Human Mental Disorders Research Articles

MeHA: A Computational Framework in Revealing the Genetic Basis of Animal Mental Health Traits Under an Intensive Farming System-A Case Study in Pigs.

Intensively farmed animals such as pigs inevitably experience a certain degree of psychological stress, which leads to a reduction in production performance. Mental health traits are currently difficult to measure, resulting in a gap in understanding their genetic basis. To address this challenge, we propose a computational framework called mental health of animals (MeHA), capable of revealing genes related to animal mental health traits. Using MeHA, we identified 109 candidate genes associated with pig mental health and discovered their intricate connections with critical functions, such as memory, cognition, and neural development, which are essential components of mental health and cognitive performance. Importantly, our findings provide evidence of the potential impact of these genes on economically important traits, including meat quality and piglet survival. This research underscores the importance of genetic studies in enhancing our understanding of animal behavior and cognition, as well as promoting agricultural practices. By applying our approach to study the genetic basis of mental health in pigs as a case, we confirmed that our framework is an effective way to reveal genetic factors affecting animal mental health traits, which contributes to animal welfare and has potential implications for understanding human mental disorders.

Impacts of human behaviors involving sound and light exposure in sleep environments on sleep and mental disorders: A cross-sectional study

Creating an optimal sleeping environment is essential. Few studies have examined how common individual behaviors alter the daily sleep environment and the subsequent health impacts of these changes among the general population. This study presented a cross-sectional analysis of 13,157 Chinese college students, utilizing binomial logistic regression models and mediation effect analysis to elucidate the associations between human behaviors involving sound and light exposure in sleep environments and outcomes related to sleep disorders, depression, and anxiety. Our results indicated that noise exposure, listening to white noise and content-based audio (audiobooks, crosstalk, and radio) before sleep, watching electronic screens in a dim environment, using noise-canceling tools during sleep, adjusting room light to be on during sleep, and using light-blocking tools during sleep was associated with an increased risk of sleep disorders by 54.9–343.4 %. The risk of mental disorders increased by 0.325–4.379 times. Pathetic (odds ratio (OR) = 1.568) and stirring music (OR = 1.279) were associated with a higher risk of sleep disorders, while gentle music was correlated with a lower risk (OR = 0.842). Additionally, warm light and gentle/cheerful music were associated with lower depression and anxiety risks (OR = 0.635–0.733). Sleep quality was found to partially mediate the relationship between these human behaviors and mental disorders, and mental disorders also mediated the relationship between these behaviors and sleep disorders. The research findings offer a scientific foundation for optimizing sleeping environments through behavior control.

Curcumin as a Multifunctional Spice Ingredient against Mental Disorders in Humans: Current Clinical Studies and Bioavailability Concerns.

Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly attracted the interest of the scientific research community. However, even if there is a plethora of naturally occurring bioactive compounds, most of them have low bioavailability, rendering them unable to insert into the bloodstream to exert their biological activities. This is a comprehensive narrative review that critically summarizes and scrutinizes the new approaches to the treatment of mental disorders using curcumin, also highlighting its bioavailability properties. The most accurate were searched using effective and relevant keywords. This narrative review reveals substantial evidence that curcumin can exert significant effects on several mental disorders. However, despite the low cost, the extensive and confirmed potency of curcumin and its involvement in signaling pathways and the scientifically confirmed data regarding its molecular mechanisms of action against mental disorders, this naturally occurring compound presents low oral bioavailability. Pharmaceutical technology has provided solutions to increase the bioavailability of curcumin. Combination with piperine, galactomannosides, liposomal formulation or nanoformulation overcomes the bioavailability and solubility disadvantages. Although curcumin demonstrates anti-anxiety, anti-depressive and anti-stress properties, studies on humans are limited and heterogeneous. Further research is highly recommended to determine the most functional formula, dose, duration, and possible side effects of curcumin on mental disorders in humans. Based on the current knowledge, the curcumin nanoformulation and Theracurmin, a form of colloidal submicroscopic particles, seem to be the most effective bioavailable formulations, which may be examined in future clinical human studies.

Exploring the similarities between risk factors triggering depression in humans and elevated in-cage "inactive but awake" behavior in laboratory mice.

Depression is a human mental disorder that can also be inferred in non-human animals. This study explored whether time spent inactive but awake ("IBA") in the home-cage in mice was further triggered by risk factors similar to those increasing vulnerability to depression in humans (early life stress, genetic predispositions, adulthood stress). Eighteen DBA/2 J and 18 C57BL/6 J females were tested, of which half underwent as pups a daily maternal separation on post-natal days 2-14 (early-life stress "ELS") (other half left undisturbed). To assess the effect of the procedure, the time the dams from which the 18 subjects were born spent active in the nest (proxy for maternal behavior) was recorded on post-natal days 2, 6, 10 and 14 for 1 h before separation and following reunion (matched times for controls), using live instantaneous scan sampling (total: 96 scans/dam). For each ELS condition, about half of the pups were housed post-weaning (i.e., from 27 days old on average) in either barren (triggering IBA and depression-like symptoms) or larger, highly enriched cages (n = 4-5 per group). Time mice spent IBA post-weaning was observed blind to ELS treatment using live instantaneous scan sampling in two daily 90-min blocks, two days/week, for 6 weeks (total: 192 scans/mouse). Data were analyzed in R using generalized linear mixed models. The dams were significantly more active in the nest over time (p = 0.016), however with no significant difference between strains (p = 0.18), ELS conditions (p = 0.20) and before/after separation (p = 0.83). As predicted, post-weaning barren cages triggered significantly more time spent IBA in mice than enriched cages (p < 0.0001). However, neither ELS (p = 0.4) nor strain (p = 0.84) significantly influenced time mice spent IBA, with no significant interaction with environmental condition (ELS × environment: p = 0.2861; strain × environment: p = 0.5713). Our results therefore only partly support the hypothesis that greater time spent IBA in mice is triggered by risk factors for human depression. We discuss possible explanations for this and further research directions.

Elucidation of the pathology of mental disorders focusing on polyunsaturated fatty acids and FABPs

Polyunsaturated fatty acids (PUFAs) are essential for brain development and function, and an imbalance of brain PUFAs is linked to mental disorders like autism and schizophrenia. However, the cellular and molecular mechanisms underlying the effects of PUFAs on the brain remain largely unknown. Since they are insoluble in water, specific transporters like fatty acid binding proteins (FABPs), are required for transport and function of PUFAs within cells. We focused on the relationship between FABP-mediated homeostasis of brain PUFAs and neural plasticity. We found that FABP3, with a high affinity for n-6 PUFAs, is predominantly expressed in the GABAergic inhibitory interneurons of the anterior cingulate cortex (ACC) in the adult mouse brain. FABP3 knockout (KO) mice show increased GABA synthesis and inhibitory synaptic transmission in the ACC. We also found that FABP7 controls lipid raft function in astrocytes, and astrocytes lacking FABP7 exhibit changes in response to external stimuli. Furthermore, in FABP7 KO mice, dendritic protrusion formation in pyramidal neurons becomes abnormal, and we have reported a decrease in spine density and excitatory synaptic transmission. Here, we introduced recent advances in the understanding of the functions of PUFAs and FABPs in the brain, focusing especially on FABP3 and FABP7, in relation to human mental disorders.

Molecular Genetic Mechanisms of Circadian Rhythm Regulation and Their Role in Psychopathology

Circadian rhythms are cyclic fluctuations in the intensity of biological processes associated with the change of day and night, to which many organisms have adapted during the evolution. Disturbances in circadian rhythms are triggered by both environmental factors (e.g., altering the time zone or the length of day/night) and disrupted internal regulation of cycles (e.g., mutations of key clock genes). These changes can lead to the pathogenesis of various diseases, including psychopathologies. Since the mechanisms underlying circadian regulation are rather evolutionarily conservative, experimental animal models are actively used to probe these processes and their relationship with psychopathologies. Here, we discuss the regulation of circadian rhythms, as well as their cross-taxon similarities and differences between mammals and teleost fish (zebrafish, Danio rerio). We also discuss recent findings on molecular genetic mechanisms underlying the regulation of circadian rhythms and their link to pathogenesis of mental disorders in humans and model organisms.

Ultrasound-Induced Prenatal Stress: New Possibilities for Modeling Mental Disorders

The development of animal models of mental disorders is an important task since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress (PS). The use of variable frequency ultrasound (US) in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of PS induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely, to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open-field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex, and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.

The unfixed light pattern contributes to depressive-like behaviors in male mice

Light pollution is now associated with an increased incidence of mental disorders in humans, and the unfixed light pattern (ULP) is a common light pollution that occurs in such as rotating shift work. However, how much contribution the ULP has to depression and its potential mechanism are yet unknown. Our study aimed to investigate the effect of the ULP on depressive-like behaviors in mice and to explore the links to the circadian-orexinergic system. Male C57BL/6 J mice were exposed to the ULP by subjecting them to an alternating light pattern every 6 days for 54 days. The tail suspension test (TST) and forced swimming test (FST) were conducted to assess depressive-like behaviors. The rhythm of locomotor activity and the circadian expression of cFOS in the suprachiasmatic nucleus (SCN), clock genes in the liver, and corticosterone (CORT) in serum were detected to observe changes in the circadian system. The circadian expression of orexin-A (OX-A) in the lateral hypothalamus area (LHA) and dorsal raphe nucleus (DRN) and serotonin (5-HT) in the DRN were measured to determine alterations in the orexinergic system. The results showed that mice exposed to the ULP exhibited increased immobility time in the TST and FST. The ULP significantly disrupted the circadian rhythm of locomotor activity, clock genes in the liver, and CORT in the serum. Importantly, when exposed to the ULP, cFOS expression in the SCN showed decreased amplitude. Its projection area, the LHA, had a lower mesor of OX-A expression. OX-A projection to the DRN and 5-HT expression in the DRN were reduced in mesor. Our research suggests that the ULP contributes to depressive-like behaviors in mice, which might be related to the reduced amplitude of circadian oscillation in the SCN and hypoactivity of the orexinergic system. These findings may provide novel insights into rotating shift work-related depression.

Electrochemical Analysis of Narcotic Drugs Using Nanomaterials Modified Electrodes – A Review

Abstract: The usage of abused illicit drugs remains an increasing challenge for drug regulatory authorities and therefore, it is important to develop advanced sensor technology that able to identify and determine drugs concentration in seized samples, biological fluids and food samples. The World Health Organization (WHO) recommends the usage of narcotic drugs legally for the medical treatments. Thus, many reports indicated that the higher dosage level led to drug addiction and mental disorders in humans. The United States record showed about 0.46 million cases of deaths due to the overdose of opioids-related drugs every year. This review discusses the electrochemical analysis (DPV, CV, EIS spectra, etc.) of various narcotic drugs using electrochemical transducers made of nanomaterials such as gold nanoparticles, single-walled carbon nanotubes, Zn2SnO4/graphene nanocomposite, cysteamine functionalized gold nanoparticle conjugated with an aptamer, etc. There were many challenges reported during the electroanalysis of narcotic drugs. Some of the wearable devices were also made for the sensing of narcotic drugs. Specifically, electro-analysis of nicotine, morphine, codeine and cathonine using 2D nanomaterials and their nanocomposites-based electrochemical sensors fabricated on flexible substrates were discussed. In particular, the linear range of detection, limit of detection (LOD), interference and real-world sample analysis were highlighted. It was concluded that wearable sensors could be used for the monitoring of illicit drugs and their derivatives in day-to-day life.

Advances in Zebrafish as a Comprehensive Model of Mental Disorders

As an important part in international disease, mental disorders seriously damage human health and social stability, which show the complex pathogenesis and increasing incidence year by year. In order to analyze the pathogenesis of mental disorders as soon as possible and to look for the targeted drug treatment for psychiatric diseases, a more reasonable animal model is imperious demands. Benefiting from its high homology with the human genome, its brain tissue is highly similar to that of humans, and it is easy to realize whole-body optical visualization and high-throughput screening; zebrafish stands out among many animal models of mental disorders. Here, valuable qualified zebrafish mental disorders models could be established through behavioral test and sociological analysis, which are simulated to humans, and combined with molecular analyses and other detection methods. This review focuses on the advances in the zebrafish model to simulate the human mental disorders; summarizes the various behavioral characterization means, the use of equipment, and operation principle; sums up the various mental disorder zebrafish model modeling methods; puts forward the current challenges and future development trend, which is to contribute the theoretical supports for the exploration of the mechanisms and treatment strategies of mental disorders.

Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs.

The neurobiological effects of repetitive transcranial magnetic stimulation are believed to run in part through the dopaminergic system. Accelerated high frequency rTMS (aHF-rTMS), a new form of stimuli delivery, is currently being tested for its usefulness in treating human and canine mental disorders. However, the short-and long-term neurobiological effects are still unclear, including the effects on the dopaminergic system. In aHF-rTMS, multiple sessions are delivered within 1 day instead of one session per day, not only to accelerate the time to response but also to increase clinical efficacy. To gain more insight into the neurobiology of aHF-rTMS, we investigated whether applying five sessions in 1 day has direct and/or delayed effects on the dopamine transporter (DAT), and on dopamine metabolites of cerebrospinal fluid (CSF) in beagles. Thirteen beagles were randomly divided into two groups: five active stimulation sessions (n = 9), and 5 sham stimulation sessions (n = 4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1 day, 1 month, and 3 months post stimulation. CSF samples were collected after each scan. Active aHF-rTMS significantly reduced striatal DAT BI 1 day post-active stimulation session (p < 0.01), and the effect lasted to 1 month (p < 0.01). No significant DAT BI change was found in sham group. No significant changes in dopamine metabolites of CSF were found. Although no significant effects on CSF dopamine metabolites were observed, five sessions of active aHF-rTMS significantly decreased striatal DAT BI after 1 day and up to 1 month post stimulation, indicating immediate and delayed effects on the brain dopaminergic system. Our findings in healthy beagles further substantiate the assumption that (a)HF-rTMS affects the brain dopaminergic system and it may pave the way to apply (a)HF-rTMS treatment in behaviorally disturbed dogs.

Validation of an ELISA kit to measure allopregnanolone in human and equine hair.

In humans, allopregnanolone plays important roles in a number of different neurodegenerative disorders, and it has been proposed for use in some therapies. Horses are commonly used as animal models for human neurodegenerative diseases, mental and behavioral disorders, and neuropsychiatric disorders, and there is interest in using hair as a biological sample to study hormones in these conditions. We validated the use of a commercial ELISA kit (DetectX allopregnanolone kit; Arbor Assays), which was designed for serum, plasma, feces, urine, and tissue samples, to assess allopregnanolone in hair samples from 30 humans and 63 horses. The ELISA kit had good precision (intra- and inter-assay CVs: 6.4% and 11.0% for equine hair; 7.3% and 11.0% for human hair, respectively), sensitivity (50.4 pg/mL for both equine and human hair), and accuracy (parallelism and recovery tests) in determining allopregnanolone concentrations in hair from both species. The allopregnanolone concentrations in human hair were 7.3-79.1 pg/mg; the concentrations were 286 ± 141 pg/mg (x̄ ± SD) in mares on the day of parturition and 16.9 ± 5.5 pg/mg in nonpregnant mares. The DetectX ELISA kit offered a simple and accessible analysis of allopregnanolone in human and equine hair samples.

Automated detection of human mental disorder

The pressures of daily life result in a proliferation of terms such as stress, anxiety, and mood swings. These feelings may be developed to depression and more complicated mental problems. Unfortunately, the mood and emotional changes are difficult to notice and considered a disease that must be treated until late. The late diagnosis appears in suicidal intensions and harmful behaviors. In this work, main human observable facial behaviors are detected and classified by a model that has developed to assess a person’s mental health. Haar feature-based cascade is used to extract the features from the detected faces from FER+ dataset. VGG model classifies if the user is normal or abnormal. Then in the case of abnormal, the model predicts if he has depression, anxiety, or other disorder according to the detected facial expression. The required assistance and support can be provided in a timely manner with this prediction. The system has achieved a 95% of overall prediction accuracy.

Biological, Functional and Network Pharmacological Exploration of Essential Oils in Treatment and Healthcare of Human Diseases

Essential oils (EOs) are natural products with bioactive functions that are obtained from various plant species, including Lavandula angustifolia and plant parts, through extraction methods, such as hydro-distillation, steam distillation and cold pressing, which can be dated back to ancient Egyptian and Greek times. Although various EOs are effective for disease treatment, such as human infectious diseases and mental disorders, the specific pharmacological mechanisms remain unclear due to its complex composition. Previous studies have attempted to recruit pharmaceutical analysis techniques, such as HPLC and MALDI-TOF, in order to elucidate the compositions of EOs. However, these have provided limited information on the mechanism of the bioactive functions of EOs. In recent years, network pharmacology has emerged as a convenient and appropriate approach to study the molecular mechanism of traditional medicines. To date, there is a lack of updated reviews on the recent progress of network pharmacology in the field of interactions between EOs and human diseases. Therefore, the present study scrutinized recent and important literatures in the field of network pharmacology and EOs, aiming to provide a timely yet brief overview of EOs as a potential treatment for diseases via network pharmacology, and facilitating the application of EOs as a complementary medicine and therapy for human diseases.

Animal Models in Neuropsychiatry: Do the Benefits Outweigh the Moral Costs?

Animal models have long been used to investigate human mental disorders, including depression, anxiety, and schizophrenia. This practice is usually justified in terms of the benefits (to humans) outweighing the costs (to the animals). The author argues on utility maximization grounds that we should phase out animal models in neuropsychiatric research. The leading theories of how human minds and behavior evolved invoke sociocultural factors whose relation to nonhuman minds, societies, and behavior has not been homologized. Thus, it is not at all clear that we are gaining the epistemic or clinical benefits we want from this animal-based research.

EQTL analysis of laying hens divergently selected for feather pecking identifies KLF14 as a potential key regulator for this behavioral disorder.

Feather pecking in chickens is a damaging behavior, seriously impacting animal welfare and leading to economic losses. Feather pecking is a complex trait, which is partly under genetic control. Different hypotheses have been proposed to explain the etiology of feather pecking and notably, several studies have identified similarities between feather pecking and human mental disorders such as obsessive-compulsive disorder and schizophrenia. This study uses transcriptomic and phenotypic data from 167 chickens to map expression quantitative trait loci and to identify regulatory genes with a significant effect on this behavioral disorder using an association weight matrix approach. From 70 of the analyzed differentially expressed genes, 11,790 genome wide significantly associated variants were detected, of which 23 showed multiple associations (≥15). These were located in proximity to a number of genes, which are transcription regulators involved in chromatin binding, nucleic acid metabolism, protein translation and putative regulatory RNAs. The association weight matrix identified 36 genes and the two transcription factors: SP6 (synonym: KLF14) and ENSGALG00000042129 (synonym: CHTOP) as the most significant, with an enrichment of KLF14 binding sites being detectable in 40 differentially expressed genes. This indicates that differential expression between animals showing high and low levels of feather pecking was significantly associated with a genetic variant in proximity to KLF14. This multiallelic variant was located 652 bp downstream of KLF14 and is a deletion of 1-3 bp. We propose that a deletion downstream of the transcription factor KLF14 has a negative impact on the level of T cells in the developing brain of high feather pecking chickens, which leads to developmental and behavioral abnormalities. The lack of CD4 T cells and gamma-Aminobutyric acid (GABA) receptors are important factors for the increased propensity of laying hens to perform feather pecking. As such, KLF14 is a clear candidate regulator for the expression of genes involved in the pathogenic development. By further elucidating the regulatory pathways involved in feather pecking we hope to take significant steps forward in explaining and understanding other mental disorders, not just in chickens.

How “old age” was withdrawn as a diagnosis from ICD-11

The classification of the causes of death and diseases dates back to the 18th century. The International Statistical Institute adopted the first international classification of diseases in 1893. After 1948, WHO assumed responsibility for publishing the International Classification of Diseases (ICD) as a global, multilingual catalogue of known human diseases, medical conditions, and mental health disorders, to standardise disease diagnosis. The 11th revision (ICD-11) was launched on Jan 1, 2022. The ICD is a platform for systematic statistical data collection, which are analysed and interpreted to compare causes of mortality and morbidity in different countries or regions of the world over time.

Human–Robot Interactive Communication and Cognitive Psychology Intelligent Decision System Based on Artificial Intelligence — Case Study

Cognitive psychology is a science of human knowledge, which means that people perceive, acquire, memorize, think, and comprehend intellectual capabilities. The psychological strategy involves controlling every action and status of the human body. The problematic states of psychological facts include mental disorders like depression, stress, anxiety, and inferiority complex, leading to memory loss. The emerged technique of cognitive psychological managing framework using artificial intelligence (CPMF-AI) is introduced. The proposed framework is extended to forecast the psychological standards of the human brain for practical well-being. There are four methods to monitor memory power, stress, and other human mental disorders. They are distant neural systems (DNS), convolutional psychology tracking systems (CPTS), intelligent neural systems (INS), and memory-building strategies (MBS). Besides language aspects, physical aspects play a vital part in human–robot interaction (HRI) and make the difference compared to the more limited HRI communication. These methodologies are integrated into four case studies to detect neural passage systems for monitoring mental issues. The simulation analysis helps enhance the framework’s accuracy and minimize the error rate. Thus, the proposed system of cognitive technology is comparatively better than the existing methods.

Enhanced wireless cell stimulation using soft and improved bipolar electroactive conducting polymer templates

Bipolar electrostimulation (BPES) invoked using organic conducting polymers (CPs) has provided a unique route to communicating with living cells. This work brings new dimensions to BPES in terms of the conducting polymer composition and the ability to implement on a soft substrate. Poly(2-methoxyaniline-5-sulfonic acid) (PMAS) has been used as a redox active, electronically conductive dopant to enhance the electrochemical properties of the host polypyrrole (PPy). Significantly, rat PC 12 cells cultivated on a multilayer, mechanically flexible, conducting polymer support show increased differentiation when BPES is applied. The soft template (PPy-PMAS-collagen/PEDOT-PSS) comprises poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) that provides mechanical and structural support to a blend of highly conducting PMAS modified PPy. In vitro cultivation and BPES of PC 12 cells on the prepared soft templates showed a significant increase in cell growth and neurites extension. Furthermore, the potential application of the soft template-based BPES system to living human cells is reported. The new BPES platform encourages human neuroblastoma SH-SY5Y cells to differentiate and form extensive neuronal phenotypes and neural networks. This represents the possibility of using the soft template based BPES system in vivo and clinical applications related to translational models of human mental disorders.

The zebrafish Multivariate Concentric Square Field: A Standardized Test for Behavioral Profiling of Zebrafish (Danio rerio).

The zebrafish (Danio rerio) is an important model organism in the study of the neurobiological basis of human mental disorders. Yet the utility of this species is limited by the quality of the phenotypical characterization tools available. Here, we present a complex testing environment for the quantification of explorative behavior in adult zebrafish, the zebrafish Multivariate Concentric Square Field™ (zMCSF), adapted from the rodent equivalent that has been used in > 40 studies. The apparatus consists of a central open area which is surrounded by a dark corner with a roof (DCR), corridors, and an inclined ramp. These areas differ in illumination, water depth, and are sheltered or exposed to different degrees. We quantified behavior of male and female wild-caught and AB strain zebrafish in the zMCSF (day 1) and cross-validated these results using the novel tank diving test (NTDT) (day 2). To assess the effect of repeated testing, AB zebrafish we tested a second time in both tests 1 week later (on days 7 and 8). We detected strong differences between the strains, with wild zebrafish swimming faster and spending more time in the corridors and on the ramp, while they avoided the open area in the center. AB zebrafish were less hesitant to enter the center but avoided the ramp, and often left one or more zones unexplored. No major sex differences in exploratory behavior were detected in either strain, except for a slightly higher velocity of AB males which has been reported before. Importantly, the zMCSF was largely resilient to repeated testing. The diving test revealed only one difference confined to one sex; wild females paid more visits to the top third than AB females. In isolation, this finding could lead to the conclusion that wild zebrafish are more risk-taking, which is incorrect given this strain’s avoidance of open areas. To conclude, our results suggest that the zMCSF presents a sophisticated behavioral tool that can distinguish between different magnitudes and types of risk, allowing the user to create an intricate behavioral profile of individual adult zebrafish.