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author:("lemke, Anna")
1.  Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression 
Psychiatry research  2012;211(2):119-126.
Psychotic major depression (PMD) is associated with deficits in verbal memory as well as other cognitive impairments. This study investigated brain function in individuals with PMD during a verbal declarative memory task. Participants included 16 subjects with PMD, 15 subjects with non-psychotic major depression (NPMD) and 16 healthy controls (HC). Functional magnetic resonance imaging (fMRI) data were acquired while subjects performed verbal memory encoding and retrieval tasks. During the explicit encoding task, subjects semantically categorized words as either “man-made” or “not manmade.” For the retrieval task, subjects identified whether words had been presented during the encoding task. Functional MRI data were processed using SPM5 and a group by condition ANOVA. Clusters of activation showing either a significant main effect of group or an interaction of group by condition were further examined using t-tests to identify group differences. During the encoding task, the PMD group showed lower hippocampus, insula, and prefrontal activation compared to HC. During the retrieval task, the PMD group showed lower recognition accuracy and higher prefrontal and parietal cortex activation compared to both HC and NPMD groups. Verbal retrieval deficits in PMD may be associated with deficient hippocampus function during encoding. Increased brain activation during retrieval may reflect an attempt to compensate for encoding deficits.
PMCID: PMC3645926  PMID: 23149036
Depression; Psychosis; Functional imaging; Verbal declarative memory; Hippocampus; Encoding deficits
2.  The mineralocorticoid receptor agonist, fludrocortisone, differentially inhibits pituitary-adrenal activity in humans with psychotic major depression 
Psychoneuroendocrinology  2012;38(1):115-121.
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been linked with major depression, particularly psychotic major depression (PMD), with mineralocorticoid receptors (MRs) playing a role in HPA-axis regulation and the pathophysiology of depression. Herein we hypothesize that the MR agonist fludrocortisone differentially inhibits the HPA axis of psychotic major depression subjects (PMDs), non-psychotic major depression subjects (NPMDs), and healthy control subjects (HCs).
Fourteen PMDs, 16 NPMDs, and 19 HCs were admitted to the Stanford University Hospital General Clinical Research Center. Serum cortisol levels were sampled at baseline and every hour from 18:00 to 23:00 h, when greatest MR activity is expected, on two consecutive nights. On the second afternoon at 16:00 h all subjects were given 0.5 mg fludrocortisone. Mean cortisol levels pre- and post-fludrocortisone and percent change in cortisol levels were computed.
There were no significant group differences for cortisol at baseline: F (2,47) = .19, p= .83. There were significant group differences for post-fludrocortisone cortisol: F (2,47) = 5.13, p = .01, which were significantly higher in PMDs compared to HCs (p = .007), but not compared to NPMDs (p = .18). There were no differences between NPMD’s and HC’s (p= .61). Also, PMDs had a lower percent change from baseline in cortisol levels at 2200 hrs than NPMDs (p =.01) or HCs (p = .009).
Individuals with psychotic major depression compared to healthy control subjects have diminished feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in response to the mineralocorticoid receptor agonist fludrocortisone. To our knowledge, this is the first study to examine HPA axis response to MR stimulation in major depression (with and without psychosis), and only the third study to demonstrate that exogenously administered fludrocortisone can down-regulate the HPA axis in humans.
PMCID: PMC3633490  PMID: 22727477
Mineralocorticoid receptor; HPA axis; Fludrocortisone; Psychotic Major Depression; Cortisol; Hippocampus
3.  Prescription of topiramate to treat alcohol use disorders in the Veterans Health Administration 
As a quality improvement metric, the US Veterans Health Administration (VHA) monitors the proportion of patients with alcohol use disorders (AUD) who receive FDA approved medications for alcohol dependence (naltrexone, acamprosate, and disulfiram). Evidence supporting the off-label use of the antiepileptic medication topiramate to treat alcohol dependence may be as strong as these approved medications. However, little is known about the extent to which topiramate is used in clinical practice. The goal of this study was to describe and examine the overall use, facility-level variation in use, and patient -level predictors of topiramate prescription for patients with AUD in the VHA.
Using national VHA administrative data in a retrospective cohort study, we examined time trends in topiramate use from fiscal years (FY) 2009–2012, and predictors of topiramate prescription in 375,777 patients identified with AUD (ICD-9-CM codes 303.9x or 305.0x) treated in 141 VHA facilities in FY 2011.
Among VHA patients with AUD, rates of topiramate prescription have increased from 0.99% in FY 2009 to 1.95% in FY 2012, although substantial variation across facilities exists. Predictors of topiramate prescription were female sex, young age, alcohol dependence diagnoses, engagement in both mental health and addiction specialty care, and psychiatric comorbidity.
Veterans Health Administration facilities are monitored regarding the extent to which patients with AUD are receiving FDA-approved pharmacotherapy. Not including topiramate in the metric, which is prescribed more often than acamprosate and disulfiram combined, may underestimate the extent to which VHA patients at specific facilities and overall are receiving pharmacotherapy for AUD.
PMCID: PMC3716908  PMID: 23835352
Alcohol use disorders; Addiction; Pharmacotherapy; Topiramate; Pharmacotherapy utilization; Veterans
4.  Alcohol Screening Scores and the Risk of New-Onset Gastrointestinal Illness or Related Hospitalization 
Excessive alcohol use is associated with a variety of negative health outcomes, including liver disease, upper gastrointestinal bleeding, and pancreatitis.
To determine the 2-year risk of gastrointestinal-related hospitalization and new-onset gastrointestinal illness based on alcohol screening scores.
Retrospective cohort study.
Male (N = 215, 924) and female (N = 9,168) outpatients who returned mailed questionnaires and were followed for 24 months.
Alcohol Use Disorder Identification Test—Consumption Questionnaire (AUDIT-C), a validated three-item alcohol screening questionnaire (0–12 points).
Two-year risk of hospitalization with a gastrointestinal disorder was increased in men with AUDIT-C scores of 5–8 and 9–12 (OR 1.54, 95% CI = 1.27–1.86; and OR 3.27; 95% CI = 2.62–4.09 respectively), and women with AUDIT-C scores of 9–12 (OR 6.84, 95% CI = 1.85 – 25.37). Men with AUDIT-C scores of 5–8 and 9–12 had increased risk of new-onset liver disease (OR 1.49, 95% CI = 1.30–1.71; and OR 2.82, 95% CI = 2.38–3.34 respectively), and new-onset of upper gastrointestinal bleeding (OR 1.28, 95% CI = 1.05–1.57; and OR 2.14, 95% CI = 1.54-2.97 respectively). Two-year risk of new-onset pancreatitis in men with AUDIT -C scores 9–12 was also increased (OR 2.14; 95% CI = 1.54–2.97).
Excessive alcohol use as determined by AUDIT-C is associated with 2-year increased risk of gastrointestinal-related hospitalization in men and women and new-onset liver disease, upper gastrointestinal bleeding, and pancreatitis in men. These results provide risk information that clinicians can use in evidence-based conversations with patients about their alcohol consumption.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-011-1688-7) contains supplementary material, which is available to authorized users.
PMCID: PMC3138581  PMID: 21455813
alcohol; AUDIT; gastrointestinal; hospitalization; new-onset; women
5.  Risk of future trauma based on alcohol screening scores: A two-year prospective cohort study among US veterans 
Severe alcohol misuse as measured by the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) is associated with increased risk of future fractures and trauma-related hospitalizations. This study examined the association between AUDIT-C scores and two-year risk of any type of trauma among US Veterans Health Administration (VHA) patients and assessed whether risk varied by age or gender.
Outpatients (215, 924 male and 9168 female) who returned mailed AUDIT-C questionnaires were followed for 24 months in the medical record for any International Statistical Classification of Diseases and Related Health Problems (ICD-9) code related to trauma. The two-year prevalence of trauma was examined as a function of AUDIT-C scores, with low-level drinking (AUDIT-C 1–4) as the reference group. Men and women were examined separately, and age-stratified analyses were performed.
Having an AUDIT-C score of 9–12 (indicating severe alcohol misuse) was associated with increased risk for trauma. Mean (SD) ages for men and women were 68.2 (11.5) and 57.2 (15.8), respectively. Age-stratified analyses showed that, for men ≤50 years, those with AUDIT-C scores ≥9 had an increased risk for trauma compared with those with AUDIT-C scores in the 1–4 range (adjusted prevalence, 25.7% versus 20.8%, respectively; OR = 1.24; 95% confidence interval [CI], 1.03–1.50). For men ≥65 years with average comorbidity and education, those with AUDIT-C scores of 5–8 (adjusted prevalence, 7.9% versus 7.4%; OR = 1.16; 95% CI, 1.02–1.31) and 9–12 (adjusted prevalence 11.1% versus 7.4%; OR = 1.68; 95% CI, 1.30–2.17) were at significantly increased risk for trauma compared with men ≥65 years in the reference group. Higher AUDIT-C scores were not associated with increased risk of trauma among women.
Men with severe alcohol misuse (AUDIT-C 9–12) demonstrate an increased risk of trauma. Men ≥65 showed an increased risk for trauma at all levels of alcohol misuse (AUDIT-C 5–8 and 9–12). These findings may be used as part of an evidence-based brief intervention for alcohol use disorders. More research is needed to understand the relationship between AUDIT-C scores and risk of trauma in women.
PMCID: PMC3414833  PMID: 22966411
Alcohol; Trauma; Fracture; AUDIT-C; Age; Gender; Screening; Women
6.  Depression and smoking cessation: Does the evidence support psychiatric practice? 
Depression and smoking are highly comorbid. The vast majority of psychiatrists treating depressed patients do not target or treat nicotine dependence, and many inpatient psychiatric facilities implicitly condone smoking by providing ‘smoke breaks’. The reasons for failure to treat are unclear, but are probably linked to the notion that depressed smokers are neither willing nor able to quit, and will become more depressed if they try. We review the clinical evidence on depression and smoking cessation, and find little support for current psychiatric practice. Although quitting smoking does appear to pose a risk for the development of depression, this risk is not clearly higher in those with a past history of depression than those without. Depressed smokers are as capable as nondepressed smokers of quitting smoking, and at least one-quarter of depressed smokers is willing to try. Sustained abstinence may even lead to improvement in depressive disorders. More research is needed to understand the relationship between depression and quitting smoking, but current clinical evidence suggests more resiliency among depressed smokers than common clinical wisdom would dictate.
PMCID: PMC2655079  PMID: 19300577
depression; smoking cessation; psychiatry; nicotine dependence; withdrawal

Results 1-6 (6)