Physical activity and energy expenditure during depressive episodes of major depression.

BACKGROUND: Recent data suggest a substantial association between physical activity and depressive symptoms, but there is a lack of research evaluating the physical activity levels in patients suffering from unipolar depression across different stages of disease in an objective way. The aim of the present pilot study was to objectively examine physical activity levels of this patient group compared to healthy controls. METHODS: Physical activity performance of 19 patients with major depressive episode and 19 healthy controls was assessed at three different time points using a multisensory armband device (SenseWear® Pro3 Armband) and was reported as total energy expenditure (TEE), active energy expenditure (EE), metabolic equivalents (METs), physical activity (PA) and time of lying down (LD), in each case over 24h. RESULTS: Over all measurements, depressive patients presented a significantly lower mean TEE and EE over 24h. Moreover, the patient group showed significantly shorter duration of PA and lower average MET over 24h. When depressive symptoms abated, physical activity parameters significantly increased in the patient group. Correlation analyses demonstrated a significant relation between depressive status/anhedonia and parameters of physical activity, especially in healthy subjects. LIMITATIONS: Results represented valid data for inpatients only. CONCLUSION: Acute unipolar depression was associated with a significantly lower level of physical activity and showed a significant increase in parallel to clinical improvement. Electronic monitoring of physical activity may be an additional tool for evaluating and controlling therapeutic effects.

The psychophysical assessment of odor valence: does an anchor stimulus influence the hedonic evaluation of odors?

Olfactory stimuli are experienced primarily in terms of their hedonic tone and the assessment of olfactory hedonic estimates is a prevalent task in scientific and industrial contexts. However, measuring conditions are poorly standardized. Our study aims to fill this gap, focusing on the influence of anchor stimuli on olfactory hedonic evaluations, frequency of anchor presentation, and temporal stability of results. In n = 31 subjects, hedonic estimates for the 16 odors of the Sniffin' Sticks identification task were assessed on a visual analog rating scale under 4 measuring conditions (nonanchor, pleasant anchor, neutral anchor, unpleasant anchor). To test for stability over time, n = 10 subjects were reassessed 2, 4, and 6 months after original testing. To analyze for possible effects of single versus repeated anchor presentation, n = 15 subjects were retested 2 months after the original session in a multiple anchor presentation format. Statistical analysis revealed significant differences between the 4 anchor conditions, thus highlighting the necessity of specifying assessment methods in scientific research. No significant differences between timepoints were observed, indicating a high temporal stability of olfactory hedonic evaluations, especially from timepoint T2 onward. No overall significant effects of single versus multiple anchor presentation were detected. Findings might help to further standardize testing procedures.

Neurocognitive impairments in non-deprived smokers--results from a population-based multi-center study on smoking-related behavior.

The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never-smoking controls) participated in a population-based case-control design. The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P<0.001) and cognitive impulsivity (P<0.006), while verbal episodic memory, verbal fluency, verbal working memory, and Stroop-interference did not differ between groups. These attention/impulsivity deficits were also present in smokers with only a low amount of cigarette consumption. Lifetime nicotine use (pack-years) was not correlated with cognition in smokers. In conclusion, this study confirmed subtle and specific cognitive deficits in non-deprived smokers. The independence of these deficits from consumption intensity may argue for an a priori deficit of some cognitive abilities in smokers. These specific deficits may constitute intermediate phenotypes for genetic research on nicotine use.

Catatonic dilemma in a 33-year-old woman: a discussion.

Case. We report a case of catatonia with elevated CK, elevated temperature, and hypoferritinemia after abrupt discontinuation of clozapine in a patient with known proneness to catatonic symptoms. Reinstatement of clozapine therapy was contraindicated due to leukopenia. Neuroleptic malign syndrome could not be ruled out by the administration of quetiapine; this prevented the quick use of other potent D2 antagonists. Some improvement was achieved through supportive therapy, high dose of lorazepam, and a series of 10 ECT sessions. Returning to baseline condition was achieved by a very careful increase of olanzapine. Discussion. Catatonic symptoms in schizophrenia as well as in NMS might be caused by a lack of striatal dopamine (CS) or dopamine D2 antagonism (NMS). CS might be a "special" kind of schizophrenia featuring both hypo- and hyperactivity of dopaminergic transmission. ECT has been described as a "psychic rectifier" or a "reset for the system." The desirable effect of ECT in cases of CS might be dopaminergic stimulation in the striatum and decrease of both the dopaminergic activity in the limbic system and the serotonergic activity on 5-HT2 receptors. The desirable effect of ECT in NMS would be explained by activation of dopaminergic transmission and/or liberation of dopaminergic receptors from the causative neuroleptics.

Olfactory perception in schizophrenia: the rating range for hedonic judgements is increased during acute episodes.

Deficits in olfactory performance have been reported in schizophrenia but results on subjective odour ratings remain unclear. Compared to controls (N=34), schizophrenia inpatients (N=34) expressed deficits concerning odour threshold, discrimination and identification but intact intensity ratings. Most interestingly, patients showed an increased rating range concerning olfactory hedonic judgements.

Schizophrenia risk polymorphisms in the TCF4 gene interact with smoking in the modulation of auditory sensory gating.

Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whether TCF4 polymorphisms also affect another proposed endophenotype of schizophrenia, namely sensory gating assessed by P50 suppression of the auditory evoked potential. Although sensorimotor gating and sensory gating are not identical, recent data suggest that they share genetic fundamentals. In a multicenter study at six academic institutions throughout Germany, we applied an auditory P50 suppression paradigm to 1,821 subjects (1,023 never-smokers, 798 smokers) randomly selected from the general population. Samples were genotyped for 21 TCF4 polymorphisms. Given that smoking is highly prevalent in schizophrenia and affects sensory gating, we also assessed smoking behavior, cotinine plasma concentrations, exhaled carbon monoxide, and the Fagerström Test (FTND). P50 suppression was significantly decreased in carriers of schizophrenia risk alleles of the TCF4 polymorphisms rs9960767, rs10401120rs, rs17597926, and 17512836 (P < 0.0002-0.00005). These gene effects were modulated by smoking behavior as indicated by significant interactions of TCF4 genotype and smoking status; heavy smokers (FTND score ≥ 4) showed stronger gene effects on P50 suppression than light smokers and never-smokers. Our finding suggests that sensory gating is modulated by an interaction of TCF4 genotype with smoking, and both factors may play a role in early information processing deficits also in schizophrenia. Consequently, considering smoking behavior may facilitate the search for genetic risk factors for schizophrenia.

Olfactory abnormalities in anxiety disorders.

The olfactory system plays an important role in both animal and human anxiety reactions. However, results on olfactory performance during the course of clinical anxiety disorders remain scarce. Therefore, we conducted an exploratory pilot study in 17 patients currently diagnosed with an anxiety disorder. Patients participated in olfactory and psychological testing and were compared to 17 healthy controls. Statistical analyses revealed significant deficits concerning olfactory discrimination in patients, while no changes in threshold and identification ability occurred. Most interestingly, patients showed higher intensity estimates and an increased rating range concerning olfactory hedonic judgements. Results are discussed in light of prior findings and related to neural correlates of olfactory perception and anxiety reactions.

ERK1/2 protein and mRNA levels in human blood are linked to smoking behavior.

From studies in cultured cells and animal models, nicotine and alcohol are known to regulate extracellular signal-regulated kinase 1 and 2 (ERK1/2). Alterations of ERK1/2 are thought to contribute to the drugs' rewarding effects. Accumulating evidence supports the importance of ERK1/2 in the molecular pathophysiology of depression and affective regulation in the hippocampus. We recently showed that the expression and phosphorylation of cyclic adenosine monophosphate response element (CRE)-binding protein (CREB) in human buffy coat were associated with smoking behavior. Because ERK1/2 is known to effect phosphorylation of CREB, the aim of the present study was to further elucidate whether cigarette smoking leads to alterations in terms of ERK1/2 in human buffy coat as well. In a comparison of 53 smokers with 146 non-smoking controls, we found significantly higher levels of ERK1/2 protein (P=0.004). In contrast, phospho-ERK1/2, phospho-/total-ERK1/2 ratio, mRNA-ERK1 and mRNA-ERK2 were not significantly different. Multiple regression analysis revealed a significant relation among the number of cigarettes smoked daily (R(2)=0.266, P=0.003), the Fagerström Test for Nicotine Dependence score (R(2)=0.149, P=0.032) and the mRNA expression of ERK1. Moreover, our analysis suggests that the mRNA expression of ERK2 might be linked to mood (model summary: R(2)=0.087, P=0.019; mRNA-ERK2: P=0.026). Given that the ERK1/2 signaling pathway plays an important role in the physiology and pathophysiology of affective and addictive behavior, our findings provide a rationale basis for additional mechanistic studies that may lead to the development of novel signaling pathway selective therapeutics in humans.

The German multi-centre study on smoking-related behavior-description of a population-based case-control study.

Tobacco smoking is a major risk factor for most of the diseases leading in mortality. Nicotine dependence (ND), which sustains regular smoking, is now acknowledged to be under substantial genetic control with some environmental contribution. At present, however, genetic studies on ND are mostly conducted in populations that have been poorly characterized with regard to ND-related phenotypes for the simple reason that the respective populations were not primarily collected to study ND. The German multi-centre study 'Genetics of Nicotine Dependence and Neurobiological Phenotypes', which is funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Priority Program (Schwerpunktprogramm) SPP1226: 'Nicotine-Molecular and Physiological Effects in CNS', was intended to overcome some of these inherent problems of current genetic studies of ND. The multi-centre study is a population-based case-control study of smokers and never-smokers (n = 2396). The study was unique worldwide because it was the first large-scale genetic study specifically addressing ND with the collection of a wide range of environmental, psychosocial and neurobiological phenotypes. Study design and major population characteristics with emphasis on risk prediction of smoking status were presented in this paper.

Psychological and hormonal features of smokers at risk to gain weight after smoking cessation--results of a multicenter study.

Preclinical and clinical data suggest modulating effects of appetite-regulating hormones and stress perception on food intake. Nicotine intake also interferes with regulation of body weight. Especially following smoking cessation gaining weight is a common but only partially understood consequence. The aim of this study was to examine the interaction between smoking habits, the appetite regulating hormone leptin, negative affectivity, and stress vulnerability on eating behavior in a clinical case-control study under standardized conditions. In a large population-based study sample, we compared leptin and cortisol plasma concentrations (radioimmunoassay) between current tobacco smokers with high cognitive restraint and disinhibition in eating behavior and smokers scoring low in both categories as assessed with the Three Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985). As a measure for smoking effects on the stress axis, the saliva cortisol concentrations were compared before and after nicotine smoking. Additionally, stress perception was assessed with the Perceived Stress Scale (PSS), symptoms of depression and anxiety with the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). In smokers showing high cognitive restraint and disinhibition we found significantly higher leptin concentrations than in the group of smokers scoring low in both categories. Furthermore there was a significant group difference in saliva cortisol concentrations after nicotine intake. Smokers showing high cognitive restraint and disinhibition were also characterized by significantly higher scores in the STAI, the PSS and the BDI. Our results suggest that smokers with a pathological eating behavior show an impaired neuroendocrine regulation of appetite and are prone to experience higher levels of stress and negative affectivity. This interaction of behavioral and neuroendocrinological factors may constitute a high risk condition for gaining weight following smoking cessation.

P50 sensory gating and smoking in the general population.

P50 gating is a major functional biomarker in research on schizophrenia and other psychiatric conditions with high smoking prevalence. It is used as endophenotype for studying nicotinic systems genetics and as surrogate endpoint measure for drug development of nicotinic agonists. Surprisingly, little is known about P50 gating in the general population and the relationship to smoking-related characteristics. In this multicenter study at six academic institutions throughout Germany, n=907 never-smokers (NS<20 cigarettes/lifetime), n=463 light smokers (LS) with Fagerström Test for Nicotine Dependence (FTND)≥4 and n=353 heavy smokers (HS, FTND<4) were randomly selected from the general population. As part of a standardized protocol for investigating the genetics of nicotine dependence (ND), an auditory P50 paradigm was applied. The main outcome measure was P50-amplitude difference followed by time-frequency analyses and functional imaging (sLORETA). Reduced P50 gating was found in HS compared to NS with LS taking an intermediate position-correlating with the degree of ND. sLORETA and time-frequency analyses indicate that high-frequency oscillations in frontal brain regions are particularly affected. With growing age, P50 gating increased in (heavy) smokers. This is the first large-scale study (normative sample data) on P50 sensory gating and smoking in the general population. Diminished gating of P50 and associated high-frequency oscillations in the frontal brain region are indications of a deficient inhibitory cortical function in nicotine-dependent smokers. The suitability and application of sensory P50 gating as functional biomarker with regard to genetic and pharmacological studies is discussed.

NACP-Rep1 relates to Beck Depression Inventory scores in healthy humans.

Alpha-synuclein (SNCA) is associated with a range of psychiatric diseases including neurodegeneration, alcohol craving, and depression. It regulates cellular homeostasis by virtue of its ability to interfere in dopaminergic, serotonergic, and noradrenergic pathways. To date, it is unclear whether the previously described association between SNCA and depressive symptomatology is limited to females with eating disorders or whether it could be extended to include healthy individuals. We included 105 women and 108 men. Genetic data and mRNA expression analyses were drawn from peripheral blood and the severity of depressive symptoms was quantified by the Beck's Depression Inventory (BDI). We found a significant association between the NACP-Rep1 length polymorphism and the BDI score (p = 0.004). Moreover, there was a significant gender dimorphism regarding mRNA expression of SNCA (p = 0.011). Our analysis revealed no further association between the In4 polymorphism or between the mRNA expression of SNCA and the BDI score. Since this investigation was limited to healthy individuals, conclusions concerning depression according to ICD-10 or DSM-IV cannot be drawn. The reported results may contribute to a better understanding of the molecular mechanisms linked to depressive symptoms.

The relation between depression, anhedonia and olfactory hedonic estimates--a pilot study in major depression.

Several studies investigating olfactory hedonics in major depression have brought conflicting results and an analysis of the relation between severity of depression, anhedonia and olfactory hedonics is still lacking. In order to investigate olfactory perception in different depressive states, we carried out olfactory testing during a depressive episode (n=37) and in a remitted state (n=17). As expected, patients were significantly less depressed (p<0.001) and less anhedonic (p=0.001) in the remitted state. A comparison of olfactory perception between age- and gender-matched patients and healthy volunteers (n=37) controlled for intrinsic olfactory deficits in major depression. In the depressive episode, we applied regression analyses to investigate the relation of olfactory hedonics, severity of depression and anhedonia. The Sniffin' Sticks Test extended by analogue rating scales for intensity and hedonic estimates was employed for olfactory testing. Depression severity was assessed with the Beck Depression Inventory (BDI), anhedonia with the Snaith-Hamilton-Pleasure-Scale (SHAPS). Odour identification ability was significantly reduced during the depressive state. In contrast, no significant differences in hedonic and intensity estimates could be found between the depressive and the remitted state and healthy controls. During the depressive episode, we found a significant relation only between anhedonia and olfactory hedonics. We concluded that anhedonia has potential impact on olfactory hedonics in major depression. Our results indicate the need for (1) confirmatory studies in severe melancholic depression and (2) investigation of the impact of anhedonia on olfactory hedonics in psychiatric diseases other than major depression.

Smoking behaviour is associated with expression and phosphorylation of CREB in human buffy coat.

Nicotine induces various acute und chronic pharmacological effects which can be long lasting and might lead to nicotine dependence. Nicotinic acetylcholine receptors (nAChRs) are involved in nicotine-induced phosphorylation of CREB (cyclic AMP response element-binding protein) in PC12h cells. Several studies, mainly done in animal models, report that CREB plays a role in anxiety, memory and substance abuse as well as in affective disorders. Information regarding nicotine effects on gene expression in humans in vivo is rare. The aim of our study was to determine whether or not there are differences between smokers and non-smoking controls in terms of CREB expression and phosphorylation in human buffy coat. Comparing 32 smokers with 76 non-smoking controls we found significantly elevated relative (p=0.043) and absolute (p=0.040) CREB phosphorylation in the blood of smokers who had smoked two cigarettes in the past 6 h. In contrast, the score of the State and Trait Anxiety Inventory, total-CREB and mRNA-CREB were not significantly different. Multiple regression analysis revealed a significant relation between the number of cigarettes smoked daily (R2=0.143, p=0.023), the Fagerström Test for Nicotine Dependence score (R2=0.145, p=0.022) and the expression of CREB. Moreover, in accord with previously published data our analysis suggests gender and age as factors that significantly influence expression and phosphorylation of CREB. It appears that human buffy coat is suitable for studying pharmacological effects of substances such as nicotine on selected signal transduction pathways in humans in vivo. This kind of study may be helpful for translating findings from animal models and cell cultures.