Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Recent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients.

Myelin oligodendrocyte glycoprotein (MOG) was evaluated in the cortex of the superior temporal gyrus (STG) and the hippocampus in 10 schizophrenic and nine age- and sex-matched normal control postmortem brains.

The expression of MOG was significantly lower in the middle layer of the neocortex of the STG and stratum lucidum of CA3 in the hippocampus in the long-term schizophrenic brains (patients with ≥30 years of illness duration) than in the age-matched controls. Furthermore, the thickness of MOG-positive fibre-like structures was significantly lower in both regions of the long-term schizophrenic brains than in the age-matched controls.

These findings suggest that a long duration of illness has a marked effect on the expression of MOG in these regions, and that myelin-oligodendrocyte abnormalities in these regions may be related to the progressive pathophysiology of schizophrenia.

The precise aetiology of schizophrenia remains unclear. The neurodevelopmental hypothesis of schizophrenia has been proposed based on the accumulation of genomic or neuroimaging studies.

In this study, we examined the catecholaminergic neuronal networks in the frontal cortices of disrupted-in-schizophrenia 1 (DISC1) knockout (KO) mice, which are considered to be a useful model of schizophrenia.

Six DISC1 homozygous KO mice and six age-matched littermates were used. The animals’ brains were cut into 20-μm-thick slices, which were then immunohistochemically stained using an anti-tyrosine hydroxylase (TH) monoclonal antibody.

The TH-immunopositive fibres detected in the orbitofrontal cortices of the DISC1 KO mice were significantly shorter than those seen in the wild-type mice.

These neuropathological findings indicate that the hypofrontal symptoms of schizophrenia are associated with higher mental function deficiencies or cognitive dysfunction such as a loss of working memory.

Malignancy-related thromboembolism, also referred to as Trousseau's syndrome, can present as acute cerebral infarction, nonbacterial thrombotic endocarditis (NBTE), and migratory thrombophlebitis. Therefore, many physical, neurological, and psychological symptoms associated with Trousseau's syndrome may occur in the clinical course.

To illustrate this, we report a case of a male patient in his 50s with carcinomatous peritonitis caused by gastric cancer, with multiple cerebral infractions that developed during disease progression. The patient was admitted to our hospital for the treatment of side effects of chemotherapy, although he strongly hoped to go home as soon as possible. In addition to making social supports plans, we were required to perform intensive total palliative care, because of his physical pain, general fatigue, anorexia, abdominal and neck pain, and psychological issues (insomnia, delirium, depression, suicidal thoughts, self-mutilation, panic attacks, agoraphobia, fear of death, and feelings of hopelessness).

To the best of our knowledge, based on the literature search, this is the first reported case of Trousseau's syndrome described in the context of total palliative care, especially psychological care.

We propose that neurological symptoms of Trousseau's syndrome cause these extensive mental disorders. Furthermore, because of the prognosis of Trousseau's syndrome, we should utilize our expertise fulfill the patient's wishes.