Longitudinal assessment of ventricular volume trajectories in early-stage schizophrenia: evidence of both enlargement and shrinkage.

BACKGROUND: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. METHODS: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. RESULTS: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. CONCLUSION: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.

Weight and metabolic changes in early psychosis-association with daily quantification of medication exposure during the first hospitalization.

BACKGROUND: The most common causes of death in schizophrenia are cardiovascular disorders, which are closely related to metabolic syndrome/obesity. To better understand the development of metabolic alterations early in the course of illness, we quantified daily medication exposure in the first days of the first hospitalization for psychosis and related it to changes in weight and metabolic markers. STUDY DESIGN: We recruited participants with first episode psychosis (FEP, N = 173) during their first psychiatric hospitalization and compared them to controls (N = 204). We prospectively collected weight, body mass index, metabolic markers, and exact daily medication exposure at admission and during hospitalization. STUDY RESULTS: Individuals with FEP gained on average 0.97 ± 2.26 BMI points or 3.46 ± 7.81 kg of weight after an average of 44.6 days of their first inpatient treatment. Greater antipsychotic exposure was associated with greater BMI increase, but only in people with normal/low baseline BMI. Additional predictors of weight gain included type of medication and duration of treatment. Medication exposure was not directly related to metabolic markers, but higher BMI was associated with higher TGC, TSH, and lower HDL. Following inpatient treatment, participants with FEP had significantly higher BMI, TGC, prolactin, and lower fT4, HDL than controls. CONCLUSION: During their first admission, people with FEP, especially those with normal/low baseline BMI, showed a rapid and clinically significant weight increase, which was associated with exposure to antipsychotics, and with metabolic changes consistent with metabolic syndrome. These findings emphasize weight monitoring in FEP and suggest a greater need for caution when prescribing metabolically problematic antipsychotics to people with lower BMI.

Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers?

Insulin-sensitizing medications were originally used in psychiatric practice to treat weight gain and other metabolic side effects that accompany the use of mood stabilizers, antipsychotics, and some antidepressants. However, in recent studies these medications have been shown to cause improvement in depressive symptoms, creating a potential new indication outside of metabolic regulation. However, it is still unclear whether the antidepressant properties of these medications are associated with improvements in metabolic markers. We performed a systematic search of the literature following PRISMA guidelines of studies investigating antidepressant effects of insulin-sensitizing medications. We specifically focused on whether any improvements in depressive symptoms were connected to the improvement of metabolic dysfunction. Majority of the studies included in this review reported significant improvement in depressive symptoms following treatment with insulin-sensitizing medications. Nine out of the fifteen included studies assessed for a correlation between improvement in symptoms and changes in metabolic markers and only two of the nine studies found such association, with effect sizes ranging from R2 = 0.26-0.38. The metabolic variables, which correlated with improvements in depressive symptoms included oral glucose tolerance test, fasting plasma glucose and glycosylated hemoglobin following treatment with pioglitazone or metformin. The use of insulin-sensitizing medications has a clear positive impact on depressive symptoms. However, it seems that the symptom improvement may be unrelated to improvement in metabolic markers or weight. It is unclear which additional mechanisms play a role in the observed clinical improvement. Some alternative options include inflammatory, neuroinflammatory changes, improvements in cognitive functioning or brain structure. Future studies of insulin-sensitizing medications should measure metabolic markers and study the links between changes in metabolic markers and changes in depression. Additionally, it is important to use novel outcomes in these studies, such as changes in cognitive functioning and to investigate not only acute, but also prophylactic treatment effects.

Effects of Transcranial Direct Current Stimulation Treatment for Anorexia Nervosa.

Background: Anorexia nervosa (AN) is a life-threatening illness with poor treatment outcomes. Although transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method, its effect in patients with AN remains unclear. Objective: This study investigated changes in maladaptive eating behavior, body mass index (BMI), and depression after 10 sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). Methods: In this double-blind, randomized controlled trial, 43 inpatients with AN were divided to receive either active (n = 22) or sham (n = 21) tDCS over the left DLPFC (anode F3/cathode Fp2, 2 mA for 30 min). All patients filled the Eating Disorder Examination Questionnaire (EDE-Q) and Zung Self-Rating Depression Scale (ZUNG), and their BMI was measured. These values were obtained repeatedly in four stages: (1) before tDCS treatment, (2) after tDCS treatment, (3) in the follow-up after 2 weeks, and (4) in the follow-up after 4 weeks. Results: Primary outcomes (EDE-Q) based on the ANOVA results do not show any between-group differences either after the active part of the study or in the follow-up. Secondary analysis reveals a reduction in some items of EDE-Q. Compared with sham tDCS, active tDCS significantly improved self-evaluation based on body shape (p < 0.05) and significantly decreased the need of excessive control over calorie intake (p < 0.05) in the 4-week follow-up. However, the results do not survive multiple comparison correction. In both sham and active groups, the BMI values improved, albeit not significantly. Conclusion: We did not observe a significant effect of tDCS over the left DLPFC on complex psychopathology and weight recovery in patients with AN. tDCS reduced the need to follow specific dietary rules and improved body image evaluation in patients with AN. Tests with a larger sample and different positions of electrodes are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03273205.