Frontotemporal dementia (FTD) is now increasingly being recognized as one of the causes of young onset dementia (YOD). The presentation of FTD can be subtle with a broad range of symptoms. This frequently causes misdiagnosis and a delay in initiating the correct treatment. While subtle personality changes, disinhibition and problems in executive functioning are frequently encountered in FTD, frank psychotic symptoms resembling schizophrenia are unusual. This is a case of a 38 year old Chinese female that highlights how obsessive compulsive symptoms which progressed to florid psychosis and disorganized speech and behavior can be a presenting picture in FTD. For seven years, this patient was treated as a case of schizophrenia and was thought to have poor response to electroconvulsive therapy (ECT) as well as antipsychotic medication. Her blood work and electroencephalogram (EEG) were normal. Magnetic resonance imaging (MRI) showed progressive cerebral atrophy. This case report suggests that psychosis should be investigated in detail especially when the clinical presentation is not typical of a functional disorder and more so when the patient is not responsive to conventional treatment. This report also highlights the importance of eliciting symptoms suggestive of an "organic" etiology, such as incontinence and disorientation. In addition, the usefulness of repeated imaging to show the rapidly progressive course of FTD has been illustrated. Other possible differential diagnoses of this patient are also discussed.
Schizophrenia is a chronic mental disorder with marked symptoms of hallucination, delusion, and impaired cognitive behaviors. Although multidimensional factors have been associated with the development of schizophrenia, the principal cause of the disorder remains debatable. Microbiome involvement in the etiology of schizophrenia has been widely researched due to the advancement in sequencing technologies. This review describes the contribution of the gut microbiome in the development of schizophrenia that is facilitated by the gut-brain axis. The gut microbiota is connected to the gut-brain axis via several pathways and mechanisms, that are discussed in this review. The role of the oral microbiota, probiotics and prebiotics in shaping the gut microbiota are also highlighted. Lastly, future perspectives for microbiome research in schizophrenia are addressed.
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address: douglas.ruderfer@vanderbilt.edu, Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium
Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.
The epigenetic changes of RELN that are involved in the development of dopaminergic neurons may fit the developmental theory of schizophrenia. However, evidence regarding the association of RELN DNA methylation with schizophrenia is far from sufficient, as studies have only been conducted on a few limited brain samples. As DNA methylation in the peripheral blood may mirror the changes taking place in the brain, the use of peripheral blood for a DNA methylation study in schizophrenia is feasible due to the scarcity of brain samples. Therefore, the aim of our study was to examine the relationship of DNA methylation levels of RELN promoters with schizophrenia using genomic DNA derived from the peripheral blood of patients with the disorder. The case control studies consisted of 110 schizophrenia participants and 122 healthy controls who had been recruited from the same district. After bisufhite conversion, the methylation levels of the DNA samples were calculated based on their differences of the Cq values assayed using the highly sensitive real-time MethyLight TaqMan® procedure. A significantly higher level of methylation of the RELN promoter was found in patients with schizophrenia compared to controls (p = 0.005) and also in males compared with females (p = 0.004). Subsequently, the RELN expression of the methylated group was 25 fold less than that of the non-methylated group. Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia. However, the definite effects of methylation on RELN function during development and also in adult life still require further elaboration.