Faculty Bibliography

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted.

OBJECTIVE: To examine the impact of a sleep course on sleep-related behaviors, mood, and anxiety in college students. PARTICIPANTS: Participants were 145 students enrolled in either the sleep course (n = 70) or a psychology course (n = 75); data were collected in September 2014, November 2014, and February 2015. METHODS: Sleep characteristics and symptoms of depression and anxiety were assessed using validated questionnaires and sleep logs. Linear, logistic and proportional odds regression models were used to test course effects. RESULTS: In November, sleep course students reported significant differences in sleep hygiene (SHI; p<0.001), perceived sleep latency (PSQI; p<0.05), and circadian sleep phase (MEQ; p<0.05), compared to controls. In February, the sleep course students maintained most of the aforementioned gains and reported fewer symptoms of depression (CES-D; p = 0.05) and anxiety (BAI; p<0.05). CONCLUSIONS: These positive preliminary results indicate that focused education has potential to improve sleep among college students.

As in life generally, so in scholarly publishing, the turn of the year inevitably encourages editors to reflect soberly and take honest stock of the progress their journals have made over the previous 12 months. In this frame of mind, my own thoughts turned to our beloved Journal of Child Psychology and Psychiatry. Of course I say ours because we who currently work at the journal, know it actually belongs to you, the world-wide community of child and adolescent psychologists and psychiatrists: We are only its stewards. We hold it in trust for the whole field. We understand the important role that it has served, in shaping the field of scientific child psychology and psychiatry. We know it has a special place in both your intellectual and working lives. We are aware how important it is to you that the journal continues, on your behalf, to help drive the promotion of science-driven and evidence-based solutions to the great, and, in some aspects, growing, burden of suffering imposed by childhood mental and neuro-developmental disorders. It is vital that we have your confidence that we do this in a transparent and fair way - without fear or favour - not letting our own preconceptions, prejudices or vested interests influence the content of what we publish - unless it is our prejudice towards, and vested interest in, finding out 'the truth of the matter'. We are acutely aware of the responsibility that all this places on our shoulders - a yoke we feel privileged to bear.

Although the Positive and Negative Syndrome Scale (PANSS) is widely used in clinical research, factor analytic studies of the scale have been inconsistent and questions remain about the underlying factor structure of schizophrenia symptoms. The purpose of this study was to examine whether the factor structure of the PANSS differs in men and women with schizophrenia. Principal components analysis (PCA) with equamax rotation was used to examine the factor structure of the PANSS separately in 124 males and 74 females with schizophrenia related psychoses. In males, a four factor structure was identified: (1) Negative, (2) Cognitive, (3) Positive, and (4) Hostility. In females, a four-factor structure also emerged: (1) Negative, (2) Cognitive, (3) Positive and (4) Depression. The most notable difference between the male and female PCAs was the presence of a depression factor in the females and a hostility factor in males. These results support sex differences in the factor structure of schizophrenia symptoms, which has important implications for clinical research.

BACKGROUND: Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia. The efficacy of NMDAR agonists in the treatment of persistent symptoms of schizophrenia has been variable, potentially reflecting limitations in functional target engagement. We recently demonstrated significant improvement in auditory mismatch negativity (MMN) with once-weekly treatment with d-serine, a naturally occurring NMDAR glycine-site agonist. This study investigates effects of continuous (daily) NMDAR agonists in schizophrenia/schizoaffective disorder. METHODS: Primary analysis was on MMN after double-blind crossover (60mg/kg/d, n=16, 6weeks) treatment with d-serine/placebo. Secondary measures included clinical symptoms, neurocognition, and the effects of open-label (30-120mg/kg/d, n=21) d-serine and bitopertin/placebo (10mg, n=29), a glycine transport inhibitor. RESULTS: Double-blind d-serine treatment led to significant improvement in MMN frequency (p=0.001, d=2.3) generation and clinical symptoms (p=0.023, d=0.80). MMN frequency correlated significantly with change in symptoms (r=-0.63, p=0.002) following co-variation for treatment type. d-Serine treatment led to a significant, large effect size increase vs. placebo in evoked alpha-power in response to standards (p=0.036, d=0.81), appearing to normalize evoked alpha power relative to previous findings with controls. While similar results were seen with open-label d-serine, no significant effects of bitopertin were observed for symptoms or MMN. CONCLUSIONS: These findings represent the first randomized double-blind placebo-controlled study with 60mg/kg d-serine in schizophrenia, and are consistent with meta-analyses showing significant effects of d-serine in schizophrenia. Results overall support suggest that MMN may have negative, as well as positive, predictive value in predicting efficacy of novel compounds. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov: NCT00322023/NCT00817336 (d-serine); NCT01116830 (bitopertin).

A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents ("risk analysis"); 2) assess the effect of ADHD medications on this risk ("medication analysis"). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI=1.40,1.67) and 1.39 (95% CI=1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a "difference in differences" methodology)]. The pooled effect size was 0.879 (95% CI=0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies.

Emotional dysregulation (ED) is a dysfunction in modifying an emotional state in an adaptive and goal oriented way, with excitability, ease anger, and mood lability. It is present in up to 70% of adults with ADHD, regardless of other comorbidities, and substantially worsens the psychosocial outcomes of the disorder. Besides fronto-parietal circuits mediating top-down control, brain regions involved in bottom-up processes (e.g., amygdala, orbitofrontal cortex, and ventral striatum) are implicated in ED. We performed a systematic review/meta-analysis of double-blind randomized controlled trials of ADHD medications to assess their effects on ED in adults with ADHD. We searched an extensive set of databases, international trials registries, and contacted study authors/drug companies for unpublished data. We retained 21 trials. We found small-to-moderate effects (methylphenidate: SMD=0.34, 95% CI=0.23-0.45; atomoxetine: SMD=0.24, 95% CI=0.15-0.34; lisdexamfetamine: SMD=0.50, 95% CI=0.21-0.8). We suggest that, whilst ADHD medications are effective on ADHD core symptoms, they may be less effective on bottom-up mechanisms underlying ED. Further research on novel pharmacological and non-pharmacological strategies for ED in adults with ADHD is warranted.