Distinct Situational Cue Processing in Individuals with Kleptomania: A Preliminary Study

「万引き」依存症のメカニズムを解明 --窃盗症が不適応な学習である証拠の発見--. 京都大学プレスリリース. 2023-02-16.BACKGROUND: Impulse control disorder has been suggested to meet the criteria of addiction and is often considered a behavioral addiction; however, few studies have examined whether the disorder involves altered responses to situational cues that are associated with symptoms. In this study, we examined behavioral and neural responses to situational cues among individuals with an impulse control disorder, i.e., kleptomania. METHODS: Healthy adults and kleptomania patients whose symptoms were characterized by repetitive, uncontrolled shoplifting of sales goods in stores were recruited. Images with and without situational cues (e.g., a grocery store) were presented, and gazing patterns for the images were detected with the eye-tracker. Additionally, prefrontal cortical (PFC) responses were measured using functional near-infrared spectroscopy. PFC activities were further examined while subjects were watching video clips in virtual reality with and without situational cues. RESULTS: Among kleptomania patients, the gazing pattern for an image with situational cues was distinct from gazing patterns for other images; such differences were not observed in healthy subjects. Consistent with gazing patterns, PFC local network responses by hemoglobin changes to images and videos with situational cues were substantially different from other images and videos in kleptomania patients, whereas PFC responses were consistent across all image and video presentations in healthy subjects. CONCLUSIONS: These results suggest that kleptomania patients may perceive situational cues associated with their problematic behaviors differently from healthy subjects

Neurodevelopmental Disruption of Cortico-Striatal Function Caused by Degeneration of Habenula Neurons

The habenula plays an important role on cognitive and affective functions by regulating monoamines transmission such as the dopamine and serotonin, such that its dysfunction is thought to underlie a number of psychiatric conditions. Given that the monoamine systems are highly vulnerable to neurodevelopmental insults, damages in the habenula during early neurodevelopment may cause devastating effects on the wide-spread brain areas targeted by monoamine innervations.Using a battery of behavioral, anatomical, and biochemical assays, we examined the impacts of neonatal damage in the habenula on neurodevelopmental sequelae of the prefrontal cortex (PFC) and nucleus accumbens (NAcc) and associated behavioral deficits in rodents. Neonatal lesion of the medial and lateral habenula by ibotenic acid produced an assortment of behavioral manifestations consisting of hyper-locomotion, impulsivity, and attention deficit, with hyper-locomotion and impulsivity being observed only in the juvenile period, whereas attention deficit was sustained up until adulthood. Moreover, these behavioral alterations were also improved by amphetamine. Our study further revealed that impulsivity and attention deficit were associated with disruption of PFC volume and dopamine (DA) receptor expression, respectively. In contrast, hyper-locomotion was associated with decreased DA transporter expression in the NAcc. We also found that neonatal administration of nicotine into the habenula of neonatal brains produced selective lesion of the medial habenula. Behavioral deficits with neonatal nicotine administration were similar to those caused by ibotenic acid lesion of both medial and lateral habenula during the juvenile period, whereas they were different in adulthood.Because of similarity between behavioral and brain alterations caused by neonatal insults in the habenula and the symptoms and suggested neuropathology in attention deficit/hyperactivity disorder (ADHD), these results suggest that neurodevelopmental deficits in the habenula and the consequent cortico-striatal dysfunctions may be involved in the pathogenesis and pathophysiology of ADHD

The effects of prenatal and postnatal environmental interaction: Prenatal environmental adaptation hypothesis.

Adverse antenatal maternal environments during pregnancy influence fetal development that consequently increases risks of mental health problems including psychiatric disorders in offspring. Therefore, behavioral and brain alterations caused by adverse prenatal environmental conditions are generally considered as deficits. In this article, we propose a novel hypothesis, along with summarizing a body of literatures supporting it, that fetal neurodevelopmental alterations, particularly synaptic network changes occurring in the prefrontal cortex, associated with adverse prenatal environmental conditions may be adaptation to cope with expected severe postnatal environments, and therefore, psychiatric disorders may be able to be understood as adaptive strategies against severe environmental conditions through evolution. It is hoped that the hypothesis presented in this article stimulates and opens a new venue on research toward understanding of biological mechanisms and therapeutic treatments of psychiatric disorders

Prefrontal cortical dopamine from an evolutionary perspective.

First online: 23 January 2015In this article, we propose the hypothesis that the prefrontal cortex (PFC) acquired neotenic development as a consequence of mesocortical dopamine (DA) innervation, which in turn drove evolution of the PFC into becoming a complex functional system. Accordingly, from the evolutionary perspective, decreased DA signaling in the PFC associated with such adverse conditions as chronic stress may be considered as an environmental adaptation strategy. Psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder may also be understood as environmental adaptation or a by-product of such a process that has emerged through evolution in humans. To investigate the evolutionary perspective of DA signaling in the PFC, domestic animals such as dogs may be a useful model

Habenula and ADHD: Convergence on time.

Attention deficit/hyperactivity disorder (ADHD) is a childhood-onset psychiatric condition characterized by hyperactivity, impulsivity, and attention deficit. In addition to these core symptoms, accumulating evidence suggests that ADHD may also involve alterations in circadian rhythms, sleep disturbance, and time perception. The habenula is a brain region transmitting limbic information to the midbrain monoamine systems and is thereby involved in the regulation of monoamine release in such target brain areas as the striatum, where it is part of the biological substrates that process time perception. The habenula is additionally a part of the circadian rhythm network and is involved in sleep regulation. Our recent study provides a new insight that a habenula lesion created early in development produces behavioral and brain alterations resembling those observed in ADHD. We propose that the habenula may be a promising target for understanding the pathogenesis of ADHD

Reconsideration of animal models of schizophrenia and other psychiatric disorders with evolutionary perspective.

Studies utilizing animal models for understanding biological mechanisms of such psychiatric disorders as schizophrenia have been now flourishing. Animal models are a essential part of translational research, and without them, it is not possible to develop therapeutic strategies to treat psychiatric disorders. Accordingly, importance of animal models has been increasingly emphasized. However, on the other side, limitations of such an animal model approach have been growingly deceptive. The aim of this review article is to discuss limitations of translational research utilizing animal models, and propose a new direction of research with evolutionary perspective to understand psychiatric disorders

Dopamine in socioecological and evolutionary perspectives: implications for psychiatric disorders.

Dopamine (DA) transmission in brain areas such as the prefrontal cortex (PFC) and nucleus accumbens (NAcc) plays important roles in cognitive and affective function. As such, DA deficits have been implicated in a number of psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder (ADHD). Accumulating evidence suggests that DA is also involved in social behavior of animals and humans. Although most animals organize and live in social groups, how the DA system functions in such social groups of animals, and its dysfunction causes compromises in the groups has remained less understood. Here we propose that alterations of DA signaling and associated genetic variants and behavioral phenotypes, which have been normally considered as "deficits" in investigation at an individual level, may not necessarily yield disadvantages, but even work advantageously, depending on social contexts in groups. This hypothesis could provide a novel insight into our understanding of the biological mechanisms of psychiatric disorders, and a potential explanation that disadvantageous phenotypes associated with DA deficits in psychiatric disorders have remained in humans through evolution

The Roles of Serotonin in Decision-making under Social Group Conditions

People in a social group often have to make decisions under conflict, for instance, to conform to the group or obey authority (subjects at higher social rank in the group). The neural mechanisms underlying how social group setting affects decision-making have largely remained unclear. In this study, we designed novel behavioral tests using food access priority and fear conditioning paradigms that captured decision-making under conflict associated with social group environments in mice and examined the roles of serotonin (5-HT) on these processes. Using these behavioral tests, administration of the selective 5-HT reuptake inhibitor, which increased 5-HT transmission, was found to attenuate conflicts in decision-making that may be associated with human cases of social obedience and conformity in mice under group housing. The results suggest that 5-HT plays important roles in the regulation of individual behaviors that organize social group dynamics