Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of schizophrenia. It is noteworthy that atypical antipsychotic drugs (AAPDs), e.g., clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT(1A) receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence. The neural network underlying the ability of 5-HT(1A) agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid neurons. A novel strategy for cognitive enhancement in psychosis may be benefited by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT(1A) agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g., event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some AAPDs acting directly or indirectly on 5-HT(1A) receptors. These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia

Resting-state electroencephalogram in drug-free subjects with at-risk mental states who later developed psychosis: a low-resolution electromagnetic tomography analysis

Background and objectivesSeveral studies have reported on the resting-state electroencephalogram (EEG) power in patients with schizophrenia, with a decrease in α (especially α2) and an increase in δ and β1 power compared with healthy control; however, reports on at-risk mental states (ARMS) are few. In this study, we measured the resting-state EEG power in ARMS, and investigated its features and the relationship between the power of the frequency bands and their diagnostic outcomes.MethodsPatients with ARMS who were not on any psychotropic medication and met the Comprehensive Assessment of At-Risk Mental State criteria were included. Patients who developed psychotic disorders were labeled as the ARMS-P group, while patients with ARMS who were followed up prospectively for more than 2 years and did not develop psychotic disorders were classified as the ARMS-NP group. EEGs were measured in the resting state, and frequencies were analyzed using standardized low-resolution brain electromagnetic tomography (sLORETA). Seven bands (δ, θ, α1, α2, β1–3) underwent analysis. The sLORETA values (current source density [CSD]) were compared between the ARMS-P and ARMS-NP groups. Clinical symptoms were assessed at the time of EEG measurements using the Positive and Negative Syndrome Scale (PANSS).ResultsOf the 39 patients included (25 males, 14 females, 18.8 ± 4.5 years old), eight developed psychotic disorders (ARMS-P). The ARMS-P group exhibited significantly higher CSD in the β1 power within areas of the left middle frontal gyrus (MFG) compared with the ARMS-NP group (best match: X = −35, Y = 25, Z = 50 [MNI coordinates], Area 8, CSD = 2.33, p < 0.05). There was a significant positive correlation between the β1/α ratio of the CSD at left MFG and the Somatic concern score measured by the PANSS.DiscussionIncreased β1 power was observed in the resting EEG before the onset of psychosis and correlated with a symptom. This suggests that resting EEG power may be a useful marker for predicting future conversion to psychosis and clinical symptoms in patients with ARMS

Age-related changes in EEG signal using triple correlation values

The alpha rhythm in human electroencephalography (EEG) is known to decrease in frequency with age. Previous study has shown that elderly individuals with dementia exhibit higher S values (spatial variability) and SD values (temporal variability) in the triple correlation of the occipital region (P3, P4, Oz) compared to healthy elderly individuals. The objective of this research is to examine changes in S and SD values of the alpha band with aging in healthy individuals using triple correlation values from the frontal region. The subjects were 50 healthy elderly subjects (mean age 73.0 ± 5.1 years), 34 healthy younger subjects (mean age 28.1 ± 4.6 years), and 21 dementia patients (mean age 70.1 ± 9.1 years). The methodology involved recording EEG for 5 min during rest with closed eyes, and then calculating S and SD values of the alpha band (8-13 Hz) using three electrodes in the frontal region (F3, F4, Fpz). The findings indicated that the S values of young individuals were significantly higher than those of elderly individuals (p < 0.01), whereas the SD values of young individuals tended to be lower than those of elderly individuals. The elevated S values in young individuals imply greater spatial variability akin to individuals with dementia, whereas the reduced SD values in young individuals suggest lower temporal variability unlike individuals with dementia. The discrepancy between the S value and SD value in healthy young individuals suggests that the normal cortical dipole in the frontal regions might be more abundant in them compared to healthy elderly individuals

Evolutionary origins of synchronization for integrating information in neurons

The evolution of brain-expressed genes is notably slower than that of genes expressed in other tissues, a phenomenon likely due to high-level functional constraints. One such constraint might be the integration of information by neuron assemblies, enhancing environmental adaptability. This study explores the physiological mechanisms of information integration in neurons through three types of synchronization: chemical, electromagnetic, and quantum. Chemical synchronization involves the diffuse release of neurotransmitters like dopamine and acetylcholine, causing transmission delays of several milliseconds. Electromagnetic synchronization encompasses action potentials, electrical gap junctions, and ephaptic coupling. Electrical gap junctions enable rapid synchronization within cortical GABAergic networks, while ephaptic coupling allows structures like axon bundles to synchronize through extracellular electromagnetic fields, surpassing the speed of chemical processes. Quantum synchronization is hypothesized to involve ion coherence during ion channel passage and the entanglement of photons within the myelin sheath. Unlike the finite-time synchronization seen in chemical and electromagnetic processes, quantum entanglement provides instantaneous non-local coherence states. Neurons might have evolved from slower chemical diffusion to rapid temporal synchronization, with ion passage through gap junctions within cortical GABAergic networks potentially facilitating both fast gamma band synchronization and quantum coherence. This mini-review compiles literature on these three synchronization types, offering new insights into the physiological mechanisms that address the binding problem in neuron assemblies

Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease

Background: Galectin-9 (Gal-9) induces apoptosis in activated T helper 1 (T(H)1) cells as a ligand for T cell immunoglobulin mucin-3 (Tim-3). Gal-9 also inhibits the G1 phase cell cycle arrest and hypertrophy in db/db mice, the hallmark of early diabetic nephropathy, by reversing the high glucose-induced up-regulation of cyclin dependent kinase inhibitors such as p27(Kip1) and p21(Cip1). Methods: We investigated the serum levels of Gal-9 in the patients with type 2 diabetes and various stages of chronic kidney disease (CKD) (n = 182). Results: Serum Gal-9 levels in the patients with type 2 diabetes were 131.9 +/- 105.4 pg/ml and Log(10)Gal-9 levels significantly and positively correlated with age (r = 0.227, p = 0.002), creatinine (r = 0.175, p = 0.018), urea nitrogen (r = 0.162, p = 0.028) and osmotic pressure (r = 0.187, p = 0.014) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.188, p = 0.011). Log(10)Gal-9 levels increased along with the progression of GFR categories of G1 to G4, and they were statistically significant by Jonckheere-Terpstra test (p = 0.012). Log(10)Gal-9 levels remained similar levels in albuminuria stages of A1 to A3. Conclusion: The elevation of serum Gal-9 in the patients with type 2 diabetes is closely linked to GFR and they may be related to the alteration of the immune response and inflammation of the patients with type 2 diabetes and CKD

Effect of calcium supplementation on bone deformity and histopathological findings of skin papules in a pediatric patient with vitamin D–dependent rickets type 2A: A case report

Vitamin D–dependent rickets type 2A (VDDR2A) is an autosomal recessive disease caused by pathogenic variants of the vitamin D receptor (VDR) gene. VDDR2A rickets are usually resistant to native or active vitamin D treatment because of impaired active calcium absorption against the calcium concentration gradient, which is a ligand-dependent VDR action in the small intestine. Alopecia due to an impaired skin follicular cycle is occasionally observed in patients with VDDR2A. Among the pathogenic VDR variants, most in the DNA-binding domain and some in the ligand-binding domain, which affect the dimerization of VDR with the retinoic X receptor, are associated with alopecia. Herein, we report a case of VDDR2A caused by compound heterozygous pathogenic variants of the DNA-binding domain of VDR. Active vitamin D treatment did not ameliorate genu varum, rachitic changes in the roentgenogram, or abnormal laboratory findings. However, oral administration of calcium lactate dramatically improved these findings. The patient also experienced hair loss at two months of age and multiple papules on the skin at two yr of age, which did not improve with vitamin D or calcium supplementation. We also report the histopathological findings of skin papules in this patient

Study of childcare anxieties and way coping in O city

本研究の目的は,母親たちが育児に関して直面している不安を把握し,その不安に対する保健師の対処の実態を明らかにすることである｡そこでO市にあるN保健センターの家庭訪問と月1回の育児相談会において,保健師が受けた育児に関する相談を分析した｡対象はN保健センター管内の4つの地区で,1歳2ヶ月未満の児を持つ母親からの216件の相談内容である｡その結果,母親たちの育児不安で最も多かったのは児の身体や栄養についてであった｡さらに不安は出産順位によっても差があり,また児の月齢により変化し,その内容は児の成長発達と深く関係していた｡そして,育児に関する情報は増えているものの,個別性に欠けていることや,母親たちの知識に偏りがあることも明らかになった｡これらの結果をもとに,現在の母親が抱える不安の傾向を考察し,N保健センターで実施している育児支援活動を踏まえ,母親の不安の対処について検討した｡The purpose of this study is to identify childcare anxieties of mothers and how public health nurses cope with them. The data was collected from the contents of 216 consultations of mothers with children under 14th months of age carried by public health nurses of N public health center, O city. It was revealed that most of the consultations were about child's physical and nutritious concerns. The childcare anxieties associated with growth and birth order and the child's age in months. Moreover, we found that even though there is a large volume of information available about childcare, it is too general. Based on the research findings, we made clear tendency of childcare anxiety of mothers and how the public health nurses coped with them

Specific effects of antitumor active norspermidine on the structure and function of DNA

We compared the effects of trivalent polyamines, spermidine (SPD) and norspermidine (NSPD), a chemical homologue of SPD, on the structure of DNA and gene expression. The chemical structures of SPD and NSPD are different only with the number of methylene groups between amine groups,[N-3-N-4-N] and [N-3-N-3-N], respectively. SPD plays vital roles in cell function and survival, including in mammals. On the other hand, NSPD has antitumor activity and is found in some species of plants, bacteria and algae, but not in humans. We found that both polyamines exhibit biphasic effect; enhancement and inhibition on in vitro gene expression, where SPD shows definitely higher potency in enhancement but NSPD causes stronger inhibition. Based on the results of AFM (atomic force microscopy) observations together with single DNA measurements with fluorescence microscopy, it becomes clear that SPD tends to align DNA orientation, whereas NSPD induces shrinkage with a greater potency. The measurement of binding equilibrium by NMR indicates that NSPD shows 4–5 times higher affinity to DNA than SPD. Our theoretical study with Monte Carlo simulation provides the insights into the underlying mechanism of the specific effect of NSPD on DNA

Pituitary Volume and Socio-Cognitive Functions in Individuals at Risk of Psychosis and Patients With Schizophrenia

Objectives: Increased pituitary volume, which probably reflects hypothalamic-pituitary-adrenal (HPA) hyperactivity, has been reported in patients with schizophrenia and individuals at risk of psychosis. On the basis of potential role of abnormal HPA axis function on cognitive impairments in psychosis, we aimed to examine possible relations between the pituitary volume and socio-cognitive impairments in these subjects.Methods: This magnetic resonance imaging study examined the pituitary gland volume in 38 subjects with at-risk mental state (ARMS) [of whom 4 (10.5%) exhibited the transition to schizophrenia], 63 patients with schizophrenia, and 61 healthy controls. Social and cognitive functions of the ARMS and schizophrenia groups were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS).Results: Both the ARMS and schizophrenia groups had a significantly larger pituitary volume compared to controls. In the schizophrenia group, the pituitary volume was negatively associated with the BACS working memory score. No association was found between the pituitary volume and clinical variables (medication, symptom severity) in either clinical group.Conclusion: Our findings support the notion of common HPA hyperactivity in the ARMS and schizophrenia groups, but abnormal HPA axis function may contribute differently to cognitive deficits according to the illness stages of schizophrenia

Long-Term Effects of Labor Market Conditions on Family Formation for Japanese Youth

This study aims to examine how each cohort's family formation is affected by labor market conditions experienced in youth in Japan. Although deterioration in youth employment opportunities has often been blamed for Japan's declining marriage and fertility rates, the effects of slack labor market conditions on marriage and fertility are theoretically unclear. We estimate the effects of regional labor market conditions on marriage and fertility, controlling for nation-wide year effects and prefecture fixed effects, and find the following. First, the male unemployment rate is negatively correlated with marriage of women in the local labor market, although the correlation is weak and concentrated on the less educated group. Second, high school-educated women who experienced a recession while entering the labor market are less likely to have children and tend to marry later. In contrast, a recession at entry to the labor market rather increases fertility among college-educated women. The overall impact of labor market conditions experienced in youth on family formation is relatively weak, compared to the substantial losses in earnings and employment stability documented by the existing studies