Development and validation of a risk score model for predicting autism based on pre- and perinatal factors

BackgroundThe use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism.MethodsA stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort.ResultsFive factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism.ConclusionThis risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application

Genome-Wide DNA Methylation Analysis in Male Methamphetamine Users With Different Addiction Qualities

This paper aimed to explore the genome-wide DNA methylation status of methamphetamine (MA) abusers with different qualities to addiction and to identify differentially methylated candidate genes. A total of 207 male MA abusers with an MA abuse frequency of &gt;= 10 times and an MA abuse duration of &gt;= 1 year were assigned to the high MA addiction quality group (HMAQ group; 168 subjects who met the diagnostic criteria for MA dependence according to the DSM-IV) or to the low MA addictive quality group (LMAQ group; 39 subjects who did not meet the criteria for MA dependence). In addition 105 healthy controls were recruited. Eight HMAQ subjects, eight LMAQ subjects, and eight healthy controls underwent genome-wide DNA methylation scans with an Infinium Human Methylation 450 array (Illumina). The differentially methylated region (DMR) data were entered into pathway analysis, and the differentially methylated position (DMP) data were screened for candidate genes and verified by MethyLight qPCR with all samples. Seven specific pathways with an abnormal methylation status were identified, including the circadian entrainment, cholinergic synapse, glutamatergic synapse, retrograde endocannabinoid signaling, GABAergic synapse, morphine addiction and PI3K-Akt signaling pathways. SLC1A6, BHLHB9, LYNX1, CAV2, and PCSK9 showed differences in their methylation levels in the three groups. Only the number of methylated copies of CAV2 was significantly higher in the LMAQ group than in the HMAQ group. Our findings suggest that the circadian entrainment pathway and the caveolin-2 gene may play key roles in MA addiction quality. Further studies on their functions and mechanisms will help us to better understand the pathogenesis of MA addiction and to explore new targets for drug intervention.</p

Comparison of demographic characteristics and psychiatric comorbidity among methamphetamine-, heroin- and methamphetamine-heroin co- dependent males in Hunan, China

Abstract Background There is little research of psychiatric comorbidity differences among people with different types of drug dependence in Chinese population. We explored demographic and comorbid psychiatric differences among methamphetamine- dependent males (MDs), heroin-dependent males (HDs) and methamphetamine and heroin co-dependent males (M/HDs) in Hunan province, China. Methods A cross-sectional, structured and clinical interview method was used to examine differences in DSM-IV-TR Axis I Disorders among 346 MDs, 698 HDs and 247 M/HDs from three compulsory rehabilitation centers and two voluntary rehabilitation centers in Hunan. Results MDs and M/HDs were younger, more likely to choose inhalation administration, less likely to have a family history of substance use, less likely to have undergone detoxification treatment, had higher incomes and shorter duration of drug use than HDs. Overall, methamphetamine-dependence related to higher rates of current and lifetime psychotic disorders, lifetime hallucinogen use disorders. Heroin-dependence related to higher rates of current and lifetime substance-induced mood disorders, sedative/hypnotic/anxiolytic and other drug use disorders and current alcohol use disorder. For M/HDs, they were more likely to have any other lifetime substance use disorders than MDs and HDs. Conclusions There were substantial differences in epidemiological characteristics and comorbidity among MD, HD and M/HD groups, which highlights the urgent need to develop treatment services and policies for drug-specific users in China

Lower synaptic density associated with gaming disorder: an 18F-SynVesT-1 PET imaging study

Background Internet gaming disorder (IGD) is an ideal model to study the mechanisms underlying synaptic deficits in addiction as it eliminates the confounding effects of substance use. Synaptic loss and deficits are hypothesised to underlie the enduring maladaptive behaviours and impaired cognitive function that contribute to IGD.Aims This study aimed to determine whether subjects with IGD have lower synaptic density than control subjects and the relationship between synaptic density and IGD severity.Methods Eighteen unmedicated subjects diagnosed with current IGD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and 16 demographically matched healthy controls (HCs) participated in the study and underwent 18F-labelled difluoro-analogue of UCB-J (18F-SynVesT-1) positron emission tomography scans to assess the density of synaptic vesicle glycoprotein 2A (SV2A). The Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), Barratt Impulsiveness Scale Version 11 (BIS-11), Stroop Colour-Word Test (SCWT), stop-signal paradigms and N-back tasks were administered to all subjects.Results Patients with IGD had significantly higher scores on the IGDS9-SF, HAMD, HAMA and BIS-11 than HCs. HCs performed better on the two-back and SCWT tests as well as in terms of stop-signal reaction times (SSRTs) in the stop-signal paradigms than patients with IGD. Lower uptake was found in the bilateral putamen, right pregenual anterior cingulate cortex and Rolandic operculum of patients with IGD compared with HCs. Furthermore, in the IGD group, IGDS9-SF scores and daily gaming hours were negatively correlated with the standardised uptake value ratios of 18F-SynVesT-1 in the bilateral putamen. Longer SSRTs were significantly associated with lower SV2A density in the right pregenual anterior cingulate cortex and right Rolandic operculum.Conclusions The in vivo results in this study suggest that lower synaptic density contributes to the severity and impairments in inhibitory control of IGD. These findings may provide further incentive to evaluate interventions that restore synaptic transmission and plasticity to treat IGD

Duration of Untreated Psychosis in Chinese and Mauritian: Impact of Clinical Characteristics and Patients’ and Families’ Perspectives on Psychosis

<div><p>Background</p><p>Duration of untreated psychosis (DUP) is a potentially modifiable prognostic factor of course and prognosis of psychiatric disorders. Few studies have demonstrated that different cultural backgrounds or perspectives on psychosis may be important factors to the DUP. This study attempted to explore whether the DUP was different in Chinese and Mauritians and to clarify potential influencing factors to a long DUP (>3 months).</p><p>Methods</p><p>200 patients from China and 100 patients from Mauritius were enrolled in the study. Their respective family members were also recruited. Demographic and clinical characteristics were collected, and the Internalized Stigma of Mental Illness (ISMI) scale was adapted to measure the stigma in all subjects. Binary logistic regression analysis was used to find the potential influencing factors to the long DUP.</p><p>Results</p><p>35.3% of the enrolled patients had a long DUP. No significant difference was found in frequency of long DUP between the two countries. Chinese patients had relatively less perceptions of stigma. Furthermore, Chinese patients with a long DUP had more perception of breakup due to mental illness (OR = 2.22, p = 0.04) and more families’ perception of the patient being disinherited due to mental illness (OR = 6.47, p = 0.01). Mauritian patients with a long DUP were less likely to have high monthly income (OR = 0.12, p<0.01), while they had less patients’ awareness of mental illness (OR = 0.31, p<0.05) and less families’ awareness of mental illness (OR = 0.14, p<0.01).</p><p>Conclusion</p><p>The results of this study underlined the importance of DUP in economic conditions, racial and sociocultural factors, and public awareness on psychosis in developing countries.</p></div

Comparison of basic demographic and clinical characteristics, and stigma aspects between long and short DUP in Changsha and Mauritius.

<p>Comparison of basic demographic and clinical characteristics, and stigma aspects between long and short DUP in Changsha and Mauritius.</p

Factors independently associated with long and short DUP in Mauritius: binary logistic regression analysis^a.

<p>Factors independently associated with long and short DUP in Mauritius: binary logistic regression analysis<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157083#t006fn001" target="_blank">^a</a>.</p

Factors independently associated with long and short DUP in Changsha: binary logistic regression analysis^a.

<p>Factors independently associated with long and short DUP in Changsha: binary logistic regression analysis<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157083#t005fn001" target="_blank">^a</a>.</p