Self-selected intensity exercise in the treatment of major depression: A pragmatic RCT.

OBJECTIVE: The purpose of the study was to determine the therapeutic effect of physical exercise for patients with unipolar depression. Participants took part in an 8-week walking/running aerobic exercise program at a local sports club. METHODS: Forty-six outpatients aged 18-65 years and diagnosed with mild to severe depression (ICD-10 criteria) were randomly assigned to an intervention group or wait list. Treatment as usual was continued. The Hamilton Rating Scale for Depression (HRSD-17) served as the main outcome measure. Secondary outcome measures were Beck Depression Inventory (BDI-II), Fitness Index (FI), and VO(2) max as estimated by Urho Kaleka Kekkonen or UKK 2-km Walk Test. RESULTS: Out of forty-six participants, 24% dropped out. Participants attended 58% of exercise sessions. All randomized participants were included in intention-to-treat (ITT) analysis. Analysis of covariance or ANCOVA showed a large reduction of depressive symptoms in HRSD-17 scores (Cohen's d: 1.8; mean change 8.2, p < .0001). BDI-II (Cohen's d: 0.50; mean change: 4.7, p = 0.09), FI scores (Cohen's d: 0.27; mean change: 5.3, p = 0.08), and VO2 max did not change significantly. CONCLUSIONS: We observed a large and clinically significant change in HRSD-17 scores. Moderate changes in BDI-II scores without clinical significance and small changes in physical fitness assessments were observed.

Structure and activity of the only human RNase T2.

Mutations in the gene of human RNase T2 are associated with white matter disease of the human brain. Although brain abnormalities (bilateral temporal lobe cysts and multifocal white matter lesions) and clinical symptoms (psychomotor impairments, spasticity and epilepsy) are well characterized, the pathomechanism of RNase T2 deficiency remains unclear. RNase T2 is the only member of the Rh/T2/S family of acidic hydrolases in humans. In recent years, new functions such as tumor suppressing properties of RNase T2 have been reported that are independent of its catalytic activity. We determined the X-ray structure of human RNase T2 at 1.6 Å resolution. The α+ß core fold shows high similarity to those of known T2 RNase structures from plants, while, in contrast, the external loop regions show distinct structural differences. The catalytic features of RNase T2 in presence of bivalent cations were analyzed and the structural consequences of known clinical mutations were investigated. Our data provide further insight into the function of human RNase T2 and may prove useful in understanding its mode of action independent of its enzymatic activity.

Exercise capacity and quality of life in patients with schizophrenia.

The aim of this study was to resolve the relationship between physical capacity (PC) and quality of life (Qol) in schizophrenic patients and healthy controls. 31 patients (PG: 18 male, 13 female) and a control group (CG) of 50 healthy subjects (15 male, 35 female) were involved. PC was assessed as peak oxygen uptake [VO2peak, (ml (min kgKG)(-1))] and power output expressed as watts per kilogram (W kg(-1)). Qol was assessed using the SF-36 questionnaire. Patients with schizophrenia showed reduced VO2peak (male: PG 29 ± 5 vs. CG 44 ± 10; female: PG 21 ± 4 vs. CG 30 ± 8) and power output (male: PG 2.04 ± 0.47 vs. CG 3.43 ± 0.70; female PG 1.40 ± 0.28 vs. CG 2.43 ± 0.52). Scales of the SF-36 questionnaire were lower in the PG. While in the CG correlations were found between PC and several subscales of Qol, this was not the case in the PG. The restricted PC seen in the PG showed no relation to their subjectively assessed worsened Qol, which would indicate that schizophrenic patients evaluate limitations arising from this differently than healthy control subjects.

Comorbidity of alcohol and substance dependence with attention-deficit/hyperactivity disorder (ADHD).

AIMS: Attention-deficit/hyperactivity disorder (ADHD) is of great clinical importance not only because of its high prevalence but also due to the frequent comorbid illnesses that are connected with this disorder. Several studies were able to demonstrate that ADHD constitutes a significant risk factor for the exacerbation of habit-forming illnesses, i.e. addictions. METHODS: We conducted a study on 152 adult patients with alcohol dependence (n = 91) or multiple substance addiction (n = 61) to determine whether or not these patients were affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to assess the persisting symptoms of ADHD in adults. RESULTS: 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed evidence of retrospective ADHD affliction in childhood. With the help of CAARS, ADHD was proved to be persistent in 33.3% of the adult patients. In the group of substance-addicted patients 50.8% (WURS-k) and 54.1% (DSM-IV) presented with diagnostic criteria for ADHD in childhood and 65.5% (CAARS) showed evidence of ADHD persisting in adulthood. CONCLUSIONS: These results reveal that habit-forming illnesses can be associated with a high comorbidity with ADHD, expressed in the form of alcohol abuse and also in consumption of illegal drugs. The results underline the great importance of early and adequate diagnostics and therapy of ADHD for the prevention of habit-forming illnesses.

Sleep-endocrine effects of growth hormone-releasing hormone (GHRH) in patients with schizophrenia.

Changes in sleep-EEG after endocrine stimulation tests in patients with schizophrenia include reduced sleep efficiency, prolonged sleep latency and increased awaking after sleep onset Findings on sleep associated growth hormone (GH) secretion were ambiguous. The aim of this study was to elucidate the sleep-endocrine activity especially in the GH system of patients with schizophrenia after repeated administration of GHRH. The effect of repetitive injections of 4 × 50 µg GHRH between 22.00 and 01.00 h on sleep endocrine parameters was investigated in 9 patients diagnosed for schizophrenia. Patients did not receive any medication for one week. Concentrations of ACTH, cortisol, prolactin and GH were determined. Patients spent three consecutive nights in the sleep laboratory. Blood was taken every 20min. Results were compared with matched healthy controls. A non-significant prolonged sleep onset latency and increased time awake was found in patients compared to controls. Sleep stage 2 was significantly reduced in patients. No significant difference in ACTH and cortisol was detected, whereas the GH secretion in patients following GHRH stimulation was significantly elevated compared to controls. Our results in drug free patients confirm already known changes in sleep-EEG in these patients. The GH response to GHRH-stimulation indicates a different regulatory sensitivity of the system between daytime and night-time.

Elevated prolactin serum levels and history of alcohol withdrawal seizures.

BACKGROUND: Prolactin has been discussed to be useful for differential diagnosis in epilepsia. Aim of the present study was to investigate the association between prolactin serum levels and previous alcohol withdrawal seizures. METHODS: We assessed 118 male patients admitted for detoxification treatment. Previous withdrawal seizures were recorded and prolactin serum levels were measured using an enzymatic immunoassay. RESULTS: Patients with a history of alcohol withdrawal seizures had significantly higher prolactin levels (17.8 ng/ml, SD=12.1) than patients without previous seizures (13.0 ng/ml, SD=8.1, p<0.05). Logistic regression revealed significant predictive qualities for prolactin serum levels (B=0.05, Wald=5.30, p=0.021, OR=1.06, 95%CI=1.01-1.11). CONCLUSIONS: The present findings show an association between elevated prolactin serum levels and a history of withdrawal seizures. Hence, the results suggest that prolactin elevation at admission may be a clinical marker for an increased risk of withdrawal seizures.

Effects of methylphenidate in ADHD adults on target evaluation processing reflected by event-related potentials.

Attention deficit/hyperactivity disorder (ADHD) is a widely examined disease in childhood. There is evidence that the disease responds well to medication with methylphenidate (MPH). The effect of MPH in adults with ADHD is a question that is often raised, because many adults request such therapy today. As yet, there is a lack of studies on event-related potentials (ERPs) and MPH in ADHD adults. In the present study we examined 10 adults diagnosed with ADHD, with and without MPH medication (30 mg daily), by means of ERP in a visual Go/NoGo experiment to gain information about target evaluation processing in these patients and about the effects on these attentional processes during medication with MPH. Visually, there seem to be differences in the frontal electrodes for the N2 and in the parietal electrodes for the P300. But these differences do not achieve statistical significance. There are also no statistically relevant differences for the N1 or the slow wave. MPH does not seem to have an effect on target evaluation processing, when comparing the ERPs of non-medicated and medicated ADHD adults. Especially the P3 does not appear to be modulated by medication with MPH in these ADHD adults, in contrast to findings in ADHD children.

Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis.

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.

Nicotine and alcohol dependence in patients with comorbid attention-deficit/hyperactivity disorder (ADHD).

AIMS: Several studies have shown that attention-deficit/hyperactivity disorder (ADHD) represents a significant risk factor for the onset and development of an addiction. Thirty-five per cent of adult ADHD patients are known to be addicted to alcohol. Many ADHD patients also have an increased nicotine consumption, which typically, leads to an improvement of attention, ability to concentrate and control of impulses. There may be pathophysiological connections here. On the other hand, it can also be assumed that there is a high prevalence of addicted patients with undiagnosed ADHD. METHODS: Ninety-one adult alcohol-dependent patients were examined for ADHD in this study, using the Wender Utah Rating Scale (WURS-k), Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptom check-list for ADHD and the Conners' Adult ADHD Rating Scales (CAARS, Long Version). The patients were divided into diagnostic sub-groups according to DSM-IV (inattentive type, impulsive type, combined type). Nicotine consumption was investigated using the Fagerström Test of Nicotine Dependence (FTND) and then graded as 'minimal', 'average' or 'high' nicotine dependence. RESULTS: There were 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the patients addicted to alcohol, who showed evidence of ADHD in childhood. With the help of CAARS, it could be demonstrated that 33.3% of the patients who fulfilled the diagnostic criteria of ADHD, according to DSM-IV, had persisting ADHD in adulthood. The FTND showed a statistically significant difference in nicotine dependence between alcohol-dependent patients with and without ADHD in childhood. Patients numbering 76.2% with ADHD, demonstrated an 'average to high' level of nicotine dependence compared to 45.7% of those patients without ADHD. Furthermore, the number of patients not addicted to nicotine (19%) was significantly lower than among those without ADHD (36.6%) (P = 0.029). CONCLUSIONS: The results of this investigation reveal that a large number of ADHD patients suffer from alcohol dependence, and an even greater number from excessive nicotine dependence. The outcome indicates that there are most likely pathophysiological connections with alcohol and nicotine dependence, and that this substance abuse is probably a form of 'self-medication'. The results clearly underline the great importance of early and adequate diagnosis and therapy of ADHD, in order to prevent exacerbation of addictive illness.

Hannover study on long-stay hospitalization - part II: Characteristics and care conditions of long-stay hospitalization in cases of chronic mental illness.

BACKGROUND: Long-stay hospitalization is often a consequence of insufficient care structures. This article examines the characteristics and care conditions of long-stay hospitalization (LSH) in an urban area in Germany. METHODS: Extensive data of patients in the urban catchment area of the Medical School of Hannover, capital of Lower Saxony, were evaluated during a 10 years period. RESULTS AND CONCLUSION: Community psychiatric efforts certainly help to reduce long-stay hospitalization, but cannot fully prevent it. Reference figures are given for comparable urbanized areas: consequently 500 chronically mentally ill persons per 100.000 inhabitants must be expected, 20% of which must be considered as long stay hospitalized according to a given definition. We estimate 250 places per 100.000 inhabitants to be required for institutionalised outpatient care, further 30 places for day clinic and full-time in-patient treatment and 40 places for residential home treatment. We suggest these results as a guidance for psychiatric planning in comparable communities.

Nicotine dependence is associated with compulsive alcohol craving.

AIMS: To investigate a possible association of nicotine dependence and alcohol craving. DESIGN: A prospective cross-sectional study on patients diagnosed with alcohol dependence. SETTING: Detoxification unit of a regional psychiatric hospital. PARTICIPANTS: A total of 127 smoking male patients were included in the study at admission for detoxification from alcohol. MEASUREMENTS: The Fagerström Test for Nicotine Dependence (FTND) was used to assess the severity of nicotine dependence while the Obsessive Compulsive Craving Scale (OCDS) was used to measure alcohol craving. The OCDS was assessed at admission and after 7 days of withdrawal treatment, distinguishing the total score, the obsessive and the compulsive subscale. FINDINGS: Spearman's correlation revealed a significant association between the extent of alcohol craving and the FTND score (day 0, n = 127: OCDS total score r = 0.238, P = 0.007; OCDS compulsive score r = 0.280, P = 0.001; day 7; n = 94: OCDS total score r = 0.212, P = 0.040; OCDS compulsive score r = 0.225, P = 0.029). CONCLUSIONS: The severity of nicotine dependence is associated with higher craving in alcohol-dependent patients. These results point towards shared pathophysiological mechanisms in alcohol craving and nicotine addiction.

Possible criteria for inpatient psychiatric admissions: which patients are transferred from emergency services to inpatient psychiatric treatment?

BACKGROUND: Patients with psychiatric problems often seek help and assistance in hospital emergency departments. An important task of emergency room staff is to decide whether such patients need to be admitted or whether they can be treated on an outpatient basis. METHODS: Psychiatric treatments given in the Central Interdisciplinary Emergency Department (CED) at the Medical University of Hannover (MHH) in 2002 were analysed. RESULTS: Of a total of 2632 patients seeking psychiatric help, 51.4% were admitted for inpatient treatment. Patients with dementia syndromes were admitted more frequently than patients with other psychiatric diseases. Suicidality was often the reason for admission. Accompanied patients were less likely to be hospitalised, unless a care-order was in force. Restraining measures and acute medication also had an impact on the rate of admissions. CONCLUSION: The results may help psychiatrists in the emergency department to make a more effective decision regarding inpatient admission in the interest of the individual patient.

Aripiprazole augmentation of clozapine in treatment-resistant schizophrenia: a clinical observation.

BACKGROUND: Therapeutic options for patients with treatment-resistant schizophrenia are limited, and combination treatment with atypical antipsychotic drugs is an often used strategy. We tested the hypothesis that the combination of aripiprazole and clozapine would lead to an improvement in this patient group. METHODS: Eleven patients with treatment-resistant schizophrenia participated in this clinical trial and received a combination of aripiprazole and clozapine. Patients had to have remained on a stable dose of clozapine for at least 6 months in order to ensure a reasonable opportunity to respond to clozapine monotherapy. Clinical status was evaluated at baseline and at 3 months' follow-up using the Brief Psychiatric Rating Scale (BPRS). RESULTS: All patients completed 3 months' combination treatment. There was a significant reduction in the mean BPRS score in seven patients (63.6%) over the 3 months of combination treatment. Augmentation with aripiprazole in clozapine-treated patients did not result in a corresponding increase in adverse effects. Use of the combination allowed a significant reduction in the daily dose of clozapine. CONCLUSIONS: Combined application of clozapine and aripiprazole is in accordance with a neurobiological rationale and appears to be safe and well tolerated without increased risk of adverse effects.

Hannover study on long-stay hospitalization - part I: prediction of long-stay hospitalisation in cases of chronic mental illness.

BACKGROUND: The problem of long-stay hospitalization is still a pressing issue. In this study we examined the possibility of detecting and characterising the group at risk of long-stay hospitalization in advance. METHODS: This study examines the data of patients in the urban catchment area of the Medical University of Hannover, capital of Lower Saxony, Germany, during a period of 10 years. RESULTS AND CONCLUSION: The introduced "psychosocial risk-score", calculated at the first institutional contact, was able to predict the risk of long-term hospitalization. Characteristics of social disintegration, especially with regard to employment status, are of particular importance.

Combination of clozapine and ziprasidone in treatment-resistant schizophrenia: an open clinical study.

OBJECTIVES: Therapeutic options for patients with treatment-resistant schizophrenia are limited. In such patients, combined application of atypical antipsychotic drugs is an often-used strategy. The authors tested the hypothesis that the combination of ziprasidone and clozapine would lead to an improvement in this patient group. METHODS: Nine patients with treatment-resistant schizophrenia participated in this open clinical trial and received a combination regimen of ziprasidone and clozapine. Patients had to have remained on a stable dose of clozapine for at least 6 months to ensure a reasonable opportunity to respond to clozapine monotherapy. Clinical status was evaluated at baseline, and at 3 and 6 months' follow-up using the Brief Psychiatric Rating Scale (BPRS). RESULTS: All patients completed the 6-month combination treatment. The mental state of 7 patients (77.8%) was improved and there was a significant reduction in the mean BPRS score over the 6 months treatment. The coadministration of ziprasidone in clozapine-treated patients did not result in a corresponding increase in side effects. The combination allowed a 18% reduction of the daily clozapine dose. CONCLUSION: The combined application of clozapine and ziprasidone follows a neurobiologic rationale and appears to be safe and well tolerated without increasing the risk of side effects.

Apolipoprotein E4 genotype is not associated with short-term cognition deficits during alcohol withdrawal.

Aim of this prospective study was to investigate a possible association between the apolipoprotein E4 (ApoE4) genotype and clinically well-known cognition deficits during alcohol withdrawal. We examined 172 patients with alcohol dependence (137 men, 35 women) during withdrawal treatment. The ApoE genotype was determined in all patients using polymerase chain reaction. Cognitive function was assessed applying the c.I.-Test on day 0 (admission) and on day 7 of withdrawal treatment. Using Pearson's chi2 test we found no significant association between the ApoE4 genotype and cognition deficits for both dates (day 0: p=.463; day 7: p=.760). Moreover, multivariate logistic regression analyses revealed no significant association between presence of the ApoE4 allele and cognitive dysfunction. Even though ApoE4 plays an important role in alcoholism-related brain atrophy and cognition deficits in demented as well as in nondemented healthy elderly people, this study provides no evidence for an association with short-term cognition deficits during alcohol withdrawal.

Psychiatric patients turnaround times in the emergency department.

BACKGROUND: To analyze the turnaround times of psychiatric patients within the Emergency Department (ED) from registration to discharge or hospitalization in a University Hospital in 2002. METHODS: Data from a one-year period of psychiatric admissions to the emergency service at a University Hospital were monitored and analyzed focused on turnaround times within the ED. Information on patients variables such as age, sex, diagnosis, consultations and diagnostic procedures were extracted from the patients' charts. RESULTS: From 34.058 patients seen in the ED in 2002, 2632 patients were examined by psychiatrists on duty. Mean turnaround time in the ED was 123 (SD 97) minutes (median 95). Patients to be hospitalized on a psychiatric ward stayed shorter within the ED, patients who later were admitted to another faculty, were treated longer in the ED. Patients with cognitive or substance related disorders stayed longer in the ED than patients with other psychiatric diagnoses. The number of diagnostic procedures and consultations increased the treatment time significantly. CONCLUSION: As the number of patients within the examined ED increases every year, the relevant variables responsible for longer or complicated treatments were assessed in order to appropriately change routine procedures without loss of medical standards. Using this basic data, comparisons with the following years and other hospitals will help to define where the benchmark of turnaround times for psychiatric emergency services might be.

Intravenous administration of the neuropeptide galanin has fast antidepressant efficacy and affects the sleep EEG.

OBJECTIVE: Recently, we demonstrated that the intravenous administration of the neuropeptide galanin acts on the sleep EEG of healthy young subjects similar to sleep deprivation. As this effect could imply an antidepressive potency we studied the effect of intravenous galanin administration on psychopathology and sleep EEG in patients with depression. METHODS: Galanin was administered to 10 patients with depression, who were on a stable dose of trimipramine. A placebo controlled double blind randomized design was used. Intravenous boli of galanin in a dose of 4 x 50 microg or placebo were administered hourly between 09:00 and 12:00 h. Galanin or placebo, respectively were administered on 2 days each. The sequence of the galanin or placebo days was randomized, allowing for various crossovers. The Hamilton depression rating scale score (HAMD) was performed 30 min before the first and 30 min after the last injection. The mean of the HAMD change between 08:30 and 12:30 h was chosen as primary efficacy variable. Sleep EEGs were recorded once post placebo treatment and once post verum treatment. In this case, recordings started at 23:00 h and ended at 07:00 h the next morning. RESULTS: The HAMD-difference between 08:30 and 12:30 h was significantly greater at the days of galanin-treatment compared to placebo-treatment. MANOVA revealed a significant change in sleep-EEG parameters (p < 0.05), mainly due to an increase in REM-latency (p < 0.06). CONCLUSION: The data provide preliminary evidence for an acute antidepressive efficacy of galanin, probably by a mechanism related to that of therapeutic sleep deprivation.

The renin-angiotensin-aldosterone system in patients with depression compared to controls--a sleep endocrine study.

BACKGROUND: Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA) axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS) as 1. adrenocorticotropic hormone (ACTH) is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR) agonists 3. angiotensin II (ATII) releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM)-nonREM cycle. METHODS: Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD) 53.3 +/- 14.4 yr.) and 7 age matched controls (2 males, 5 females, age: 54.7 +/- 19.5 yr.). After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC) for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h) were used for statistical analysis, with analysis of co variance being performed with age as a covariate. RESULTS: No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p < 0.06). Aldosterone was largely increased in the first (p < 0.05) and second (p < 0.01) half of the night. Cross correlations between hormone concentrations revealed that in contrast to earlier findings, which included only male subjects, in our primarily female sample, renin and aldosterone secretion were not coupled and no difference between patients and controls could be found, suggesting a gender difference in RAAS regulation. No difference in conventional sleep EEG parameters were found in our sample. CONCLUSION: Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression.