Association of hypertension, type 2 diabetes mellitus and dyslipidemia with the duration of inpatient treatments and recurrence of schizophrenia.

OBJECTIVE: People with schizophrenia have an increased cardiovascular risk with higher mortality than the general population. Only a few studies have investigated the impact of cardiovascular risk on the later course of schizophrenia. This study aims to explore the association of cardiovascular risk factors, as detected during an index inpatient treatment for schizophrenia, with the duration of psychiatric inpatient treatments and number of inpatient admissions in the subsequent 10 years, in patients with schizophrenia. METHODS: Cardiovascular risk factors of 736 patients with schizophrenia, identified through retrospective chart review, were assessed by hypertension, type 2 diabetes mellitus and dyslipidemia during an index inpatient stay. The duration of inpatient treatments, assessed by the total duration of psychiatric inpatient treatments in days, and the number of inpatient admissions, over the next 10 years were assessed and analyzed for an association with cardiovascular risk factors. RESULTS: Hypertension associated with longer duration of inpatient treatments and higher number of inpatient admissions. Type 2 diabetes mellitus and dyslipidemia associated with a higher number of psychiatric inpatient treatments. Hypertension remained significantly associated with the duration of inpatient treatments (ß = 0.174; p < 0.001) and the number of inpatient treatments (ß = 0.144; p < 0.001), when adjusting for age, sex and BMI. CONCLUSION: Out of the investigated cardiovascular risk factors documented during an index inpatient stay for schizophrenia, only hypertension associated with an increased duration of in-hospital stay and an increased number of re-hospitalizations during the subsequent ten years when adjusting for confounders. Screening for hypertension should be considered in all patients with schizophrenia.

The Prevalence and Characteristics of Phantom Limb Pain and Non-Painful Phantom Phenomena in a Nationwide Survey of 3,374 Unilateral Limb Amputees.

The experience of phantom limb pain (PLP) is a common consequence of limb amputation, resulting in severe impairments of the affected person. Previous studies have shown that several factors such as age at or site of amputation are associated with the emergence and maintenance of PLP. In this cross-sectional study we assessed the presence of several phantom phenomena including PLP and other amputation-related information in a sample of 3,374 unilateral upper and lower limb amputees. Clinical and demographic variables (age at amputation, level of amputation) explained 10.6% of the variance in PLP and perceptual variables (intensity of phantom limb sensation [PLS], referred sensations, intensity of telescoping, residual limb pain [RLP] intensity) explained 16.9% of the variance. These variables were specific for PLP and not for RLP. These results suggest that distinct variables are associated with PLP (age at amputation, level of amputation, PLS intensity, referred sensations, intensity of telescoping, RLP intensity) and RLP (PLP intensity) and point at partly different mechanisms for the emergence and maintenance of PLP and RLP. PERSPECTIVE: Clinical/demographic variables as well as perceptual variables are 2 major components related to PLP and explain ∼11% and ∼17% of the variance. These results could potentially help clinicians to understand which factors may contribute to chronic phantom limb pain.

Detecting significant genotype-phenotype association rules in bipolar disorder: market research meets complex genetics.

BACKGROUND: Disentangling the etiology of common, complex diseases is a major challenge in genetic research. For bipolar disorder (BD), several genome-wide association studies (GWAS) have been performed. Similar to other complex disorders, major breakthroughs in explaining the high heritability of BD through GWAS have remained elusive. To overcome this dilemma, genetic research into BD, has embraced a variety of strategies such as the formation of large consortia to increase sample size and sequencing approaches. Here we advocate a complementary approach making use of already existing GWAS data: a novel data mining procedure to identify yet undetected genotype-phenotype relationships. We adapted association rule mining, a data mining technique traditionally used in retail market research, to identify frequent and characteristic genotype patterns showing strong associations to phenotype clusters. We applied this strategy to three independent GWAS datasets from 2835 phenotypically characterized patients with BD. In a discovery step, 20,882 candidate association rules were extracted. RESULTS: Two of these rules-one associated with eating disorder and the other with anxiety-remained significant in an independent dataset after robust correction for multiple testing. Both showed considerable effect sizes (odds ratio ~ 3.4 and 3.0, respectively) and support previously reported molecular biological findings. CONCLUSION: Our approach detected novel specific genotype-phenotype relationships in BD that were missed by standard analyses like GWAS. While we developed and applied our method within the context of BD gene discovery, it may facilitate identifying highly specific genotype-phenotype relationships in subsets of genome-wide data sets of other complex phenotype with similar epidemiological properties and challenges to gene discovery efforts.

Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm.

BACKGROUND: Mother-infant interaction provides important training for the infant's ability to cope with stress and the development of resilience. Prenatal stress (PS) and its impact on the offspring's development have long been a focus of stress research, with studies highlighting both harmful and beneficial effects. The aim of the current study was to examine the possible influence of both psychological stress and hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy with mother-child dyadic behavior following stress exposure. METHODS: The behavior of 164 mother-infant dyads during the still-face situation was filmed at six months postpartum and coded into three dyadic patterns: 1) both positive, 2) infant protesting-mother positive, and 3) infant protesting-mother negative. PS exposure was assessed prenatally according to psychological measures (i.e., psychopathological, perceived and psychosocial PS; n = 164) and HPA axis activity measures (maternal salivary cortisol, i.e., cortisol decline and area under the curve with respect to ground (AUCg); n = 134). RESULTS: Mother-infant dyads in both the high- and low-stress groups showed decreasing positive and increasing negative dyadic behavior in the reunion episode, which is associated with the well-known "still-face" and "carry-over" effect. Furthermore, mother-infant dyads with higher psychosocial PS exhibited significantly more positive dyadic behavior than the low psychosocial PS group in the first play episode, but not in the reunion episode. Similarly, mother-infant dyads with high HPA axis activity (i.e. high AUCg) but steeper diurnal cortisol decline (i.e. cortisol decline) displayed significantly less negative behavior in the reunion episode than dyads with low HPA axis activity. No significant results were found for psychopathological stress and perceived stress. CONCLUSIONS: The results suggest a beneficial effect of higher psychosocial PS and higher prenatal maternal HPA axis activity in late gestation, which is in line with "stress inoculation" theories.

Impact of prenatal stress on the dyadic behavior of mothers and their 6-month-old infants during a play situation: role of different dimensions of stress.

Prenatal stress (PS) is an established risk factor in the etiology of mental disorders. Although mother-child interaction is the infant's first important training in dealing with stress, little is yet known about the impact of PS on mother-infant dyadic behavior. The current study aimed to elucidate the prospective influence of psychological and physiological stresses during pregnancy on mother-infant dyadic behavior. Mother-infant interactions were videotaped at 6-month postpartum and coded into three dyadic patterns: (1) both positive; (2) infant protesting-mother positive; and (3) infant protesting-mother negative, using the infant and caregiver engagement phases. Exposure to PS was assessed during pregnancy using psychological (i.e., psychopathological, perceived, and psychosocial PS; n = 164) and physiological stress measures (i.e., maternal cortisol; n = 134). Group comparisons showed that psychosocial PS was predictive of mother-infant behavior at 6-month postpartum, indicating that dyads of prenatally high-stressed mothers exhibited significantly more positive interaction patterns (i.e., infant positive-mother positive) as compared to the prenatally low-stressed group. Physiological PS was unrelated to mother-infant behavior. These results suggest that mild psychosocial PS may be advantageous for positive mother-infant dyadic behavior, which is in accordance with the stress-inoculation model that assumes a beneficial effect of PS.

Negative Association Between MR-Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats.

BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence. RESULTS: In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. CONCLUSIONS: Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity.

AIDE-Acute Illness and Depression in Elderly Patients. Cognitive Behavioral Group Psychotherapy in Geriatric Patients With Comorbid Depression: A Randomized, Controlled Trial.

BACKGROUND: Comorbid depression is highly prevalent in geriatric patients and associated with functional loss, frequent hospital re-admissions, and a higher mortality rate. Cognitive behavioral psychotherapy (CBT) has shown to be effective in older depressive patients living in the community. To date, CBT has not been applied to older patients with acute physical illness and comorbid depression. OBJECTIVES: To evaluate the effectiveness of CBT in depressed geriatric patients, hospitalized for acute somatic illness. DESIGN: Randomized controlled trial with waiting list control group. SETTING: Postdischarge intervention in a geriatric day clinic; follow-up evaluations at the patients' homes. PARTICIPANTS: A total of 155 randomized patients, hospitalized for acute somatic illness, aged 82 ± 6 years and suffering from depression [Hospital Anxiety and Depression Scale (HADS) scores >7]. Exclusion criteria were dementia, delirium, and terminal state of medical illness. INTERVENTION: Fifteen, weekly group sessions based on a CBT manual. Commencement of psychotherapy immediately after discharge in the intervention group and a 4-month waiting list interval with usual care in the control group. MEASUREMENTS: HADS depression total score after 4 months. Secondary endpoints were functional, cognitive, psychosocial and physical status, resource utilization, caregiver burden, and amount of contact with physician. RESULTS: The intervention group improved significantly in depression scores (HADS baseline 18.8; after 4 months 11.4), whereas the control group deteriorated (HADS baseline 18.1; after 4 months 21.6). Significant improvement in the intervention group, but not in the control group, was observed for most secondary outcome parameters such as the Barthel and Karnofsky indexes. Intervention effects were less pronounced in patients with cognitive impairment or acute fractures. CONCLUSIONS: CBT is feasible and highly effective in geriatric patients. The benefits extend beyond effective recovery and include improvement in physical and functional parameters. Early diagnosis, good access to psychotherapy, and early intervention could improve care for depressive older patients. CLINICAL TRIAL REGISTRATION: www.germanctr.de German Trial Register DRKS 00004728.

New-born females show higher stress- and genotype-independent methylation of SLC6A4 than males.

BACKGROUND: Research has demonstrated an association between exposure to early life stress and an increased risk of psychiatric disorders in later life, in particular depression. However, the mechanism through which early life stress contributes to disease development remains unclear. Previous studies have reported an association between early life stress and altered methylation of the serotonin transporter gene (SLC6A4), a key candidate gene for several psychiatric disorders. These differences in methylation are influenced by sex and genetic variation in the SLC6A4-linked polymorphic region (5-HTTLPR). Furthermore, one study indicated that stress during pregnancy may induce methylation changes in SLC6A4 in the newborn. The present study is the first to investigate whether early life stress during pregnancy impacts on SLC6A4 methylation in newborns, taking into account the influence of genetic variation and sex. METHODS: Cord blood was obtained from newborns with high (n = 45) or low (n = 45) early life stress, defined as maternal stress during pregnancy. The effect on methylation of early life stress, 5-HTTLPR genotype, and sex was assessed at four cytosin-phosphate-guanine dinucleotide (CpG) sites in the promoter associated CpG island north shore (CpG 1 to 4). The epigenetic analyses focused on these CpG sites, since research has shown that CpG island shore methylation has functional consequences. RESULTS: Significant sex-specific methylation was observed, with females displaying higher methylation levels than males (p < 0.001). Importantly, this effect was influenced by neither early life stress nor genotype. CONCLUSIONS: The present data suggest that sex-specific methylation of SLC6A4 is present at birth, and is independent of early life stress and 5-HTTLPR genotype. This may contribute to the sex-specific prevalence of depression.

Recovery-stress balance and injury risk in professional football players: a prospective study.

Professional football is a contact sport with a high risk of injury. This study was designed to examine the contribution of stress and recovery variables as assessed with the Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) to the risk of injury in professional football players. In a prospective, non-experimental cohort design, 22 professional football players in the highest German football league were observed over the course of 16 months. From January 2010 until April 2011, the players completed the RESTQ-Sport a total of 222 times in monthly intervals. In addition, injury data were assessed by the medical staff of the club. Overall, 34 traumatic injuries and 10 overuse injuries occurred. Most of the injuries were located in the lower limb (79.5%), and muscle and tendon injuries (43.2%) were the most frequently occurring injury type. In a generalised linear model, the stress-related scales Fatigue (OR 1.70, P = 0.007), Disturbed Breaks (OR 1.84, P = 0.047) and Injury (OR 1.77, P < 0.001) and the recovery-related scale Sleep Quality (OR 0.53, P = 0.010) significantly predicted injuries in the month after the assessment. These results support the importance of frequent monitoring of recovery and stress parameters to lower the risk of injuries in professional football.

Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder.

The objective of this study was to investigate the hypothesis that borderline personality disorder (BPD) and bipolar disorder (BD) share genetic variation through analysis of known genetic risk factors for BD in a well-characterized BPD case-control cohort. Genotyping of five genome-wide significant variants identified for BD (in CACNA1C, ANK3, and ODZ4) was performed in 673 BPD cases and 748 controls. A nominally significant association with BPD was found for rs1006737 in CACNA1C (P=0.0498). Sex-specific analysis showed that this signal was present only in women. This is the first report of an association between a BD risk gene and BPD where selection was not based on a priori hypotheses about its function, but on an unbiased hypothesis-free screening of the genome. Genome-wide association data of large samples of BPD are warranted and will eventually identify new risk genes and the overlap between BPD and BD if it exists.

Genetic fate mapping of type-1 stem cell-dependent increase in newborn hippocampal neurons after electroconvulsive seizures.

Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP-expressing stem-like cells (type-1 cells) and their progeny are selectively labeled with the reporter protein ß-galactosidase to track the process of neurogenesis in the dentate gyrus over 3 months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type-1 cell divisions. While this led to an expansion of the type-1 cell pool after high-frequency ECS sessions for 5 consecutive days (5-ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)-expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5-ECS could be traced back to proliferating type-1 cells. Low-frequency continuation ECS (c-ECS) consisting of five single ECS sessions administered every 2 weeks resulted in a similar increase in newborn neurons as the high-frequency 5-ECS protocol. Moreover, the combination of 5-ECS and c-ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high-frequency ECT followed by continuation ECT in severely depressed patients. The ability of high- and low-frequency ECS to induce normally quiescent type-1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT.

Leptin plasma concentrations increase during antidepressant treatment with amitriptyline and mirtazapine, but not paroxetine and venlafaxine: leptin resistance mediated by antihistaminergic activity?

Treatment with several psychopharmacological agents has been associated with increased leptin plasma concentrations. We measured leptin plasma concentrations in 76 adult depressed patients after a 6-day washout phase and again after 35 days of treatment with amitriptyline or paroxetine, as well as in 73 depressed patients after 28 days of treatment with either mirtazapine or venlafaxine. Leptin plasma concentrations increased during treatment with amitriptyline and mirtazapine, even after controlling for increased body mass index and irrespective of response to treatment [14.5 (13.8) vs 20.3 (18.7) ng/mL, and 12.2 (15.8) vs 14.4 (16.5) ng/mL in the 2 cohorts, respectively]. In contrast, paroxetine and venlafaxine treatment was not associated with changes in leptin plasma concentrations [14.8 (12.0) vs 13.6 (10.6); 15.9 (17.3) vs 13.5 (14.6) ng/mL] nor with weight gain. We conclude that treatment with amitriptyline or mirtazapine is associated with an increase in leptin secretion beyond change in weight. Thus, high leptin levels apparently are ineffective in the control of weight gain, indicating leptin resistance. Leptin resistance may be mediated by an antihistaminergic effect on hypothalamic nuclei integrating signals relevant for energy balance.

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.

Translational magnetic resonance spectroscopy reveals excessive central glutamate levels during alcohol withdrawal in humans and rats.

BACKGROUND: In alcoholism, excessive glutamatergic neurotransmission has long been implicated in the acute withdrawal syndrome and as a key signal for dependence-related neuroplasticity. Our understanding of this pathophysiological mechanism originates largely from animal studies, but human data are needed for translation into successful medication development. METHODS: We measured brain glutamate levels during detoxification in alcohol-dependent patients (n = 47) and in healthy control subjects (n = 57) as well as in a rat model of alcoholism by state-of-the-art ¹H-magnetic magnetic resonance spectroscopy at 3 and 9.4 T, respectively. RESULTS: We found significantly increased glutamate levels during acute alcohol withdrawal in corresponding prefrontocortical regions of treatment-seeking alcoholic patients and alcohol-dependent rats versus respective control subjects. The augmented spectroscopic glutamate signal is likely related to increased glutamatergic neurotransmission because, enabled by the high field strength of the animal scanner, we detected a profoundly elevated glutamate/glutamine ratio in alcohol-dependent rats during acute withdrawal. All dependence-induced metabolic alterations normalize within a few weeks of abstinence in both humans and rats. CONCLUSIONS: Our data provide first-time direct support from humans for the glutamate hypothesis of alcoholism, demonstrate the comparability of human and animal magnetic resonance spectroscopy responses, and identify the glutamate/glutamine ratio as potential biomarker for monitoring disease progression.

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.

[Initial and extension applications for psychodynamic therapy according to the German Guidelines for Psychotherapy]. / Erst- und Umwandlungsanträge bei den psychodynamischen Therapieverfahren in der Richtlinien-Psychotherapie.

RESEARCH QUESTION: According to the German Guidelines for Psychotherapy, psychotherapists need the consent of the respective insurance company to commence outpatient therapy. They have two options: (1) To begin a so-called short-term therapy (KZT) for up to 25 sessions--a quick and easy procedure requiring few formal expenses. Afterwards the therapist must provide the reasons for extending the therapy in a formal expert assessment request (extension request). (2) It is also possible to obtain the consent of the insurance company at the beginning of therapy (initial request) for up to 50 sessions (psychodynamic long-term therapy) or even for up to 160 sessions (analytical psychotherapy), both of which require the same expert assessment to be filled out beforehand (LZT). This study examines the initial and extension requests submitted for evaluation for psychodynamic therapies according to the German Guidelines for Psychotherapy. The question is posed as to what influences are important in the selection of therapists for these two types of request. METHODOLOGY: In the context of the MARS study, we evaluated a total of 362 randomly chosen requests submitted between May 2007 and June 2008, 128 of which were initial requests and 234 of which were requests for an extension. The evaluation of the reports proceeded on the basis of a previously developed documentation system with various modules comprising information on the sociodemographics and morbidity of the patients as well as information on the therapists themselves. Further modules are assessed in this review. RESULTS: There were many more requests for an extension submitted than initial requests. Initial requests were preferably made when planning analytical psychotherapy. Patients for whom initial requests were submitted were also distinctly younger. The morbidity of the patients had no noticeable influence on the choice of procedure. In particular, diagnoses that could require crisis intervention were not more common in the requests for an extension than in the initial requests. Variables among the therapists had no influence on the form of procedure. These results were confirmed by a multivariate statistical analysis. DISCUSSION: The inconsistencies found in the reported and encoded morbidity of the patients confirm earlier results. Basic conditions, like the guidelines themselves or the payment of trial treatment, seem to determine therapists' behaviour. We also discuss whether or not the advantages of the current procedures to both the patient and the therapist outweigh the possible disadvantages..

Salivary cortisol in a middle-aged community sample: results from 990 men and women of the KORA-F3 Augsburg study.

OBJECTIVE: Analysis of salivary cortisol concentrations and derived indices is increasingly used in clinical and scientific medicine. However, comprehensive data on these parameters in the general population are scarce. The aim of this study was to evaluate the concentrations of salivary cortisol in a large middle-aged community sample and to identify major factors associated with altered hormone levels. DESIGN: We conducted a cross-sectional study within the Cooperative Health Research in the Region of Augsburg (KORA)-F3 study. A total of 1484 participants aged 50-69 years (52% women) had agreed to provide four saliva samples during a regular weekday. METHODS: We measured salivary cortisol concentrations at wake-up (F0), (1/2) h (F(1/2)), 8 h (F8), and 14 h (F14) after waking. We calculated cortisol awakening response (CAR), slope, and area under the curve (AUC(G)) of the circadian cortisol secretion. Sociodemographic and clinical characteristics were evaluated by interview and questionnaires, sampling conditions by protocol. In total, 1208 participants returned saliva samples, exclusion criteria left 990 subjects for final analyses. RESULTS: Salivary cortisol levels were (means+/-s.d.) F0=13.7+/-7.6, F(1/2)=20.5+/-9.8, F8=5.4+/-3.3, and F14=2.0+/-1.8 nmol/l. Earlier sampling times were associated with higher CAR and smaller slope. Cortisol secretion was also influenced by gender and smoking habits. Higher perceived social support was associated with lower AUC(G) and smaller slope. CONCLUSIONS: We provide data on salivary cortisol concentrations in a large middle-aged community sample. Gender, sampling time, smoking habits, and perceived social support appeared as determinants of cortisol secretion.

Why is disulfiram superior to acamprosate in the routine clinical setting? A retrospective long-term study in 353 alcohol-dependent patients.

AIMS: To compare the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence and their effectiveness in regard to patient characteristics, within a naturalistic outpatient treatment setting. METHOD: Retrospective data from 2002 to 2007 were analysed on 353 alcohol-dependent subjects in outpatient treatment, who, according to the patient's and the clinician's mutual decision, received either supervised DSF (with thrice-weekly appointments) or ACP (once-weekly appointments) following an inpatient alcohol detoxification treatment. Abstinence was assessed by alcohol breathalyzer, patients' self-report, urine and serum analyses, and overall physicians' rating. RESULTS: Baseline data in terms of current addictive behaviour and course of disease differed between groups to the disadvantage of the DSF group; compared to the ACP group, subjects treated with DSF showed a longer duration of alcohol dependence, higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history. In follow-up, Kaplan-Meier survival analysis revealed significant differences between groups in the primary and secondary measures of outcome (P always <0.01). Time elapsed before the first alcohol relapse as well as attendance to outpatient treatment and cumulative alcohol abstinence achieved within outpatient treatment was explicitly longer in the DSF group. A longer duration of alcohol dependence predicted a favourable treatment outcome in the DSF group, while for the ACP group the chances for a successful treatment increased with shorter duration of alcohol dependence. CONCLUSIONS: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence.

Emotional lability in children and adolescents with attention deficit/hyperactivity disorder (ADHD): clinical correlates and familial prevalence.

BACKGROUND: The goal of this study was to investigate the occurrence, severity and clinical correlates of emotional lability (EL) in children with attention deficit/hyperactivity disorder (ADHD), and to examine factors contributing to EL and familiality of EL in youth with ADHD. METHODS: One thousand, one hundred and eighty-six children with ADHD combined type and 1827 siblings (aged 6-18 years) were assessed for symptoms of EL, ADHD, associated psychopathology and comorbid psychiatric disorders with a structured diagnostic interview (PACS) as well as parent and teacher ratings of psychopathology (SDQ; CPRS-R:L; CTRS-R:L). Analyses of variance, regression analyses, chi(2)-tests or loglinear models were applied. RESULTS: Mean age and gender-standardized ratings of EL in children with ADHD were >1.5 SD above the mean in normative samples. Severe EL (>75th percentile) was associated with more severe ADHD core symptoms, primarily hyperactive-impulsive symptoms, and more comorbid oppositional defiant, affective and substance use disorders. Age, hyperactive-impulsive, oppositional, and emotional symptoms accounted for 30% of EL variance; hyperactive-impulsive symptoms did not account for EL variance when coexisting oppositional and emotional problems were taken into account, but oppositional symptoms explained 12% of EL variance specifically. Severity of EL in probands increased the severity of EL in siblings, but not the prevalence rates of ADHD or ODD. EL and ADHD does not co-segregate within families. CONCLUSION: EL is a frequent clinical problem in children with ADHD. It is associated with increased severity of ADHD core symptoms, particularly hyperactivity-impulsivity, and more symptoms of comorbid psychopathology, primarily symptoms of oppositional defiant disorder (ODD), but also affective symptoms, and substance abuse. EL in ADHD seems to be more closely related to ODD than to ADHD core symptoms, and is only partly explainable by the severity of ADHD core symptoms and associated psychopathology. Although EL symptoms are transmitted within families, EL in children with ADHD does not increase the risk of ADHD and ODD in their siblings.