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Biomedical subjects

Jennifer Keller

Publications and source records attributed to Jennifer Keller.

7 recordsLinked to original sources
PubMed2006

The neuropsychological profile of psychotic major depression and its relation to cortisol.

BACKGROUND: Our study described the neuropsychological profile of psychotic major depression (PMD) compared to nonpsychotic major depression (NPMD) patients and psychiatrically healthy controls (HC). We predicted that higher cortisol levels would be associated with greater cognitive deficits. METHODS: Twenty-nine PMDs, 24 NPMDs, and 26 HCs were recruited at Stanford University Medical Center. Psychiatric ratings, cortisol levels from 1800-0900 hours, and neuropsychological test data were obtained. RESULTS: PMDs had more severe cognitive impairments compared with NPMDs and HCs with the exception of simple verbal attention. PMDs had elevated mean cortisol levels from 1800 to 0100 hours which were significantly correlated with poorer verbal memory and psychomotor speed performance. Cortisol slopes from 1800 to 0100 hours were also significantly correlated with verbal memory and working memory. CONCLUSIONS: While PMDs' ability to attend passively to information appears intact, they have more difficulty processing, manipulating, and encoding new information. Elevated cortisol levels, as seen in PMD patients, are associated with poorer cognitive performance especially related to verbal memory for lists of words and working memory.

Adrenocorticotropic Hormone↗
PubMed2006

Cortisol circadian rhythm alterations in psychotic major depression.

BACKGROUND: Increased hypothalamic-pituitary-adrenal axis activity is well described in psychotic depression with an emphasis on 24-hour, urinary free cortisol levels or dexamethasone suppression tests. There are limited data on cortisol levels during specific times of the day. METHODS: Patients with depression with (PMD) and without (NPMD) psychosis and healthy control subjects were studied using rating scales of depression and psychosis and measures of HPA activity, including overnight cortisol and adrenocorticotropin levels. We used analysis of variance to determine group differences and regression analyses to assess contributions of specific measures to cortisol levels. RESULTS: PMDs had higher cortisol during the evening hours than did NPMDs or control subjects, who did not differ from one another. Regression analyses suggest that depression and the combination of depressive and psychotic symptoms were important contributors to variance in evening cortisol. CONCLUSIONS: PMD is associated with increased cortisol levels during the quiescent hours. Enhanced cortisol activity, particularly a higher nadir, was related to depression severity and the interaction of depressive and psychotic symptoms. This increase suggests a defect in the action of the circadian timing system and HPA axis, creating a hormonal milieu similarly seen in early Cushing's syndrome and potentially an (im)balance of mineralocorticoid and glucocorticoid receptor activity.

Adrenocorticotropic Hormone↗
PubMed2006

Normal N400 in mood disorders.

Individuals diagnosed with major depression have been characterized as having a variety of cognitive problems based on a number of behavioral and psychophysiological measures, but it is not clear whether there is a consistent language processing abnormality in depression. Three studies sought to determine whether diverse mood disordered samples show abnormal semantic processing, as indexed by a failure to show increased N400 event-related brain potential amplitudes to passively viewed incongruent, relative to congruent sentence endings. Individuals with major depression (N = 50) or dysthymia (N = 14) had N400 amplitudes similar to those of controls (N = 41) in this sentence processing paradigm. These results are consistent with a small behavioral literature suggesting intact semantic processing in depression and further indicate that abnormal controlled processing in some tasks does not simply reflect a generalized deficit.

Adult↗
PubMed2006

Clinical and biological effects of mifepristone treatment for psychotic depression.

Psychotic major depression (PMD) is found to be a relatively common psychiatric condition that affects up to nearly 20% of patients with major depression. Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone, in addition to restoring a more normal afternoon cortisol release. The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed. In total, 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a randomized double-blind manner. The Hamilton Depression Rating Scale (HDRS) and the Brief Psychiatric Rating Scale (BPRS) were administered at baseline and again after 8 days of treatment. Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment. Significantly, more patients in the mifepristone group (seven of 15) showed a 50% or greater decline on the BPRS positive symptom subscale, an index of psychotic symptoms, as compared to the placebo group (two of 15). Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo, but these differences were not statistically significant. In addition, mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo. Clinical and biological effects of mifepristone were comparable among males and females. Age was found to significantly and positively correlate with changes in cortisol and ACTH. These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis. Additional blinded studies are warranted.

Adrenocorticotropic Hormone↗
PubMed2006

Mood and neuropsychological changes in women with midlife depression treated with escitalopram.

OBJECTIVE: This study assessed mood and neuropsychological function in a population of middle-aged women with major depressive disorder treated with escitalopram. METHODS: Psychometric data measuring severity of depression were collected from 19 women and neuropsychological data were collected from 17 women aged between 45 and 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depression in a study in the Behavioral Neuroendocrinology Program at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine. All women were treated with escitalopram in an open-label design. Mean age was 55.94 years and mean number of years of education was 16.36 years. Diagnosis of major depressive disorder was assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and mood was evaluated with the 21-item Hamilton Depression Rating Scale (HAM-D) at baseline and at weekly follow-ups for 12 weeks. Cognition was assessed at baseline and 3 months after treatment using a neuropsychological test battery, which included an abbreviated measure of Full Scale Intelligence Quotient, measures of attention and processing speed, verbal and nonverbal memory, executive functioning, and verbal fluency. Self-report data were collected on current menopause status and current hormone therapy use in the postmenopausal women. Paired sample t tests were used to analyze the change in total HAM-D scores and neuropsychological variables. RESULTS: Statistically significant improvements were found in total HAM-D score, Wechsler Memory Scale III Logical Memory 1st Recall, I, and II scores, Wechsler Memory Scale III Visual Reproduction I scores, and Trail Making Test Part B scores. There was a statistically significant decrease in Controlled Oral Word Association Test FAS scores. CONCLUSIONS: Treatment of depression with escitalopram in a population of middle-aged women was shown to improve mood and cognitive efficiency in complex attention, short- and long-term recall of contextual information, short-term recall of visual information, and cognitive flexibility; however, it was shown to worsen phonemic fluency.

Antidepressive Agents, Second-Generation↗
PubMed2005

Detecting psychotic major depression using psychiatric rating scales.

OBJECTIVE: The aim of this study was to assess whether individual or clusters of psychiatric symptoms can differentiate patients with psychotic major depression (PMD) from those with nonpsychotic depression (NPMD). METHOD: Data were pooled from two studies investigating patients with moderate depression. A total of 129 subjects were studied. Patients in Sample 1 were unmedicated, while the majority of the patients in Sample 2 were taking psychotropic medications. Baseline rating scales were obtained for all subjects, including the Hamilton depression rating scale and the brief psychiatric rating scale (BPRS). We used discriminant function analyses, logistic regression, and ROC analyses to determine the patterns in symptoms that differentiated the groups. RESULTS: Psychotic patients were adequately differentiated by the unusual thought content (UTC) item of the BPRS. Even mild UTC endorsement was an indicator of PMD. Furthermore, results suggest that the positive symptom subscale of the BPRS was even better at differentiating PMD from NMPD patients. Sensitivity and specificity for this scale were 84% and 99%, respectively. CONCLUSION: Psychotic major depression is often undiagnosed and poorly treated. One reason for this trend is the failure of physicians to inquire in a more detailed manner about positive symptoms in patients with primary mood symptoms. Although physicians are not likely to have the time to conduct an entire BPRS during an evaluation, our results suggest that a few key symptoms, if assessed directly, may aid the psychiatrist to more effectively diagnose and subsequently treat their depressed patients.

Adult↗