity was very common, most notably mood and anxiety disorders, but also ADHD and psychotic disorders. The frequency of these diagnoses did not differ between the ASD subgroups or between males and females. Antisocial personality disorder and substance abuse were more common in the PDD NOS group. Of all subjects, few led an independent life and very few had ever had a long-term relationship. Female subjects more often reported having been bullied at school than male subjects. CONCLUSION: ASDs are clinical syndromes characterized by impaired social interaction and non-verbal communication in adulthood as well as in childhood. They also carry a high risk for co-existing mental health problems from a broad spectrum of disorders and for unfavourable psychosocial life circumstances. For the next revision of DSM, our findings especially stress the importance of careful examination of the exclusion criterion for adult patients with ASDs.
Asunto(s)
Trastorno Autístico/diagnóstico , Inteligencia/clasificación , Adolescente , Adulto , Factores de Edad , Atención Ambulatoria , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/epidemiología , Trastorno Autístico/epidemiología , Trastorno Autístico/psicología , Niño , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Relaciones Interpersonales , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/epidemiología , Comunicación no Verbal/psicología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , PsicometríaRESUMEN
To examine age at onset of substance abuse in relation to other factors of relevance to criminal behavior, we compared Life History of Aggression (LHA) scores, traits of psychopathy according to the Psychopathy Checklist--Revised (PCL-R), and violent recidivism in 100 violent offenders with early (before the age of 18) versus late onset of abuse or dependence. Of 56 subjects with a history of alcohol and/or drug abuse, an early onset was ascertained in 31. The duration of abuse did not correlate with the LHA and PCL-R scores or with violent recidivism, but the age at onset correlated strongly with all these factors and also remained their strongest correlate in multivariate models including childhood-onset attention deficit/hyperactivity disorder, conduct disorder, and drug abuse as covariates. Strong mathematical associations with aggression, psychopathy, and recidivism pointed to age at onset of substance abuse as a marker of possible complications that require preventive social, educational and medical measures.
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Agresión/psicología , Trastorno de Personalidad Antisocial/epidemiología , Crimen/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Edad de Inicio , Trastorno de Personalidad Antisocial/diagnóstico , Trastorno de Personalidad Antisocial/psicología , Femenino , Humanos , Delincuencia Juvenil/estadística & datos numéricos , Masculino , Curva ROC , Trastornos Relacionados con Sustancias/diagnósticoRESUMEN
This 3-year follow-up study compares background variables, extent of criminality and criminal recidivism in the form of all court convictions, the use of inpatient care, and number of early deaths in Swedish institutionalized adolescents (N=100) with comorbid substance use disorders (SUD) and Attention-Deficit/Hyperactivity Disorder (ADHD) (n=25) versus those with SUD but no ADHD (n=30), and those without SUD (n=45). In addition it aims to identify whether potential risk factors related to these groups are associated with persistence in violent criminality. Results showed almost no significant differences between the three diagnostic groups, but the SUD plus ADHD group displayed a somewhat more negative outcome with regard to criminality, and the non-SUD group stood out with very few drug related treatment episodes. However, the rate of criminal recidivism was strikingly high in all three groups, and the use of inpatient care as well as the number of untimely deaths recorded in the study population was dramatically increased compared to a age matched general population group. Finally, age at first conviction emerged as the only significant predictor of persistence in violent criminality with an AUC of .69 (CI (95%) .54-.84, p=.02). Regardless of whether SUD, with or without ADHD, is at hand or not, institutionalized adolescents describe a negative course with extensive criminality and frequent episodes of inpatient treatment, and thus requires a more effective treatment than present youth institutions seem to offer today. However, the few differences found between the three groups, do give some support that those with comorbid SUD and ADHD have the worst prognosis with regard to criminality, health, and untimely death, and as such are in need of even more extensive treatment interventions.
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Crimen/legislación & jurisprudencia , Crimen/estadística & datos numéricos , Servicios de Salud/legislación & jurisprudencia , Servicios de Salud/estadística & datos numéricos , Delincuencia Juvenil/legislación & jurisprudencia , Delincuencia Juvenil/estadística & datos numéricos , Tratamiento Domiciliario/legislación & jurisprudencia , Tratamiento Domiciliario/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Comorbilidad , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Delincuencia Juvenil/psicología , Masculino , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Recurrencia , Factores de Riesgo , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/psicología , Suecia , Violencia/legislación & jurisprudencia , Violencia/prevención & control , Violencia/psicología , Adulto JovenRESUMEN
OBJECTIVE: The authors describe personality development and disorders in relation to symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders. METHOD: Consecutive adults referred for neuropsychiatric investigation (N=240) were assessed for current and lifetime ADHD and autism spectrum disorders and completed the Temperament and Character Inventory. In a subgroup of subjects (N=174), presence of axis II personality disorders was also assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). RESULTS: Patients with ADHD reported high novelty seeking and high harm avoidance. Patients with autism spectrum disorders reported low novelty seeking, low reward dependence, and high harm avoidance. Character scores (self-directedness and cooperativeness) were extremely low among subjects with neuropsychiatric disorders, indicating a high overall prevalence of personality disorders, which was confirmed with the SCID-II. Cluster B personality disorders were more common in subjects with ADHD, while cluster A and C disorders were more common in those with autism spectrum disorders. The overlap between DSM-IV personality disorder categories was high, and they seem less clinically useful in this context. CONCLUSIONS: ADHD and autism spectrum disorders are associated with specific temperament configurations and an increased risk of personality disorders and deficits in character maturation.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno Autístico/diagnóstico , Carácter , Desarrollo de la Personalidad , Inventario de Personalidad/estadística & datos numéricos , Temperamento , Adulto , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno Autístico/epidemiología , Trastorno Autístico/psicología , Estudios de Cohortes , Comorbilidad , Conducta Cooperativa , Estudios Transversales , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Conducta Exploratoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/epidemiología , Trastornos de la Personalidad/psicología , Prevalencia , Escalas de Valoración Psiquiátrica , Estudios RetrospectivosRESUMEN
BACKGROUND: Autism spectrum disorders (ASD) are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2. The analysis of rare variations of 8 candidate genes among the 27 genes located in this region suggested SEZ6L2 as a compelling candidate. METHODOLOGY/PRINCIPAL FINDINGS: We further explored the role of SEZ6L2 variations by screening its coding part in a group of 452 individuals, including 170 patients with ASD and 282 individuals from different ethnic backgrounds of the Human Genome Diversity Panel (HGDP), complementing the previously reported screening. We detected 7 previously unidentified non-synonymous variations of SEZ6L2 in ASD patients. We also identified 6 non-synonymous variations present only in HGDP. When we merged our results with the previously published, no enrichment of non-synonymous variation in SEZ6L2 was observed in the ASD group compared with controls. CONCLUSIONS/SIGNIFICANCE: Our results provide an extensive ascertainment of the genetic variability of SEZ6L2 in human populations and do not support a major role for SEZ6L2 sequence variations in the susceptibility to ASD.
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Trastornos Generalizados del Desarrollo Infantil/genética , Cromosomas Humanos Par 16/genética , Estudios de Asociación Genética , Variación Genética , Proteínas de la Membrana/genética , Estudios de Casos y Controles , Niño , Femenino , Genética de Población , Genoma Humano/genética , Humanos , Masculino , LinajeRESUMEN
The purpose of the present study was to assess which types of neuropsychological deficits appear to be most commonly associated with autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) in adults. The effect of the combination of ASD with ADHD (ASD/ADHD) was also studied. One hundred and sixty-one adult individuals (≥18 years of age) were included in the study. None had full scale IQ less than 71. The neuropsychological investigations included measures of intellectual ability, learning and memory, attention/executive function and theory of mind. The three diagnostic groups showed reduced performance in most cognitive domains. However, within these domains differentiating distinct features could be seen. The dysfunctions of the ASD/ADHD group cannot be seen as a summary of the dysfunctions found in the ASD and ADHD groups. The ADHD seemed to have the most severe neuropsychological impairments of the three groups. No domain-specific deficit typical of any of the diagnostic groups was found.
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Síndrome de Asperger/psicología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno Autístico/psicología , Pruebas Neuropsicológicas , Adolescente , Adulto , Síndrome de Asperger/complicaciones , Síndrome de Asperger/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno Autístico/complicaciones , Trastorno Autístico/diagnóstico , Femenino , Humanos , Pruebas de Inteligencia , Masculino , Memoria a Largo Plazo , Memoria a Corto Plazo , Índice de Severidad de la Enfermedad , Teoría de la Mente , Aprendizaje Verbal , Adulto JovenRESUMEN
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.
Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/genética , Receptores de Melatonina/genética , Adulto , Animales , Células COS , Línea Celular , Niño , Chlorocebus aethiops , AMP Cíclico/metabolismo , Femenino , Humanos , Masculino , Microscopía Fluorescente , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Mutación/genética , Receptor de Melatonina MT1/genética , Receptor de Melatonina MT2/genéticaRESUMEN
OBJECTIVE: To assess prevalence figures for psychiatric disorders among institutionalized adolescents due to behavioural problems and/or delinquency. METHOD: Participants were recruited from consecutive referrals to/or treated at two Swedish adolescent units, SIS1 (n = 60) and SIS2 (n = 70) with ranging age of 12-20.3 years (mean age = 16.2; SD = 1.8) during 1 year. Clinical and diagnostic information was used to generate DSM-IV diagnoses. RESULTS: One or several neuropsychiatric disorders were diagnosed in 53% of all subjects: 39% met DSM-IV diagnostic criteria for attention deficit/hyperactivity disorder (AD/HD), 15% for a pervasive developmental disorder (referred to as autism spectrum disorders, ASDs) and 8% had a mental retardation (referred to as a learning disability, LD). The collapsed prevalence for psychiatric disorders requiring specialist attention was 66%, counting severe depression and psychotic disorders but not substance use. About one in three of all adolescents in the study were given psychopharmacological treatment. CONCLUSION: Published studies and this clinical survey clearly indicate that systematic studies of mental health needs among institutionalized adolescents are warranted to form the basis of adequate treatment and support measures.