Background: Schizophrenia (SZ) and bipolar disorder (BD) share many features: overlap in mood and psychotic symptoms, common genetic predisposition, treatment with antipsychotics (APs), and similar metabolic comorbidities. The pathophysiology of both is still not well defined, and no biomarkers can be used clinically for diagnosis and management. This study aimed to assess the plasma proteomics profile of patients with SZ and BD maintained on APs compared to those who had been off APs for 6 months and to healthy controls (HCs). Methods: We analyzed the data using functional enrichment, random forest modeling to identify potential biomarkers, and multivariate regression for the associations with metabolic abnormalities. Results: We identified several proteins known to play roles in the differentiation of the nervous system like NTRK2, CNTN1, ROBO2, and PLXNC1, which were downregulated in AP-free SZ and BD patients but were "normalized" in those on APs. Other proteins (like NCAM1 and TNFRSF17) were "normal" in AP-free patients but downregulated in patients on APs, suggesting that these changes are related to medication's effects. We found significant enrichment of proteins involved in neuronal plasticity, mainly in SZ patients on APs. Most of the proteins associated with metabolic abnormalities were more related to APs use than having SZ or BD. The biomarkers identification showed specific and sensitive results for schizophrenia, where two proteins (PRL and MRC2) produced adequate results. Conclusions: Our results confirmed the utility of blood samples to identify protein signatures and mechanisms involved in the pathophysiology and treatment of SZ and BD.
We report a consanguineous family in which schizophrenia segregates in a manner consistent with recessive inheritance of a rare, partial-penetrance susceptibility allele. From 4 marriages between 2 sets of siblings who are half first cousins, 6 offspring have diagnoses of psychotic disorder. Homozygosity mapping revealed a 6.1-Mb homozygous region on chromosome 13q22.2-31.1 shared by all affected individuals, containing 13 protein-coding genes. Microsatellite analysis confirmed homozygosity for the affected haplotype in 12 further apparently unaffected members of the family. Psychiatric reports suggested an endophenotype of milder psychiatric illness in 4 of these individuals. Exome and genome sequencing revealed no potentially pathogenic coding or structural variants within the risk haplotype. Filtering for noncoding variants with a minor allele frequency of <0.05 identified 17 variants predicted to have significant effects, the 2 most significant being within or adjacent to the SCEL gene. RNA sequencing of blood from an affected homozygote showed the upregulation of transcription from NDFIP2 and SCEL. NDFIP2 is highly expressed in brain, unlike SCEL, and is involved in determining T helper (Th) cell type 1 and Th2 phenotypes, which have previously been implicated with schizophrenia.
Chromosomes, Human, Pair 13/genetics , Consanguinity , Genes, Recessive/genetics , Genetic Predisposition to Disease/genetics , Psychotic Disorders/genetics , Schizophrenia/genetics , Endophenotypes , Female , Genetic Loci , Humans , Male , Pedigree , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology
The article Self-Reported Sleep and Exercise Patterns in Patients with Schizophrenia: a Cross-Sectional Comparative Study written by Nancy Kiwan, Ziyad Mahfoud, Suhaila Ghuloum, Rifka Chamali, Arij Yehya, Samer Hammoudeh, Yahya Hani, Iman Amro, and Hassen Al-Amin.
BACKGROUND: Adequate sleep and physical activity have been linked to the overall well-being of both medical and psychiatric patients. Patients with schizophrenia have shown abnormal sleep patterns and decreased physical activity that were linked to their psychopathology and physical health. These phenomena are not studied yet in Arab patients with schizophrenia. The purpose of this study is to study the sleep and exercise patterns in Arab patients with schizophrenia compared with those of healthy controls. METHOD: A total of 99 patients with schizophrenia and 101 controls were recruited. Arabic versions of sleep, exercise, socio-demographic, and clinical questionnaires were administered as well as the validated scales to measure psychopathology, depression, and suicidality in these participants. RESULTS: The majority of patients with schizophrenia slept more than 8 h per day and exercised less when compared with controls. Sleep quality was worse in those with higher depression score and higher suicidality scores were seen in patients with lower sleep duration. Multinomial regression showed that patients with schizophrenia have higher odds of sleeping more than 8 h even after controlling for the intake of antipsychotics, age, gender, smoking status, and other confounding factors. CONCLUSION: Our results showed that Arab patients with schizophrenia are at increased risk of having longer sleep duration with inadequate physical activity, which are correlating with worsening of depressive symptoms and suicidality. Thus, more attention should be paid to the changes in sleep patterns and level of exercise when treating Arab patients with schizophrenia.
Schizophrenia/physiopathology , Sleep/physiology , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Self Report , Surveys and Questionnaires , Young Adult
BACKGROUND: Disturbances in sleep duration and quality have been associated with obesity and other metabolic changes. Patients with mental disorders (MD) are known to have more sleep problems, and antipsychotics (AP), used in the treatment of these patients, can also cause weight gain. This study aimed to compare the self-reported sleep patterns between psychiatric patients (on or off AP) and controls. We also evaluated the associations between the clinical and metabolic profiles with short or long sleep duration. METHODS: A total of 339 subjects was recruited: Mentally ill patients maintained on AP for at least six months (MD+AP, n=112), patients not taking AP for at least the last six months before enrollment (MD/noAP, n=101), and non-psychiatry controls (HC, n=126). Multinomial regression analysis was applied to find the predictors of irregular sleep duration in this sample. RESULTS: More mentally ill patients (MD+AP and MD/noAP) reported a sleep duration of >8 hrs than HC. Patients from MD/noAP showed more insomnia than HC. Sleep disturbances were significantly more frequent in MD+AP than HC. Participants who reported sleeping >8 hrs had higher body mass index and waist circumference than those who slept <7 hrs. CONCLUSION: Female gender, central obesity and being mentally ill were independently associated with long sleep duration (>8h) in the population of Qatar.
