Genetic and phenotypic spectrum in the NONO-associated syndromic disorder.

The non-POU domain-containing octamer-binding (NONO) protein is involved in multiple steps of gene regulation such as RNA metabolism and DNA repair. Hemizygous pathogenic variants in the NONO gene were confirmed to cause a rare X-linked syndromic disorder. Through our in-house diagnostics and subsequent matchmaking, we identified six unrelated male individuals with pathogenic or likely pathogenic NONO variants. For a detailed comparison, we reviewed all published characterizations of the NONO-associated disorder. The combined cohort consists of 16 live-born males showing developmental delay, corpus callosum anomalies, non-compaction cardiomyopathy and relative macrocephaly as leading symptoms. Seven prenatal literature cases were characterized by cardiac malformations. In this study, we extend the phenotypic spectrum through two more cases with epilepsy as well as two more cases with hematologic anomalies. By RNA expression analysis and structural modeling of a new in-frame splice deletion, we reinforce loss-of-function as the pathomechanism for the NONO-associated syndromic disorder.

A fast and simple method to monitor carbonation of MSWI bottom ash under static and dynamic conditions.

Accelerated carbonation may be employed to improve the leaching behaviour and the geotechnical properties of MSWI bottom ash (BA). Here we report on a novel method to monitor and evaluate the progress of carbonation in both static and dynamic reactor systems. The method is based on following the pressure drop in the gas phase induced by the CO2-uptake of BA and was benchmarked against carbonate contents as measured by thermogravimetry. Laboratory results demonstrated the serviceability and reproducibility of the method. Complementary logging of relative humidity and temperature showed constant moisture conditions and self-heating induced by the exothermal carbonation reaction, respectively. Under dynamic conditions BA carbonation was higher than in the static reactor. Consistently, the self-heating was more pronounced. After a reaction time of 120 min the pressure records indicated a CO2-uptake of 1.5 g CO2/100 g BA (static tests) and of 2.6 g CO2/100 g BA (dynamic tests). The proposed method is suited to study carbonation processes at minimum analytical expense and integrates over the small-scale heterogeneity of BA.

Cannabis use and cannabis use disorders and their relationship to mental disorders: a 10-year prospective-longitudinal community study in adolescents.

BACKGROUND: Whereas the role of externalizing disorders is relatively well established in predicting the onset of cannabis use (CU) or cannabis use disorder (CUD), the status of anxiety and mood disorders in predicting CU and CUD remains controversial. OBJECTIVE: (1) To examine cross-sectional and prospective associations of CU and CUD with a range of mental disorders and whether anxiety and mood disorders are associated with CU/CUD after adjusting for externalizing disorders. METHODS: N=1395 community subjects aged 14-17 at baseline were followed-up at three waves prospectively over 10 years. Substance use, substance disorders and mental disorders were assessed using the DSM-IV/M-CIDI. RESULTS: (1) The baseline prevalence rates where 19.3% at t(0) for CU and 2.6% for CUD. Cumulative incidence rates at t(3) were 54.3% for CU and 13.7% for CUD. (2) In cross-sectional and prospective analyses other substance use disorders, mood and anxiety disorders were associated with CU and CUD. (3) Associations of panic-anxiety with CU and of depressive and bipolar disorders with CU and CUD were significant after controlling for externalizing disorders. CONCLUSION: A range of psychopathological conditions, including depressive, bipolar and less consistently anxiety disorders as well as the degree of their comorbidity are significantly associated with incident CU and progression to CUD, even when controlling for externalising disorders. A better understanding of this complex interplay may result in better aetiological models and intervention strategies.

DSM-IV pain disorder in the general population. An exploration of the structure and threshold of medically unexplained pain symptoms.

BACKGROUND: Despite an abundance of questionnaire data, the prevalence of clinically significant and medically unexplained pain syndromes in the general population has rarely been examined with a rigid personal-interview methodology. OBJECTIVE: To examine the prevalence of pain syndromes and DSM-IV pain disorder in the general population and the association with other mental disorders, as well as effects on disability and health-care utilization. METHODS: Analyses were based on a community sample of 4.181 participants 18-65 years old; diagnostic variables were assessed with a standardized diagnostic interview (M-CIDI). RESULTS: The 12-month prevalence for DSM-IV pain disorder in the general population was 8.1%; more than 53% showed concurrent anxiety and mood disorders. Subjects with pain disorder revealed significantly poorer quality of life, greater disability, and higher health-care utilization rates compared to cases with pain below the diagnostic threshold. The majority had more than one type of pain, with excessive headache being the most frequent type. CONCLUSIONS: Even when stringent diagnostic criteria are used, pain disorder ranks among the most prevalent conditions in the community. The joint effects of high prevalence in all age groups, substantial disability, and increased health services utilization result in a substantial total burden, exceeding that of depression and anxiety.

Substance use and substance use disorders in a community sample of adolescents and young adults: incidence, age effects and patterns of use.

OBJECTIVE: We present the prevalence and incidence rates of alcohol, nicotine, and illicit substance use, abuse, and dependence in a sample of German adolescents and young adults. Patterns of onset, cohort trends, and use of various substance classes are also analyzed. METHOD: A prospective longitudinal epidemiological study with a representative sample of adolescents and young adults (n = 3,021; baseline age range = 14-24 years) was conducted in Munich, Germany. Participants were assessed between 1995 and 1999 with the Munich-Composite International Diagnostic Interview. RESULTS: Cumulative lifetime incidence (up to age 28) of any substance abuse or dependence was 43.8%, and 12-month prevalence of any substance abuse or dependence was 24.4%. The lifetime incidence of nicotine dependence was most frequent (24.8%), followed by alcohol abuse (19.3%) and alcohol dependence (9.2%); 61.7% endorsed the regular use of a substance for at least one circumscribed period during their lifetime. Age-specific incidence rates and age at onset of substance use disorders differed by age cohorts. Furthermore, nicotine dependence was significantly associated with illicit substance use disorders (HR = 2.6, 95% CI 1.7-4.0). An interactive relationship between age, age at onset of nicotine dependence, and subsequent onset of illicit substance use disorders was found. CONCLUSIONS: Since the baseline investigation in 1995, high incidence rates of substance use disorders and substance use have been observed in this young German sample. Especially younger cohorts report significantly earlier ages at onset of abuse and dependence. There also seems to be a trend towards a secondary age at onset peak of nicotine dependence after the onset of illicit drug use disorders. Further investigations are needed to study these patterns in younger samples. However, results emphasize the need for a combined prevention of illicit drugs and nicotine dependence.

Where have they been? Service use of regular substance users with and without abuse and dependence.

OBJECTIVE: To present lifetime rates of service use for psychological and substance use related problems among regular substance users and to examine factors associated with service use. METHOD: Data come from a prospective-longitudinal, epidemiological study of a community sample of adolescents and young adults (n = 2548, age 14-24 years at baseline) in Munich, Germany. The Munich-Composite International Diagnostic Interview (M-CIDI) was used at baseline and at two follow-ups to assess substance use and service use. RESULTS: Cumulated lifetime incidence of any substance abuse or dependence was 43.7%. Of those with abuse and dependence 23% had ever used any services for psychological or substance use related problems. Illicit substance users especially those with dependence had the highest rates of lifetime service use (52.1%). Psychotherapists and counseling services were contacted most frequently among regular substance users over their lifetimes. Utlilisation rates of substance abuse services were low (2%). Comorbid anxiety disorders and distressing life events were associated with increased lifetime service use. CONCLUSIONS: Only a minority of adolescents and young adults with substance use disorders have ever sought professional help. Specialized substance abuse services play only a minor role. The core role of psychotherapists and non-substance abuse specialized services needs critical research attention. Linkages between psychotherapists and the substance use service system should be strengthened to detect and intervene at early developmental stages of abuse and dependence.