Abstract
Schizophrenia is frequently accompanied by depressive symptoms, but the pathological mechanisms remain to be elucidated. In this study, we used chronic unpredicted mild stress plus MK801 injection to generate a mouse model of schizophrenia with depression, in which in vivo 2-photon calcium imaging and electrophysiological recordings were performed in conjunction with behavioral phenotyping. Compared to mice models with classical depression or to schizophrenia models, the animal models with schizophrenia and depression comorbidity presented worse psychotic and depressive symptoms. These behavioral deficits are associated with impaired neuronal calcium activities in the frontal cortex and thalamic nuclei. Moreover, in sharp contrast to classical models that have a satisfactory response to antipsychotic or antidepressant drugs, this novel schizophrenia with depression model is resilient to combined drug treatment in terms of behavioral and functional recovery. Taken together, these data indicate that schizophrenia with depression likely involves a unique pathophysiology that is different from schizophrenia or depression alone.
Highlights
It is estimated that up to 80% of patients with schizophrenia experience depressive episodes at least once during the early phase of the disease (Upthegrove et al, 2010)
N-methyl-D-aspartic acid (NMDA) receptor antagonist MK801 and chronic unpredicted mild stress (CUMS) were combined to generate a murine model of depression with schizophrenia (CUMS + MK801) and another model that mimics schizophrenia with depression (MK801 + CUMS)
It is further noticed that a previous report indicates an anti-depressant effect of single MK801 in a mouse CUMS model (Yang et al, 2018), our CUMS + MK801 group did not have any significant improvement of depressive phenotypes
Summary
It is estimated that up to 80% of patients with schizophrenia experience depressive episodes at least once during the early phase of the disease (Upthegrove et al, 2010). Argue against such opinions by stating that these comorbidities predict worse schizophrenia prognoses (Siris, 2000; Yung et al, 2007; Upthegrove et al, 2010; Gardsjord et al, 2016; Helfer et al, 2016). The neural mechanism underlying schizophrenia with depression remains largely unknown. Some studies argue for the impairment of the cortico-limbic circuit as the one underlying neuropsychiatric comorbidity (Totterdell, 2006), and a few studies suggest the role of neuroinflammation in schizophrenia and
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