Implications For Mental Disorders Research Articles

Emerging role of the lateral habenula in conditioned inhibition and depression.

Associating a neutral conditioned stimulus (CS) with the absence of a biologically significant unconditioned stimulus (US) confers conditioned inhibitory properties upon the CS, referred to as conditioned inhibition. Conditioned inhibition and conditioned excitation, an association of a CS with the presence of the US, are fundamental components of associative learning. While the neural substrates of conditioned excitation are well established, those of conditioned inhibition remain poorly understood. Recent research has shed light on the lateral habenula (LHb) engagement in conditioned inhibition, along with the midbrain dopaminergic neurons. This article reviews behavioral tasks conducted to assess conditioned inhibition and how experimental LHb manipulations affect performance in these tasks. These results underscore the critical role of the LHb in conditioned inhibition. Intriguingly, stress increases LHb reactivity and impairs performances in tasks consisting of a component of conditioned inhibition in animals. Dysfunction of the LHb is observed in patients with depression. The ability of an organism to perform conditioned inhibition is closely linked to altered neuronal activity in the LHb, which has implications for mental disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neuromicrobiology, an emerging neurometabolic facet of the gut microbiome?

The concept of the gut microbiome is emerging as a metabolic interactome influenced by diet, xenobiotics, genetics, and other environmental factors that affect the host's absorption of nutrients, metabolism, and immune system. Beyond nutrient digestion and production, the gut microbiome also functions as personalized polypharmacy, where bioactive metabolites that our microbes excrete or conjugate may reach systemic circulation and impact all organs, including the brain. Appreciable evidence shows that gut microbiota produce diverse neuroactive metabolites, particularly neurotransmitters (and their precursors), stimulating the local nervous system (i.e., enteric and vagus nerves) and affecting brain function and cognition. Several studies have demonstrated correlations between the gut microbiome and the central nervous system sparking an exciting new research field, neuromicrobiology. Microbiome-targeted interventions are seen as promising adjunctive treatments (pre-, pro-, post-, and synbiotics), but the mechanisms underlying host-microbiome interactions have yet to be established, thus preventing informed evidence-based therapeutic applications. In this paper, we review the current state of knowledge for each of the major classes of microbial neuroactive metabolites, emphasizing their biological effects on the microbiome, gut environment, and brain. Also, we discuss the biosynthesis, absorption, and transport of gut microbiota-derived neuroactive metabolites to the brain and their implication in mental disorders.

The mental health of children and young people living in big cities in a revolving postpandemic world.

The world's population is increasingly urban, with most children and young people growing up and living in cities. Evidence suggests that urbanicity is linked to an increased risk for the development of mental health disorders. Rather than an accumulation of risk factors, urbanization is a complex process that profoundly structures living conditions. In this sense, it is timely to discuss what are the social and structural determinants of mental health of children and young people in such settings. Three domains of determinants of mental health were selected for discussion: economics and living conditions, crime and violence, and urban layouts. For each, we debated realities faced by urban children and young people, providing an overview of recent evidence on implications for mental disorders and well being. We also discuss the potential impacts of the covid-19 pandemic on each domain, as well as recommendations for future action. Structural factors are of major relevance for the mental health of children and young people living in cities. The agenda of mental health promotion and prevention must include whole-of-society interventions aimed at improving living conditions, including economic and social capital, violence prevention and urbanistic planning.

Stress Impairs Intentional Memory Control through Altered Theta Oscillations in Lateral Parietal Cortex.

Accumulating evidence suggests that forgetting is not necessarily a passive process but that we can, to some extent, actively control what we remember and what we forget. Although this intentional control of memory has potentially far-reaching implications, the factors that influence our capacity to intentionally control our memory are largely unknown. Here, we tested whether acute stress may disrupt the intentional control of memory and, if so, through which neural mechanism. We exposed healthy men and women to a stress (n = 27) or control (n = 26) procedure before they aimed repeatedly to retrieve some previously learned cue-target pairs and to actively suppress others. While control participants showed reduced memory for suppressed compared with baseline pairs in a subsequent memory test, this suppression-induced forgetting was completely abolished after stress. Using magnetoencephalography (MEG), we show that the reduced ability to suppress memories after stress is associated with altered theta activity in the inferior temporal cortex when the control process (retrieval or suppression) is triggered and in the lateral parietal cortex when control is exerted, with the latter being directly correlated with the stress hormone cortisol. Moreover, the suppression-induced forgetting was linked to altered connectivity between the hippocampus and right dorsolateral prefrontal cortex (PFC), which in turn was negatively correlated to stress-induced cortisol increases. These findings provide novel insights into conditions under which our capacity to actively control our memory breaks down and may have considerable implications for stress-related psychopathologies, such as posttraumatic stress disorder (PTSD), that are characterized by unwanted memories of distressing events.SIGNIFICANCE STATEMENT It is typically assumed that forgetting is a passive process that can hardly be controlled. There is, however, evidence that we may actively control, to some extent, what we remember and what we forget. This intentional memory control has considerable implications for mental disorders in which patients suffer from unwanted (e.g., traumatic) memories. Here, we demonstrate that the capacity to intentionally control our memory breaks down after stress. Using magnetoencephalography (MEG), we show that this stress-induced memory control deficit is linked to altered activity in the lateral parietal cortex and the connectivity between the hippocampus and right prefrontal cortex (PFC). These findings provide novel insights into conditions under which memory control fails and are highly relevant in the context of stress-related psychopathologies.

Psychobiological Model of Volition— Implications for Mental Disorders

A new psychobiological model of volitive processes and its implications for the etiopathology of mental disorders is proposed. The model is based on five elementary volitive processes. These are the volition to act; the volition to self-instrumentalize; the volition to program intentions, the volition to generate realities; and the volition to permanent existence. Imbalances in information processing in tripartite synapses and their network may be responsible for dysfunctions of self-instrumentalization. It is suggested that the volition to permanent existence unconsciously works in mental disorders, but the volition to intentional programming of realities and the volition to generate realities by communication with subjects and objects in their environment are impaired. In depression, the volition to act is constrained by hyperintentional programs that are non-feasible in the environment. In mania volitive processes are totally oriented on events in the environment without any goal-directed pro-gramming. Dysfunctions of volitive processes in schizophrenia are fun-damentally caused by severe impairments of self-instrumentalization. As shown in tripartite synapses a gap between sensory information pro-cessing in the neuronal network and the inner glial networks causes the inability of schizophrenics to distinguish between the self and the other. In delusions, the destiny for communication becomes staged as pseu-do-communication. Together, the study outlines a new model of volitive processes and deduces dysfunctions responsible for communication pa-thology and abnormal reality experiences of patients with mental disor-ders.

The assessment of social disabilities with GSDS-II in persons hospitalized in psychiatric day units and inpatient wards

Social disabilities due to mental disorders have a similar or even more severe impact on daily activities than some of the chronic, severe somatic disorders. The second version of the Groningen Social Disabilities Schedule (GSDS-II) is used in the assessment of social disability in persons with mental disorders. To date, in Poland the conducted research studies focused on this matter only in patients consulted in outpatient clinics and day units. Our study is the first in the country that aims to measure the social disabilities in persons hospitalized in psychiatric inpatient wards. The objective of the study is to assess the degree of social disability using GSDS-II as well as to analyze the impact of clinical, socio-demographic and economic factors on social disabilities in patients diagnosed with psychotic, mood or anxiety disorder (diagnostic codes: F20-F29, F30-F39 and F40-F48, according to ICD-10), aged 18–65, in a day unit and an inpatient ward settings. The excluding criteria are: substance abuse co-morbidity and/or a diagnosed dementia process. The study presents the data gathered from a sample of 50 patients of both genders diagnosed with the aforementioned mental disorders who gave their informed consent to participate in the study. Due to important socio-economic implications of mental disorders that frequently result in the loss of ability of the patients to fulfill their societal roles, a study leading to a better insight on social disabilities will provide useful data for the possible improvement of the mental health care and social policy designed for these persons.Disclosure of interestThe authors have not supplied their declaration of competing interest.

All of Me: The Embodied Nature of Self and Its Implications for Mental DisordersAll of Me: The Embodied Nature of Self and Its Implications for Mental Disorders

All of Me: The Embodied Nature of Self and Its Implications for Mental DisordersAll of Me: The Embodied Nature of Self and Its Implications for Mental Disorders

DISC1, astrocytes and neuronal maturation: a possible mechanistic link with implications for mental disorders

Disrupted-In-Schizophrenia 1 (DISC1) is a genetic risk factor implicated in major mental disorders that involve disrupted neurodevelopment and synaptic signaling. Glial cells such as astrocytes can regulate neuronal and synaptic maturation. Although astrocytes express DISC1, the role of astrocyte DISC1 in synaptic regulation remains unknown. We expressed a pathogenic, dominant-negative form of DISC1, mutant DISC1, in astrocytes to elucidate the roles of astrocytic DISC1 in maturation of dendrites and excitatory and inhibitory synapses using a co-culture model. We found that wild-type primary neurons exhibited less elaborated dendritic arborization when co-cultured with astrocytes that express mutant DISC1, compared to control astrocytes. We observed significantly decreased density of excitatory but not inhibitory synapses on wild-type primary neurons that were co-cultured with astrocytes that express mutant DISC1, compared to control astrocytes. Treatment of co-cultures with D-serine restored dendritic development and density of excitatory synapses. Our findings show for the first time that mutant DISC1 diminished the capacity of astrocytes to support dendritic and synaptic maturation in co-cultured neurons, and that D-serine can restore the dendritic and synaptic abnormalities. The results provide a new insight into the mechanisms whereby genetic risk factors within astrocytes could contribute the pathogenesis of psychiatric disorders. Expression of mutant DISC1 (mDISC1) in astrocytes (A) decreases binding of endogenous DISC1 to serine racemase (SR) and production of D-serine (blue triangles) from L-serine (red triangles). As a result, neurons co-cultured with mutant DISC1 astrocytes exhibit diminished dendritic arborization (DIV10) and decreased linear density of VGLUT+(red)/PSD95+ (green) excitatory synapses (DIV14). Filled circles with arrows denote membrane transporters for D-serine. Read the Editorial Highlight for this article on doi: 10.1111/jnc.13699.

PT674. VGF overexpression mice exhibited several behavioral abnormalities with disruption of brain organization: implication in mental disorders.

PT674. VGF overexpression mice exhibited several behavioral abnormalities with disruption of brain organization: implication in mental disorders.

Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript) has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

A German Adaptation of the UPPS Impulsive Behavior Scale: Psychometric Properties and Factor Structure

Impulsivity occupies a prominent place in psychopathology, yet the precise nature of its implication in mental disorders is still poorly understood. This is partly due to inconsistencies among existing conceptualizations and measurements of impulsivity. In an attempt to overcome these inconsistencies, S. P. Whiteside and D. R. Lynam (2001) developed the UPPS Impulsive Behavior Scale, which distinguishes four facets of impulsivity: urgency, lack of premeditation, lack of perseverance, and sensation seeking. The present study examined the psychometric properties of a German adaptation of the UPPS Impulsive Behavior Scale by administering it to a sample of psychology students. Exploratory and confirmatory factor analyses of the responses of 310 native German speaking participants suggested a four-factor solution similar to that found in the original study. Results indicated that these four subscales possess very good internal consistency.

Neuroendocrine mechanisms of stress and social interaction: implications for mental disorders

The purpose of the present review is to consider further evidence for the role of neuroendocrine mechanisms in mental disorders by focusing on recent trends and advances in the field of psychoneuroendocrinology. Recent studies confirm the importance of the hypothalamic-pituitary-adrenal axis for the development and course of mental disorders. Notably, the neuropeptide oxytocin has been shown to reduce the responsiveness of the hypothalamic-pituitary-adrenal axis to social stress and to improve social approach behavior. A better understanding of the neuroendocrine mechanisms of action underlying normal behavior has recently been translated to studies investigating novel therapeutic approaches using hormone administration. Neuroendocrine systems relevant to behavior clearly demonstrate their impact for the field of psychiatry. Further neuroendocrine research provides insight into the origins of mental disorders both from an etiological perspective and an interventional perspective.

Severe mental illness and airports – the scope of the problem

Aims and MethodMental illness may cause specific problems in the environment of an international airport. The aim of our study was to assess frequency, presentation and safety implications of mental disorders requiring formal admission at an international airport. We performed a retrospective study over 4 years including patients who were detained by the police and admitted.ResultsThe frequency of admissions was one per million passengers, the frequency of incidents raising safety concerns was four per 10 million passengers. An in-flight disturbance occurred in 1.4 per 10 million arriving passengers. Most common were schizophrenia or schizotypal disorder (46.8%) and mania (22.6%). Twenty per cent of patients presented with wandering.Clinical ImplicationsEmergency admissions and incidents causing safety concerns were rare. Airport wandering was a frequent presenting sign that should be recognised.

Role for dopamine in the behavioral functions of the prefrontal corticostriatal system: implications for mental disorders and psychotropic drug action

We have discussed the role of dopamine in modulating the interactions between cortical and striatal regions that are involved in behavioral regulation. The evidence reviewed seems to suggest that dopamine acts, overall, to promote stimulus-induced responding for conditioned or reward-related stimuli by integrative actions at multiple forebrain sites. It is thus not surprising that dopaminergic dysfunction has been implicated in a number of neuropsychiatric disorders that involve abnormal cognitive and affective function. Future studies aimed at pinpointing the precise anatomical sites of action and molecular mechanisms involved in dopaminergic transmission within the corticolimbic circuit are critical for trying to disentangle the cellular mechanisms by which dopamine exerts its actions. Moreover, the afferent control of dopamine neurons from brainstem and forebrain sites need to be fully explored in order to begin to understand what mechanisms are involved in regulating the dopaminergic response to stimuli with incentive value. Finally, the post-synaptic consequences of prolonged and supranormal dopaminergic activation need to be investigated in order to understand what persistent neuroadaptations result from chronic activation of this neuromodulatory system (e.g. in drug addiction). Answers to these sorts of questions will undoubtedly provide important insights into the nature of dopaminergic function in the animal and human brain.