Trends in psychiatric diagnoses, medications and psychological therapies in a large Swedish region: a population-based study.

BACKGROUND: Health services utilization for mental health disorders is reported to increase sharply in many countries. The aim of this study was to report trends in all aspects of mental health care utilization in a total population sample. METHODS: Repeated cross-sectional register study of the Stockholm Region (VAL) including both primary and secondary care. Trends in the proportion of adults in the total population of Stockholm Region with a recorded ICD-10 psychiatric diagnosis or psychological therapy during 2007-2017 as well as claims of psychiatric medication from 2011 were calculated. RESULTS: The proportion of adults utilizing any mental health care increased from 13.2% in 2011 to 16.1% in 2017. In 2017, 49.3% were treated in primary care, 32.2% in secondary care and 18.5% were jointly managed. The increase was most pronounced in younger adults. Women were more likely to receive mental health care than men in all ages. Medication decreased from 71.0 to 67.7%, while psychological therapy increased from 33.1 to 37.6%. The use of psychiatric medication increased with age while psychological therapy decreased. All time trends were statistically significant (p < .0001). CONCLUSION: Care for mental health disorders has been increasing mainly in primary care and was delivered to one in seven adult individuals in 2017. Interventions are needed to address the growing burden of mental health disorders while avoiding overtreatment.

Menopause in Latin America: Symptoms, attitudes, treatments and future directions in Costa Rica.

Similar to their US counterparts, Costa Rican women enter menopause at ∼50 years of age, have similar symptoms, including hot flashes and night sweats, as well as an overall negative attitude toward the menopausal transition. One study of rural women in Monteverde reported that women knew little about the menopausal transition, as the subject was not discussed. Similar to other Latin American women, the use of hormone therapy by Costa Rican women is low and instead they use alternative therapies, including massage, dietary changes and herbal medicines. A wide variety of herbal therapies are used, and some of these herbs have estrogenic activities in vitro. However, clinical data on the safety and efficacy of any of these treatments is lacking. Recently, a disturbing increase in the incidence of human papilloma virus infections in menopausal women has been reported, due in part to more sexual freedom after menopause. Fortunately, the strain of HPV infecting these women is not associated with cervical cancer. Overall, there is a significant lack of scientific and medical research on menopausal women in Costa Rica. Considering the aging population, the high use of herbal medicines by menopausal women and the lack of clinical studies on these treatments, future research should focus on gaining a better understanding of menopause in this population. Furthermore, new educational programs for these women and the health professionals who serve them are necessary, as well as investigations of the safety and efficacy of the herbal supplements women use to manage their menopausal symptoms.

Elaborating European Pharmacopoeia monographs for biotherapeutic proteins using substances from a single source.

For more than twenty years, the European Pharmacopoeia (Ph. Eur.) monographs for biotherapeutic proteins have been elaborated using the multisource approach (Procedure 1), which has led to robust quality standards for many of the first-generation biotherapeutics. In 2008, the Ph. Eur. opened up the way towards an alternative mechanism for the elaboration of monographs (Procedure 4-BIO pilot phase), which is applied to substances still under patent protection, based on a close collaboration with the Innovator company, to ensure a harmonised global standard and strengthen the quality of the upcoming products. This article describes the lessons learned during the P4-BIO pilot phase and addresses the current thinking on monograph elaboration in the field of biotherapeutics. Case studies are described to illustrate the standardisation challenges associated with the complexity of biotherapeutics and of analytical procedures, as well as the approaches that help ensure expectations are met when setting monograph specifications and allow for compatibility with the development of biosimilars. Emphasis is put on monograph flexibility, notably by including tests that measure process-dependent microheterogeneity (e.g. glycosylation) in the Production section of the monograph. The European Pharmacopoeia successfully concluded the pilot phase of the P4-BIO during its 156th session on 22-23 November 2016.

Comparing cohort incidence of schizophrenia with that of bipolar disorder and affective psychosis in individuals born in Stockholm County 1955-1967.

BACKGROUND: Perinatal factors are associated with increased risk for both schizophrenia and bipolar disorder. Improvements in obstetric and maternal healthcare and positive socioeconomic development in Sweden from the 1950s onwards could be expected to affect incidence estimates. However, commonly incidence rates are calculated during a specific year, i.e. time of diagnosis, which mirrors proximal precipitating risk factors. To examine whether incidence estimates are compatible with the hypothesis of an impact of perinatal exposures on the risk of the different disorders we here instead calculate incidence rates for consecutive birth cohorts born between 1955 and 1967. We hypothesized that schizophrenia incidence would be more affected compared to bipolar disorder and other affective psychoses since most perinatal risk factors are more pronounced in schizophrenia aetiology. METHOD: Birth cohorts of individuals born in Sweden and resident in Stockholm (N = 2,16,322), were followed in The National Patient Register regarding incident inpatient episodes Incident cases/10,000 person-years and birth cohort were calculated. Linear regression was used to estimate change in incidence rate. RESULTS: We found stable birth cohort-based incidence estimates for bipolar disorder and other affective psychoses, but a continuous reduction in incidence estimates for schizophrenia as well as other non-affective psychoses in subsequent birth cohorts from 1955 to 1967. CONCLUSIONS: The consecutive birth cohort-based incidence estimates unveiled patterns that are compatible with the hypothesis of an impact of early life exposures decreasing over time, in the aetiology of schizophrenia, whereas this pattern is less apparent in affective psychoses..

Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators.

A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28-29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one-stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed.

Testing Ødegaard's selective migration hypothesis: a longitudinal cohort study of risk factors for non-affective psychotic disorders among prospective emigrants.

BACKGROUND: The selection hypothesis posits that the increased rates of psychosis observed among migrants are due to selective migration of people who are predisposed to develop the disorder. To test this hypothesis, we examined whether risk factors for psychosis are more prevalent among future emigrants. METHOD: A cohort of 49,321 Swedish military conscripts was assessed at age 18 years on cannabis use, IQ, psychiatric diagnosis, social adjustment, history of trauma and urbanicity of place of upbringing. Through data linkage we examined whether these exposures predicted emigration out of Sweden. We also calculated the emigrants' hypothetical relative risk compared with non-emigrants for developing a non-affective psychotic disorder. RESULTS: Low IQ [odds ratio (OR) 0.5, 95% confidence interval (95% CI) 0.3-0.9] and 'poor social adjustment' (OR 0.4, 95% CI 0.2-0.8) were significantly less prevalent among prospective emigrants, whereas a history of urban upbringing (OR 2.3, 95% CI 1.4-3.7) was significantly more common. Apart from a non-significant increase in cannabis use among emigrants (OR 1.6, 95% CI 0.8-3.1), there were no major group differences in any other risk factors. Compared to non-emigrants, hypothetical relative risks for developing non-affective psychotic disorder were 0.7 (95% CI 0.4-1.2) and 0.8 (95% CI 0.7-1.0), respectively, for emigrants narrowly and broadly defined. CONCLUSIONS: This study adds to an increasing body of evidence opposing the selection hypothesis.

Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture.

AIMS: Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011's effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines. METHODS: Muscle cell cultures derived from lean, overweight and diabetic-obese subjects were used. Expression of pro-inflammatory genes and inflammatory response of human myotubes were evaluated by real-time polymerase chain reaction (RT-PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays. RESULTS: We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFα (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in myotubes derived from diabetic-obese subjects as compared with myotubes derived from normal-lean subjects. In line with this, basal Akt phosphorylation (Ser473) was significantly higher, while insulin-stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal-overweight and diabetic-obese subjects compared with normal-lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin-stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine-induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue. CONCLUSIONS: PMI 5011 improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines.

Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study.

OBJECTIVE: To examine the risk of psychosis associated with severe bereavement stress during the antenatal and postnatal period, between conception to adolescence, and with different causes of death. DESIGN: Population based cohort study. SETTING: Swedish national registers including births between 1973 and 1985 and followed-up to 2006. PARTICIPANTS: In a cohort of 1,045,336 Swedish births (1973-85), offspring born to mothers exposed to severe maternal bereavement stress six months before conception or during pregnancy, or exposed to loss of a close family member subsequently from birth to 13 years of age were followed until 2006. Admissions were identified by linkage to national patient registers. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios for all psychosis, non-affective psychosis, and affective psychosis. RESULTS: Maternal bereavement stress occurring preconception or during the prenatal period was not associated with a significant excess risk of psychosis in offspring (adjusted odds ratio, preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95, 0.58 to 1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to 1.66). Risks increased modestly after exposure to the loss of a close family member from birth to adolescence for all psychoses (adjusted odds ratio 1.17, 1.04 to 1.32). The pattern of risk was generally similar for non-affective and affective psychosis. Thus estimates were higher after death in the nuclear compared with extended family but remained non-significant for prenatal exposure; the earlier the exposure to death in the nuclear family occurred in childhood (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9 years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide. Following suicide, risks were especially higher for affective psychosis (birth to 2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68, 1.84 to 3.92). Adjustment for key confounders attenuated but did not explain associations with risk. CONCLUSIONS: Postnatal but not prenatal bereavement stress in mothers is associated with an increased risk of psychosis in offspring. Risks are especially high for affective psychosis after suicide in the nuclear family, an effect that is not explained by family psychiatric history. Future studies are needed to understand possible sources of risk and resilience so that structures can be put in place to support vulnerable children and their families.

Inhibition of carnitine palymitoyltransferase1b induces cardiac hypertrophy and mortality in mice.

Recent reports suggest that short-term pharmacological carnitine palmitoyltransferase 1 (Cpt1) inhibition improves skeletal muscle glucose tolerance and insulin sensitivity. Although this appears promising for the treatment of diabetes, these Cpt1 inhibitors are not specific to skeletal muscle and target multiple Cpt1 isoforms. To assess the effects of inhibiting the Cpt1b isoform we generated mice with a heart- and skeletal muscle-specific deletion of the Cpt1b, Cpt1b(HM-/-). These mice seem to develop normally with similar bodyweights as control mice. However, premature mortality was observed by 15 weeks of age in the Cpt1b(HM-/-) mice. The hearts of Cpt1b(HM-/-) mice were four times the size of controls. Cpt1b(HM-/-) mice were also subject to stress-induced seizures that accompanied an increased risk for premature mortality. Our data suggests that prolonged Cpt1b inhibition poses severe cardiac risk and emphasizes that attempts to improve insulin sensitivity by targeting Cpt1 with current inhibitors is not viable.

Neonatal levels of acute phase proteins and later risk of non-affective psychosis.

Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log(2)-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85-0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78-0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32-0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.

Hearing and speech impairment at age 4 and risk of later non-affective psychosis.

BACKGROUND: Schizophrenia often becomes manifest in late adolescence and young adulthood but deviations in physical and behavioural development may already be present in childhood. We investigated the relationship between hearing impairment (measured with audiometry) and speech impairment (broadly defined) at age 4 years and adult risk of non-affective psychosis. METHOD: We performed a population-based, case­control study in Sweden with 105 cases of schizophrenia or other non-affective psychoses and 213 controls matched for sex, date and place of birth. Information on hearing and speech impairment at age 4, along with potential confounding factors, was retrieved from Well Baby Clinic (WBC) records. RESULTS: Hearing impairment [odds ratio (OR) 6.0, 95% confidence interval (CI) 1.6­23.2] and speech impairment (OR 2.6, 95% CI 1.4­4.9) at age 4 were associated with an increased risk of non-affective psychotic illness. These associations were mutually independent and not explained by parental psychiatric history, occupational class or obstetric complications. CONCLUSIONS: These results support the hypothesis that psychosis has a developmental aspect with presentation of antecedent markers early in childhood, long before the disease becomes manifest. Our findings add to the growing evidence that early hearing impairment and speech impairment are risk indicators for later non-affective psychosis and possibly represent aetiological clues and potentially modifiable risk factors. Notably, speech impairment and language impairment are both detectable with inexpensive, easily accessible screening.

Creation of damage-free ferroelectric nanostructures via focused ion beam milling.

We present a novel method for creating damage-free ferroelectric nanostructures with a focused ion beam milling machine. Using a standard e-beam photoresist followed by a dilute acid wash, nanostructures ranging in size from 1 µm down to 250 nm were created in a 90 nm thick lead zirconate titanate (PZT) wafer. Transmission electron microscopy and piezoresponse force microscopy (PFM) confirmed that the surfaces of the nanostructures remained damage free during fabrication, and showed no gallium implantation, and that there was no degradation of ferroelectric properties. In fact DC strain loops, obtained using PFM, demonstrated that the nanostructures have a higher piezoresponse than unmilled films. As the samples did not have any top hard mask, the method presented is unique as it allows for imaging of the top surface to understand edge effects in well-defined nanostructures. In addition, as no post-mill annealing was necessary, it facilitates investigation of nanoscale domain mechanisms without process-induced artefacts.

Nanoscale domain switching behaviour in polycrystalline ferroelectric thin films.

We report on the nanoscale domain switching behaviour in polycrystalline tetragonal perovskite lead zirconate titanate (PZT) ferroelectric thin films investigated via piezoresponse force microscopy (PFM). Local domain structures were imaged as a function of varying biasing conditions and spatial location of the tip within 50-100 nm sized grains. Nanoscale piezoresponse images provided direct visual evidence of the complex interplay between electrical and mechanical fields in a polycrystalline system, which causes effects such as correlated switching between the grain of interest and neighbouring grains, ferroelastic domain switching, inhomogeneous piezostrain profiles and domain pinning on very minute length scales. Detailed investigations on mechanisms which induce such domain behaviour are presented.

Reversible ubiquitination regulates the Smad/TGF-beta signalling pathway.

TGF-beta (transforming growth factor-beta) signals through serine/threonine kinase receptors and intracellular Smad transcription factors. An important regulatory step involves specific ubiquitination by Smurfs (Smad-ubiquitin regulatory factors), members of the HECT (homologous to E6-associated protein C-terminus) ubiquitin ligase family, which mediate the proteasomal degradation of Smads and/or receptors. Recently, we have defined a novel interaction between Smads and UCH37 (ubiquitin C-terminal hydrolase 37), a DUB (de-ubiquitinating enzyme) that could potentially counteract Smurf-mediated ubiquitination. We have demonstrated specific interactions between UCH37 and inhibitory Smad7, as well as weaker associations with Smad2 and Smad3. Importantly, Smad7 can act as an adaptor able to recruit UCH37 to the type I TGF-beta receptor. Consequently, UCH37 dramatically up-regulates TGF-beta-dependent gene expression by de-ubiquitinating and stabilizing the type I TGF-beta receptor. Our findings suggest that competing effects of ubiquitin ligases and DUBs in complex with Smad7 can serve to fine-tune responses to TGF-betas under various physiological and pathological conditions. Studies are currently under way using activity-based HA (haemagglutinin)-tagged ubiquitin probes to identify the full spectrum of DUBs that impact on Smad/TGF-beta signalling activity.

Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells.

AIM: Ganoderma lucidum is a commonly used Chinese herb and an important ingredient in traditional Chinese medicine herbal formulations for immune dysfunction related illnesses. The effects of this medicinal mushroom on human colorectal cancer cells have not yet been evaluated. In this study, we investigated the effects of Ganoderma lucidum extract using SW 480 human colorectal cancer cell line. MATERIALS AND METHODS: Two different fractions of Ganoderma lucidum extract, i.e., a fraction containing mainly polysaccharides (GLE-1), and a triterpenoid fraction without polysaccharides (GLE-2) were analyzed. Their antiproliferative activity was evaluated by cell proliferation assay and 3H-thymidine incorporation assay. Scavenging effects of DPPH radical were assessed using ESR-spectroscopy. RESULTS: Our data showed that both GLE-1 and GLE-2 significantly inhibited the proliferation of SW 480 cells. The inhibitory effect of GLE-2 was much stronger than that of GLE-1. GLE-1 inhibited DNA synthesis in the cells and reduced the formation of DPPH radicals. CONCLUSION: Ganoderma lucidum extract inhibits proliferation of human colorectal cancer cells and possesses antioxidant properties.

Social adversity contributes to high morbidity in psychoses in immigrants--a national cohort study in two generations of Swedish residents.

BACKGROUND: Recent reports have indicated that immigrants have an elevated risk of schizophrenia as well as an increasing tendency for social exclusion. The aim of this study was to compare rates of schizophrenia and other psychoses in immigrants and their children of different ethnic groups with the majority population in Sweden in relation to social adversity. METHOD: The study population consists of a national cohort of 1.47 million adults (born 1929-1965) and 1.16 million children and youth (born 1968-1979) in family households from the national census of 1985. Multivariate Cox regression analyses was used to study hospital discharge data during 1991-2000 in relation to socio-economic household indicators from 1985 and 1990 (single adult household, adults having received social welfare, parental unemployment, urban residency, housing and socio-economic status). RESULTS: First as well as second generation immigrants had higher age and sex adjusted risk ratios for schizophrenia as well as for other psychoses (RRs 1.4-3.1 and 1.0-2.0 respectively) compared with the Swedish majority population. These risk ratios decreased considerably after adjusting for socio-economic indicators, for all groups, but particularly for the non-European immigrants. However, an elevated risk still remained in the Finnish and Eastern and Southern European study groups. CONCLUSIONS: A higher risk of schizophrenia and psychoses was found in two generations of immigrants of diverse ethnicity. The results indicate that social adversity contributes to the higher risk.

New Glucocorticosteroids with an improved therapeutic ratio?

Glucocorticoids (GCs) remain the most effective therapy for inflammatory disorders. In terms of asthma, topical steroids are the mainstay for controlling the inflammatory component of the disease. However, their use is limited by the constellation of adverse effects associated with chronic, oral steroid use and the long-term adverse effects associated with inhaled steroid use. These include suppression of hypothalamic--pituitary axis, osteoporosis, reduced bone growth in the young, opportunistic infections, behavioural alterations, and disorders of lipid metabolism. Most of these effects may be attributable to the endocrine activity of steroids and are largely identical to the syndromes of endogenous corticosteroid excess (Cushing's Syndrome). Thus, the Holy Grail of steroid pharmacology is the development of agents which have a markedly improved therapeutic ratio than current steroids, especially on systemic administration. This may be achieved by the identification of molecules which elicit marked antiinflammatory effects, but have a minor impact on endocrine responses. Dissociated corticosteroids are ligands for the glucocorticoid receptor that may offer the potential for a more selective antiinflammatory profile.

Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map.

Single nucleotide polymorphisms (SNPs) are valuable genetic markers of human disease. They also comprise the highest potential density marker set available for mapping experimentally derived mutations in model organisms such as Caenorhabditis elegans. To facilitate the positional cloning of mutations we have identified polymorphisms in CB4856, an isolate from a Hawaiian island that shows a uniformly high density of polymorphisms compared with the reference Bristol N2 strain. Based on 5.4 Mbp of aligned sequences, we predicted 6,222 polymorphisms. Furthermore, 3,457 of these markers modify restriction enzyme recognition sites ('snip-SNPs') and are therefore easily detected as RFLPs. Of these, 493 were experimentally confirmed by restriction digest to produce a snip-SNP map of the worm genome. A mapping strategy using snip-SNPs and bulked segregant analysis (BSA) is outlined. CB4856 is crossed into a mutant strain, and exclusion of CB4856 alleles of a subset of snip-SNPs in mutant progeny is assessed with BSA. The proximity of a linked marker to the mutation is estimated by the relative proportion of each form of the biallelic marker in populations of wildtype and mutant genomes. The usefulness of this approach is illustrated by the rapid mapping of the dyf-5 gene.

Time trends in first admissions for schizophrenia and paranoid psychosis in Stockholm County, Sweden.

Several studies have reported decreasing time trends in first diagnosed schizophrenia patients. The aim of this study was to analyze time trends for first admissions with a diagnosis of schizophrenia or a diagnosis of either schizophrenia or paranoid psychosis during 1978-1994 in Stockholm County, Sweden, with a population of around 1.8million. Information about first psychiatric admission with the diagnosis schizophrenia or paranoid psychosis for residents of Stockholm County was obtained from the Swedish population-based psychiatric inpatient register. Age-adjusted average yearly changes in first hospitalization rates were estimated in a Poisson regression model. Time trends in first admission rates were calculated from 1978 to 1994, while admissions during 1971 to 1977 were observed only to eliminate later re-admissions. First admissions for schizophrenia declined by 1.9% annually for females and by 1.3% for males, while first admissions for schizophrenia and paranoid psychosis together were unchanged over the study period for both genders. Our results indicate that the incidence of schizophrenia and paranoid psychosis taken together was essentially the same over the studied time period in Stockholm County, and that the apparent decline in first admission rates for schizophrenia may be an effect of changes in clinical diagnosis over time.