Search

Contains fulltext : 227418.pdf (Publisher’s version ) (Closed access) The COVID-19 pandemic has led to unprecedented societal changes limiting us in our mobility and our ability to connect with others in person. These unusual but widespread changes provide a unique opportunity for studies using digital phenotyping tools. Digital phenotyping tools, such as mobile passive monitoring platforms (MPM), provide a new perspective on human behavior and hold promise to improve human behavioral research. However, there is currently little evidence that these tools can reliably detect changes in behavior. Considering the Considering the COVID-19 pandemic as a high impact common environmental factor we studied potential impact on behavior of participants using our mobile passive monitoring platform BEHAPP that was ambulatory tracking them during the COVID-19 pandemic. We pooled data from three MPM studies involving Schizophrenia (SZ), Major Depressive Disorder (MDD) and Bipolar Disorder (BD) patients (N = 12). We compared the data collected on weekdays during three weeks prior and three weeks subsequent to the start of the quarantine. We hypothesized an increase in communication and a decrease in mobility. We observed a significant increase in the total time spent on communication applications (median 179 and 243 min per week respectively, p = 0.005), and a significant decrease in the number of unique places visited (median 6 and 3 visits per week respectively, p = 0.007), while the total time spent at home did not change significantly (median 64 and 77 h per week, respectively, p = 0.594). The data provides a proof of principle that digital phenotyping tools can identify changes in human behavior incited by a common external environmental factor. 6 p.

Current limitations impeding on data reproducibility are often poor statistical design, underpowered studies, lack of robust data, lack of methodological detail, biased reporting and lack of open data sharing, coupled with wrong research incentives. To improve data reproducibility, robustness and quality for brain disease research, a Preclinical Data Forum Network was formed under the umbrella of the European College of Neuropsychopharmacology (ECNP). The goal of this network, members of which met for the first time in October 2014, is to establish a forum to collaborate in precompetitive space, to exchange and develop best practices, and to bring together the members from academia, pharmaceutical industry, publishers, journal editors, funding organizations, public/private partnerships and non-profit advocacy organizations. To address the most pertinent issues identified by the Network, it was decided to establish a data sharing platform that allows open exchange of information in the area of preclinical neuroscience and to develop an educational scientific program. It is also planned to reach out to other organizations to align initiatives to enhance efficiency, and to initiate activities to improve the clinical relevance of preclinical data. Those Network activities should contribute to scientific rigor and lead to robust and relevant translational data. Here we provide a synopsis of the proceedings from the inaugural meeting.

The behavioral characterization of animal models of psychiatric disorders is often based upon independent traits measured at adult age. To model the neurodevelopmental aspects of psychiatric pathogenesis, we introduce a novel approach for a developmental behavioral analysis in mice. C57BL/6J (C57) mice were used as a reference strain and compared with 129S1/SvImJ (129Sv), BTBR T+tf/J (BTBR) and A/J (AJ) strains as marker strains for aberrant development. Mice were assessed at pre-adolescence (4 weeks), adolescence (6 weeks), early adulthood (8 weeks) and in adulthood (10-12 weeks) on a series of behavioral tasks measuring general health, neurological reflexes, locomotor activity, anxiety, short- and long-term memory and cognitive flexibility. Developmental delays in short-term object memory were associated with either a hypo-reactive profile in 129Sv mice or a hyper-reactive profile in BTBR mice. Furthermore, BTBR mice showed persistent high levels of repetitive grooming behavior during all developmental stages that was associated with the adult expression of cognitive rigidity. In addition, strain differences in development were observed in puberty onset, touch escape, and body position. These data showed that this longitudinal testing battery provides sufficient behavioral and cognitive resolution during different development stages and offers the opportunity to address the behavioral developmental trajectory in genetic mouse models for neurodevelopmental disorders. Furthermore, the data revealed that the assessment of multiple behavioral and cognitive domains at different developmental stages is critical to determine confounding factors (e.g., impaired motor behavior) that may interfere with the behavioral testing performance in mouse models for brain disorders.

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder with a lifetime prevalence of 2-3%. Recent work has shown that OCD rituals were not only characterized by a high rate of repetition but also by an increased behavioral repertoire due to additional non-functional unique acts. These two behavioral characteristics may provide an ethological basis for studying compulsive behavior in an animal model of OCD. Here, quinpirole induced behavior (so far only investigated in rats) has been studied in A/J and C57BL/6J mice by using behavioral pattern analysis. The aim of this study is to investigate whether genetic background is mediating this behavior. Results showed that open field motor activity levels of saline treated C57BL/6J mice was significantly higher compared to A/J treated saline mice. Long-term quinpirole treatment increased open field motor activity levels in A/J, but not in C57BL/6J. Quinpirole treatment induced a strain dependent difference in behavioral repertoire. There was a dose dependent increase in the number of different behavioral patterns in A/J, whereas, in C57BL/6J there was a dose dependent decrease. This data suggest that genetic background is important in expressing quinpirole induced compulsive like behavior. Following quinpirole treatment, A/J mice express a greater behavioral repertoire with a high rate of repetition. This phenotype resembles that of OCD rituals in patients and indicates that this strain is very interesting to further validate for studying neurobiological mechanisms of compulsive behavior.

Excessive physical activity plays an important role in the progression of anorexia nervosa (AN) by accelerating weight loss during dietary restriction. To search for mechanisms underlying this trait, a panel of mouse chromosome substitution strains derived from C57BL/6J and A/J strains was exposed to a scheduled feeding paradigm and to voluntary running wheel (RW) access. Here, we showed that A/J chromosomes 4, 12 and 13 contribute to the development of a disrupted RW activity in response to daily restricted feeding. This pattern is characterized by intense RW activity during the habitual rest phase and leads to accelerated body weight loss. Regions on mouse chromosomes 4, 12 and 13 display homology with regions on human chromosomes linked with anxiety and obsessionality in AN cohorts. Therefore, our data open new roads for interspecies genetic studies of AN and for unraveling novel mechanisms and potential effective treatment strategies for these neurobehavioral traits.

Background Currently, neuropsychiatric disorders are separated by convention based clustering of qualitative symptoms, not underlying aetiology. This methodology might be sufficient for general clinical management, but it disregards neurobiology. A better understanding of the neurobiology and the application of this knowledge will lead to enhanced treatment efficacy and would provide patients with improved understanding of their condition. A first step in linking nosology to neuroscience is showing how neuropsychiatric symptoms can be measured by quantitative biological parameters and, how these quantitative biological parameters are shaped by neurobiological processes. For example, Schizophrenia, Alzheimer’s disease, Major Depressive disorder and autism spectrum disorder have one overlapping symptom, social withdrawal [1]. This suggests that neurobiological mechanisms might overlap. Thus, scrutinizing the characteristics of this behavioural deficit could elucidate mechanisms relevant for multiple neuropsychiatric disorders. Animal studies are essential in this endeavour, as behaviour and the underlying mechanisms can be examined in more detail. However, efforts are needed to establish the definition and assessment tools for social withdrawal that is relevant beyond the diagnostic boundaries. In earlier studies, the focus has primarily been on scrutinizing social withdrawal in a dyadic interaction, in which a single animals can engage in social behaviour with a single other (e.g., [2]). This, however, does not allow for the natural behavioural potential, such as the natural burrowing behaviour of these animals. Studying social behaviour in a semi-natural environment would allow for a translational setting in which the full range of behaviours can be explored. This study proposes the visible burrow system (VBS) for this purpose. This system consists of an open arena and a burrow with separate nests, from which the latter is exposed to constant darkness. Mimicking the natural setting, this system allows rodents to display natural behaviours and withdraw into one of the nests. Aim This study aims to explore the full behavioural range of the BTBR mouse, a mouse line showing aberrant social behaviours, in a semi-natural VBS environment to study social withdrawal. Furthermore we aim to connect this to GABA, which has been shown to play a key role in social behaviour [3]. Method In assessing the full range of behavioural deficits accompanying social withdrawal, BTBR and C57BL/6J reference mice are placed in the VBS. Colonies of 8 mice (6 males and 2 females) are exposed to the VBS for five consecutive days after which animals are sacrificed and brains are extracted for GABA measurement by mean of HPLC. Statistical analyses is performed by means of ANOVA (longitudinal) and Student’s T-test (week means), comparing BTBR with C57Bl/6j mice (α=0.05). Results/Conclusion In accordance with previous data [4], BTBR mice showed a significant decrease in social behaviours and an increase in non-social behaviour. This coincided with a reduction of GABA in both the prefrontal cortex and the amygdala. Taken together, these data suggests the VBS as a tool for studying translation behavioural characteristics regarding social withdrawal and its neurochemical correlates.

The majority of medical disciplines utilize a measurement-based approach for the prevention and early detection of major medical events by monitoring measures that indicate the onset of such an event. However, in psychiatry treatment is often preceded by a major psychiatric crisis or even hospitalization and is followed by a long period of disability and slow recovery. The focus on acute care in psychiatry is due to a lack of valid temporal and objective measures of behavior that translate into day-to-day functioning. Several Behavioral changes in day-to-day functioning are identified as prodromal symptoms for several neuropsychiatric disorders [1,2]. A measurement-based approach is needed in psychiatry to monitor daily functioning and improve patient outcome [3]. Therefore, we have developed a passive behavioral monitoring (PBM) application, called BeHapp (https://behapp.org/), that collects a rich longitudinal trace of real-world social and behavioral data with minimal awareness. PBM is based on the ubiquity of smartphones, and monitors behavior by utilizing the large extend of smartphone sensor modalities available. These modalities allows us to formulate several features related to social behavior, e.g. number of contacts, duration of phone calls, social media usage, and places visited. We studied the predictive power of PBM in differentiating between non-diagnosed controls and neuropsychiatric patients by using smartphone modalities that relate to social behavior. We collected preliminary data from 24 neuropsychiatric patients (9 Major depression, 11 Schizophrenia, 4 Alzheimer’s Disease) and 72 non-diagnosed controls by installing BeHapp on the participant’s own android smartphone. Participants were included over several different ongoing studies and psychiatric screening data was available for 20 non-diagnosed controls. Average participation time was 13.4 days (sd = 5.9), variation is due to early removal of the application. We used GPS, application usage, and WiFi data to generate features that translate into daily social functioning. Simple two-sided t-tests were used to evaluate the difference in means between the neuropsychiatric patient and non-diagnosed control group. Additionally, we applied t-distributed stochastic neighbour embedding clustering [4] to group participants into a two-dimensional space regardless of their diagnosis. Our preliminary results revealed social-behavioral differences between the two groups (pooled patients versus controls) in social media usage; frequency of WhatsApp usage (p Our results suggest that PBM is sensitive in detecting differences in day-to-day social functioning and therefore a potential candidate for a measurement-based approach in psychiatry.

Activity-based anorexia (ABA) mimics starvation and hyperactivity of anorexia nervosa patients in rats. Activation of the melanocortin (MC) system leads to hypophagia and increased energy expenditure in ad libitum fed rats. Therefore, activation of the MC system might underlie the development and propagation of ABA. Pro-opiomelanocortin (POMC) gene expression is normally decreased during negative energy balance. Strikingly, we found a transient up-regulation of POMC mRNA levels in the arcuate nucleus during the development of ABA, indicating a hyperactive MC system. However, wheel running and food intake were not influenced by treating ABA rats with the competitive antagonist SHU9119. This suggests that agonism of MC receptors by endogenous alpha-melanocyte-stimulating hormone (alpha-MSH) levels does not underlie ABA. Instead, treatment with the inverse agonist AgRP(83-132) did ameliorate signs of ABA. This implies that modulation of constitutive MC receptor activity rather than antagonizing putative alpha-MSH release contributes to the development and propagation of ABA.

significant effect on mGlu2 receptor expression level [One-way ANOVA, F(3.41) = 22.8, p< 0.0001]. Moreover Dunnett’s Multiple Comparison Test analysis shows that level of mGlu2 receptor surface expression in cells after double thymidine block was significantly higher compared to receptor expression level in asynchronously growing cells (p< 0.01). In contrast, the expression level of mGlu2 receptor was significantly decreased in M phase blocked cells (p< 0.01) and cells after serum starvation (p< 0.01). Conclusions: The results indicate that modification of the inducible expression system by cell synchronisation seems to have significant effect on surface mGluR2 expression level.

Cognitive rigidity is a defining characteristic of various psychiatric disorders, such as autism spectrum disorders (ASD) and anorexia nervosa (AN). For instance, reversal learning is considered a core component of cognitive rigidity, a behavioral domain affected in both ASD and AN. Genetic factors that are implicated in both these disorders, such as the contactin-4 (CNTN4) gene, may be particularly relevant to understand how rigidity is mediated [1]. Here, we performed an extensive developmental behavioral and morphological characterization of Cntn4-knockout mice [2]. Cognitive rigidity was assessed in adulthood using the set-shifting task, a mouse analog of the Wisconsin Card Sorting Test. This task includes intra-dimensional (affective) and extra-dimensional (attentional) set-shifting [3]. We found that mice lacking the Cntn4 gene made significantly more errors before reaching the criterion for intra-dimensional set-shifting compared to wild type mice. In contrast, no effect was found on extra-dimensional set-shifting. Moreover, no genotype effects were detected in the longitudinal assessment of general health measures and other behavioral domains. Brain morphology analyses revealed a significant reduction of cortical layer thickness in the motor cortex, but not in nonfrontal areas, including somatosensory cortex and visual cortex. Our results in Cntn4-knockout mice confirm a specific role for this gene in the regulation of cognitive rigidity. Taken together, these findings suggest that this mouse model is highly suitable to examine neurobiological underpinnings of cognitive rigidity in neurodevelopmental disorders. Ultimately, this approach may lead to the development of therapeutic strategies with cross-diagnostic relevance.