Georgios Paslakis

Oral administration of the NMDA receptor antagonist S-ketamine as add-on therapy of depression: a case series.

We intended to assess safety, response to treatment and time to response of 1.25 mg/kg oral S-ketamine as add-on to standard antidepressants in four depressed patients. Two patients with melancholic depression responded early and stayed in remission, while two patients with distinct somatic symptoms, chronicity or atypical features did not respond. The limited number of patients does not allow conclusions about efficacy. Oral S-ketamine was well tolerated and could merit being studied in randomised controlled trials due to its higher practicability compared to (S-)ketamine infusion therapy. Clinical subtyping should be considered.

Cognition and Sensation in Very High Static Magnetic Fields: A Randomized Case-Crossover Study with Different Field Strengths

PURPOSE To establish the extent to which representative cognitive functions in subjects undergoing magnetic resonance (MR) imaging are acutely impaired by static magnetic fields of varying field strengths. MATERIALS AND METHODS This study was approved by the local ethics committee, and informed consent was obtained from all subjects. In this single-blind case-crossover study, 41 healthy subjects underwent an extensive neuropsychologic examination while in MR units of differing field strengths (1.5, 3.0, and 7.0 T), including a mock imager with no magnetic field as a control condition. Subjects were blinded to field strength. Tests were performed while subjects were lying still in the MR unit and while the examination table was moved. The tests covered a representative set of cognitive functions, such as memory, eye-hand coordination, attention, reaction time, and visual discrimination. Subjective sensory perceptions were also assessed. Effects were analyzed with a repeated-measures analysis of variance; the within-subject factors were field strength (0, 1.5, 3.0, and 7.0 T) and state (static, dynamic). RESULTS Static magnetic fields were not found to have a significant effect on cognitive function at any field strength. However, sensory perceptions did vary according to field strength. Dizziness, nystagmus, phosphenes, and head ringing were related to the strength of the static magnetic field. CONCLUSION Static magnetic fields as high as 7.0 T did not have a significant effect on cognition.

Discrimination between patients with melancholic depression and healthy controls: Comparison between 24-h cortisol profiles, the DST and the Dex/CRH test

Diurnal (24-h) cortisol profiles were compared to DST and Dex/CRH test outcomes with regard to their discriminative power in depressive disorder. With regard to several statistical measures (effect sizes, area under the curve) we found 24-h cortisol profiles to better discriminate between healthy controls and inpatients with the melancholic subtype of depression compared to the DST and Dex/CRH test. In search of a shortened time interval we found the 2-h time window 1000-1200 h of the cortisol profile to be the one with the highest sensitivity (83.3%) and specificity (87.9%). The specificity of the DST was 93.3% and somewhat higher than that of the cortisol profiles and the Dex/CRH test (87.9% and 78.8.%, respectively). However, the sensitivity of the DST was very low (30.8%), in fact similar to that of the Dex/CRH test (30.8%), but much lower than that of the 1000-1200 h interval (83.3%). The assessment of cortisol in plasma is an easy to perform, cost-saving method for the evaluation of the HPA system activity, which may have a series of clinical and scientific implications for the depressive disorder.

Intranasal insulin-like growth factor I (IGF-I) as a plausible future treatment of depression

Depression remains a highly prevalent and mostly recurrent disorder causing an increased need to optimize and broaden the current therapy options. An enormous body of evidence links the regulation of specific neurotrophic proteins, like the brain-derived neurotrophic factor (BDNF), to depression and it may be assumed that the behavioral effects of antidepressants require functional BDNF signaling in the brain. Another neurotrophin, insulin-like growth factor-I (IGF-I), also produces antidepressant-like behavioral effects. Data have shown that BDNF plus IGF-I are more effective than either neurotrophin alone in activating neurotrophic cascades and promoting survival of hippocampal neurons. In fact, it has been suggested that the increase in hippocampal BDNF following antidepressant treatment or physical exercise in animal models is IGF-I-dependent and that antidepressant treatment increases IGF-I in human cerebrospinal fluid (CSF). Thus, BDNF and IGF-I seem to act synergistically in the same cascade of transmission and neuroplasticity. In order to avoid the pitfalls of systemic application (e.g. possible peripheral side effects) while directly targeting central nervous circuitries, the clinical intranasal administration of IGF-I appears to be a plausible and promising treatment option of depression.

Venlafaxine and mirtazapine treatment lowers serum concentrations of dehydroepiandrosterone-sulfate in depressed patients remitting during the course of treatment

OBJECTIVES The adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) seems to be involved in the pathophysiology of depression, although its precise role in the etiology and remission of depression remains unclear. In the present study we intended to examine possible differential effects of venlafaxine and mirtazapine in a randomised open trial with regard to DHEA-S serum concentrations in patients suffering from major depressive episode compared to healthy controls. METHODS We assessed DHEA-S concentrations both at baseline and after a 4-week treatment period in 70 depressed patients (n=33 for venlafaxine and n=37 for mirtazapine) and 33 matched healthy controls. RESULTS We describe the decrease of DHEA-S levels in depressive patients who remitted after treatment with both venlafaxine or mirtazapine. Patients without remission of depression did not show a significant decline in DHEA-S concentrations. CONCLUSIONS Our results suggest an effect of treatment outcome upon DHEA-S concentrations rather than a direct drug effect. The change of plasma DHEA-S levels as a marker of treatment-response of depression warrant further investigation.

A single DEX/CRH test in male drug-free depressed patients is associated with the clinical response to treatment with fluoxetine

OBJECTIVES The DEX/CRH test has been proposed to be suitable as a biomarker for the prediction of treatment response in depression. METHODS We performed the DEX/CRH test in 10 severely depressed male patients with melancholic features before initiation of antidepressant treatment with 20 mg fluoxetine. RESULTS We found a low cortisol response (as measured by cortisol AUC) to a single DEX/CRH test to be associated with clinical response to treatment. CONCLUSIONS A strength of this study lies in the inclusion of patients after a drug wash-out phase. Despite a certain inconsistency described in the literature, several studies support the notion that it might be of importance to measure baseline HPA system activity before choice of treatment. Further systematic studies are warranted.

Visceral and subcutaneous fat in patients treated with olanzapine: a case series.

Objectives:We hypothesized that olanzapine may contribute to visceral adiposity, a core symptom of metabolic syndrome. Methods:Using computed tomography, we examined the effect of olanzapine on visceral and subcutaneous fat distribution, body mass index, fasting glucose, and lipids in an unselected population of 14 schizophrenic patients. Results:We found a 6-week olanzapine treatment to be related to increased body mass index and proportion of total fat at the level of the fourth vertebral body. Conclusions:On the basis of these findings, we conclude that weight gain after a 6-week olanzapine treatment is partly attributable to increased visceral fat and may thus contribute to metabolic syndrome.

Intrauterine Exposure to Cigarette Smoke Is Associated with Increased Ghrelin Concentrations in Adulthood

Background: The appetite-stimulating hormone ghrelin is a fundamental regulator of human energy metabolism. A series of studies support the notion that long-term appetite and weight regulation may be already programmed in early life and it could be demonstrated that the intrauterine environment affects the ghrelin system of the offspring. Animal studies have also shown that intrauterine programming of orexigenic systems persists even until adolescence/adulthood. Methods: We hypothesized that plasma ghrelin concentrations in adulthood may be associated with the intrauterine exposure to cigarette smoke. We examined this hypothesis in a sample of 19-year-olds followed up since birth in the framework of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study of the long-term outcome of early risk factors. Results: As a main finding, we found that ghrelin plasma concentrations in young adults who had been exposed to cigarette smoke in utero were significantly higher than in those without prenatal smoke exposure. Moreover, individuals with intrauterine nicotine exposure showed a significantly higher prevalence of own smoking habits and lower educational status compared to those in the group without exposure. Conclusion: Smoking during pregnancy may be considered as an adverse intrauterine influence that may alter the endocrine-metabolic status of the offspring even until early adulthood.

A cross-over study of effects on the hypothalamus-pituitary-adrenal (HPA) axis and the sympathoadrenergic system in magnetic field strength exposure from 0 to 7 T.

The concept of stress is relevant to magnetic resonance imaging (MRI) examination in various ways. First, levels of stress to staff and patients have not been quantified in ultra-high magnetic fields. Second, research is increasingly interested in experimentally defining regional brain activity during stress. It is therefore important to know whether exposure to the ultra-high static magnetic fields per se might also lead to neurohormonal responses in the hypothalamus–pituitary–adrenal axis and the sympathoadrenal systems. In the present blinded case cross-over study with 41 healthy participants, we measured cortisol not only before and after but also during static magnetic field exposure in MRI scanners. Measures of catecholamines before and after exposure were also part of the study protocol. Using three different field strengths (1.5, 3 and 7 T) and a mock scanner (0 T), we examined whether not only the MRI procedure but also the static magnetic field per se has an influence on the neuroendocrine responses. We found no significant differences in the course of cortisol or catecholamine concentrations between the different static magnetic fields. Our study suggests that the results of MRI studies using stress-paradigms are not influenced by the static magnetic field itself.

Women are more strongly affected by dizziness in static magnetic fields of magnetic resonance imaging scanners.

Increasing field strengths in MRI necessitate the examination of potential side effects. Previously reported results have been contradictory, possibly caused by imbalanced samples. We aimed to examine whether special groups of people are more prone to develop side effects that might have led to contradictory results in previous studies. We examined the occurrence of sensory side effects in static magnetic fields of MRI scanners of 1.5, 3, and 7 T and a mock scanner in 41 healthy participants. The contribution of field strength, sex, age, and attention to bodily processes, and stress hormone levels to the sensation of dizziness was examined in separate univariate analyses and in a joint analysis that included all variables. Field strength and sex were significant factors in the joint analysis (P=0.001), with women being more strongly affected than men by dizziness in higher static magnetic fields. This effect was not mediated by the other variables such as attention to bodily symptoms or stress hormones. Further research needs to elucidate the underlying factors of increased dizziness in women in static magnetic fields in MRI. We hypothesize that imbalanced samples of earlier studies might be one reason for previous contradictory results on the side effects of static magnetic fields.