Clemente Garcia-Rizo

Metabolic profile of antipsychotic-naive individuals with non-affective psychosis

BACKGROUND Some studies suggest individuals with schizophrenia have an increased risk of diabetes prior to antipsychotic use. Small sample sizes and the potential for confounding by hypercortisolaemia have decreased confidence in those results. AIMS To examine diabetes-related factors in newly diagnosed, antipsychotic-naive people with non-affective psychosis. METHOD Participants with psychosis (the psychosis group; n = 50) and matched controls (the control group; n = 50) were given a 2 h oral glucose tolerance test. Fasting concentrations were also determined for adiponectin, interleukin-6 and C-reactive protein. RESULTS Compared with the control group, the psychosis group had significant increases in 2 h glucose and interleukin-6 concentrations, and in the prevalence of abnormal glucose tolerance (16% of psychosis group v. 0% of control group). Adiponectin and C-reactive protein concentrations did not differ significantly between the two groups. These findings could not be attributed to differences in cortisol concentrations, smoking, gender, neighbourhood of residence, body mass index, aerobic conditioning, ethnicity, socioeconomic status or age. CONCLUSIONS Individuals with non-affective psychosis appear to have an increased prevalence of abnormal glucose tolerance prior to antipsychotic treatment, as well as abnormalities in a related inflammatory molecule. These underlying problems may contribute to the metabolic side-effects of antipsychotic medications.

Brain Effects of Cognitive Remediation Therapy in Schizophrenia: A Structural and Functional Neuroimaging Study

BACKGROUND Cognitive remediation therapy positively affects cognition and daily functioning in patients with schizophrenia. However, studies on the underlying neurobiological mechanisms of this treatment are scarce. The aim of the current study was to investigate functional and structural connectivity brain changes in schizophrenia patients after cognitive remediation therapy using a whole-brain approach that combined functional magnetic resonance imaging and diffusion tensor imaging. METHODS A randomized controlled trial with 30 schizophrenia outpatients and 15 healthy volunteers. A strategy-learning-based treatment was used as a cognitive remediation therapy. A social skills training that provides useful information about illness management was used as an active control. We investigated changes in the pattern of functional connectivity assessed during an n-back task by tensorial independent component analysis as implemented in the multivariate exploratory linear decomposition into independent components and in the fractional anisotropy index of white matter integrity using tract-based spatial statistics. RESULTS Brain networks activation pattern significantly changed in patients exposed to the cognitive treatment in the sense of normalizing toward the patterns observed in healthy control subjects. Additionally, in white matter, they showed an increase in fractional anisotropy index in the anterior part of the genu of the corpus callosum. Cognitive improvement, functional, and also structural changes showed statistically significant correlations. CONCLUSIONS Improvement in brain functioning detected after cognitive remediation therapy in schizophrenia patients might be based on an increase of the interhemispheric information transfer between the bilateral prefrontal cortexes via the corpus callosum.

Glucose abnormalities in the siblings of people with schizophrenia

BACKGROUND Some studies suggest that schizophrenia may be associated with an increased risk of diabetes, independently of antipsychotic medications and other confounding factors. Previous studies have also suggested that there is an increased prevalence of diabetes in the relatives of schizophrenia probands. METHOD First-degree siblings of schizophrenia probands (N=6) and control subjects (N=12) were administered a glucose tolerance test. Subjects were matched for gender, age, body mass index, neighborhood of residence, socio-economic status and smoking habits. RESULTS The siblings of schizophrenia probands had a significantly increased two-hour mean glucose concentration compared to the control subjects (respective means [SD] were 100.5 mg/dL [27.7] vs. 78.0 [12.3]; p<0.03). Baseline glucose concentrations did not differ. CONCLUSIONS Although confirmation with larger samples is needed, these results and other studies suggest that diabetes may share familial risk factors with schizophrenia.

Is abnormal glucose tolerance in antipsychotic-naive patients with nonaffective psychosis confounded by poor health habits?

INTRODUCTION Some but not all previous studies have found abnormal glucose tolerance or fasting glucose concentrations in antipsychotic-naïve patients with nonaffective psychosis. Our finding of abnormal glucose tolerance in patients with nonaffective psychosis could not be attributed to confounding by age, ethnicity, gender, smoking, socioeconomic status (SES), hypercortisolemia, or body mass index (BMI). However, other factors merit consideration as potential confounders of this association. METHODS An extended sample of newly diagnosed, antipsychotic-naive patients with schizophrenia and related disorders and matched controls were administered an oral glucose tolerance test. Confounding factors related to diet, self-care/access to care, and drug abuse were evaluated. RESULTS After accounting for the variance due to age, ethnicity, gender, smoking, SES, morning cortisol concentrations, BMI (or waist-hip ratio), our previous finding of abnormal glucose tolerance in these patients was confirmed. This difference could not be attributed to confounding by substance abuse; blood concentrations of vitamin B12, folate, or homocysteine; aerobic conditioning as measured by resting heart rate; or duration of untreated psychosis. DISCUSSION These results provide further evidence that people with schizophrenia and related disorders have abnormal glucose tolerance and an increased risk of diabetes prior to antipsychotic treatment and independent of health habits and access to care. Other measures should also be examined.

Abnormal glucose tolerance, white blood cell count, and telomere length in newly diagnosed, antidepressant-naïve patients with depression

Chronic mood disorders have been associated with a shortened telomere, a marker of increased mortality rate and aging, and impaired cellular immunity. However, treatment may confound these relationships. We examined the relationship of glucose tolerance, white blood cell count and telomere length to depression in newly diagnosed, antidepressant-naïve patients. Subjects with major depression (n=15), and matched healthy control subjects (n=70) underwent a two-hour oral glucose tolerance test and evaluation of blood cell count and telomere content. The depression group had significantly higher two-hour glucose concentrations and a lower lymphocyte count than control subjects (respective means [SD] for two-hour glucose were 125.0mg/dL [67.9] vs 84.6 [25.6] (p<.001); for lymphocyte count 2.1×10(9)/L [0.6] vs 2.5×10(9)/L [0.7] p=.028). Telomere content was significantly shortened in the depression group (87.9 [7.6]) compared to control subjects (101.0 [14.3]; p<0.01). Abnormal glucose tolerance, lymphopenia and a shortened telomere are present early in the course of depression independently of the confounding effect of antidepressant treatment, supporting the concept of major depression as an accelerated aging disease.

Prolactin concentrations in newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis

BACKGROUND Previous studies have found increased prolactin concentrations in antipsychotic-naïve patients with schizophrenia. However, the roles of other hormones, and of potentially confounding variables such as gender and smoking, have not been considered. METHODS Blood from newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis (13 women and 20 men) and matched controls (12 women and 21 men) was assayed for prolactin, as well as three other hormones that impact prolactin concentrations: thyrotropin-stimulating hormone (TSH), ghrelin, and cortisol. RESULTS Patients had significantly higher prolactin concentrations: female patients had a mean [SD] of 37.1 ng/mL [24.9] vs. 13.5 ng/mL [7.2] for female control subjects (p=.001), while male patients had a mean of 15.3 ng/mL [9.5] vs. 7.6 ng/mL [2.2] for male control subjects (p=.006). Patients and control subjects did not differ on concentrations of TSH, ghrelin, or cortisol. The group differences could not be attributed to differences in age, gender, smoking, body mass index, ethnicity, or the socioeconomic status of the family of origin. CONCLUSIONS Increased prolactin concentrations in antipsychotic-naïve patients do not appear to be due to important confounding variables, or to the effects of elevated TSH, ghrelin, or cortisol.

Differences in glucose tolerance between deficit and nondeficit schizophrenia

Some studies suggest that schizophrenia is associated with an increased risk of diabetes independently of antipsychotic use. People with deficit schizophrenia, which is characterized by primary (or idiopathic), enduring negative symptoms, differ from those with nondeficit schizophrenia on course of illness, treatment response, risk factors, and biological correlates. We hypothesized that deficit and nondeficit subjects would also differ with regard to glucose tolerance. Newly diagnosed, antipsychotic-naïve subjects with nonaffective psychosis and matched control subjects were administered a 75 g oral glucose tolerance test (GTT). Two-hour glucose concentrations were significantly higher in the nondeficit patients (N=23; mean [SD] of 121.6 [42.0]) than in deficit (N=23; 100.2 [23.1]) and control subjects (N=59; 83.8 [21.9]); the deficit subjects also had significantly higher two-hour glucose concentrations than did the control subjects. These results provide further support that the deficit group has a distinctive etiopathophysiology.

Inflammatory markers in antipsychotic-naïve patients with nonaffective psychosis and deficit vs. nondeficit features.

Newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis appear to have increases in pro-inflammatory cytokines. Patients characterized by primary, enduring negative symptoms (deficit symptoms) differ from patients without such features with regard to course of illness, treatment response, risk factors and metabolic disturbances. We hypothesized that they would also differ on concentrations of the inflammatory markers interleukin-6 (IL6) and C-reactive protein (CRP). Newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis were categorized into deficit (N=20) and nondeficit (N=42) groups, and were matched on age, gender, body mass index, smoking, cortisol level, socioeconomic status, and the severity of psychotic symptoms. Fasting concentrations of IL6 were significantly higher in deficit (mean [S.D.]) (8.0 pg/ml [12.7]) than nondeficit patients (0.3 pg/ml [1.3]). CRP levels were also significantly higher in the deficit patients (0.3 mg/dl [0.4]) vs. (0.2 mg/dl [0.4]), respectively. In contrast, 2-h glucose concentrations (2HG) in a glucose tolerance test were lower in the deficit than the nondeficit group. Our results show a double dissociation with regard to glucose intolerance and inflammation: the deficit group has greater inflammation, but less severe glucose intolerance. These results provide further evidence for the validity of the deficit/nondeficit categorization.

Testosterone in newly diagnosed, antipsychotic-naive men with nonaffective psychosis: a test of the accelerated aging hypothesis.

Objective: Schizophrenia has been associated with age-related abnormalities, including abnormal glucose tolerance, increased pulse pressure, increased inflammation, abnormal stem cell signaling, and shorter telomere length. These metabolic abnormalities and other findings suggest that schizophrenia and related disorders might be associated with accelerated aging. Testosterone activity has a progressive decline with increasing age. Methods: We tested the hypothesis that circulating biologically active testosterone is lower in newly diagnosed, antipsychotic-naive male patients with nonaffective psychosis than in matched control subjects. Results: Patients (n = 33) were matched to control subjects (n = 33) for age, sex, body mass index, socioeconomic status of the family of origin, and smoking. The free androgen index, a measure of biologically active testosterone, was significantly lower in the psychosis group (mean [standard deviation] = 57.7% [26.1]) than in control subjects (71.6% [27.0], p = .04), with an effect size of 0.53. Multivariate analysis also supported the findings. In the psychosis group, free androgen index had a significant negative correlation with the conceptual disorganization item (r = −0.35, p = .049) but not with reality distortion (r = −0.21, p = .24), negative symptoms (r = 0.004, p = .98), or depression (r = −0.014, p = .94). Conclusions: Lower testosterone level is consistent with accelerated aging in nonaffective psychosis, but further testing of this hypothesis is needed.FAI = free androgen index; SHBG = sex hormone-binding globulin; SES = socioeconomic status; BMI = body mass index; WHR = waist-to-hip ratio

Metabolic effects of olanzapine in patients with newly diagnosed psychosis.

Antipsychotic medications are associated with an increased risk of diabetes. Previous studies have also found an increased risk of type 2 diabetes mellitus in the relatives of schizophrenia probands. The aim of this study was to explore the metabolic adverse effects of olanzapine in a cohort of patients with newly diagnosed psychosis and minimal or no exposure to antipsychotics. Patients with newly diagnosed psychosis (n = 30) were enrolled in a 16-week open trial of olanzapine. Body mass index, fasting glucose, hemoglobin A1c, fasting insulin, IL-6, and a fasting lipid profile were measured at baseline and at 4-week intervals. There was a significant, linear increase over time in fasting glucose (P = 0.043), weight (P < 0.001), body mass index (P < 0.001), total cholesterol (P = 0.005), triglycerides (P = 0.003), and low-density lipoprotein (P = 0.013), but not hemoglobin A1c (P = 0.691), fasting insulin (P = 0.690), IL-6 (P = 0.877), or high-density lipoprotein (P = 0.446). An abnormal baseline IL-6 was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and low-density lipoprotein (P < 0.01). Otherwise, neither parental history of type 2 diabetes mellitus nor baseline IL-6 predicted changes in metabolic measures. Changes in metabolic measures with olanzapine treatment can be detected early in the treatment of patients who are previously antipsychotic naive. The absence of a change in fasting insulin suggests a failure of pancreatic islet cells to compensate for the increase in fasting glucose.