Mizanur Khondoker

Cognitive-behavioral therapy for psychogenic nonepileptic seizures A pilot RCT

Objective: To compare cognitive-behavioral therapy (CBT) and standard medical care (SMC) as treatments for psychogenic nonepileptic seizures (PNES). Methods: Our randomized controlled trial (RCT) compared CBT with SMC in an outpatient neuropsychiatric setting. Sixty-six PNES patients were randomized to either CBT (plus SMC) or SMC alone, scheduled to occur over 4 months. PNES diagnosis was established by video-EEG telemetry for most patients. Exclusion criteria included comorbid history of epilepsy, <2 PNES/month, and IQ <70. The primary outcome was seizure frequency at end of treatment and at 6-month follow-up. Secondary outcomes included 3 months of seizure freedom at 6-month follow-up, measures of psychosocial functioning, health service use, and employment. Results: In an intention-to-treat analysis, seizure reduction following CBT was superior at treatment end (group × time interaction p < 0.0001; large to medium effect sizes). At follow-up, the CBT group tended to be more likely to have experienced 3 months of seizure freedom (odds ratio 3.125, p = 0.086). Both groups improved in some health service use measures and on the Work and Social Adjustment Scale. Mood and employment status showed no change. Conclusions: Our findings suggest that cognitive-behavioral therapy is more effective than standard medical care alone in reducing seizure frequency in PNES patients. Classification of evidence: This study provides Class III evidence that CBT in addition to SMC, as compared to SMC alone, significantly reduces seizure frequency in patients with PNES (change in median monthly seizure frequency: baseline to 6 months follow-up, CBT group, 12 to 1.5; SMC alone group, 8 to 5).

Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.

UNLABELLED Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. METHODS We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. RESULTS Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16-1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. CONCLUSIONS Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.

Can Psychological Interventions Reduce Perfectionism? A Systematic Review and Meta-analysis

BACKGROUND Perfectionism is implicated in a range of psychiatric disorders, impedes treatment and is associated with poorer treatment outcomes. AIMS The aim of this systematic review and meta-analysis was to summarize the existing evidence for psychological interventions targeting perfectionism in individuals with psychiatric disorders associated with perfectionism and/or elevated perfectionism. METHOD Eight studies were identified and were analysed in meta-analyses. Meta-analyses were carried out for the Personal Standards and Concern over Mistakes subscales of the Frost Multi-Dimensional Perfectionism Scale (FMPS) and the Self Orientated Perfectionism and Socially Prescribed Perfectionism subscales of the Hewitt and Flett MPS (HMPS) in order to investigate change between pre and postintervention. RESULTS Large pooled effect sizes were found for the Personal Standards and Concern over Mistakes subscales of the FMPS and the Self Orientated Perfectionism subscale of the HMPS, whilst a medium sized effect was found for change in Socially Prescribed Perfectionism. Medium pooled effect sizes were also found for symptoms of anxiety and depression. CONCLUSIONS There is some support that it is possible to significantly reduce perfectionism in individuals with clinical disorders associated with perfectionism and/or clinical levels of perfectionism. There is also some evidence that such interventions are associated with decreases in anxiety, depression, eating disorder and obsessive compulsive symptoms. Further research is needed in order to investigate the optimal dosage and format of such interventions as well as into specific disorders where there is a lack of evidence for their effectiveness.

Identification of a human neonatal immune-metabolic network associated with bacterial infection

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

Differences in HPA-axis and heart rate responsiveness to psychosocial stress in children with autism spectrum disorders with and without co-morbid anxiety

Children and adolescents with autism spectrum disorder (ASD) have much higher rates of anxiety disorders relative to their typically developing peers. However, there have been few attempts to investigate what physiological parameters may be associated with this elevated rate of anxiety. Therefore, this study investigated the physiological correlates of anxiety in ASD, with a focus on whether measures of heart rate and cortisol responsiveness to psychosocial stress differentiate those participants with ASD with and without a co-occurring anxiety disorder. A total of 75 male participants aged 10-16 years with normal intellectual ability underwent a psychosocial stress test. The participants included healthy controls (n=23), ASD only (ASD; n=20) and ASD with a comorbid anxiety disorder (ASDanx; n=32). Heart rate, heart rate variability and salivary cortisol were compared by fitting a piecewise regression model to examine baseline levels and change over time within and between the rest, stress and recovery phases of the stress test. The ASDanx group had different response patterns from both the ASD and control groups. The ASDanx group was characterized by a blunted cortisol and heart rate response to psychosocial stress. Furthermore, in the ASDanx group, reduced heart rate and cortisol responsiveness were significantly related to increased anxiety symptoms. This is the first study to report a possible physiological basis for co-occurring anxiety disorders in children and adolescents with ASD. It is possible that a non-adaptive physiological response to psychosocial stress may be related to the high prevalence of co-occurring anxiety disorders in people with ASD.

Characteristics of trafficked adults and children with severe mental illness: a historical cohort study

BACKGROUND Evidence regarding the mental health needs of trafficked people is limited; however, prevalence of depression and post-traumatic stress disorder is high among trafficked people who are in contact with shelter services. We aimed to investigate the sociodemographic and clinical characteristics of trafficked people with severe mental illness. METHODS We did a historical cohort study of trafficked people in contact with secondary mental health services in South London, UK, between Jan 1, 2006, and July 31, 2012. We searched and retrieved comprehensive clinical electronic health records for over 200 000 patients from the Case Register Interactive Search database to identify trafficked patients. A matched cohort of non-trafficked adults was generated by simple computer-generated random selection of potential controls for each case within the parameters of matching criteria. We extracted data on sociodemographic and clinical characteristics and abuse history, and used multiple imputation to deal with missing data. We fitted logistic regression models to compare trafficked and non-trafficked patients. FINDINGS We identified 133 trafficked patients, including 37 children. 78 (81%) of 96 adults and 25 (68%) of 37 children were female. 19 (51%) of 37 children were trafficked for sexual exploitation. Among both adults and children, the most commonly recorded diagnoses were post-traumatic stress disorder, severe stress, or adjustment disorder (27 adults [28%] and ten children [27%]) and affective disorders (33 adults [34%] and ten children [27%]). Records documented childhood physical or sexual abuse among trafficked adults (41 [43%]) and children (28 [76%]), and adulthood abuse among trafficked adults (58 [60%]). Trafficked adults were more likely to be compulsorily admitted as a psychiatric inpatient than non-trafficked adults (adjusted odds ratio 7·61, 95% CI 2·18-26·60; p=0·002) and had longer admissions (1·48, 1·01-2·15; p=0·045). No association was found between trafficking status and either adverse pathway into care (adjusted odds ratio 0·91, 95% CI 0·40-2·05; p=0·82) or substance misuse problems (0·55, 0·27-1·17; p=0·12). INTERPRETATION Severe mental illness in trafficked people is associated with longer admissions and high levels of abuse before and after trafficking. Evidence is needed on the effectiveness of interventions to promote recovery for this vulnerable group. FUNDING Department of Health Policy Research Programme.

Statistical estimation of gene expression using multiple laser scans of microarrays

UNLABELLED We propose a statistical model for estimating gene expression using data from multiple laser scans at different settings of hybridized microarrays. A functional regression model is used, based on a non-linear relationship with both additive and multiplicative error terms. The function is derived as the expected value of a pixel, given that values are censored at 65 535, the maximum detectable intensity for double precision scanning software. Maximum likelihood estimation based on a Cauchy distribution is used to fit the model, which is able to estimate gene expressions taking account of outliers and the systematic bias caused by signal censoring of highly expressed genes. We have applied the method to experimental data. Simulation studies suggest that the model can estimate the true gene expression with negligible bias. AVAILABILITY FORTRAN 90 code for implementing the method can be obtained from the authors.

Fluorescence Lifetime Imaging of Quantum Dot Labeled DNA Microarrays

Quantum dot (QD) labeling combined with fluorescence lifetime imaging microscopy is proposed as a powerful transduction technique for the detection of DNA hybridization events. Fluorescence lifetime analysis of DNA microarray spots of hybridized QD labeled target indicated a characteristic lifetime value of 18.8 ns, compared to 13.3 ns obtained for spots of free QD solution, revealing that QD labels are sensitive to the spot microenvironment. Additionally, time gated detection was shown to improve the microarray image contrast ratio by 1.8, achieving femtomolar target sensitivity. Finally, lifetime multiplexing based on Qdot525 and Alexa430 was demonstrated using a single excitation-detection readout channel.

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style

Objective This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored. Method The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures. Results There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs. Conclusion Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed.

Human Trafficking and Health: A Survey of Male and Female Survivors in England

OBJECTIVES To investigate physical and mental health and experiences of violence among male and female trafficking survivors in a high-income country. METHODS Our data were derived from a cross-sectional survey of 150 men and women in England who were in contact with posttrafficking support services. Interviews took place over 18 months, from June 2013 to December 2014. RESULTS Participants had been trafficked for sexual exploitation (29%), domestic servitude (29.3%), and labor exploitation (40.4%). Sixty-six percent of women reported forced sex during trafficking, including 95% of those trafficked for sexual exploitation and 54% of those trafficked for domestic servitude. Twenty-one percent of men and 24% of women reported ongoing injuries, and 8% of men and 23% of women reported diagnosed sexually transmitted infections. Finally, 78% of women and 40% of men reported high levels of depression, anxiety, or posttraumatic stress disorder symptoms. CONCLUSIONS Psychological interventions to support the recovery of this highly vulnerable population are urgently needed.