HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition.

The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.

HPA axis genetic variation, cortisol and psychosis in major depression.

Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with non-psychotic major depression (NPMD); and 29 HCs. Collection of genetic material was added one third of the way into a larger study on cortisol, cognition and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 1800 to 0900 h and for the assessment of alleles for six genes involved in HPA axis regulation. Two of the six genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression and psychosis, and medication status, only allelic variation for the glucocorticoid receptor (GR) gene accounted for a significant variance for mean cortisol levels from 1800 to 0100 h (r(2)=0.288) and from 0100 to 0900 h (r(2)=0.171). In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.

Neural correlates of timbre change in harmonic sounds.

Timbre is a major structuring force in music and one of the most important and ecologically relevant features of auditory events. We used sound stimuli selected on the basis of previous psychophysiological studies to investigate the neural correlates of timbre perception. Our results indicate that both the left and right hemispheres are involved in timbre processing, challenging the conventional notion that the elementary attributes of musical perception are predominantly lateralized to the right hemisphere. Significant timbre-related brain activation was found in well-defined regions of posterior Heschl's gyrus and superior temporal sulcus, extending into the circular insular sulcus. Although the extent of activation was not significantly different between left and right hemispheres, temporal lobe activations were significantly posterior in the left, compared to the right, hemisphere, suggesting a functional asymmetry in their respective contributions to timbre processing. The implications of our findings for music processing in particular and auditory processing in general are discussed.

Depression in Individuals with Epilepsy.

Depression in epilepsy patients is not only extremely common, but is often poorly recognized and inadequately treated. Depression can have significant consequences including increased medical utilization, poor quality of life, social disability, and mortality. Etiology of depression is multifaceted with prominent psychosocial determinants. Salient medical issues include iatrogenic causes, especially side effects of antiepileptic drugs (AEDs). In addition, seizures with increased frequency and with "forced normalization" can be associated with mood disturbance. After a thorough search for correctable causes, treatment should not be delayed, and should include both psychotherapy and pharmacologic therapies. Antidepressants remain the mainstay of pharmacologic intervention with the selective serotonin reuptake inhibitors (SSRIs) considered first-line treatment. Venlafaxine, nefazadone, and tricyclic antidepressants (TCAs) can also be used, but with some important caveats. Decreasing the seizure threshold is a common side effect of all antidepressants, but the risk can be minimized and should not prevent vigorous treatment of the depressive state. Other side effects present with varying frequency from the common (eg, sexual dysfunction as seen with SSRIs) to uncommon withdrawal reactions and rare complications of serotonin syndrome. Depression must also be considered a recurring disease, and when a successful regimen is ascertained, adequate continuation of treatment is a necessity. Care must be taken to treat the patient until complete resolution is achieved. Many patients with a major depressive disorder (MDD) will improve with inadequate treatment, but remain encumbered by a smoldering, low-level dysthymia that, in itself, can severely restrict the patient's quality of life.

Performance of the ImmunoCard STAT! E. coli O157:H7 test for detection of Escherichia coli O157:H7 in stools.

ImmunoCard STAT! E. coli O157:H7 (Meridian Diagnostics, Inc., Cincinnati, Ohio) is a novel rapid (10-min) test for the presence of Escherichia coli O157:H7 in stools. The test may be performed either directly on stool specimens or on an overnight broth culture of stool. In a multicenter prospective study, 14 of 14 specimens positive by culture for E. coli O157:H7 were positive by the ImmunoCard STAT! O157:H7 test, and there were no false positives from 263 culture-negative specimens. In a retrospective study, the test was positive in 339 (81%) of 417 stored culture-positive specimens and the specificity was 95% (98 of 103 specimens). No false positives were associated with alternate stool pathogens. The ImmunoCard STAT! O157:H7 test has high sensitivity and specificity.

Isolated meningeal vasculopathy associated with Clostridium septicum infection.

A 28-year-old patient with acute lymphoblastic leukemia and neutropenia developed necrotizing enterocolitis and Clostridium septicum bacteremia, followed by rhabdomyolysis, skin rash, and acute neurologic changes. Numerous cortical leptomeningeal enhancements were present on head MRI. Meningeal and brain biopsy showed segmental, full-thickness lysis of smooth muscle cells of medium-sized meningeal vessels with overall preservation of the structure of the vessel wall.

[Personality structure and subjective illness concepts of neurotically depressed patients. Qualitative comparison of 11 individual cases analyses of initial psychotherapy interviews]. / Persönlichkeitsstruktur und subjektive Krankheitsvorstellungen neurotisch Depressiver. Qualitativer Vergleich von 11 Einzelfallanalysen psychotherapeutischer Erstgespräche.

Verbatim transcripts of 11 psychotherapeutic interviews with patients suffering from depressive neurosis were examined, focusing on subjective theories of illness, biography, and descriptions of the patient's own personality. The results of our qualitative content analysis allow reconstruction of some characteristic features of these patients, like over identification with social roles and norms (1), feeling of being dependent and injured by another person (2), problems of self-esteem (3), shyness (4), unfulfilled wishes to be loved and accepted (5). These findings are discussed in the context of psychopathological and psychoanalytic concepts of depression.

[Anticaries effectiveness of D(+)-galactose]. / Uber die kariostatische Wirksamkeit von D(+)-Galaktose.

The influence of different galactose concentrations on the cariogenic effect of Streptococcus mutans (strains: DSM 20381 and DSM 20523) in a sucrose diet (33%) was examined in an animal experiment. The treated Wistar rats were free of pathogenic germs at the beginning of the experiment. The experimental conditions were approximately in accordance with the "Consensus statement" of the American Dental Association. The sides of the teeth, the amount of film, the abrasion of the chewing surfaces, the amount of surface and fissure caries and the animals general condition were evaluated. The anticaries effectiveness of galactose is dependent on its concentration: 5.0% galactose reduces the amount of caries on a high significance level, lowers the abrasion of the chewing surfaces, possibly because of the increased amount of serum calcium related to this galactose concentration, and diminishes the amount of film. 1.5% galactose prevents caries significantly and strongly reduces the amount of film; 0.5% galactose reduces the amount of caries non-significantly, but diminishes the amount of film. The effect is based on the property of galactose to occupy the receptors of the pellicle (layer of glycoprotein on the tooth enamel), hence the adherence of specific germs (for example, Streptococcus mutans) ceases in whole or in part.