Faculty Bibliography

Apolipoprotein E (ApoE) is an important lipid carrier in both the periphery and the brain. The ApoE ε4 allele (ApoE4) is the single most important genetic risk-factor for Alzheimer's disease (AD) while the ε 2 allele (ApoE2) is associated with a lower risk of AD-related neurodegeneration compared to the most common variant, ε 3 (ApoE3). ApoE genotype affects a variety of neural circuits; however, the olfactory system appears to provide early biomarkers of ApoE genotype effects. Here, we directly compared olfactory behavior and olfactory system physiology across all three ApoE genotypes in 6-month- and 12-month-old mice with targeted replacement for the human ApoE2, ApoE3, or ApoE4 genes. Odor investigation and habituation were assessed, along with, olfactory bulb and piriform cortical local field potential activity. The results demonstrate that while initial odor investigation was unaffected by ApoE genotype, odor habituation was impaired in E4 relative to E2 mice, with E3 mice intermediate in function. There was also significant deterioration of odor habituation from 6 to 12 months of age regardless of the ApoE genotype. Olfactory system excitability and odor responsiveness were similarly determined by ApoE genotype, with an ApoE4 > ApoE3 > ApoE2 excitability ranking. Although motivated behavior is influenced by many processes, hyper-excitability of ApoE4 mice may contribute to impaired odor habituation, while hypo-excitability of ApoE2 mice may contribute to its protective effects. Given that these ApoE mice do not have AD pathology, our results demonstrate how ApoE affects the olfactory system at early stages, prior to the development of AD.

Extra-curricular programmes that unite police officers and youth (hereafter: "police-youth programmes") have long been recommended to ameliorate the often-strained relationship between these groups. Baltimore's history of police-youth programming includes initiating and discontinuing a variety of programmes. Researchers conducted in-depth interviews and focus group discussions among diverse stakeholders to identify barriers to sustaining police-youth programmes. Stakeholders described lack of political will, conflicting policing philosophies, and negative police-community dynamics. Participants were optimistic about the potential impact of quality programming, despite these barriers. Police-youth programmes have the capacity to improve police-youth relationships in Baltimore. Strategies to ensure sustainability and increase impact are discussed.

OBJECTIVE:The role of zinc homeostasis in various psychopathologies is an emerging area of interest. Zinc is strongly implicated in depressive disorders but is inadequately studied in schizophrenia, despite growing evidence of abnormal zinc transporters associated with schizophrenia. A meta-analysis of serum zinc concentrations in persons with schizophrenia was conducted to address this gap. METHOD/METHODS:PubMed and Embase were searched for all articles published through February 2018 that reported serum zinc concentrations in individuals with schizophrenia and in comparison subjects. A random-effects meta-analysis was carried out to compare mean serum zinc concentrations between the groups in terms of the weighted mean difference. RESULTS:The current meta-analysis combined 10 studies, including a total of 658 schizophrenia patients and 1008 controls. Serum zinc concentration was significantly lower in individuals with schizophrenia than controls (12.81 μg/dl (1.96 μmol/l), t = -2.59, 95% CI: -22.50 to -3.12, p < 0.05). The reduction in zinc levels was more pronounced among inpatients and newly diagnosed, drug-naïve patients. CONCLUSIONS:The current meta-analysis supports a disturbance of zinc homeostasis in individuals with schizophrenia compared to healthy controls, although the relationship between reduced serum zinc levels and psychotic symptoms remains unknown. Altered serum zinc might be linked to defective transporters and/or inflammation that impact the brain's glutamatergic system.

OBJECTIVE:Research assessing the social skills of children with ADHD has predominantly relied upon North American samples. In addition, most existing work has been conducted using methodology that fails to use a controlled peer stimulus; such methods may be more vulnerable to cultural influence. METHOD/METHODS:We examined the social skills of 52 Spanish children (ages 8-12) with and without ADHD using a controlled Chat Room Task, which simulates a virtual social environment where peers' responses are held constant, so that participants' social skills may be assessed. RESULTS:After statistical control of typing and reading comprehension skills, Spanish children with ADHD gave fewer prosocial comments and had greater difficulty remembering central details from the conversation between the peers, relative to comparison children. CONCLUSION/CONCLUSIONS:The virtual Chat Room Task may be useful to assess social skills deficits using a controlled paradigm, resulting in the identification of common social deficiencies cross-culturally.

Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning. We found that rapamycin attenuated the consolidation of extinction memory. In contrast, genetic deletion and pharmacological inhibition of S6K1, a downstream effector of mTORC1, blocked within-session extinction, indicating a role for S6K1 independent of protein synthesis. Indeed, the activation of S6K1 during extinction required extracellular signal-regulated kinase (ERK) activation in the basolateral nucleus of the amygdala (BLA) and was necessary for increased phosphorylation of the GluA1 (Thr840) subunit of the AMPA receptor following extinction training. Mice exposed to brief uncontrollable stress showed impaired within-session extinction as well as a downregulation of ERK and S6K1 signaling in the amygdala. Finally, using fiber photometry we were able to record calcium signals in vivo, and we found that inhibition of S6K1 reduces extinction-induced changes in neuronal activity of the BLA. These results implicate a novel ERK-S6K1-GluA1 signaling cascade critically involved in extinction.

A review of the current literature regarding bilingualism demonstrates that bilingualism is linked to higher levels of controlled attention and inhibition in executive control and can protect against the decline of executive control in aging by contributing to cognitive reserve. Bilinguals may also have smaller vocabulary size and slower lexical retrieval for each language. The joint activation theory is proposed to explain these results. Older trilingual adults experience more protection against cognitive decline and children and young adults showed similar cognitive advantages to bilinguals in inhibitory control. Second language learners do not yet show cognitive changes associated with multilingualism. The Specificity Principle states that the acquisition of multiple languages is moderated by multiple factors and varies between experiences. Bilingualism and multilingualism are both associated with immigration but different types of multilingualism can develop depending on the situation. Cultural cues and language similarity also play a role in language switching and multiple language acquisition.

The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.

Objective To evaluate attachment patterns in subjects with schizophrenia and their relationships to early traumatic events, psychotic symptoms and comorbidities. Methods Twenty patients diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) underwent retrospective symptom assessment and careful assessment of the number and manner of childhood caregiver changes. The Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD) was used to assess symptoms related to schizophrenia (positive and negative symptoms), depression and mania. Anxiety disorder comorbidities were assessed by the Liebowitz Social Anxiety Scale (LSAS), Yale-Brown Obsessions and Compulsions Scale (Y-BOCS) and Panic and Schizophrenia Interview (PaSI). Experience in Close Relationships - Relationship Structures (ECR-RS) and Early Trauma Inventory Self Report-Short Form (ETISR-SF) were used to assess attachment patterns and traumatic history, respectively. Results Moderate and significant correlations between attachment patterns and early trauma showed that greater severity of anxious attachment was predicted by a higher frequency of total early traumas (Spearman ρ = 0.446, p = 0.04), mainly general traumas (ρ = 0.526, p = 0.017; including parental illness and separation, as well as natural disaster and serious accidents). Among the correlations between early trauma and comorbid symptoms, panic attacks occurring before the onset of schizophrenia showed significant and positive correlations with ETISR-SF total scores and the sexual trauma subscale. Conclusion Children with an unstable early emotional life are more vulnerable to the development of psychopathology, such as panic anxiety symptoms. Traumatic events may also predict later schizophrenia.