Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment ("chemobrain"), a condition that significantly impairs the quality of life of many cancer survivors.

Patients with cancer are experiencing long-term survival following chemotherapy, but the treatment may also be associated with short and long-term toxicity, including the possibility of cognitive dysfunction. A literature overview indicated a significant association between chemotherapy and cognitive impairment but prospective longitudinal research is warranted to examine the degree and persisting nature of this decline. Although chemotherapeutic agents are unlikely to cross the blood-brain barrier, it has been alleged that the occurrence of neurotoxicity is linked to the pro-inflammatory cytokine pathways. Moreover in most cases many other factors could play an ancillary and concomitant role. The contribution of hormone therapy as well as emotional, social, behavioural and genetic factors should always be considered. Especially physical activity and cognitive training appear promising in the management of cognitive impairment but additional studies are required to establish their efficacy.

Cognitive impairment and chemotherapy: a brief overview.

The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery-Asberg depression rating scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, whereas the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides-Prevotella group, Atopobium Cluster, Enterobacter spp, and Clostridium Cluster IV were higher, whereas the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio and represents microbial colonization resistance). After treatment, MADRS scores were reduced, whereas the levels of Eubacterium rectale, Bifidobacteria, and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR-COC-17011401, URL: http://www.chictr.org.cn/listbycreater.aspx.

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Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

The Chinese Imaging Genetics (CHIMGEN) study establishes the largest Chinese neuroimaging genetics cohort and aims to identify genetic and environmental factors and their interactions that are associated with neuroimaging and behavioral phenotypes. This study prospectively collected genomic, neuroimaging, environmental, and behavioral data from more than 7000 healthy Chinese Han participants aged 18–30 years. As a pioneer of large-sample neuroimaging genetics cohorts of non-Caucasian populations, this cohort can provide new insights into ethnic differences in genetic-neuroimaging associations by being compared with Caucasian cohorts. In addition to micro-environmental measurements, this study also collects hundreds of quantitative macro-environmental measurements from remote sensing and national survey databases based on the locations of each participant from birth to present, which will facilitate discoveries of new environmental factors associated with neuroimaging phenotypes. With lifespan environmental measurements, this study can also provide insights on the macro-environmental exposures that affect the human brain as well as their timing and mechanisms of action.

/pdf/chimgen-a-chinese-imaging-genetics-cohort-to-enhance-cross-lc9kotbyvw.pdf

CHIMGEN: a Chinese imaging genetics cohort to enhance cross-ethnic and cross-geographic brain research

Objectives
Cognitive dysfunction affects a substantial proportion of patients with bipolar disorder (BD), and genetic-imaging paradigms may aid in the elucidation of mechanisms implicated in this symptomatic domain The Val allele of the functional Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working memory in BD

Methods
Sixty-four outpatients with BD in full or partial remission were stratified according to COMT Val158Met genotype (ValVal [n=13], ValMet [n=34], and MetMet [n=17]) The patients completed a spatial n-back working memory task during fMRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory test outside the scanner

Results
During high working memory load (2-back vs 1-back), Val homozygotes displayed decreased activity relative to ValMet individuals, with Met homozygotes displaying intermediate levels of activity in the right dorsolateral prefrontal cortex (dlPFC) (P=016) Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI Outside the MRI scanner, Val carriers performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤006), with deficits being most pronounced in Val homozygotes

Conclusions
The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive impairments in BD

/pdf/the-catechol-o-methyltransferase-comt-val158met-genotype-48x880rb94.pdf

The catechol-O-methyltransferase ( COMT ) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder

L K Hoeffding

Papers

The catechol-O-methyltransferase ( COMT ) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder