Human Mental Disorders Research Articles

A Robot Science Approach to Simulating the Pathogenesis of Dissociative Identity Disorder

Abstract Our research group has been studying dissociative identity disorder (DID) with a view to promoting further understanding of advanced mental disorders in humans. We constructed a conscious system using consciousness modules called MoNADs and have been attempting to reproduce dissociation symptoms. Previously, as we reported at the 2018 Annual International Conference on Biologically Inspired Cognitive Architectures (BICA 2018), we incorporated two types of units, a recording device (EXM) and a MoNAD filter value, into our conscious system and attempted to achieve highly reproducible dissociation symptoms and the onset process. In this paper we present the development of our robot science based conscious program, describe various experimental simulations based on this model, and present the results. Finally, from the results of our simulations, we will consider the symptoms of the dissociative disorder group including DID and the reproducibility of the onset process in this consciousness model.

Экспериментальные модели когнитивных нарушений при нейродегенеративных и органических расстройствах

Animal models of mental disorders play an important role in the study of pathophysiological mechanisms of behavior and translation of these data for the identification of causes, biomarkers and potential treatments of mental disorders in humans. This article presents a review of literature on animal models of Alzheimer's disease, cognitive impairment in vascular dementia and organic brain disease. Pharmacological, genetic models, their mechanisms and typical manifestations are covered. While pharmacological models have been widely used in studies of pathogenesis and treatment of cognitive impairment for many years, more modern transgenic models with their advantages are becoming increasingly popular in recent years. Currently there is no model that would combine all the cognitive, behavioral, biochemical and histological characteristics of a particular type of dementia, but a variety of animal models gives a lot of opportunities for preclinical research.

Ancient foes and helpers: Research sheds new light on the role that retroviruses play in disease, innate immunity and neural plasticity.

Ancient retrovirus infections played a role in human evolution and are still involved in innate immunity and neural plasticity.

A Robot Model of OC-Spectrum Disorders: Design Framework, Implementation, and First Experiments

Computational psychiatry is increasingly establishing itself as a valuable discipline for understanding human mental disorders. However, robot models and their potential for investigating embodied and contextual aspects of mental health have been, to date, largely unexplored. In this article, we present an initial robot model of obsessive-compulsive (OC) spectrum disorders based on an embodied motivation-based control architecture for decision-making in autonomous robots. The OC family of conditions is chiefly characterized by obsessions (recurrent, invasive thoughts) and/or compulsions (an urge to carry out certain repetitive or ritualized behaviors). The design of our robot model follows and illustrates a general design framework that we have proposed to ground research in robot models of mental disorders and to link it with existing methodologies in psychiatry, notably in the design of animal models. To test and validate our model, we present and discuss initial experiments, results, and quantitative and qualitative analyses regarding the compulsive and obsessive elements of OC-spectrum disorders. While this initial stage of development only models basic elements of such disorders, our results already shed light on aspects of the underlying theoretical model that are not obvious simply from consideration of the model.

The Role of Tryptophan-Kynurenine in Feather Pecking in Domestic Chicken Lines.

Research into the role of tryptophan (TRP) breakdown away from the serotonergic to the kynurenine (KYN) pathway by stimulating the brain-endocrine-immune axis system interaction has brought new insight into potential etiologies of certain human behavioral and mental disorders. TRP is involved in inappropriate social interactions, such as feather-destructive pecking behavior (FP) in birds selected for egg laying. Therefore, our goal was to determine the effect of social disruption stress on FP and the metabolism of the amino acids TRP, phenylalanine (PHE), tyrosine (TYR), their relevant ratios, and on large neutral amino acids which are competitors with regard to their transport across the blood-brain barriers, at least in the human system, in adolescent birds selected for and against FP behavior. We used 160 laying hens selected for high (HFP) or low (LFP) FP activity and an unselected control line (UC). Ten pens with 16 individuals each (4 HFP birds; 3 LFP birds; 9 UC birds) were used. At 16 weeks of age, we disrupted the groups twice in 5 pens by mixing individuals with unfamiliar birds to induce social stress. Blood plasma was collected before and after social disruption treatments, to measure amino acid concentrations. Birds FP behavior was recorded before and after social disruption treatments. HFP birds performed significantly more FP and had lower KYN/TRP ratios. We detected significantly higher FP activity and significantly lower plasma PHE/TYR ratios and a trend to lower KYN/TRP ratios in socially disrupted compared to control pens. This might indicate that activating insults for TRP catabolism along the KYN axis in laying hens differs compared to humans and points toward the need for a more detailed analysis of regulatory mechanisms to understand the role of TRP metabolism for laying hen immune system and brain function.

The Effects of Lavender Essential Oils on the Anxious Behavior of Zebrafish

In the United States, anxiety disorders are becoming increasingly prominent, affecting as many as 30% of Americans with more cases found each year. Currently, lavender essential oils are being utilized by people to relieve anxiety symptoms although there is little research to validate the scientific basis for the relief of symptoms. Some research has indicated that lavender in essential oils can inhibit the serotonin reuptake transporter similar to the mechanism of action for many oral antidepressants. Zebrafish have become an accepted model for anxious behavior due to their visible and inherent diving behavior when presented with negative stimuli. In addition, zebrafish share 82% of the genes associated with mental disorders in humans and have similar endocrine responses such as the release of cortisol. To test the effect of lavender essential oil on the anxious behavior, zebrafish were exposed to a stressful stimulus and given varying doses of lavender oil to determine their shoaling behavior. In addition, to determine the effects on endocrine response, cortisol levels were tested in each condition. We have found that lavender essential oils decrease diving behavior in zebrafish compared with those who are untreated. Therefore, the goal of the research was to exhibit the relief of anxious symptoms with the treatment of lavender oil in zebrafish by documenting their behavioral changes when treated with lavender essential oils compared with anxious behavior in those with no treatment.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Can Playing Games Help Students Master Concepts from General Psychology Classes?

As part of a final project for a general psychology course, students were required to play a game, either digital/video or on a board. Students selected their own games, and were asked to identify psychological principles in their game play. Topics included the brain, sensation and perception, human development, learning, motivation, intelligence, personality, and mental disorders. Students successfully applied all topics to game play, but to varying degrees. Student discussions on the brain and intelligence were well covered. Discussions on personality and psychological disorders issues were relatively poor. Students were able to make connections between concepts and their game-play experiences.

Freudarwin: Evolutionary Thinking as a Root of Psychoanalysis.

This essay synthesizes the place of biological evolutionism in the early history of psychoanalysis, and shows the implicit significance of German Darwinism in Sigmund Freud’s whole psychoanalytical works. In particular, Freud, together with Sándor Ferenczi (1873–1933), applied to mental disorders hypotheses inspired by August Pauly’s (1850–1914) psychological Lamarckism and Ernst Heckel (1834–1919) theory of recapitulation. Both of these theories rested upon the principle of inheritance of acquired characteristics, and were disproved by biological discoveries during the interwar period. However, despite these scientific progresses, Freud never gave up his idea of inherited unconscious memories, and we try here to sketch out what would have cost him a renunciation to such outdated biological principles. Notwithstanding, Sigmund Freud was the first to elaborate on evolutionary causes of mental syndromes, which makes of him the forerunner of current neo-Darwinian psychopathology, with few continuators to date within the psychoanalytic field. Nowadays, the extended neo-Darwinian synthesis and affective neuroscience may pave the way for a rational Darwinian approach to human mental disorders, which would take into account the whole neurological and psychological evolution of species, and be centered on emotions and their vicissitudes.

Mental and Behavioral Disorders and Air Pollution

Aim: The aim of this work is to study the human mental disorders in Cyprus and their relationship to smoking and air pollution. Methods: The statistical methods were used to derive the results of this work are Student t-test in order to check the statistical significance of the human mental disorders in relation to gender, One-Way ANOVA test in order to check the statistical significance of human mental disorders in relation to age and the Pearson correlation coefficient for the relationship between these disorders of both predisposing factors of smoking and air pollution. Results: The results showed that there is no statistically significant difference in the number of human mental disorders in relation to gender, there is a statistically significant relationship between these disorders and age, and in particular they occur mainly at ages 15-44. Finally, there is a statistically significant relationship between the numbers of incidents of human mental disorders with air pollution and there is no statistically significant relationship with smoking. Conclusions: This study has shown that human mental and behavioral disorders differ in the incidence in terms of age while air pollution is a significant predisposition. Moreover, from all mental and behavioral disorders, mood affective disorders hold the first place in deaths of both men and women.

Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls.

Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.

Neuroimmune Impacts of Early-Life Stress on Development and Psychopathology.

Maltreatment and trauma in childhood, termed early-life stress (ELS), has long-term effects on the immune system. ELS impacts immune signaling at the time of exposure but also disrupts the developmental trajectory of certain immunological processes, both in the periphery and in the brain. One consequence of these early alterations is a heightened immune response to stressors later in life. However, chronic and sustained inflammatory response can also lead to excitotoxicity and prevent typical brain development. In this chapter, we discuss current progress toward understanding the contribution of neuroimmune signaling to ELS-attributable dysfunction or maladaptation with a focus on postnatal experiences. To do so we first present an operational definition of ELS. Then, we offer a brief overview of the immune system and neuroimmune development, followed by a section discussing the interaction between immunity, childhood trauma, and mental disorders in humans. We present evidence from animal models about immune alterations after ELS and discuss the ways in which ELS-induced immune changes ultimately affect brain and behavior, as well as the importance of individual differences and future directions in this field. Taken together, we submit that when encountered with ELS, some core brain circuits could develop differently via various mechanisms involving dysfunctional immune reprograming. However, given the remarkable plasticity of both the brain and the immune system, many of the deleterious effects of ELS may be mitigated with interventions that account for sex and target neuroimmune interactions over the lifespan.

Duże zwierzęta jako potencjalne modele zaburzeń psychicznych i zachowania człowieka

Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder). This data indicates many large animal disorders which can be models to examine the above human mental and behavioral disorders.

The stress response HPA-axis hormone, glucocorticoid, reduces cellular SKA complex gene expression

The Spindle- and Kinetochore-Associated (SKA) complex has been proven to be involved in many human mental behavioral disorders. Glucocorticoid, a hypothalamic-pituitary-adrenal (HPA) axis hormone, is a critical mediator of stress response in neurons. However, the underlying mechanisms of glucocorticoid's effects on human neuronal cells remain unclear. This study demonstrates that increased extracellular glucocorticoid levels significantly reduce neuronal cell SKA complex genes’ expression levels, followed by altered neuronal cell viability and neurite development. The results suggest that the abnormality of this HPA-axis hormone could impact the neuronal cell functions through the alternation of SKA complex functions, which might induce cell death.

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells

Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions.

Digital gene atlas of neonate common marmoset brain

Interest in the common marmoset (Callithrix jacchus) as a primate model animal has grown recently, in part due to the successful demonstration of transgenic marmosets. However, there is some debate as to the suitability of marmosets, compared to more widely used animal models, such as the macaque monkey and mouse. Especially, the usage of marmoset for animal models of human cognition and mental disorders, is still yet to be fully explored. To examine the prospects of the marmoset model for neuroscience research, the Marmoset Gene Atlas (https://gene-atlas.bminds.brain.riken.jp/) provides a whole brain gene expression atlas in the common marmoset. We employ in situ hybridization (ISH) to systematically analyze gene expression in neonate marmoset brains, which allows us to compare expression with other model animals such as mouse. We anticipate that these data will provide sufficient information to develop tools that enable us to reveal marmoset brain structure, function, cellular and molecular organization for primate brain research.

精神疾患, 行動, アレルギー性疾患に対するゲノム解析(シンポジウムI/21世紀における心身医学への期待)

精神疾患, 行動, アレルギー性疾患に対するゲノム解析(シンポジウムI/21世紀における心身医学への期待)

Gene expression patterns of chicken neuregulin 3 in association with copy number variation and frameshift deletion

BackgroundNeuregulin 3 (NRG3) plays a key role in central nervous system development and is a strong candidate for human mental disorders. Thus, genetic variation in NRG3 may have some impact on a variety of phenotypes in non-mammalian vertebrates. Recently, genome-wide screening for short insertions and deletions in chicken (Gallus gallus) genomes has provided useful information about structural variation in functionally important genes. NRG3 is one such gene that has a putative frameshift deletion in exon 2, resulting in premature termination of translation. Our aims were to characterize the structure of chicken NRG3 and to compare expression patterns between NRG3 isoforms.ResultsDepending on the presence or absence of the 2-bp deletion in chicken NRG3, 3 breeds (red junglefowl [RJF], Boris Brown [BB], and Hinai-jidori [HJ]) were genotyped using flanking primers. In the commercial breeds (BB and HJ), approximately 45% of individuals had at least one exon 2 allele with the 2-bp deletion, whereas there was no deletion allele in RJF. The lack of a homozygous mutant indicated the existence of duplicated NRG3 segments in the chicken genome. Indeed, highly conserved elements consisting of exon 1, intron 1, exon 2, and part of intron 2 were found in the reference RJF genome, and quantitative PCR detected copy number variation (CNV) between breeds as well as between individuals. The copy number of conserved elements was significantly higher in chicks harboring the 2-bp deletion in exon 2. We identified 7 novel transcript variants using total mRNA isolated from the amygdala. Novel isoforms were found to lack the exon 2 cassette, which probably harbored the premature termination codon. The relative transcription levels of the newly identified isoforms were almost the same between chick groups with and without the 2-bp deletion, while chicks with the deletion showed significant suppression of the expression of previously reported isoforms.ConclusionsA putative frameshift deletion and CNV in chicken NRG3 are structural mutations that occurred before the establishment of commercial chicken lines. Our results further suggest that the putative frameshift deletion in exon 2 may potentially affect the expression level of particular isoforms of chicken NRG3.

Polymorphisms in sex steroid receptors: From gene sequence to behavior.

Sex steroid receptors have received much interest as potential mediators of human behaviors and mental disorders. Candidate gene association studies have identified about 50 genetic variants of androgen and estrogen receptors that correlate with human behavioral phenotypes. Because most of these polymorphisms lie outside coding regions, discerning their effect on receptor function is not straightforward. Thus, although discoveries of associations improve our ability to predict risk, they have not greatly advanced our understanding of underlying mechanisms. This article is intended to serve as a starting point for psychologists and other behavioral biologists to consider potential mechanisms. Here, I review associations between polymorphisms in sex steroid receptors and human behavioral phenotypes. I then consider ways in which genetic variation can affect processes such as mRNA transcription, splicing, and stability. Finally, I suggest ways that hypotheses about mechanism can be tested, for example using in vitro assays and/or animal models.

Circuits regulating pleasure and happiness: evolution and role in mental disorders.

Taking the evolutionary development of the forebrain as a starting point, the authors developed a biological framework for the subcortical regulation of human emotional behaviour which may offer an explanation for the pathogenesis of the principle symptoms of mental disorders. Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behaviour are essential for all free-moving animals to stay alive and to have offspring. Even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must therefore have been capable of generating these behaviours. Our earliest vertebrate ancestors, with a brain comparable with the modern lamprey, had a sophisticated extrapyramidal system generating and controlling all motions as well as a circuit including the habenula for the evaluation of the benefits of their actions. Almost the complete endbrain of the first land animals with a brain comparable with that of amphibians became assimilated into the human amygdaloid and hippocampal complex, whereas only a small part of the dorsal pallium and striatum developed into the ventral extrapyramidal circuits and the later insular cortex. The entire neocortex covering the hemispheres is of recent evolutionary origin, appearing first in early mammals. During the entire evolution of vertebrates, the habenular system was well conserved and maintained its function in regulating the intensity of reward-seeking (pleasure-related) and misery-fleeing (happiness-related) behaviour. The authors propose that the same is true in humans. Symptomatology of human mental disorders can be considered to result from maladaptation within a similar amygdalo/hippocampal-habenular-mesencephalic-ventral striatal system.

Potential Applications of the National Institute of Mental Health's Research Domain Criteria (RDoC) to Clinical Psychiatric Practice: How RDoC Might Be Used in Assessment, Diagnostic Processes, Case Formulation, Treatment Planning, and Clinical Notes.

Offering a new framework for understanding and studying basic dimensions of normal and abnormal human functioning and mental disorders, the National Institute of Mental Health (NIMH) has initiated the Research Domain Criteria (RDoC) project in which a series of higher order domains, representing major systems of emotion, cognition, motivation, and social behavior, and their constituent operationally defined constructs serve as organizing templates for further research and inquiry, eg, to discover validated biomarkers and endophenotypes. Cutting across traditional DSM diagnoses, the domains are defined as Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Systems for Social Processes, and Arousal/Regulatory Systems. To inform educators, trainees, and practitioners about RDoC, alert them to potential practical applications, and encourage their broad exploration in clinical settings, this article reviews the RDoC domains and their subsystem constructs with regard to potential current clinical considerations and applications. We describe ways in which the RDoC domains and constructs offer transdiagnostic frameworks for complementing traditional practice; suggest clinical questions to help elucidate salient information; and, translating RDoC domains and constructs headings into clinically friendly language, offer a template for the psychiatric review of systems that can serve in clinical notes.