Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

BACKGROUND: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts. METHODS: We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models. RESULTS: Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition. CONCLUSIONS: Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.

Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.

The Ultra-High-Risk for psychosis groups: Evidence to maintain the status quo.

Individuals are considered Ultra-High-Risk (UHR) for psychosis if they meet a set of standardised criteria including presumed genetic vulnerability (Trait), or a recent history of Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS). Recent calls to revise these criteria have arisen from evidence that Trait, APS and BLIPS groups may transition to psychosis at different rates. Concurrently, it has become clear that the UHR status confers clinical risk beyond transition to psychosis. Specifically, most UHR individuals will not develop psychosis, but will experience high rates of non-psychotic disorders, persistent APS and poor long-term functional outcomes. Rather than focus on transition, the present study investigated whether UHR groups differ in their broader clinical risk profile by examining baseline clinical characteristics and long-term outcomes other than transition to psychosis. Four UHR groups were defined: Trait-only, APS-only, Trait+APS, and any BLIPS. Participants (N=702) were recruited upon entry to early intervention services and followed-up over a period of up to 13years (mean=4.53, SD=3.84). The groups evidenced similar symptom severity (SANS for negative symptoms, BPRS for positive and depression/anxiety symptoms) and psychosocial functioning (SOFAS, GAF, QLS) at baseline and follow-up as well as similar prevalence of non-psychotic disorders at follow-up. Our findings demonstrate that UHR groups evidence a similar clinical risk profile when we expand this beyond transition to psychosis, and consequently support maintaining the existing UHR criteria.

Further examination of the reducing transition rate in ultra high risk for psychosis samples: The possible role of earlier intervention.

BACKGROUND: The rate of transition to psychotic disorder in ultra high risk (UHR) patients has declined in recent cohorts. The reasons for this are unclear, but may include a lead-time bias, earlier intervention, a change in clinical characteristics of cohorts, and treatment changes. AIMS: In this paper we examined the two possibilities related to reduction in duration of symptoms prior to clinic entry, i.e., lead-time bias and earlier intervention. METHOD: The sample consisted of all UHR research participants seen at the PACE clinic, Melbourne between 1993 and 2006 (N=416), followed for a mean of 7.5years (the 'PACE 400' cohort). Duration of symptoms was analysed by four baseline year time periods. Analysis of transition rate by duration of symptoms was restricted to more homogenous sub-samples (pre-1998 and pre-2001) in order to minimize confounding effects of change in patient characteristics or treatments. These cohorts were divided into those with a short and long duration of symptoms using a cut-point approach. RESULTS: Duration of symptoms prior to entry did not reduce significantly between 1993 and 2006 (p=0.10). The group with a short duration of symptoms showed lower transition rates and did not catch up in transition rate compared to the long duration of symptoms group. DISCUSSION: These data suggest that, while earlier intervention or lead-time bias do not fully account for the declining transition rate in UHR cohorts, it appears that earlier intervention may have exerted a stronger influence on this decline than length of follow-up period (lead-time bias).

Randomized Controlled Trial of Clozapine and CBT for First-Episode Psychosis with Enduring Positive Symptoms: A Pilot Study.

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria (n = 48) were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time.

Outcome of suicidal ideation and behavior in a young, help-seeking population over a 2-year period.

Suicidal behavior is associated with negative outcomes, including completed suicide. This study examined the prevalence of suicidal behavior in a sample of referrals to a youth psychiatric service and investigated the stability of suicidality over 2 years. Of the 140 people (mean age 17.8) who were referred to a youth psychiatric service, 82 who were accepted for treatment (RA group) and 58 who were not accepted (RNA group) were assessed; 57% reported considering suicide and 39% reported attempting suicide in the 12 months prior to referral. Participants who reported suicidal ideation were significantly more likely than nonsuicidal participants to have multiple Axis I diagnoses and lower levels of functioning. At the 2-year follow-up there was a significant reduction in suicidality in the RA group, but not in the RNA group. In conclusion, suicidality is prevalent among young people referred to psychiatric services. Even brief contact with services results in a reduction in suicidality over 2 years.

Stress and HPA-axis functioning in young people at ultra high risk for psychosis.

It is thought that hypothalamic-pituitary-adrenal (HPA) axis functioning mediates between the experience of stress and development of psychotic symptoms. This study aimed to evaluate this model in a cohort of young people at ultra high risk (UHR) of psychosis. Information about the experience of psychological symptoms and recent stressful experiences was obtained from 23 young people who met UHR criteria. Plasma samples were taken to assess cortisol and glucocorticoid receptor numbers, and an MRI scan was also performed. Plasma cortisol levels were significantly and positively correlated with the experience of 'hassles' but not with the experience of stressful life events. Significant positive associations were also found between plasma cortisol levels and level of depression and anxiety. No significant relationships were found between plasma cortisol level and global psychopathology, psychotic symptomatology, functioning or pituitary and hippocampal volumes. These results suggest that the number of hassles experienced by young people at UHR of psychosis could be an important factor in raising their cortisol levels, which might, in turn, affect the severity of depressive and anxiety symptoms. No other relationships were found between plasma cortisol levels and the experience of psychotic symptoms, functioning or hippocampal and pituitary volumes. These results indicate possible impairment in HPA-axis functioning in the early stages of psychotic illness, but further investigation of the relationships between these parameters is required.

Treated incidence of first-episode psychosis in the catchment area of EPPIC between 1997 and 2000.

OBJECTIVE: To identify the treated incidence of psychosis in catchment of the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. METHOD: Cases were aged 15-29 years with a first episode of a psychotic disorder accepted into EPPIC between 1997 and 2000. Age- and sex-specific incidence rates per 10,000 person-years were calculated in 5 year age bands. Rate ratios were used for age group comparisons. RESULTS: The age-specific treated incidence of first-episode psychosis in 15-29-year old individuals was 16.7 per 10,000 person-years in males, and 8.1 per 10,000 person-years in females. The incidence was highest in 20-24-year-old males and in 15-19-year-old females. For both sexes, incidence rates were significantly lower in the 25-29-year age group. CONCLUSIONS: The incidence of psychosis in the catchment of EPPIC was higher than previously reported, especially in female teenagers. Peak rates in 15-24 year olds suggest a youth model approach to early psychosis may be indicated.

Early-onset of symptoms predicts conversion to non-affective psychosis in ultra-high risk individuals.

OBJECTIVE: We examined if age of onset of psychiatric symptoms and/or sex predict conversion to non-affective or affective psychosis in individuals considered to be at ultra-high risk for schizophrenia. METHOD: Participants (n=86) were offered treatment and monthly follow-up until transition to psychosis, or for 12 months if they did not meet exit criteria for psychotic disorder. Individuals without transition to psychosis at 12-month were reassessed approximately 3 years after the end of the treatment phase. Ultra-high risk was defined by the presence of subthreshold and/or self-limiting psychotic symptoms and/or having a family history of psychotic disorder combined with functional decline. Cox regressions after adjustment for treatment interventions were applied to investigate associations between age of onset, sex, and other baseline measures with progression to psychotic outcomes. RESULTS: Early age of onset of psychiatric symptoms, in particular onset before age 18 was the only tested variable that significantly predicted non-affective psychosis. Independent significant predictors of affective psychosis were poor functioning, female sex and the presence of a combination of intake criteria (family history of psychosis plus drop in functioning, and attenuated and/or brief limited psychotic symptoms) at baseline. CONCLUSIONS: Age of onset of psychiatric symptoms is the single most important factor associated with conversion to non-affective psychosis in ultra-high risk individuals.

Classical capacity of the lossy bosonic channel: the exact solution.

The classical capacity of the lossy bosonic channel is calculated exactly. It is shown that its Holevo information is not superadditive, and that a coherent-state encoding achieves capacity. The capacity of far-field, free-space optical communications is given as an example.

Suicide prevention in first episode psychosis: the development of a randomised controlled trial of cognitive therapy for acutely suicidal patients with early psychosis.

BACKGROUND: Young people with early psychosis are at particularly high risk of suicide. However, there is evidence that early intervention can reduce this risk. Despite these advances, first episode psychosis patients attending these new services still remain at risk. To address this concern, a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre (EPPIC). The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy (LifeSPAN therapy) for acutely suicidal patients with psychosis. We describe the development of these interventions in this paper. METHOD: Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC. Second, staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service. Third, a suicide risk monitoring system was introduced to identify those at highest risk. Finally, patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a randomised controlled trial. RESULTS: Fifty-six suicidal patients with first episode psychosis were randomly assigned to standard clinical care or standard care plus LifeSPAN therapy. Forty-two patients completed the intervention. Clinical ratings and measures of suicidality and risk were assessed before, immediately after the intervention, and 6 months later. Benefits were noted in the treatment group on indirect measures of suicidality, e.g., hopelessness. The treatment group showed a greater average improvement (though not significant) on a measure of suicide ideation. CONCLUSIONS: Early intervention in psychosis for young people reduces the risk of suicide. Augmenting early intervention with a suicide preventative therapy may further reduce this risk.

Urban/rural and gender differentials in suicide rates: east and west.

BACKGROUND: Many epidemiological studies indicate suicide rates are higher for males than females and for urban than rural. Here we re-examine gender, urban and rural differentials in suicide in Australia and Beijing (China). More specifically, to test the two hypotheses (i) that the male to female ratio is larger than one; (ii) that the urban suicide rate is higher than the rural in both places. METHODS: Suicide data with information of gender, rural and urban regions for Australia and Beijing (China) for the period of 1991-1996 were used. Ratios between the gender-specific urban and rural suicides rates with the associated confidence intervals were constructed to examine gender, urban and rural differentials in Australia and Beijing. RESULTS: The rural suicide rate in Beijing for both genders was higher than for their urban counterparts. Further, the elderly had the highest suicide rate followed by women aged 20-29. Also, the male to female ratio in China was less than one. In Australia, the rural male suicide rate was higher than the urban whereas the urban female suicide rate was higher than the rural. The male to female ratio was 4 to 1. The differences in rural to urban and male to female ratios between Australia and Beijing are statistically significant. CONCLUSIONS: In contrast to the west, male suicide rates are not higher than female rates in China. Urban rates are not necessarily higher than rural rates --not even in a western setting. Cultural factors and regional differences in socio-economic situation are significant in explaining the low gender ratio and the relatively higher suicide rates in rural China. LIMITATIONS: The suicide rate in the Beijing region might not exactly reflect the same for the whole of China.

The intraoperative assessment of ascending aortic atheroma: epiaortic imaging is superior to both transesophageal echocardiography and direct palpation.

OBJECTIVES: To determine the optimal method for detecting ascending aortic atheroma intraoperatively by comparing manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging); and to assess risk factors for severe aortic atheroma. DESIGN: A longitudinal prospective study. Assessment of the atheroma by manual palpation was blinded to the results of the ultrasound images. SETTING: The study was performed in a single university tertiary referral hospital. PARTICIPANTS: One hundred consecutive patients undergoing coronary bypass or valve surgery were studied after their written, informed consent. INTERVENTIONS: Potential risk factors were evaluated by both a patient questionnaire and examination of prior hospital records. The ascending aorta was assessed by the following methods: manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging) performed by an echocardiologist. For analysis, the ascending aorta was divided into three equal segments: proximal, mid, and distal, corresponding to regions of different operative manipulations. MEASUREMENTS AND MAIN RESULTS: Age older than 70 years and hypertension were significant risk factors for severe ascending aortic atheroma with adjusted odds ratios of 3.3 (95% CI, 1.2 to 9.3) and 3.9 (95% CI, 1.3 to 12.0), respectively. There was no significant difference in atheroma detection between the two ultrasonic epiaortic probes in any segment; however, epiaortic probes were superior to manual palpation in all segments and also superior to transesophageal echocardiography in the mid and distal segments of the ascending aorta. CONCLUSIONS: Age older than 70 years and hypertension are significant risk factors for severe ascending aortic atheroma. Intraoperative detection of ascending aortic atheroma is best achieved by epiaortic ultrasound with either a linear or phased array transducer. Transesophageal echocardiography is an insensitive technique for evaluation of mid and distal ascending aortic atheroma and, therefore, of little value in guiding surgical manipulations such as cross-clamping.

A study of breast feeding rates at a large Australian obstetric hospital.

A prospective breast feeding survey in a large obstetric hospital was carried out from 1988 to 1991. For each year, a sample of women were interviewed following delivery and data was collected which included the method of feeding, patient status (public or private patients), age, parity, (including previous breast feeding experience), marital status, country of birth and the number of babies. The mother's feeding method after delivery and on discharge from hospital were recorded. Women who were breast feeding on discharge were interviewed at 3 months. When putting the figures for the 4 years together, the breast feeding commencement rate was 88%, the breast feeding rate on discharge was 80% and the breast feeding rate at 3 months was between 51% and 57%. Factors found to be affecting the breast feeding rate at 3 months included patient status, age and parity. Problems experienced by the mothers after discharge from hospital included nipple pain, nipple trauma and mastitis. Private patients reported a significantly higher rate of mastitis than public patients.

Scheme for realizing a photon number amplifier.

A scheme for realizing a photon number amplifier by use of a high-quantum-efficiency photodetector and a number-state semiconductor laser is analyzed. It is found that the photon number amplifier is not significantly limited by the electronic amplifier noise or by the laser quantum efficiency for input states that are nearly classical.