Clinical and organizational factors predicting readmission for mental health patients across Italy.

PURPOSE: The aims of our study are: to explore rehospitalization in mental health services across Italian regions, Local Health Districts (LHDs), and hospitals; to examine the predictive power of different clinical and organizational factors. METHODS: The data set included adult patients resident in Italy discharged from a general hospital episode with a main psychiatric diagnosis in 2012. Independent variables at the individual, hospital, LHD, and region levels were used. Outcome variables were individual-level readmission and LHD-level readmission rate to any hospital at 1-year follow-up. The association with readmission of each variable was assessed through both single- and multi-level logistic regression; descriptive statistics were provided to assess geographical variation. Relevance of contextual effects was investigated through a series of random-effects regressions without covariates. RESULTS: The national 1-year readmission rate was 43.0%, with a cross-regional coefficient of variation of 6.28%. Predictors of readmission were: admission in the same LHD as residence, psychotic disorder, higher length of stay (LoS), higher rate of public beds in the LHD; protective factors were: young age, involuntary admission, and intermediate number of public healthcare staff at the LHD level. Contextual factors turned out to affect readmission only to a limited degree. CONCLUSIONS: Homogeneity of readmission rates across regions, LHDs, hospitals, and groups of patients may be considered as a positive feature in terms of equity of the mental healthcare system. Our results highlight that readmission is mainly determined by individual-level factors. Future research is needed to better explore the relationship between readmission and LoS, discharge decision, and resource availability.

Overview of post-discharge predictors for psychiatric re-hospitalisations: a systematic review of the literature.

BACKGROUND: High levels of hospital readmission (rehospitalisation rates) is widely used as indicator of a poor quality of care. This is sometimes also referred to as recidivism or heavy utilization. Previous studies have examined a number of factors likely to influence readmission, although a systematic review of research on post-discharge factors and readmissions has not been conducted so far. The main objective of this review was to identify frequently reported post-discharge factors and their effects on readmission rates. METHODS: Studies on the association between post-discharge variables and readmission after an index discharge with a main psychiatric diagnosis were searched in the bibliographic databases Ovid Medline, PsycINFO, ProQuest Health Management, OpenGrey and Google Scholar. Relevant articles published between January 1990 and June 2014 were included. A systematic approach was used to extract and organize in categories the information about post-discharge factors associated with readmission rates. RESULTS: Of the 760 articles identified by the initial search, 80 were selected for this review which included a total number of 59 different predictors of psychiatric readmission. Subsequently these were grouped into four categories: 1) individual vulnerability factors, 2) aftercare related factors, 3) community care and service responsiveness, and 4) contextual factors and social support. Individual factors were addressed in 58 papers and were found to be significant in 37 of these, aftercare factors were significant in 30 out of the 45 papers, community care and social support factors were significant in 21 out of 31 papers addressing these while contextual factors and social support were significant in all seven papers which studied them. CONCLUSIONS: This review represents a first attempt at providing an overview of post-discharge factors previously studied in association with readmission. Hence, by mapping out the current research in the area, it highlights the gaps in research and it provides guidance future studies in the area.

Pre-discharge factors predicting readmissions of psychiatric patients: a systematic review of the literature.

BACKGROUND: Readmission rate is considered an indicator of the mental health care quality. Previous studies have examined a number of factors that are likely to influence readmission. The main objective of this systematic review is to identify the studied pre-discharge variables and describe their relevance to readmission among psychiatric patients. METHODS: Studies on the association between pre-discharge variables and readmission after discharge with a main psychiatric diagnosis were searched in the bibliographic databases Ovid Medline, PsycINFO, ProQuest Health Management and OpenGrey. Relevant publications published between January 1990 and June 2014 were included. For each variable, the number of papers that considered it as a predictor of readmission and that found a significant association was recorded, together with the association direction and whether it was found respectively in bivariate and in multivariate analyses. RESULTS: Of the 734 articles identified in the search, 58 papers were included in this review, mainly from the USA and concerning patients with severe mental disorders. Analysed variables were classified according to the following categories: patients' demographic, social and economic characteristics; patients' clinical characteristics; patients' clinical history; patients' attitude and perception; environmental, social and hospital characteristics; and admission and discharge characteristics. The most consistently significant predictor of readmission was previous hospitalisations. Many socio-demographic variables resulted as influencing readmission, but the results were not always homogeneous. Among other patients' clinical characteristics, diagnosis and measures of functional status were the most often used variables. Among admission characteristics, length of stay was the main factor studied; however, the results were not very consistent. Other relevant aspects resulted associated with readmission, including the presence of social support, but they have been considered only in few papers. Results of quality assessment are also reported in the review. The majority of papers were not representative of the general psychiatric population discharged from an inpatient service. Almost all studies used multivariate analytical methods, i.e., confounders were controlled for, but only around 60% adjusted for previous hospitalisation, the variable most consistently considered associated to readmission in the literature. CONCLUSIONS: The results contribute to increase knowledge on pre-discharge factors that could be considered by researchers as well as by clinicians to predict and prevent readmissions of psychiatric patients. Associations are not always straightforward and interactions between factors have to be considered.

Late preterm birth, post-term birth, and abnormal fetal growth as risk factors for severe mental disorders from early to late adulthood.

BACKGROUND: Late preterm births constitute the majority of preterm births. However, most evidence suggesting that preterm birth predicts the risk of mental disorders comes from studies on earlier preterm births. We examined if late preterm birth predicts the risks of severe mental disorders from early to late adulthood. We also studied whether adulthood mental disorders are associated with post-term birth or with being born small (SGA) or large (LGA) for gestational age, which have been previously associated with psychopathology risk in younger ages. METHOD: Of 12 597 Helsinki Birth Cohort Study participants, born 1934-1944, 664 were born late preterm, 1221 post-term, 287 SGA, and 301 LGA. The diagnoses of mental disorders were identified from national hospital discharge and cause of death registers from 1969 to 2010. In total, 1660 (13.2%) participants had severe mental disorders. RESULTS: Individuals born late preterm did not differ from term-born individuals in their risk of any severe mental disorder. However, men born late preterm had a significantly increased risk of suicide. Post-term birth predicted significantly increased risks of any mental disorder in general and particularly of substance use and anxiety disorders. Individuals born SGA had significantly increased risks of any mental and substance use disorders. Women born LGA had an increased risk of psychotic disorders. CONCLUSIONS: Although men born late preterm had an increased suicide risk, late preterm birth did not exert widespread effects on adult psychopathology. In contrast, the risks of severe mental disorders across adulthood were increased among individuals born SGA and individuals born post-term.

Mortality and life expectancy of people with alcohol use disorder in Denmark, Finland and Sweden.

OBJECTIVE: To analyse mortality and life expectancy in people with alcohol use disorder in Denmark, Finland and Sweden. METHOD: A population-based register study including all patients admitted to hospital diagnosed with alcohol use disorder (1,158,486 person-years) from 1987 to 2006 in Denmark, Finland and Sweden. RESULTS: Life expectancy was 24-28 years shorter in people with alcohol use disorder than in the general population. From 1987 to 2006, the difference in life expectancy between patients with alcohol use disorder and the general population increased in men (Denmark, 1.8 years; Finland, 2.6 years; Sweden, 1.0 years); in women, the difference in life expectancy increased in Denmark (0.3 years) but decreased in Finland (-0.8 years) and Sweden (-1.8 years). People with alcohol use disorder had higher mortality from all causes of death (mortality rate ratio, 3.0-5.2), all diseases and medical conditions (2.3-4.8), and suicide (9.3-35.9). CONCLUSION: People hospitalized with alcohol use disorder have an average life expectancy of 47-53 years (men) and 50-58 years (women) and die 24-28 years earlier than people in the general population.

Structural and cognitive social capital and depression among older adults in two Nordic regions.

OBJECTIVE: To study the association between structural and cognitive aspects of social capital and depression among older adults in two Nordic regions. METHOD: Data were retrieved from a postal survey targeting older adults aged 65, 70, 75 and 80 years (N=6 838, response rate=64%) residing in the Västerbotten region (Sweden), and the Österbotten region (Finland) in 2010. The associations between structural (measured by frequency of social contact with friends and neighbours) and cognitive (measured by experienced trust in friends and neighbours) aspects of social capital and depression (measured by Geriatric Depression Scale, GDS-4) were tested by logistic regression analyses. RESULTS: Both low structural and cognitive social capital as defined in the study showed statistically significant associations with depression in older adults. Only experienced trust in neighbours failed to show significant association with depression. In addition, being single and being 80 years of age indicated a higher risk of depression as defined by GDS-4. CONCLUSION: The findings underline the connection between adequate levels of both structural and cognitive individual social capital and mental health in later life. They also suggest that the connection differs depending on various network types; the cognitive aspect of relationships between friends was connected to depression, while the connection was not found for neighbours. Further, the oldest age group in the sample (80 years of age) is pointed out as a population especially vulnerable for depression that should not be overlooked in mental health promotion and depression prevention.

The balance of adult mental health care: provision of core health versus other types of care in eight European countries.

AIMS: Although many mental health care systems provide care interventions that are not related to direct health care, little is known about the interfaces between the latter and core health care. 'Core health care' refers to services whose explicit aim is direct clinical treatment which is usually provided by health professionals, i.e., physicians, nurses, psychologists. 'Other care' is typically provided by other staff and includes accommodation, training, promotion of independence, employment support and social skills. In such a definition, 'other care' does not necessarily mean being funded or governed differently. The aims of the study were: (1) using a standard classification system (Description and Evaluation of Services and Directories in Europe for Long Term Care, DESDE-LTC) to identify 'core health' and 'other care' services provided to adults with mental health problems; and (2) to investigate the balance of care by analysing the types and characteristics of core health and other care services. METHODS: The study was conducted in eight selected local areas in eight European countries with different mental health systems. All publicly funded mental health services, regardless of the funding agency, for people over 18 years old were identified and coded. The availability, capacity and the workforce of the local mental health services were described using their functional main activity or 'Main Types of Care' (MTC) as the standard for international comparison, following the DESDE-LTC system. RESULTS: In these European study areas, 822 MTCs were identified as providing core health care and 448 provided other types of care. Even though one-third of mental health services in the selected study areas provided interventions that were coded as 'other care', significant variation was found in the typology and characteristics of these services across the eight study areas. CONCLUSIONS: The functional distinction between core health and other care overcomes the traditional division between 'health' and 'social' sectors based on governance and funding. The overall balance between core health and other care services varied significantly across the European sites. Mental health systems cannot be understood or planned without taking into account the availability and capacity of all services specifically available for this target population, including those outside the health sector.

Glutamatergic drugs for schizophrenia.

BACKGROUND: It has been shown that central nervous system dopamine can play a major role in the pathophysiology of schizophrenia. Brain glutamate is thought to mediate symptoms in schizophrenia due to the influence of glutamate neurons on the dopaminergic transmission in the brain. It might be possible to decrease negative symptoms and the cognitive impairment of people with schizophrenia by treatment with glutamatergic drugs. OBJECTIVES: To determine the efficacy of glutamatergic drugs in the treatment of schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Trials Register (May 2002 and October 2003), inspected references of all identified studies and contacted relevant authors. SELECTION CRITERIA: We included all randomised controlled trials in which glutamatergic medication was administered to people with schizophrenia. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis. MAIN RESULTS: We included eighteen short-term trials with 358 randomised participants. The single studies were small with numbers of participants ranging between six and 51. All trials were short-term trials with a maximum duration of 12 weeks. In all of these trials, glycine, D-serine, D-cycloserine, or ampakine CX516 was used to augment the effect of antipsychotic drugs. D-cycloserine, a partial agonist of NMDA receptors' glycine site, seemed ineffective towards the symptoms of schizophrenia. NMDA receptor co-agonists glycine and D-serine showed some effects in reducing the negative symptoms of schizophrenia (n=132, SMD -0.66, CI -1.0 to -0.3, p=0.0004), but the magnitude of the effect was moderate. Furthermore, when responder rates rather than mean scores of negative symptoms were analysed the data were inconsistent: There was no difference in responder rates between glycine and the control in terms of more than 20% improvement of negative symptoms (n=62, RR 0.70, CI 0.3 to 1.71) and only a borderline significant superiority in terms of more than 50% improvement (n=62, RR 0.87, CI 0.8 to 1.00). There were also some effects in favour of glycine and/or D-serine in terms of overall and general symptoms, but the results were again inconsistent and depended on the response definition applied. Available rating scale data on positive symptoms and cognitive functioning did not indicate a statistically significant effect of glycine or D-serine. AUTHORS' CONCLUSIONS: In general, all glutamatergic drugs appeared to be ineffective in further reducing positive symptoms of the disease when added to the existing antipsychotic treatment. Glycine and D-serine may somewhat improve negative symptoms when added to regular antipsychotic medication, but the results were not fully consistent and data are too few to allow any firm conclusions. Many participants in the included trials were treatment-resistant which may have reduced treatment response. Additional research on glutamatergic mechanisms of schizophrenia is needed.

Discrimination in the workplace, reported by people with major depressive disorder: a cross-sectional study in 35 countries.

OBJECTIVE: Whereas employment has been shown to be beneficial for people with Major Depressive Disorder (MDD) across different cultures, employers' attitudes have been shown to be negative towards workers with MDD. This may form an important barrier to work participation. Today, little is known about how stigma and discrimination affect work participation of workers with MDD, especially from their own perspective. We aimed to assess, in a working age population including respondents with MDD from 35 countries: (1) if people with MDD anticipate and experience discrimination when trying to find or keep paid employment; (2) if participants in high, middle and lower developed countries differ in these respects; and (3) if discrimination experiences are related to actual employment status (ie, having a paid job or not). METHOD: Participants in this cross-sectional study (N=834) had a diagnosis of MDD in the previous 12 months. They were interviewed using the Discrimination and Stigma Scale (DISC-12). Analysis of variance and generalised linear mixed models were used to analyse the data. RESULTS: Overall, 62.5% had anticipated and/or experienced discrimination in the work setting. In very high developed countries, almost 60% of respondents had stopped themselves from applying for work, education or training because of anticipated discrimination. Having experienced workplace discrimination was independently related to unemployment. CONCLUSIONS: Across different countries and cultures, people with MDD very frequently reported discrimination in the work setting. Effective interventions are needed to enhance work participation in people with MDD, focusing simultaneously on decreasing stigma in the work environment and on decreasing self-discrimination by empowering workers with MDD.

Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood.

BACKGROUND: Nutritional factors in early life may contribute to the neurodevelopmental deficit in schizophrenia. This study explores the influence of maternal body size, size at birth, and childhood growth on future risk for schizophrenia. SUBJECTS AND METHODS: This population-based cohort study comprised births at Helsinki University Central Hospital in Helsinki, Finland, from 1924 to 1933. Prospective data from birth and school health records of 7086 individuals were collected and linked to the Finnish Hospital Discharge Register. RESULTS: Schizophrenia or schizoaffective disorder had been diagnosed in 114 individuals. A lower late-pregnancy maternal body mass index (BMI) increased the risk (odds ratio [OR], 1.09 per kilogram/meter(2); 95% confidence interval [CI], 1.02-1.17) for schizophrenia among the offspring. The risk of schizophrenia increased with low birth weight (OR, 1.48 per kilogram; 95% CI, 1.03-2.13), shortness at birth (OR, 1.12 per centimeter; 95% CI, 1.03-1.22), and low placental weight (OR, 1.22 per 100 g; 95% CI, 1.04-1.43). Schizophrenia cases were thinner than comparison subjects from 7 to 15 years of age. In a joint model comprising late-pregnancy maternal BMI, body size at birth, and childhood BMI, childhood BMI was an independent predictor of schizophrenia, whereas other factors exhibited attenuated effects. CONCLUSION: Indicators of intrauterine and childhood undernutrition are associated with an increased lifetime risk of schizophrenia.

European psychiatric treatment guidelines: is the glass half full or half empty?

PURPOSE: We assessed the quality of European treatment guidelines in the field of mental health that have been produced by national psychiatric associations. The main focus was the question of whether the development process of the guidelines followed basic principles of evidence-based medicine. METHODS: Sixty-one European clinical practice guidelines from 14 countries, published between 1998 and 2003, were assessed using the 'Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument'. The domain score was calculated for each of the six domains of the AGREE instrument. The seven items of the domain "rigor of development" and one additional item concerning national particularities were assessed in detail. RESULTS: The mean scores in the six domains were rather low, although the quality varied among the different guidelines. The highest mean score was obtained in the domain clarity and presentation (70.8% S.D. 23.5), the lowest on editorial independence (19.7% S.D. 29.3). The recommendations of about half of the assessed guidelines could be considered to be evidence-based. CONCLUSION: The assessed guidelines showed a broad range of quality: some producers attached importance to an evidence-based development process; but in spite of this, a large number of guidelines were only of middling quality. As national particularities are only rarely mentioned and the development process of guidelines is complex, an international collaboration that aims toward the production of shareable guidelines might be promising.

Elevated plasma vasopressin and normal cerebrospinal fluid angiotensin-converting enzyme in chronic pain disorder.

The study was performed proceeding from the hypothesis that pain proneness in chronic pain disorder (CPD) is a result of alterations in central mechanisms regulating pain sensations. To elucidate the function of the central renin-angiotensin system, the levels of angiotensin-converting enzyme (ACE) and arginine vasopressin (AVP) in cerebrospinal fluid (CSF) and peripheral blood were measured in 15 CPD patients and 19 healthy controls. Plasma AVP levels (p = .01) as well as the serum osmolality (p = .01) were significantly higher in the CPD group. No significant differences in CSF ACE levels were found. AVP is a stress-related peptide, but central antinociceptive effects have also been reported. Elevated plasma AVP levels possibly may constitute a response to chronic stress.

Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: The purpose of this study was to evaluate all available trial-based evidence on the effectiveness of clozapine in schizophrenia as compared with conventional neuroleptics. METHOD: All randomized, controlled trials comparing clozapine with a conventional neuroleptic in which there was satisfactory concealment of patients' treatment allocation were located through electronic searches in all languages of several databases and through contacting authors of recent trials as well as the manufacturer of clozapine. At least two independent reviewers assessed trials for inclusion in the study and extracted data for meta-analysis. RESULTS: The review included 2,530 randomly assigned participants in 30 trials, most of them short-term. Clozapine-treated patients showed more clinical improvement and experienced significantly fewer relapses during treatment, although the risk of blood dyscrasias in long-term treatment may be as high as 7%. Scores on symptom rating scales showed greater improvement among clozapine-treated patients, who were also more satisfied with their treatment. However, there was no evidence that the superior clinical effect of clozapine is reflected in levels of functioning; on the other hand, global functional and pragmatic outcomes were frequently not reported. Clinical improvement was most pronounced in patients with treatment-resistant illness. CONCLUSIONS: This meta-analysis confirms that clozapine is more effective than conventional neuroleptics in reducing symptoms of patients with both treatment-resistant and nonresistant schizophrenia. Future trials should be long-term pragmatic community trials or should address the effectiveness of clozapine in special patient populations. An international standard set of outcomes, including pragmatic assessments of functioning, would greatly enhance the comparison and summation of trials and future assessments of effectiveness.

Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study.

BACKGROUND: The postpartum period is a time when women are vulnerable to depressive disorders, which can be severe and have long-lasting adverse sequelae. In spite of multiple contacts with health care providers, women with postpartum depression often remain unrecognized and untreated. To evaluate the association between estradiol and postpartum depression, we measured serum estradiol concentration and performed an open-label study of physiologic 17beta-estradiol. METHOD: Twenty-three women fulfilling ICD-10 criteria for major depression with postpartum onset were consecutively recruited from a psychiatric emergency unit. Serum estradiol concentrations were measured at baseline and weekly during sublingual 17beta-estradiol treatment for 8 weeks. The treatment effect was assessed using a clinician-rated depression symptom scale, the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: At baseline, all patients were severely depressed (mean MADRS total score = 40.7; range, 35-45) and had a low serum estradiol concentration (mean = 79.8 pmol/L; range, 23-140 pmol/L); in 16/23 patients, the concentration was even lower than the threshold value for gonadal failure. During the first week of estradiol treatment, depressive symptoms diminished significantly, resulting in a mean MADRS score of 11.0 (Z = -4.20, p < .001), and serum estradiol concentrations approached those of the follicular phase (mean +/- SD = 342 +/- 141 pmol/L). At the end of the second week of treatment, the MADRS scores were compatible with clinical recovery in 19/23 patients. CONCLUSION: This preliminary study shows that depression symptoms may be rapidly reduced in patients with postpartum depression who have documented estradiol deficiency by treatment with 17beta-estradiol and suggests that estradiol can have significance in the pathophysiology of this condition and may be an option in the treatment of women vulnerable to postpartum depression.

Dropout rates in randomised antipsychotic drug trials.

RATIONALE: It has been assumed that new atypical drugs improve treatment compliance due to fewer adverse effects. Data supporting this assumption are scarce. OBJECTIVES: The aim of this study was to study attrition rates in randomised controlled trials of oral administration of conventional antipsychotic drugs, atypical antipsychotic drugs and placebo. METHODS: The database of the Schizophrenia Module of the Cochrane Library was utilised for the present study. The data in the Cochrane Module are collected by identifying relevant randomised controlled trials from several electronic databases and other sources. Number of dropouts was defined as patients leaving the study preterm due to any reason. RESULTS: Data from 328 treatment groups, consisting of 18,585 randomised subjects from 163 drug trials, were entered in the analysis. One-third of the subjects had dropped out of the trials. The dropout rates significantly increased for each calendar year. Year of trial publication, type of drug and trial length remained statistically significant contributors to dropout rates. In a model incorporating year of publication and trial length, placebo groups and groups treated with conventional antipsychotics had significantly higher attrition rates than groups treated with atypical drugs. When clozapine-treated groups were excluded from the analysis, no statistically significant advantage for atypical drugs over conventional drugs remained. CONCLUSIONS: Trial data implicate that a better compliance can be achieved by favouring atypical drugs rather than conventional alternatives in the treatment of schizophrenia. However, this effect is found only when groups treated with the atypical antipsychotic clozapine are included in the analysis. Our study did not find evidence for a statistically significant superiority in acceptability of novel atypical drugs when compared to conventional antipsychotics.

Elevated angiotensin-converting enzyme (kininase II) in the cerebrospinal fluid of neuroleptic-treated schizophrenic patients.

Disturbances of water homeostasis have frequently been reported in schizophrenia. Water homeostasis is regulated by arginine vasopressin (AVP), the renin-angiotensin system and natriuretic hormones. The aim of this study was to determine the activity of the central renin-angiotensin system in schizophrenia by measuring levels of angiotensin-converting enzyme (ACE) in the cerebrospinal fluid (CSF) and blood in 14 in-patients with schizophrenia on neuroleptic medication and in 9 healthy volunteers. The levels of CSF ACE were significantly higher in the schizophrenia group. There were no correlations between CSF ACE and gender, age, age at first episode, duration of illness, term of hospitalization or neuroleptic dosage. No correlations between CSF ACE and serum ACE were found in either group. The authors suggest an activated central renin-angiotensin system in schizophrenia at least during antipsychotic drug treatment, which may cause 'psychogenic' polydipsia in some patients. ACE and the brain renin-angiotensin system may also play a role in the regulation of neuron growth and differentiation in schizophrenia.

Cerebrospinal fluid angiotensin-converting enzyme (ACE) correlates with length of illness in schizophrenia.

The aim of the study was to evaluate a possible progression with time of cerebrospinal fluid (CSF) angiotensin-converting enzyme (ACE) levels in treated schizophrenia patients. CSF ACE was determined in duplicate by a sensitive inhibitor-binding assay (IBA) from morning CSF samples of 56 acute and chronic in-patients with schizophrenic psychoses diagnosed according to DSM-IV. CSF ACE correlated significantly with length of schizophrenic psychosis (r=0.39, p=0.003). There was also a positive significant correlation between CSF ACE and duration of current psychotic episode (r=0.39, p=0.003) as well as duration of current hospitalization (r=0.66, p<0.001). These significances were maintained even when patients who were not treated with antipsychotics at the time of sampling were excluded. The correlations also remained significant when controlling for current neuroleptic dose in chlorpromazine equivalents. Serum ACE did not correlate with any clinical variable. No significant correlations between serum or CSF ACE and age, diagnostic subgroup, gender, serum ACE, CSF to serum albumin ratios, or neuroleptic dose in chlorpromazine equivalents were detected. The elevation of CSF ACE seemed to be confined to a subgroup of chronic patients with few positive symptoms. Elevated CSF ACE may reflect an increased solubilization of ACE from cell membranes in the central nervous system or constitute an increased expression of the ACE gene in response to some stimuli. This may be a function of treatment or a result of the deteriorating schizophrenic process.

Efficacy of beta-blocker supplementation for schizophrenia: a systematic review of randomized trials.

Adrenergic beta-receptor antagonists, commonly used in the field of cardiovascular diseases, have also been recommended for treatment-resistant schizophrenia. We systematically review quality assessed trials on beta-blocker supplementation of antipsychotic treatment for schizophrenia. All randomized controlled trials comparing any beta-blocking agent added to any antipsychotic with a placebo added to any antipsychotic, and lasting for at least 1 week, were located through electronic searches in all languages of several databases. The trials were assessed by at least two independent reviewers for inclusion, quality score, and data extraction. The reviewers located five studies with 117 participants. The data were poorly presented in these short-term studies and did not evidence any effect of beta-blockers as an adjunct to conventional antipsychotic medication. At present beta-blockers cannot be recommended in the treatment of schizophrenia, and schizophrenia treatment guidelines advocating use of beta-blockers should be revised.

Neuropeptide FF-like immunoreactivity in human cerebrospinal fluid of chronic pain patients and healthy controls.

Neuropeptide FF (NPFF) is a neuropeptide with some antiopioid characters found in several mammalian species. In human brain it might be an important pain-regulating peptide. Using a specific and sensitive radioimmunoassay we found a mean concentration of NPFF in human cerebrospinal fluid (CSF) of healthy volunteers of 1.6 +/- 1.1 pg/ml (n = 19) and in chronic pain (CPD) patients of 1.4 +/- 1.2 pg/ml (n = 16). The NPFF concentrations in CSF and plasma did not correlate. There was no difference in the NPFF concentrations in CSF and plasma between CPD patients and healthy controls. NPFF in CPD patients did not correlate significally with any pain characteristic. This study provides evidence for the presence of NPFF in human brain, but does not support the hypothesis that chronic pain is a consequence of elevated production of NPFF.

Higher cerebrospinal fluid angiotensin-converting enzyme levels in neuroleptic-treated than in drug-free patients with schizophrenia.

The aim of this study was to replicate our earlier finding of elevated angiotensin-converting enzyme (ACE) in cerebrospinal fluid (CSF) in schizophrenia and to elucidate the role of neuroleptic treatment in this phenomenon. Drug-free and medicated patients with acute schizophrenic psychoses, as well as healthy controls were recruited. Levels of ACE were measured in CSF and serum from 7 drug-free patients, 36 neuroleptic-treated patients, and 19 healthy control subjects. Although ACE levels in CSF did not differ between patients and controls, the drug-free patients showed significantly lower levels than the neuroleptic-treated patients. Serum ACE did not differ between groups. The elevation of CSF ACE may be more prominent in patients with deficit symptoms than in those with mainly psychotic symptoms. The possible enhancement of CSF ACE production or solubility by neuroleptic treatment is discussed. Elevated ACE levels in CSF may, together with other possible factors, cause polydipsia, stimulate secretion of arginine vasopressin, and even affect neuron growth and differentiation in schizophrenic psychoses.