Jane Caudle

Schizophrenia, substance use, and brain morphology

The high rate of comorbid substance abuse in schizophrenia and the consistently poor outcome of this comorbidity are well established findings in the research literature. However, the reasons for the high rate of comorbidity are not adequately understood, and the question of why some patients with schizophrenia abuse substances and others do not remains unanswered. There is widespread agreement about the clinical heterogeneity of schizophrenia, and there is some evidence suggesting that the heterogeneous clinical presentation may reflect a parallel underlying heterogeneity of brain morphology. We were interested in examining the possibility that the high rate of substance abuse and the characteristically poor outcome may be associated with the underlying brain morphology. Our hypothesis was that study subjects with schizophrenia and substance abuse would have higher rates of gross brain abnormalities than subjects with only schizophrenia. In an attempt to explore this possibility, we looked at qualitative differences in magnetic resonance imaging scans for a large sample (n = 176) of schizophrenia patients. In the group of patients who abused both alcohol and drugs, we found the rate of gross brain abnormalities to be slightly less than half the rate found among the patients with no history of alcohol or substance abuse (8 vs. 19). Although these results are not statistically significant, they reflect a trend that is compatible with previous findings, suggesting that substance abuse history may be accompanied by less impairment in certain areas, which in turn may be reflected in a better premorbid adjustment. However, our findings are not compatible with previous findings that show substance abuse to be associated with more severe symptoms and a poorer outcome in schizophrenia.

Unrecognized glucose intolerance is not associated with depression. Screening for Impaired Glucose Tolerance study 3 (SIGT 3)

Aims  To understand the metabolic and temporal links in the relationship between diabetes and depression, we determined the association between depressive symptoms and unrecognized glucose intolerance.

All pre-diabetes is not the same: metabolic and vascular risks of impaired fasting glucose at 100 versus 110 mg/dl: the Screening for Impaired Glucose Tolerance study 1 (SIGT 1).

The dramatic increase in incidence of diabetes (1) has prompted efforts to identify individuals who have milder glucose intolerance, because early management with lifestyle change and/or medication can delay progression to diabetes with its attendant morbidity, mortality, and cost (2). It has long been recognized that impaired glucose tolerance (IGT) is a diabetes precursor, but recognition of IGT requires oral glucose tolerance tests (OGTTs), which many health care providers are reluctant to order (3). As a more convenient alternative, the American Diabetes Association has emphasized screening by measurement of fasting plasma glucose (FPG) and lowered the cutoff for abnormal FPG progressively from 140 to 125 to 110 mg/dl. However, compared with IGT, an impaired fasting glucose (IFG) cutoff of 110 mg/dl provided good specificity but reduced sensitivity for detecting risk of developing diabetes (4–6). To obtain increased sensitivity, the American Diabetes Association recently lowered the cutoff for IFG from 110 to 100 mg/dl (7), and application of this cutoff has increased the number of Americans thought to have “pre-diabetes” to 41 million (8). Although such individuals are considered candidates for management aimed at decreasing their risk of progressing to diabetes (9), the metabolic and cardiovascular risks of individuals with very modest abnormalities in FPG are not well understood. In this study, we compared measures of risk in individuals with fasting glucose 100–109 mg/dl (IFG100) with those with fasting glucose 110–125 mg/dl (IFG110). The …

Use of a Uniform Treatment Algorithm Abolishes Racial Disparities in Glycemic Control

PURPOSE The purpose of this study is to compare glycemic control between blacks and whites in a setting where patient and provider behavior is assessed, and where a uniform treatment algorithm is used to guide care. METHODS This observational cohort study was conducted in 3542 patients (3324 blacks, 218 whites) with type 2 diabetes with first and 1-year follow-up visits to a municipal diabetes clinic; a subset had 2-year follow-up. Patient adherence and provider management were determined. The primary endpoint was A1c. RESULTS At presentation, A1c was higher in blacks than whites (8.9% vs 8.3%; P < .001), even after adjusting for demographic and clinical characteristics. During 1 year of follow-up, patient adherence to scheduled visits and medications was comparable in both groups, and providers intensified medications with comparable frequency and amount. After 1 year, A1c differences decreased but remained significant (7.7% vs 7.3%; P = .029), even in multivariable analysis (P = .003). However, after 2 years, A1c differences were no longer observed by univariate (7.6% vs 7.5%; P = .51) or multi-variable analysis (P = .18). CONCLUSIONS Blacks have higher A1c than whites at presentation, but differences narrow after 1 year and disappear after 2 years of care in a setting where patient and provider behavior are comparable and that emphasizes uniform intensification of therapy. Presumably, racial disparities at presentation reflected prior inequalities in management. Use of uniform care algorithms nationwide should help to reduce disparities in diabetes outcomes.

Age, BMI, and Race Are Less Important Than Random Plasma Glucose in Identifying Risk of Glucose Intolerance: The Screening for Impaired Glucose Tolerance Study (SIGT 5)

OBJECTIVE—Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously. RESEARCH DESIGN AND METHODS—Random plasma glucose (RPG) was measured and 75-g oral glucose tolerance tests were performed in 1,139 individuals without known diabetes. Screening performance was assessed by logistic regression and area under the receiver operating characteristic curve (AROC). RESULTS—NIDDK/ADA indicators age >45 years and BMI >25 kg/m2 provided significant detection of both diabetes and dysglycemia (both AROCs 0.63), but screening was better with continuous-variable models of age, BMI, and race and better still with models of age, BMI, race, sex, and family history (AROC 0.78 and 0.72). However, screening was even better with RPG alone (AROCs 0.81 and 0.72). RPG >125 mg/dl could be used to prompt further evaluation with an OGTT. CONCLUSIONS—Use of age, BMI, and race/ethnicity in guidelines for screening to detect diabetes and pre-diabetes may be less important than evaluation of RPG. RPG should be investigated further as a convenient, inexpensive screen with good predictive utility.

Natural killer cell activity in schizophrenia and schizoaffective disorder : a pilot study

Natural killer cell activity was prospectively studied in 15 patients with chronic schizophrenia and in seven patients with schizoaffective disorder, depressed type. These patients were compared to individually matched normal controls. No mean differences in natural killer cell activity between the patient groups and their controls were observed.

Sex differences in verbal IQ-performance IQ discrepancies among patients with schizophrenia and normal volunteers

Substantial verbal IQ (VIQ)-performance IQ (PIQ) discrepancies may reflect brain dysfunction. The authors examined 159 patients with schizophrenia (115 men and 44 women) or schizoaffective disorder (25 men and 19 women) and 79 normal participants (33 men and 46 women), calculated mean VIQ-PIQ discrepancy scores by sex and diagnosis, and identified persons with large VIQ-PIQ discrepancies (15-point difference in either direction). Schizophrenic/schizoaffective men had a larger mean VIQ-PIQ discrepancy than did other groups. The proportion of all patients with either VIQ > PIQ or PIQ > VIQ (17.8%) was not significantly different from that of normal participants (22.8%). However, significantly more men than women with schizophrenia exhibited a VIQ > PIQ pattern (20% vs. 3.2%). No unusual discrepancy patterns were noted among normal participants. Results were interpreted in light of theories of hemisphere dysfunction in schizophrenia.

Age, BMI, and Race are Less Important Than Random Plasma Glucose To Identify Risk Of Glucose Intolerance. SIGT 5

OBJECTIVE—Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously. RESEARCH DESIGN AND METHODS—Random plasma glucose (RPG) was measured and 75-g oral glucose tolerance tests were performed in 1,139 individuals without known diabetes. Screening performance was assessed by logistic regression and area under the receiver operating characteristic curve (AROC). RESULTS—NIDDK/ADA indicators age >45 years and BMI >25 kg/m2 provided significant detection of both diabetes and dysglycemia (both AROCs 0.63), but screening was better with continuous-variable models of age, BMI, and race and better still with models of age, BMI, race, sex, and family history (AROC 0.78 and 0.72). However, screening was even better with RPG alone (AROCs 0.81 and 0.72). RPG >125 mg/dl could be used to prompt further evaluation with an OGTT. CONCLUSIONS—Use of age, BMI, and race/ethnicity in guidelines for screening to detect diabetes and pre-diabetes may be less important than evaluation of RPG. RPG should be investigated further as a convenient, inexpensive screen with good predictive utility.

Medication reconciliation: comparing a customized medication history form to a standard medication form in a specialty clinic (CAMPII 2).

Background Medication history forms completed by patients are an essential part of the medication reconciliation process. Objective In a crossover prospective study, investigators compared the accuracy and acceptability of a “fill-in-the blank” medication history form (USUAL) to a customized form (CUSTOM) that contained a checklist of the 44 most frequently prescribed diabetes clinic medications. Methods The content of both forms was compared to a “gold-standard” medication list compiled by a clinical pharmacist who conducted a medication history and reviewed pharmacy profiles and medical chart. Subject preference and time to complete the forms were also determined. Accurate was defined as complete and correct (name, dose, and frequency) relative to the gold standard. Results A total of 77 subjects completed both forms. Complete list accuracy was poor; there was no difference in the accuracy between CUSTOM (6.5%) and USUAL (9.1%) (odds ratio [OR], 0.33; P = 0.62). Out of a total of 648 medications, subjects accurately listed 43.7% of medications on CUSTOM and 45.5% on USUAL (OR, 0.88; P = 0.41). The 44 medications on the checklist were more than twice as likely to be accurately reported using CUSTOM than with USUAL (OR, 2.1; P = 0.0002). More subjects preferred CUSTOM (65.7%) compared with USUAL (32.8%, P = 0.007). Conclusion Medication self-report is very poor, and few subjects created an accurate list on either form. Subjects were more likely to report the drugs on the checklist using CUSTOM than when they used USUAL; however, there was no difference in the overall accuracy between CUSTOM and USUAL.

An Association between Increased Concentrations of Cerebrospinal Fluid Dopamine Sulfate and Higher Negative Symptom Scores in Patients with Schizophrenia and Schizoaffective Disorder

There has been much speculation as to the role of dopamine in the etiology and/or manifestation of positive and negative symptoms. Traditionally, cerebrospinal fluid (CSP) concentrations of homovanillic acid (HVA) has been used as an index of central dopaminergic activity. Relea~l dopamine is metabolized to HVA, by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) (Cooper et al 1991). A review of the CSF HVA literature, however, reveals no consistent correlations between HVA and schizophrenic symptomatoiogy (reviewed by Pickax et al ! 9907. Yet there is sufficient data to suggest that dopamine activity is abnormal in schizophrenia (Davis et al 19917. Therefore the evaluation of other putative measures of dopamine release or metabolism seems warranted. Released dopamine is also converted to dopamine sulfate (DASO47 by the enzyme phenolsulphotransferase (PST7 (Jenner and Rose, 1973). in the brain, it appears that the sulfoconjugation of dopamine occurs primarily outside of dopaminergic neurons (Tyce et al 1988). Therefore CSF DASO~ concentrations may reflect an important alternate route of dopamine metabolism. Assessment of PST-dependent DASO4 independently, or in re-