Adiposity and insulin sensitivity derived from intravenous glucose tolerance tests in antipsychotic-treated patients.

Cardiovascular disease is more common in schizophrenia patients than in the general population, with a hypothesized contribution from increases in adiposity produced by antipsychotic medications. We sought to test the relationship between adiposity and insulin resistance using frequently sampled intravenous glucose tolerance tests (FSIVGTTs) to quantify whole-body insulin sensitivity in chronically treated patients with schizophrenia or schizoaffective disorder and untreated healthy controls. FSIVGTTs, body mass index (BMI), and waist circumference were obtained in nondiabetic patients (n=63) receiving olanzapine, risperidone, ziprasidone, or first generation antipsychotics, as well as in healthy controls (n=14). Subject groups (including untreated healthy controls) were matched for BMI and all treated patient groups were additionally matched for age. Bergman's minimal model (MinMod) was used to calculate insulin sensitivity (S(I)), as well as secondary measures of interest. BMI and waist circumference significantly predicted insulin sensitivity measured as MinMod S(I) (F(1,62)=35.11, p<0.0001 and F(1,46)=24.48, p<0.0001, respectively). In addition, BMI and waist circumference significantly predicted the acute plasma insulin response to the glucose challenge (AIR(G)), consistent with a beta cell compensatory response to insulin resistance (MinMod AIR(G) F(1,65)=22.42, p<0.0001 and F(1,49)=11.72, p=0.0013, respectively). Adiposity levels occurring during antipsychotic treatment are strongly related to insulin resistance, confirming that antipsychotic-induced weight gain can contribute to increased cardiometabolic risk in this population.

Alterations in stress cortisol reactivity in depressed preschoolers relative to psychiatric and no-disorder comparison groups.

BACKGROUND: Despite the robust and widely replicated finding of elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity in depressed adults, studies of depressed children have yielded ambiguous findings. Animal models of early depression and studies of children experiencing early psychosocial deprivation have suggested that alterations in HPA axis reactivity are evident in early "depressive-like" conditions. The current study is, to our knowledge, the first investigation of HPA axis reactivity in very young children with a clinical depressive syndrome for which content validity has been established. METHODS: Depressed, psychiatric, and no-disorder comparison children aged 3 through 5.6 years were studied for HPA axis reactivity in response to experimental psychosocial stressors. The children were diagnosed using a developmentally appropriate, structured psychiatric interview. Salivary cortisol was obtained at 3 time points during a laboratory assessment before and after stressors involving separation from the parent and frustrating tasks. RESULTS: Repeated measures of multivariate analysis of variance revealed a significant interaction between the diagnostic group and 2 cortisol percent change scores. Depressed preschoolers displayed a pattern of increasing cortisol levels throughout the assessment in response to both separation and frustration stressors. In contrast, both comparison groups showed decreasing cortisol levels in response to the separation stressor. All groups displayed increasing cortisol levels in response to frustrating tasks. Preschoolers with a presumptive melancholic depressive subtype displayed these alterations at a greater magnitude relative to comparison groups. CONCLUSIONS: To our knowledge, these findings are the first to demonstrate altered HPA axis reactivity in depressed preschoolers. These alterations are consistent with those described in depressed adults and in animal models of early depression. These findings provide evidence for possible continuity of HPA axis alterations in depressive disorders across the lifespan and are discussed in the context of prior studies of HPA axis reactivity in clinically depressed children and adolescents, suggesting that younger age and inpatient status are features associated with altered HPA axis reactivity.

Modification of DSM-IV criteria for depressed preschool children.

OBJECTIVE: This study compared the severity of depression in preschoolers diagnosed by standard versus modified DSM-IV criteria for major depression. METHOD: A group of 145 preschoolers and their caregivers underwent a diagnostic assessment for preschool children. A factor analysis of depressive symptoms from the group was performed to derive a depression severity score. Scores were compared among four groups: standard DSM-IV major depression, modified DSM-IV major depression, DSM-IV attention deficit hyperactivity disorder and/or oppositional defiant disorder, and no disorder. RESULTS: A hierarchy in severity emerged, with significant differences among all four groups. Preschoolers meeting standard criteria displayed the highest severity, followed by those who met modified criteria. Both depressed groups had significantly higher severity than the two comparison groups. CONCLUSIONS: Standard DSM-IV criteria captured the most severely affected preschoolers, missing a substantial proportion of children with potentially clinically significant but less severe symptoms who were captured by modified DSM-IV criteria.

The clinical picture of depression in preschool children.

OBJECTIVE: To investigate the clinical characteristics of depression in preschool children. METHOD: One hundred seventy-four subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview for parents. Modifications were made to the assessment of major depressive disorder (MDD) criteria so that age-appropriate manifestations of symptom states could be captured. Typical and "masked" symptoms of depression were investigated in three groups: depressed (who met all MDD criteria except duration criterion), those with nonaffective psychiatric disorders (who met criteria for attention-deficit/hyperactivity disorder and/or oppositional defiant disorder), and those who did not meet criteria for any psychiatric disorder. RESULTS: Depressed preschool children displayed "typical" symptoms and vegetative signs of depression more frequently than other nonaffective or "masked" symptoms. Anhedonia appeared to be a specific symptom and sadness/irritability appeared to be a sensitive symptom of preschool MDD. CONCLUSIONS: Clinicians should be alert to age-appropriate manifestations of typical MDD symptoms and vegetative signs when assessing preschool children for depression. "Masked" symptoms of depression occur in preschool children but do not predominate the clinical picture. Future studies specifically designed to investigate the specificity and sensitivity of the symptoms of preschool depression are now warranted.

Preschool major depressive disorder: preliminary validation for developmentally modified DSM-IV criteria.

OBJECTIVE: To investigate the validity of developmentally modified DSM-IV criteria for preschool major depressive disorder (MDD). METHOD: Subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview with the parent about the child. Minor developmental modifications to the formal DSM-IV MDD criteria were tested, including translations of symptoms to describe age-appropriate manifestations and setting aside the duration criterion. Preschool children who met modified criteria were compared with psychiatric and normal control groups. RESULTS: Validation for the modified criteria was supported by a specific and stable symptom constellation, social impairment, greater family histories of affective disorders, and higher child-reported symptoms of depression on an age-appropriate puppet interview. Preschool children with MDD displayed "typical" symptoms of depression, as well as vegetative signs. Standard DSM-IV criteria failed to capture 76% of children who met these modified criteria. CONCLUSIONS: Evidence that preschool children can manifest typical symptoms of MDD when age-adjusted symptoms states are assessed is provided. Findings also suggest that standard DSM-/V criteria may not be sufficiently sensitive for preschool children, as they failed to capture a substantial proportion of symptomatic children. Minor modifications to DSM-IV criteria are recommended to capture clinically significant preschool MDD.