Glucagon-like peptide agonists for weight management in antipsychotic-induced weight gain: A systematic review and meta-analysis.

INTRODUCTION: Managing body weight in patients with antipsychotic-induced weight gain (AIWG) is challenging. Besides lifestyle interventions, pharmacological interventions may contribute to weight loss. This systematic review and meta-analysis evaluated the effect on weight loss and adverse effects of glucagon-like peptide-1 (GLP-1) agonists in patients with AIWG. MATERIALS AND METHODS: Following PRISMA guidelines, we performed a meta-analysis of blinded and open-label randomised controlled trials (RCTs), non-randomised controlled trials and cohort studies that evaluated treatment with GLP-1 in patients with AIWG, regardless of psychiatric diagnosis. PubMed, Embase, PsycINFO and Cochrane Library databases were searched. Primary outcome measures were changes in body weight and BMI. Secondary outcomes were changes in adverse effects and severity of psychopathology due to GLP-1 agonists. RESULTS: Only data for exenatide and liraglutide could be included, that is, five RCTs and one cohort study. For exenatide the mean weight loss was -2.48 kg (95% Confidence Interval (CI) -5.12 to +0.64; p = 0.07), for liraglutide the mean weight loss was -4.70 kg (95% CI -4.85 to -4.56; p < 0.001). The mean change in BMI was -0.82 (95% CI -1.56 to -0.09; p = 0.03) in the exenatide groups and -1.52 (95% CI -1.83 to -1.22; p < 0.001) in the liraglutide groups. Exenatide and liraglutide did not adversely affect psychopathology. The most common adverse events were nausea, vomiting, and diarrhoea. CONCLUSION: The GLP-1 agonists exenatide and liraglutide are promising drugs for inducing weight loss in patients with AIWG. The adverse effects are acceptable, and the addition of GLP-1 does not increase the severity of psychopathology. However, more research is needed.

Childhood trauma- and cannabis-associated microstructural white matter changes in patients with psychotic disorder: a longitudinal family-based diffusion imaging study.

BACKGROUND: Decreased white matter (WM) integrity in patients with psychotic disorder has been a consistent finding in diffusion tensor imaging (DTI) studies. However, the contribution of environmental risk factors to these WM alterations is rarely investigated. The current study examines whether individuals with (increased risk for) psychotic disorder will show increased WM integrity change over time with increasing levels of childhood trauma and cannabis exposure. METHODS: DTI scans were obtained from 85 patients with a psychotic disorder, 93 non-psychotic siblings and 80 healthy controls, of which 60% were rescanned 3 years later. In a whole-brain voxel-based analysis, associations between change in fractional anisotropy (ΔFA) and environmental exposures as well as interactions between group and environmental exposure in the model of FA and ΔFA were investigated. Analyses were adjusted for a priori hypothesized confounding variables: age, sex, and level of education. RESULTS: At baseline, no significant associations were found between FA and both environmental risk factors. At follow-up as well as over a 3-year interval, significant interactions between group and, respectively, cannabis exposure and childhood trauma exposure in the model of FA and ΔFA were found. Patients showed more FA decrease over time compared with both controls and siblings when exposed to higher levels of cannabis or childhood trauma. CONCLUSIONS: Higher levels of cannabis or childhood trauma may compromise connectivity over the course of the illness in patients, but not in individuals at low or higher than average genetic risk for psychotic disorder, suggesting interactions between the environment and illness-related factors.

Aggression on the psychiatric ward: Prevalence and risk factors. A systematic review of the literature.

INTRODUCTION: On psychiatric wards, aggressive behaviour displayed by patients is common and problematic. Understanding factors associated with the development of aggression offers possibilities for prevention and targeted interventions. This review discusses factors that contribute to the development of aggression on psychiatric wards. METHOD: In Pubmed and Embase, a search was performed aimed at: prevalence data, ward characteristics, patient and staff factors that are associated with aggressive behaviour and from this search 146 studies were included. RESULTS: The prevalence of aggressive behaviour on psychiatric wards varied (8-76%). Explanatory factors of aggressive behaviour were subdivided into patient, staff and ward factors. Patient risk factors were diagnosis of psychotic disorder or bipolar disorder, substance abuse, a history of aggression, younger age. Staff risk factors included male gender, unqualified or temporary staff, job strain, dissatisfaction with the job or management, burn-out and quality of the interaction between patients and staff. Staff protective factors were a good functioning team, good leadership and being involved in treatment decisions. Significant ward risk factors were a higher bed occupancy, busy places on the ward, walking rounds, an unsafe environment, a restrictive environment, lack of structure in the day, smoking and lack of privacy. CONCLUSION: Despite a lack of prospective quantitative data, results did show that aggression arises from a combination of patient factors, staff factors and ward factors. Patient factors were studied most often, however, besides treatment, offering the least possibilities in prevention of aggression development. Future studies should focus more on the earlier stages of aggression such as agitation and on factors that are better suited for preventing aggression such as ward and staff factors. Management and clinicians could adapt staffing and ward in line with these results.

The details of structural disconnectivity in psychotic disorder: A family-based study of non-FA diffusion weighted imaging measures.

BACKGROUND: Diffusion tensor imaging (DTI) studies in psychotic disorder have shown reduced FA, often interpreted as disturbed white matter integrity. The observed 'dysintegrity' may be of multifactorial origin, as changes in FA are thought to reflect a combination of changes in myelination, fiber organization and number of axons. Examining the structural substrate of the diffusion tensor in individuals with (risk for) psychotic disorder may provide better understanding of the underlying structural changes. METHODS: DTI scans were acquired from 85 patients with psychotic disorder, 93 siblings of patients with psychotic disorder and 80 controls. Cross-sectional group comparisons were performed using Tract-Based Spatial Statistics (TBSS) on six DTI measures: axial diffusivity (AXD), radial diffusivity (RD), mean diffusivity (MD), and the case linear (CL), case planar (CP) and case spherical (CS) tensor shape measures. RESULTS: AXD did not differ between the groups. RD and CS values were significantly increased in patients compared to controls and siblings, with no significant differences between the latter two groups. MD was higher in patients compared to controls (but not siblings), with no difference between siblings and controls. CL was smaller in patients than in siblings and controls, and CP was smaller in both patients and siblings as compared to controls. CONCLUSION: The differences between individuals with psychotic disorder and healthy controls, derived from detailed diffusion data analyses, suggest less fiber orientation and increased free water movement in the patients. There was some evidence for association with familial risk expressed by decreased fiber orientation.

Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study.

BACKGROUND: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. METHODS: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models. RESULTS: Siblings revealed a significant mean FA decrease over time compared to controls (B = -0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = -0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group × region interaction (χ2 = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata. CONCLUSION: Whole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study.

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication.

Microstructural white matter alterations in psychotic disorder: a family-based diffusion tensor imaging study.

BACKGROUND: There is evidence for microstructural white matter alterations in patients with psychotic disorder, suggesting altered interregional connectivity. Less is known about the presence and role of white matter alterations in well individuals at higher than average genetic risk for psychotic disorder. METHODS: 85 patients with psychotic disorder, 93 non-psychotic siblings of patients with psychotic disorder and 80 healthy controls underwent a diffusion tensor imaging (DTI) scanning protocol. In a whole brain voxel-based analysis using Tract Based Spatial Statistics (TBSS), fractional anisotropy (FA) values were compared between the three groups. Effects of antipsychotic medication and drug use were examined. RESULTS: The patients displayed significantly lower mean FA than the controls in the following regions: corpus callosum (genu, body, splenium), forceps major and minor, external capsule bilaterally, corona radiata (anterior, posterior) bilaterally, left superior corona radiata and posterior thalamic radiation bilaterally. Similar FA differences existed between the patients and siblings; the siblings did not differ from the controls. CONCLUSION: Profound microstructural white matter alterations were found in the corpus callosum and other tracti and fasciculi in the patients with psychotic disorder, but not in siblings and the controls. These alterations may reflect brain pathology associated with the illness, illness-related environmental risk factors, or its treatment, rather than genetic risk.