Depressive and psychotic symptoms in schizophrenia:Focus on networks and treatment

This thesis has two main aims. First, to review and increase knowledge concerning symptom interaction in patients with schizophrenia, with a specific focus on co-occurring depressive symptoms and its neural correlates in major depressive disorder (Part I and II). Second, to review and investigate different treatment aspects and outcomes in schizophrenia (quality of life, depressive symptoms and mortality) (Part III). In sum, both network studies showed the importance of depressive symptoms in the symptom networks of patients with schizophrenia and showed the stability of such a network structure. Although the network approaches has several issues of debate, it is a promising new way of thinking about psychopathology. The network approach is an example of a new conceptualisation of psychopathology as dynamic systems that change over time. Additionally, this view on mental illness facilitates a more transdiagnostic approach, in which emotion regulation should be an important target for future studies. Given the frequent co-occurrence of depressive symptoms in patients with schizophrenia, its centrality, its correlations with suicidality and influence on quality of life, it is highly important to adequately treat co-occurring depressive symptoms and episodes. Systematically following the provided treatment guide to treat depressive symptoms or episodes might be useful. Additionally, meta-analyses showed that schizophrenia patients who do not use antipsychotics have a higher mortality risk compared to patients that use antipsychotics. In a similar way, continuous use of clozapine was related to a lower mortality risk compared to patients using other antipsychotics

Facilitated engraftment of human hematopoietic cells in severe combined immunodeficient mice following a single injection of Cl²MDP liposomes

Transplantation of normal and malignant human hematopoietic cells into severe combined immunodeficient (SCID) mice allows for evaluation of long-term growth abilities of these cells and provides a preclinical model for therapeutic interventions. However, large numbers of cells are required for successful engraftment in preirradiated mice due to residual graft resistance, that may be mediated by cells from the mononuclear phagocytic system. Intravenous (i.v.) injection of liposomes containing dichloromethylene diphosphonate (Cl2MDP) may eliminate mouse macrophages in spleen and liver. In this study outgrowth of acute myeloid leukemia (AML) cells and umbilical cord blood (UCB) cells in SCID mice conditioned with a single i.v. injection of Cl2MDP liposomes in addition to sublethal total body irradiation (TBI) was compared to outgrowth of these cells in SCID mice that had received TBI alone. A two- to 10-fold increase in outgrowth of AML cells was observed in four cases of AML. Administration of 107 UCB cells reproducibly engrafted SCID mice that had been conditioned with Cl2MDP liposomes and TBI, whereas human cells were not detected in mice conditioned with TBI alone. As few as 2 x 104 purified CD34+ UCB cells engrafted in all mice treated with Cl2MDP liposomes. In SCID mice treated with macrophage depletion unexpected graft failures were not observed. Histological examination of the spleen showed that TBI and Cl2MDP liposomes i.v. resulted in a transient elimination of all macrophage subsets in the spleen, whereas TBI had a minor effect. Cl2MDP liposomes were easy to use and their application was not associated with appreciable side-effects. Cl2MDP liposome pretreatment in combination with TBI allows for reproducible outgrowth of high numbers of human hematopoietic cells in SCID mice

Benchmarks of subcriticality in accelerator-driven system at Kyoto University Critical Assembly

Basic research on the accelerator-driven system is conducted by combining U-235-fueled and Th-232-loaded cores in the Kyoto University Critical Assembly with the pulsed neutron generator (14 MeV neutrons) and the proton beam accelerator (100 MeV protons with a heavy metal target). The results of experimental subcriticality are presented with a wide range of subcriticality level between near critical and 10,000 pcm, as obtained by the pulsed neutron source method, the Feynman-alpha method, and the neutron source multiplication method

Neutron Generation Time in Highly-Enriched Uranium Core at Kyoto University Critical Assembly

At the Kyoto University Critical Assembly experiments on kinetics parameters are carried out at near-critical configurations, supercritical and subcritical states, in the thermal neutron spectrum made with a highly enriched uranium fuel. The main calculated kinetics parameters, the effective delayed neutron fraction (βeff) and the neutron generation time (Ʌ), are used effectively for the estimation of experimental parameters, and the accuracy of experiments on prompt neutron decay constant (α) and subcriticality (ρ$) in dollar units is attained by the numerical results of βeff and Ʌ. Furthermore, the value of βeff/Ʌ is experimentally deduced with the use of the experimental results of α and ρ$, ranging between 250 and −80 pcm. Thus, the experimentally deduced values of βeff/Ʌ that reveal good accuracy through a comparison with those by the MCNP6.1 calculations with JENDL-4.0 are then taken as an index of Ʌ by introducing an acceptable assumption of βeff at near-critical configurations. From the results of experimental and numerical analyses, the experimental value of βeff/Ʌ is important for the validation of Ʌ since kinetics parameters are successfully obtained from the clean cores of near-critical configurations in the thermal neutron spectrum

Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection

The requirement of type I interferon (IFN) for natural killer (NK) cell activation in response to viral infection is known, but the underlying mechanism remains unclear. Here, we demonstrate that type I IFN signaling in inflammatory monocytes, but not in dendritic cells (DCs) or NK cells, is essential for NK cell function in response to a mucosal herpes simplex virus type 2 (HSV-2) infection. Mice deficient in type I IFN signaling, Ifnar(-/-) and Irf9(-/-) mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 production, and lacked NK cell-derived IFN-gamma. Depletion of inflammatory monocytes, but not DCs or other myeloid cells, resulted in lower levels of IL-18 and a complete abrogation of NK cell function in HSV-2 infection. Moreover, this resulted in higher susceptibility to HSV-2 infection. Although Il18(-/-) mice had normal levels of inflammatory monocytes, their NK cells were unresponsive to HSV-2 challenge. This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response

Melting process and interface instability of highly magnetized solid 3He: Role of the magnetization gradient

Theoretical PhysicsQuantum Matter and Optic

A Network of Psychopathological, Cognitive, and Motor Symptoms in Schizophrenia Spectrum Disorders

Schizophrenia spectrum disorders (SSDs) are complex syndromes involving psychopathological, cognitive, and also motor symptoms as core features. A better understanding of how these symptoms mutually impact each other could translate into diagnostic, prognostic, and, eventually, treatment advancements. The present study aimed to: (1) estimate a network model of psychopathological, cognitive, and motor symptoms in SSD; (2) detect communities and explore the connectivity and relative importance of variables within the network; and (3) explore differences in subsample networks according to remission status. A sample of 1007 patients from a multisite cohort study was included in the analysis. We estimated a network of 43 nodes, including all the items from the Positive and Negative Syndrome Scale, a cognitive assessment battery and clinical ratings of extrapyramidal symptoms. Methodologies specific to network analysis were employed to address the study’s aims. The estimated network for the total sample was densely interconnected and organized into 7 communities. Nodes related to insight, abstraction capacity, attention, and suspiciousness were the main bridges between network communities. The estimated network for the subgroup of patients in remission showed a sparser density and a different structure compared to the network of nonremitted patients. In conclusion, the present study conveys a detailed characterization of the interrelations between a set of core clinical elements of SSD. These results provide potential novel clues for clinical assessment and intervention