Association between leptin levels and severity of suicidal behaviour in schizophrenia spectrum disorders.

OBJECTIVE: Associations between suicidality and lipid dysregulation are documented in mental illness, but the potential role of leptin remains unclear. We examined the association between leptin and suicidal behaviour in schizophrenia, together with the influence of other clinical and biological indices. METHOD: We recruited a sample of 270 participants with schizophrenia spectrum diagnoses. Blood samples were analysed for leptin, while symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS) and Inventory of Depressive Symptomatology (IDS-C). Patients' history of suicidal behaviour was categorized into three subgroups based on IDS-C suicide subscale: No suicidal behaviour, mild/moderate suicidal behaviour and severe suicidal behaviour with/without attempts. RESULTS: Mild/moderate suicidal behaviour was present in 17.4% and severe suicidal behaviour in 34.8%. Both groups were significantly associated with female gender (OR = 6.0, P = 0.004; OR = 5.9, P = 0.001), lower leptin levels (OR = 0.4, P = 0.008; OR = 0.5, P = 0.008) and more severe depression (OR = 1.2, P < 0.001; OR = 1.1, P < 0.001) respectively. Smoking (OR = 2.6, P = 0.004), younger age of onset (OR = 0.9, P = 0.003) and less use of leptin-increasing medications (OR = 0.5, P = 0.031) were associated with severe/attempts group, while higher C-reactive protein CRP (OR = 1.3, P = 0.008) was associated with mild/moderate group. CONCLUSION: Lower leptin levels were associated with higher severity of suicidal behaviour in schizophrenia.

Cardiovascular risk remains high in schizophrenia with modest improvements in bipolar disorder during past decade.

OBJECTIVE: While CVD risk has decreased in the general population during the last decade, the situation in patients with schizophrenia (SCZ) and bipolar disorder (BD) is unknown. METHODS: We compared CVD risk factors in patients with SCZ and BD recruited from 2002-2005 (2005 sample, N = 270) with patients recruited from 2006-2017 (2017 sample, N = 1011) from the same catchment area in Norway. The 2017 sample was also compared with healthy controls (N = 922) and the general population (N range = 1285-4587, Statistics Norway) from the same area and period. RESULTS: Patients with SCZ and BD in the 2017 sample had significantly higher level of most CVD risk factors compared to healthy controls and the general population. There was no significant difference in the prevalence of CVD risk factors in SCZ between the 2005 and 2017 samples except a small increase in glucose in the 2017 sample. There were small-to-moderate reductions in hypertension, obesity, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure in the BD 2017 sample compared to the 2005 sample. CONCLUSION: Despite major advances in health promotion during the past decade, there has been no reduction in the level of CVD risk factors in patients with SCZ and modest improvement in BD.

An association between YKL-40 and type 2 diabetes in psychotic disorders.

OBJECTIVE: This study examines if YKL-40 is increased in individuals with psychotic disorders and if elevated YKL-40 levels at baseline is associated with subsequent development of type 2 diabetes. METHOD: A total of 1383 patients with a diagnosis of schizophrenia or affective psychosis and 799 healthy controls were recruited in the period 2002-2015. Plasma YKL-40 and metabolic risk factors were measured and medication was recorded. Using national registry data, association between baseline risk factors and later development of type 2 diabetes was assessed using Cox proportional hazards models. RESULTS: Plasma YKL-40 was higher in patients vs. healthy controls also after adjusting for metabolic risk factors, with no difference between the schizophrenia and affective psychosis groups. Patients were diagnosed with type 2 diabetes at a significantly younger age. Multivariate Cox regression analyses showed that elevated YKL-40 (hazard ratio (HR) = 5.6, P = 0.001), elevated glucose (HR = 3.6, P = 0.001), and schizophrenia diagnosis (HR = 3.0, P = 0.014) at baseline were associated with subsequent development of type 2 diabetes. CONCLUSIONS: Patients with psychotic disorders have at baseline increased levels of YKL-40 beyond the effect of comorbid type 2 diabetes and metabolic risk factors. Elevated YKL-40 level at baseline is associated with later development of type 2 diabetes.

Persistent increase in TNF and IL-1 markers in severe mental disorders suggests trait-related inflammation: a one year follow-up study.

OBJECTIVE: We evaluated if plasma levels of inflammatory markers are persistently altered in severe mental disorders with psychotic symptoms or associated with state characteristics in a longitudinal study. METHODS: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), von Willebrand factor (VWF), and osteoprotegerin (OPG) were measured in schizophrenia (n = 69) and affective (n = 55) spectrum patients at baseline and at one-year follow-up, and compared to healthy controls (HC) (n = 92) with analysis of covariance. Association between change in symptoms and inflammatory markers was analyzed with mixed-effects models. RESULTS: sTNF-R1 was higher in the schizophrenia (P < 0.0001) and affective disorders (P = 0.02) compared to HC, while IL-1Ra was higher in schizophrenia (P = 0.01) compared to HC at one year follow-up. There were no significant differences between schizophrenia and affective groups; however, levels in the affective group were in between schizophrenia and HC for sTNF-R1 and IL-1Ra. There were no significant associations between change in symptoms and inflammatory markers. CONCLUSION: Persistently increased sTNF-R1 and IL-1Ra after one year in patients with severe mental disorders primarily reflecting data from the schizophrenia group may suggest that inflammation is a trait phenomenon, and not only the result of stress-related mechanisms associated with acute episodes.

Association between cytokine levels, verbal memory and hippocampus volume in psychotic disorders and healthy controls.

OBJECTIVE: We investigated whether elevated plasma levels of immune markers were associated with verbal memory and hippocampal subfield volumes in patients with severe mental illnesses and in healthy controls. METHOD: In total, 230 patients with a broad DSM-IV schizophrenia spectrum illness or bipolar disorder and 236 healthy controls were recruited. Memory was assessed using the Wechsler Memory Scale-Third Edition (WMS-III) Logical Memory immediate and delayed recall, and the California Verbal Learning Test summed recall over learning list (CVLT learning) and delayed free recall. We measured plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist, interleukin-6, von Willebrand factor, osteoprotegerin, high-sensitivity C-reactive protein and sCD40 ligand. Hippocampal subfield estimates were obtained using FreeSurfer. RESULTS: We found a moderate negative association between sTNF-R1 and performance on verbal memory learning and recall tests as measured by the WMS-III Logical Memory after controlling for age, sex and diagnosis. We observed no interaction effect of diagnosis and sTNF-R1 on memory scores. We also found a nominally significant positive association between CVLT learning and hippocampal volumes. CONCLUSION: The findings suggest a role for immune involvement in memory independent of severe mental disorders and may support the 'bigger is better' hypothesis of hippocampal subfield volumes.

Metabolic risk factors in schizophrenia and bipolar disorder: The effect of comedication with selective serotonin reuptake inhibitors and antipsychotics.

BACKGROUND: The aim of this observational study was to investigate the relationship between metabolic factors and use of selective serotonin reuptake inhibitors (SSRIs) combined with olanzapine, quetiapine or risperidone. METHODS: Data from the Norwegian Thematically Organized Psychosis study, a cross-sectional study on 1301 patients with schizophrenia (n=868) or bipolar disorder (n=433), were analyzed. As exposure variables in the linear regression model were included the dose or serum concentration of SSRIs (n=280) and of olanzapine (n=398), quetiapine (n=234) or risperidone (n=128). The main outcome variables were levels of total cholesterol, low and high density lipoprotein (LDL and HDL) cholesterol, triglycerides and glucose. RESULTS: One defined daily dose (DDD) per day of an SSRI in addition to olanzapine was associated with an increase in total cholesterol of 0.16 (CI 0.01 to 0.32) mmol/L (P=0.042) and an increase in LDL-cholesterol of 0.17 (CI 0.02 to 0.31) mmol/L (P=0.022). An SSRI serum concentration in the middle of the reference interval in addition to quetiapine was associated with an increase in total cholesterol of 0.39 (CI 0.10 to 0.68) mmol/L (P=0.011) and an increase in LDL-cholesterol of 0.29 (0.02 to 0.56) mmol/L (P=0.037). There were no such effects when combined with risperidone. CONCLUSIONS: The findings indicate only minor deteriorations of metabolic variables associated with treatment with an SSRI in addition to olanzapine and quetiapine, and none when combined with risperidone. These results suggest that SSRIs can be used in combination with antipsychotics, and that the possible increase in cardiovascular risk is negligible.

Treatment-related premature ovarian failure as a long-term complication after Hodgkin's lymphoma.

BACKGROUND: One of the medical sequelae that chemo- and radiotherapy may cause is premature ovarian failure (POF). The scope of this study was to investigate the risk of developing POF as a long-term complication in young women treated for Hodgkin's lymphoma. PATIENTS AND METHODS: The 99 women included in the study were treated between 1975 and 1992 at the Norwegian Radium Hospital. All patients received radiotherapy and 67 of the women also received chemotherapy. RESULTS: POF was found in 37.4% of the patients. The risk of developing POF was significantly higher if the patient received chemotherapy in addition to radiotherapy. Furthermore, the risk increased if chemotherapy included alkylating agents. Long-term follow-up revealed that women who at the time of treatment were under 30 years of age developed POF later, but with the same cumulative risk as women above 30 years of age. CONCLUSIONS: The risk of developing POF after radio- and chemotherapy is higher than earlier estimates suggest. After an observation time of 15 years the cumulative risk is 38% independent of age at the time of treatment. Age below 30 years at the time of treatment delays the development of POF, but does not decrease the life-time risk.