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The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.
Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.
There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness.
Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a–b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discordant compared to concordant monozygotic pairs. There was no significant difference in NSS and TABRC scores between subjects with schizophrenia and their co-twins without the illness. However, monozygotic discordant twins with schizophrenia had higher ABRCs on their right hands compared to their co-twins without the illness. These findings suggest that an unidentified environmental event acting between weeks 6 and 15 of gestation affects the development of monozygotic twins who go on to develop schizophrenia but does not have a corresponding effect on their co-twins who do not develop the illness. The effect of such an event on dermatoglyphic profiles appears lateralised to the right hand in affected twins.
Although there is some evidence that duration of untreated psychosis (DUP) is geographically stable, few have examined whether the phenomenon is temporally stable. We examined DUP in two cohorts within two discrete time periods (1995–1999 and 2003–2005) spanning a decade in the same geographically defined community psychiatric service with no early intervention programme. Patients were diagnosed by Structured Clinical Interview for DSM (SCID) and we determined the DUP using the Beiser Scale. The DUP of the 240 participants did not differ significantly between study periods.
The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.
Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.
The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.
The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
Research on psychotic illness is loosening emphasis on diagnostic stringency in favour of including a more dimensionally based conceptualization of psychopathology and pathobiology. However, to clarify these notions requires investigation of the full scope of psychotic diagnoses.
The Cavan–Monaghan First Episode Psychosis Study ascertained cases of first episode psychosis across all 12 DSM-IV psychotic diagnoses via all routes to care: public, private or forensic; home-based, outpatient or inpatient. There was no arbitrary upper age cut-off and minimal impact of factors associated with variations in social milieu, ethnicity or urbanicity. Cases were evaluated epidemiologically and assessed for psychopathology, neuropsychology, neurology, antecedent factors, insight and quality of life.
Among 432 cases, the annual incidence of any DSM-IV psychotic diagnosis was 34.1/100 000 of population and encompassed functional psychotic diagnoses, substance-induced psychopathology and psychopathology due to general medical conditions, through to psychotic illness that defied contemporary diagnostic algorithms. These 12 DSM-IV diagnostic categories, including psychotic disorder not otherwise specified, showed clinical profiles that were consistently more similar than distinct.
There are considerable similarities and overlaps across a broad range of diagnostic categories in the absence of robust discontinuities between them. Thus, psychotic illness may be of such continuity that it cannot be fully captured by operational diagnostic algorithms that, at least in part, assume discontinuities. This may reflect the impact of diverse factors each of which acts on one or more overlapping components of a common, dysfunctional neuronal network implicated in the pathobiology of psychotic illness.
Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice.
To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions.
Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18–65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment.
From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI − €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI −€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI − €2075 to €41 931).
Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.
As research into psychotic illness evolves along established lines, insights are emerging that deviate from those lines and challenge more fundamentally our understanding. On the background of a new generation of studies on first-episode psychosis, investigations across the gene–environment interface and the intersection with ‘normal’ human mentation heighten these concerns. Using findings from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) as an exemplar, we here review the complexity of these challenges from the perspective of this real-world setting. They range from trans-diagnostic epidemiology and clinical characterisation, through molecular genetics, social milieu, developmental pathobiology and functional outcome across arbitrary diagnostic boundaries, to the evidence base for early intervention and more radical conceptualisations and structures for provision of mental health care.
Seedling alfalfa was injured by chlorsulfuron and sethoxydim plus 2,4-DB but recovered the following year as alfalfa seed yields were comparable to the hand-weeded control. Fluazifopbutyl and flamprop-methyl (active isomer) at 0.5 kg/ha did not affect seedling alfalfa adversely; however, seed yields were lower the following year compared to those treated at the 0.25-kg/ha rate. In established alfalfa, sethoxydim alone or with 2,4-DB applied annually did not affect seed yields adversely. However, 2,4-DB alone reduced seed yields in 2 of 5 yr. Alfalfa tolerated chlorsulfuron at 0.015 kg/ha but was damaged at the 0.03-kg/ha rate. Initial injury and later recovery without adverse effects on seed yield also were observed following annual treatments with bromoxynil, MCPA plus 2,4-DB and bentazon plus 2,4-DB.
The long-term effect of repeated late-fall versus early-spring imazethapyr, hexazinone, terbacil, metribuzin, dichlobenil, or chlorsulfuron treatments, when applied on dormant stands of alfalfa was investigated at three sites for weed management of alfalfa grown for seed. Dichlobenil applied at 1.2 to 2.4 kg ha−1 and chlorsulfuron applied at 11 to 22 g ha−1 in fall or spring were the only herbicides to injure alfalfa at one location. Hexazinone provided the most consistent weed control of the herbicides evaluated. Average control of Canada thistle, catchweed bedstraw, dandelion, perennial sowthistle, quackgrass, Russian pigweed, and scentless chamomile was 80%. When averaged over three sites, weed control by hexazinone resulted in a 33% increase in seed yield.
Tolerance and subsequent yield response of established alfalfa, red clover, alsike clover, sainfoin, birdsfoot trefoil, and cicer milkvetch to sethoxydim and fluazifop spring applied and to hexazinone, metribuzin, and terbacil fall applied were determined in a field study. All legumes tolerated sethoxydim. Fluazifop was safe on all legumes except sainfoin. Alfalfa and cicer milkvetch tolerated hexazinone, metribuzin, and terbacil. Alfalfa dry matter yield was not affected by any of the herbicide treatments, but cumulative cicer milkvetch yield increased 9% over a 3-yr period with hexazinone applications. Sainfoin yield increased 20% with hexazinone and terbacil treatment. Hexazinone injured red clover and reduced yield. Alsike clover was the most susceptible legume to the residual herbicides. Weed dry matter yield associated with the legumes indicated that alfalfa and sainfoin were the most and the least competitive species, respectively. Plots treated with hexazinone contained the least amount of weeds, regardless of the legume species. Field peas seeded in rotation was not affected by herbicide residues; however, residues from terbacil applied at 1.0 kg/ha reduced seed yield of lentils.
Applications of 1.6 kg ai/ha of metribuzin [4-amino-6-tert-butyl-3-(methylthio)-as-triazin-5(4H)-one] to established alfalfa (Medicago sativa L. ‘Rambler’) at the start of each growing season for 4 yr increased seed yield by 68% and controlled established dandelion (Taraxacum officinale Weber. in Wiggers ♯ TAROF) and smooth brome (Bromus inermis Leyss. ♯ BROIN). A lesser amount of metribuzin was not sufficient for smooth brome control, and a greater amount damaged the alfalfa. Hexazinone [3-cyclohexyl-6-(dimethylamino)-methyl-1,3,5-triazine-2,4(1H,3H)-dione] applied at 1.0 kg ai/ha also controlled dandelion and smooth brome and produced increases in alfalfa seed yield. Mixtures of terbacil (3-tert-butyl-5-chloro-6-methyluracil) with reduced rates of metribuzin or hexazinone controlled dandelion well, but gave only fair control of smooth brome. Alfalfa seed yield was negatively correlated with the smooth brome population.
It is unclear whether there is a direct link between economic crises and changes in suicide rates.
The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates.
Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation.
There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged.
Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.
We used observations and modeling of Siple Dome, West Antarctica, a ridge ice divide, to infer the importance of linear deformation mechanisms in ice-sheet flow. We determined the crossover stress (a threshold value of the effective deviatoric stress below which linear flow mechanisms dominate over nonlinear flow mechanisms) by combining measurements of ice properties with in situ deformation rate measurements and a finite-element ice flow model that accounts for the effects of viscous anisotropy induced by preferred crystal-orientation fabric. We found that a crossover stress of 0.18 bar produces the best match between predicted and observed deformation rates. For Siple Dome, this means that including a linear term in the flow law is necessary, but generally the flow is still dominated by the nonlinear (Glen; n = 3) term. The pattern of flow near the divide at Siple Dome is also strongly affected by crystal fabric. Measurements of sonic velocity, which is a proxy for vertically oriented crystal fabric, suggest that a bed-parallel shear band exists several hundred meters above the bed within the Ice Age ice.
This paper examines the concept of early intervention in psychosis at primary and secondary prevention levels. Examples of early intervention service models from different countries are presented and we discuss current evidence for efficacy. We highlight the Irish experience of early intervention to date, and discuss future implementation of early intervention services in Ireland.
Background: Cognitive Behaviour Therapy (CBT) of anxiety disorders is usually delivered in weekly or biweekly sessions. There is evidence that intensive CBT can be effective in phobias and obsessive compulsive disorder. Studies of intensive CBT for posttraumatic stress disorder (PTSD) are lacking. Method: A feasibility study tested the acceptability and efficacy of an intensive version of Cognitive Therapy for PTSD (CT-PTSD) in 14 patients drawn from consecutive referrals. Patients received up to 18 hours of therapy over a period of 5 to 7 working days, followed by 1 session a week later and up to 3 follow-up sessions. Results: Intensive CT-PTSD was well tolerated and 85.7 % of patients no longer had PTSD at the end of treatment. Patients treated with intensive CT-PTSD achieved similar overall outcomes as a comparable group of patients treated with weekly CT-PTSD in an earlier study, but the intensive treatment improved PTSD symptoms over a shorter period of time and led to greater reductions in depression. Conclusions: The results suggest that intensive CT-PTSD is a feasible and promising alternative to weekly treatment that warrants further evaluation in randomized trials.
Background: Reported rates of depression in schizophrenia vary considerably.
Objective: To measure the prevalence of depression in a first episode sample of people with schizophrenia.
Methods: All referrals with a first episode of schizophrenia diagnosed using SCID interviews were assessed pre-discharge and again six months later. We used the Calgary Depression Scale for Schizophrenia (CDSS) and Positive and Negative Syndrome Scale (PANSS) to assess the severity of symptoms.
Results: Pre-discharge, 10.4% of the sample met CDSS criteria for depression. According to the PANSS depression (PANSS -D) subscale, 3% of patients were depressed, with a mean score of 7.48 (SD = 2.97). Only 3% of patients pre-discharge were found to be depressed on both the CDSS and the PANSS-D. Six months later 6.5% were depressed according to the CDSS. However none reached depression criteria according to the PANSS-D. The CDSS correlated with PANSS-D both pre-discharge and at follow-up. Feelings of depression and self-deprecation were the most common symptoms at baseline and follow-up. The CDSS was unrelated to negative symptoms at both stages. A lifetime history of alcohol abuse increased the risk for depression.
Conclusion: Rates of depression in this sample were low. The CDSS appears to discriminate between depression and negative symptoms. Like the general population, alcohol misuse is a risk factor for depression in first episode schizophrenia.
The critical period hypothesis proposes that deterioration occurs aggressively during the early years of psychosis, with relative stability subsequently. Thus, interventions that shorten the duration of untreated psychosis (DUP) and arrest early deterioration may have long-term benefits.
To test the critical period hypothesis by determining whether outcome in non-affective psychosis stabilises beyond the critical period and whether DUP correlates with 8-year outcome; to determine whether duration of untreated illness (DUI) has any independent effect on outcome.
We recruited 118 people consecutively referred with first-episode psychosis to a prospective, naturalistic cohort study.
Negative and disorganised symptoms improved between 4 and 8 years. Duration of untreated psychosis predicted remission, positive symptoms and social functioning at 8 years. Continuing functional recovery between 4 and 8 years was predicted by DUI.
These results provide qualified support for the critical period hypothesis. The critical period could be extended to include the prodrome as well as early psychosis.
Adversities operating over intrauterine life have been associated with
risk of schizophrenia, but the biology of resultant developmental
perturbation is poorly understood.
To examine the relationship of congenital anomalies and related
functional impairments in infancy to risk of schizophrenia.
Using the Congenital Anomalies data-set from the Prenatal Determinants of
Schizophrenia birth cohort, congenital anomalies and related functional
impairments were categorised and related to subsequent risk of
The presence of any hypothesis-based congenital anomaly or related
functional impairment was associated with a doubling of risk of
schizophrenia-spectrum disorder. In contrast, having any other congenital
anomaly or related functional impairment was not associated with risk of
These findings constitute evidence for early events, which may result
from both genetic predisposition and environmental insults, in the
pathogenesis of schizophrenia.
As understanding of the pathobiology of schizophrenia increases, the challenge is to relate such measures to outcome at a functional level
To consider our current understanding of how neurobiological variables relate to functional outcome and might constitute outcome measures in their own right
Critical appraisal of recent evidence on structural and functional imaging, neurological evaluation, early neurodevelopmental indices, genomics, proteomics, metabolomics and apoptotic mechanisms in relation to outcome
Studies conducted prospectively from the first episode of schizophrenia are generating more reliable findings but currently lack predictive power. Prediction of transition from ‘high-risk’ status to first episode has proved somewhat more fruitful, but the gain has been modest and circumscribed
Our current level of understanding does not yet allow the generation of predictive models on an individual patient basis. Genomic and metabolomic studies hold particular potential for generating clinically meaningful ‘biomarkers’ but considerable further work is necessary
Objective: To examine the variables that influence of duration of untreated psychosis (DUP) prior to presentation in persons with a first episode of psychosis.
Method: Prospective examination of consecutive first presentations with DSM-IV psychosis attending a community based psychiatric service.
Results: One hundred and seventy-one patients had an average duration of untreated psychosis of 18 months and a median of five months. The mean duration of untreated mania was 1.5 months, median 0.75 months. DUP was predicted by social withdrawal and diagnosis in the total group and by prodrome in the schizophrenia/schizophreniform group. DUP was not associated with age at onset of psychosis, educational years or living status.
Conclusions: There are significant differences in DUP between diagnostic groups. Increased social withdrawal is associated with a longer DUP.