Cannabis use and transition to psychosis in individuals at ultra-high risk: review and meta-analysis.

BACKGROUND: Previous research has established the relationship between cannabis use and psychotic disorders. Whether cannabis use is related to transition to psychosis in patients at ultra-high risk (UHR) for psychosis remains unclear. The present study aimed to review the existing evidence on the association between cannabis use and transition to psychosis in UHR samples. METHOD: A search of PsychInfo, Embase and Medline was conducted from 1996 to August 2015. The search yielded 5559 potentially relevant articles that were selected on title and abstract. Subsequently 36 articles were screened on full text for eligibility. Two random-effects meta-analyses were performed. First, we compared transition rates to psychosis of UHR individuals with lifetime cannabis use with non-cannabis-using UHR individuals. Second, we compared transition rates of UHR individuals with a current DSM-IV cannabis abuse or dependence diagnosis with lifetime users and non-using UHR individuals. RESULTS: We found seven prospective studies reporting on lifetime cannabis use in UHR subjects (n = 1171). Of these studies, five also examined current cannabis abuse or dependence. Lifetime cannabis use was not significantly associated with transition to psychosis [odds ratio (OR) 1.14, 95% confidence interval (CI) 0.856-1.524, p = 0.37]. A second meta-analysis yielded an OR of 1.75 (95% CI 1.135-2.710, p = 0.01), indicating a significant association between current cannabis abuse or dependence and transition to psychosis. CONCLUSIONS: Our results show that cannabis use was only predictive of transition to psychosis in those who met criteria for cannabis abuse or dependence, tentatively suggesting a dose-response relationship between current cannabis use and transition to psychosis.

Development of a stage-dependent prognostic model to predict psychosis in ultra-high-risk patients seeking treatment for co-morbid psychiatric disorders.

BACKGROUND: Current ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders. METHOD: Baseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14-35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses. RESULTS: At 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56-7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21-6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14-6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01-1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00-1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class. CONCLUSIONS: Predicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.

[Prognostic modelling and proactive intervention in psychosis: efficacy and cost-effectiveness]. / Prognostisch modelleren en proactieve interventie bij psychose: effectiviteit en kosteneffectiviteit.

BACKGROUND: Diagnoses have heterogeneous outcomes, varying from good to extremely poor. There is a need to single out an ultra-high-risk group of individuals who have illnesses that might well end unfavourably or who might later develop serious psychopathology.
AIM: To devise a screening instrument that can identify a group of individuals who run a very high risk of developing a first-episode psychosis, and to create a type of intervention that can modify the course of the illness.
METHOD: We developed a short screening instrument (PQ-16) and were able to ascertain its predictive value. We also tested an intervention that could influence risk factors and deal with emerging symptoms thereby achieving a better outcome for the patient.
RESULTS: We developed a two-step detection instrument with a positive predictive value of 44%. The intervention, involving cognitive behavioural therapy for ultra-high-risk patients, was effective and led to a risk reduction of about 50%. Using the ultra-high-risk group of patients, we were able to model three prognostic profiles, each carrying a 4%, 13%, and 70% risk of subsequently developing psychosis. The intervention was cost-effective, reducing the financial burden on the health care services and on society as a whole.
CONCLUSION: Prognostic modelling and proactive intervention can achieve improvements in health at lower costs.

Cost-effectiveness of preventing first-episode psychosis in ultra-high-risk subjects: multi-centre randomized controlled trial.

BACKGROUND: Although there is evidence for the effectiveness of interventions for psychosis among ultra-high-risk (UHR) groups, health economic evaluations are lacking. This study aimed to determine the cost effectiveness and cost-utility of cognitive-behavioural therapy (CBT) to prevent first-episode psychosis. METHOD: The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients with an 18-month follow-up. All participants were treated with routine care (RC) for non-psychotic disorders. The experimental group (n = 95) received add-on CBT to prevent first-episode psychosis. We report the intervention, medical and travel costs, as well as costs arising from loss of productivity. Treatment response was defined as psychosis-free survival and quality-adjusted life years (QALYs) gained. RESULTS: In the cost-effectiveness analysis, the proportion of averted psychoses was significantly higher in the CBT condition (89.5% v. 76.2%). CBT showed a 63.7% probability of being more cost effective, because it was less costly than RC by US$844 (£551) per prevented psychosis. In the cost-utility analysis, QALY health gains were slightly higher for CBT than for RC (0.60 v. 0.57) and the CBT intervention had a 52.3% probability of being the superior treatment because, for equal or better QALY gains, the costs of CBT were lower than those of RC. CONCLUSIONS: Add-on preventive CBT for UHR resulted in a significant reduction in the incidence of first psychosis. QALY gains show little difference between the two conditions. The CBT intervention proved to be cost saving.

Ethnicity and baseline symptomatology in patients with an At Risk Mental State for psychosis.

BACKGROUND: Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS). METHOD: In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity. RESULTS: Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group. CONCLUSIONS: The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episode.

Detection of people at risk of developing a first psychosis: comparison of two recruitment strategies.

OBJECTIVE: Better recruitment strategies are needed to improve the identification of people at ultra-high risk of developing psychosis. This study explores the effectiveness of two recruitment strategies: a screening method in a consecutive help-seeking population entering secondary mental health services for non-psychotic problems vs. a population referred to the diagnostic center of an early-psychosis clinic. METHOD: From February 2008 to February 2010, all general practitioner and self-referrals (aged 18-35 years) to the secondary mental healthcare service in The Hague and Zoetermeer were screened with the Prodromal Questionnaire; patients who scored above the cutoff of 18 and had a decline in social functioning were assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS). All referrals (aged 14-35 years) to the diagnostic center in Amsterdam were also assessed with the CAARMS. RESULTS: The screening detected a three-fold higher prevalence of at-risk mental states: these subjects were older and more often female. manova showed significantly higher scores for the screened population on depression, social anxiety, distress with positive symptoms, and a higher rate of transition to psychosis within 12 months. CONCLUSION: The screening method detects more patients with at-risk mental states than the referral method. The latter method is biased to young male patients in an earlier prodromal stage and a lower transition rate.

Magnesium deficiency and hypertension: correlation between magnesium-deficient diets and microcirculatory changes in situ.

Rats maintained for 12 weeks on diets moderately or more severely deficient in magnesium showed significant elevations in arterial blood pressure compared to control animals. Examination of the mesenteric microcirculation in situ revealed that dietary magnesium deficiency resulted in reduced capillary, postcapillary, and venular blood flow concomitant with reduced terminal arteriolar, precapillary sphincter, and venular lumen sizes. The greater the degree of dietary magnesium deficiency the greater the reductions in microvascular lumen sizes. These findings may provide a rationale for the etiology, as well as treatment, of some forms of hypertensive vascular disease.

Noise-induced hypertension and magnesium in rats: relationship to microcirculation and calcium.

It has been demonstrated that audiogenic stress (AS) can induce elevation of arterial blood pressure (ABP) in animals and humans and that noise-induced hearing loss may be associated with alterations in Mg metabolism. Experiments were designed to determine whether 1) there is a causal relationship among environmental noise stress, serum and vascular tissue (aortas and portal veins) Mg contents, and development of hypertension and 2) such noise-induced hypertension has a microcirculatory basis and what the mechanism may be. Rats maintained on normal Mg-containing diets for 12 wk (plasma [Mg] = 0.96 +/- 0.02 mM) and subjected to AS (85 dB(A), 12 h/day for 8 wk; 95 dB(A), 16 h/day for 4 wk) demonstrated significant elevation in systolic and diastolic ABP; plasma [Mg] showed a 15% deficit, whereas aortic and portal vein muscle exhibited slight reductions in Mg content and elevation in Ca. Moderate and more severely Mg-deficient animals not subjected to AS also exhibited significant elevations in systolic and diastolic ABP; vascular tissue Mg content decreased, whereas Ca content rose. Animals subjected to combined Mg deficiency and AS for 12 wk exhibited the greatest deficits in plasma and vascular muscle Mg and the greatest elevations in systolic and diastolic ABP; vascular tissue Ca contents also showed the greatest increases. In situ measurements of mesenteric arterioles, venules, and precapillary sphincters in the various subgroups revealed that the lower the plasma [Mg], the more constricted the microvessels, and the higher the ABP, the lower the plasma [Mg]. Capillary blood flow velocities were decreased in relation to the degree of plasma Mg deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary magnesium does not predict ischaemic heart disease in the Caerphilly cohort.

OBJECTIVES: To examine the association between dietary magnesium intake and the risk of an ischaemic heart disease (IHD) event. DESIGN: Estimates were made of dietary magnesium intake from food frequency records, supplemented by seven-day weighted intake records. The subsequent incidence of ischaemic heart disease events was recorded. The relative odds of an IHD event was related to base-line magnesium intake. SETTING: Data on dietary magnesium intakes are available for 2172 men aged 45-59 y in the Caerphilly cohort. These have now been followed for ten years since base-line dietary data were collected, and during this time a total of 269 IHD events occurred. Of these, 96 were acute deaths (ICD 410) and 136 were non-fatal myocardial infarctions. RESULTS: The overall mean dietary intake of magnesium was estimated to be 279 (s.d. 83) mg/day. The daily intake of those men who later experienced any IHD event was 266 (s.d. 84) mg/day and this differs from that in men who experienced no IHD event during this time (281 mg, P < 0.05). Men who suffered an acute IHD death had even lower intakes (mean 253 (s.d. 79); P < 0.005). Age, smoking habit, energy intake and alcohol consumption are all significantly associated with both Mg intake and IHD risk and are therefore possible confounding factors. Standardisation for these factors reduces the difference for all IHD events to 2.9 (s.e.m. 3.6) mg Mg/day, P > 0.05, and to 0.9 (s.e.m. 5.8) mg for acute IHD death. Similarly, when the men are ranked into fifths by their daily Mg intake, 70 of the 434 men with the lowest intakes went on to experience an IHD event, compared with only 41 of the 434 men with the highest Mg intakes. The relative odds (RO) for the fifth of men with the lowest intakes, compared with the fifth with the highest intakes, is 1.86 (P < 0.005), but standardisation for the confounding factors leads again to a loss of significance (RO 1.52, P > 0.05). CONCLUSION: Although trends in the data are suggestive, data from the Caerphilly cohort give no certain evidence that dietary magnesium intake is independently predictive of ischaemic heart disease in the population studied.

Health status as a potential effect modifier of the relation between noise annoyance and incidence of ischaemic heart disease.

AIMS: Traffic noise is a psychosocial stressor. Epidemiological studies suggest chronic noise stress to be a risk factor for cardiovascular disorders. METHODS: In a prospective cohort study, the association between annoyance and disturbances due to road traffic noise and the incidence of ischaemic heart disease (IHD) was studied in 3950 middle aged men. RESULTS: Depending on the questionnaire item, non-significant odds ratios for IHD incidence ranging from 0.9 to 1.4 were found for the highly noise annoyed/disturbed subjects when compared with the less annoyed/disturbed subjects, over the six year follow up period. However, this relation was strongly modified by the prevalence of pre-existing chronic diseases. In subjects free of any chronic disease at the beginning of the follow up, significant odds ratios between 1.7 and 3.0 were seen. In the subgroup with chronic diseases no such noise effects were seen. This surprising result of no effect in the group of people with a potential risk, due to pre-existing health problems, may be because of the dilution of the true effect due to recall bias. CONCLUSIONS: Annoyance and disturbance due to road traffic noise is associated with a higher incidence of IHD. Prevalence of disease can be an important effect modifier of the relation between noise annoyance and health outcomes.

Thiouracil-induced myocardial fibrosis.

Rabbits were fed with thiouracil for 8 months. Subsequently their hearts were examined electron microscopically as well as biochemically for collagen and hexosamine content. Chronic treatment with thiouracil induced an increase in interstitial connective tissue collagen and hexosamine without visible necrosis. As seen by electron microscopy, the increase in collagen content might have been caused by stimulation of the fibrocytes. Furthermore, the heart muscle cells showed deep indentations and bulges of the cell membrane and an enlargement of the T-system.

Increased catecholamine levels in urine in subjects exposed to road traffic noise: the role of stress hormones in noise research.

The nocturnal excretion of catecholamines in urine was studied in 30-45-year-old women whose bedroom and/or living room were facing streets of varying traffic volume. The traffic volume of the streets was used as an indicator of noise exposure; adrenaline and noradrenaline concentrations were assessed as indicators of the outcome of the physiological stress. Significant associations between traffic volume and noradrenaline concentrations in urine were found with regard to the exposure of the bedroom (not the living room), indicating a higher chronic physiological arousal in noise-exposed subjects as compared to less exposed. Subjective measures of disturbance due to traffic noise were positively correlated with the noradrenaline level. However, this was only found in subjects where closing the window could not reduce the perceived disturbance, which points to the effectiveness of individual coping mechanisms. Stress hormones are useful indicators to study associations, mechanisms, and interactions between noise, health outcomes, and effect modifiers in epidemiological noise research.

Enhanced ototoxicity of gentamicin and salicylate caused by Mg deficiency and Zn deficiency.

In rats, Mg deficiency caused a moderate hearing loss, measured by means of evoked potentials at 10 and 20 kHz, which was repaired after refeeding a normal diet. Application of 700 mg/kg salicylic acid or injection of 5 x 100 mg/kg gentamicin also caused a reversible hearing loss in normally fed rats. Treatment of Zn-deficient rats with salicylic acid produced a stronger although reversible hearing loss than in normally fed salicylate-treated rats. Treatment of Mg-deficient rats with gentamicin induced a strong hearing loss that was nearly complete and irreversible in 9 of 25 rats.

[The effect of music in discothèques on hearing ability]. / Zum Einfluss von Musik in Diskotheken auf die Hörfähigkeit.

The risk of hearing loss due to exposure to music in discotheques is discussed on the basis of VDI guideline No 2058, Bl 2. The hypothesis of a relationship was investigated in two empirical studies. In 204 pupils aged 13-19 years, a positive statistical relation of the 4 kHz hearing threshold on the music-hearing habits reported was observed. The difference between the extreme groups of noise exposure was approximately 4 dB (p less than 0.05) on a group average. The evaluation of audiograms of 3133 youths aged 16-20 years applying for a job performed during the medical tests required for employment, showed that those young people with a striking internal ear hearing loss of greater than 30 dB in the area of the C5 depression had spent significantly more time in discotheques than those without striking findings.

Subjective work noise: a major risk factor in myocardial infarction.

The relationship between subjective work noise exposure and the risk of myocardial infarction (MI) was assessed in a population based case-control study. 395 MI patients (31-65 years) were compared to 2148 controls from a random population sample with the same agelsex distribution. The relative risk (RR) for MI-adjusted for control variables (smoking, age, social status, etc.)-was found to increase significantly and steadily with noise category. Subjective work noise exposure was the second greatest risk factor for MI after smoking. Possible bias due to overreporting of subjective noise exposure is discussed. Interdisciplinary studies on the relationship between cardiovascular diseases and work-related stressors including subjective and objective noise assessment are needed to quantify the risk of MI due to work noise.

Traffic noise and cardiovascular risk. The Caerphilly study, first phase. Outdoor noise levels and risk factors.

As part of the Caerphilly study, traffic noise exposure and risk for ischemic heart disease (IHD) were studied in a sample of 2,512 men aged 45-59 yr. The traffic noise emission level ranged between Leq = 51-70 dB(A) (6-22 hr, 10 min). No association was found between traffic noise and prevalence of IHD. Associations were found between noise and potential IHD risk factors including systolic blood pressure, oestradiol, total cholesterol, plasma viscosity, antithrombin III (increases), cortisol, and platelet count (decrease). Not all results supported the hypothesis that traffic noise increases the risk for IHD. The possibility of confounding cannot be excluded, although an extensive range of potential confounding variables were included in the analysis.

Traffic noise and cardiovascular risk: the Speedwell study, first phase. Outdoor noise levels and risk factors.

As part of the Speedwell study, traffic noise exposure and risk factors for ischemic heart disease were studied in a sample of 2,348 men whose ages ranged from 45 to 63 y. The road traffic noise emission level, Leq, ranged between 51 and 70 dB(A) (6-22 h, 10-m distance). Significant associations were found between noise and potential ischemic heart disease risk factors, including total triglycerides, platelet count, plasma viscosity, glucose (increases), and systolic and diastolic blood pressure (decreases). Not all results support the hypothesis that traffic noise increases ischemic heart disease risk. The results were controlled for a number of potential confounding factors.

Traffic noise and cardiovascular risk: the Caerphilly and Speedwell studies, second phase. Risk estimation, prevalence, and incidence of ischemic heart disease.

As part of the Caerphilly and the Speedwell collaborative heart disease studies, associations between outdoor traffic noise level, risk factors for ischemic heart disease, and prevalence and incidence of ischemic heart disease were studied in two samples of 2,512 and 2,348 men, respectively, who were 45-63 y of age. Compared with the lowest noise category [Leq,6-22 h = 51-55 dB(A)], the subjects in the highest noise category [Leq,6-22 = 66-70 dB(A)] showed a slightly worse risk factor profile with respect to 9 identified endogenous risk factors. Logistic regression analysis suggested a marginal increase in risk (relative risk = 1.1) for ischemic heart disease incidence for these men based on risk factors. The prevalence of ischemic heart disease was slightly higher (relative risk = 1.2) in this noise group. The observed incidence of major ischemic heart disease within an observation period of approximately 4 y was slightly lower (relative risk = 0.8) for men in the highest noise group.

Traffic noise and cardiovascular risk: the Caerphilly and Speedwell studies, third phase--10-year follow up.

The authors tested the hypothesis that prolonged exposure to road traffic noise causes ischemic heart disease in a 10-y follow-up cohort study of middle-aged men. In the Caerphilly and Speedwell studies, 2512 and 2348 men, respectively, who were 45-59 y of age were seen in the initial cross-sectional phase and at follow-up intervals of 10 y. Adjusted odds ratios of 1.1 (95% confidence interval = 0.6, 1.9) and 0.9 (95% confidence interval = 0.6, 1.4) were found in the total cohorts. However, the relative risk was 1.3 (95% confidence interval = 0.8, 2.2) in the pooled reconstructed cohort of men who were followed for 6 y (i.e., from phase 2 to phase 3) and for whom room orientation and window-opening habits could be considered. Furthermore, the relative risk increased to 1.6 (95% confidence interval = 0.9, 3.0) in the subsample of men who had lived at least 15 y in their present homes at the time of recruitment. Living adjacent to streets with high traffic noise levels was associated with an adjusted (for covariates) increase in relative risk of 1.01-1.02/y in residence--a result that was only borderline significant (p < .10).

Acute and chronic endocrine effects of noise: Review of the research conducted at the Institute for Water, Soil and Air Hygiene.

This is a review of the research into endocrine effects of noise since the early 1980s at the Institute for Water, Soil and Air Hygiene. According to our knowledge, no other group has studied systematically the endocrine effects of acute and chronic noise exposure. Mechanisms of acute noise-induced stress reactions as well as long-term increase of stress hormones in animal and persons under chronic noise exposure were studied. Our theoretical background was Henry's psychophysiological stress model with the two reaction alternatives : (i) The fight-flight reaction, characterised by an increase in adrenalin and noradrenaline (ii) The defeat reaction with increased cortisol. Extremely intense acute noise exposure near the threshold of pain caused an increased release of cortisol from the suprarenal cortex but acute noise exposure with levels between 90 and 100 dB(A) caused an increase of catecholamines. Non-habituated noise increased primarily the release of adrenalin from the suprarenal medulla, whereas habituated noise caused a chronic increase of noradrenaline from the sympathetic synapses under longterm noise exposure at work. Environmental noise exposure (Leq >/= 60 dB(A)) caused catecholamine increase if activities such as conversation, concentration, recreation etc were disturbed through noise. In sleeping persons, traffic noise with only Leq >/= 30 dB (A) and Lmax >/= 55 dB(A) caused significant acute increase of cortisol, which developed into chronic increase if the noise exposure was repeated consistently. Parallel to cortisol, chronic noradrenaline increase was also observed. Based upon the empirical results, a noise stress model was developed which is a first step forward in the theoretical understanding of endocrine noise effects.