Search

Background: Individuals with first-episode psychosis demonstrate high rates of suicide attempt (SA).Aims: 1) To examine the prevalence of, and risk factors for, SA in a first-episode psychosis (FEP) cohort over a 7.4 year follow-up period. 2) To investigate differences between single versus multiple suicide attempters.Methods: This study reports baseline and follow-up data from a naturalistic, prospective follow-up of 413 FEP patients treated at a specialist early psychosis centre. Assessments were conducted at treatment entry, initial symptom remission or stabilization, and long term follow-up. Binary logistic regression models were used to assess unadjusted and adjusted associations between early illness and sociodemographic characteristics and two outcome measures: any SA during follow-up; and multiple SAs.Results: Follow-up data were available for 282 participants. Sixty-one (21.6%) made a suicide attempt over the follow-up period, including 12 successful suicides. The following baseline risk factors increased the risk of any SA: history of self-harm (OR=4.27; p<0.001), suicidal tendencies (OR=2.30; p=0.022), being depressed for >50% of the initial psychotic episode (OR=2.49; p=0.045), and hopelessness (OR=2.03; p=0.030). History of problem alcohol use increased the risk of multiple SAs (OR=4.43; 95% CI (1.05-18.7); p=0.043).Discussion: The prevalence of suicide attempt in this study exceeds reports from short-term FEP studies but is comparable to longer term follow-up studies, indicating that risk remains elevated for at least 7 years following commencement of treatment. The key predictor of future suicide attempt was previous self-harm, indicating that interventions for self-harm are required. [ABSTRACT FROM AUTHOR]

Background. Little research has focused on delineating the specific predictors of emotional over-involvement (EOI) and critical comments (CC) in the early course of psychosis. The purpose of this study was to investigate the differential relationships of EOI and CC with relevant predictors in relatives of first-episode psychosis (FEP) patients. Method. Baseline patient-related factors including psychotic symptoms, depression and duration of untreated psychosis (DUP) and carer attributes comprising CC, EOI, burden of care and carers' stress and depression were assessed in a cohort of 63 remitted FEP patients and their relatives. Carers were reassessed at 7 months follow-up. Results. Baseline analysis showed that EOI was more strongly correlated with family stress compared with CC, whereas CC yielded a stronger association with DUP than EOI. Carers' CC at follow-up was not significantly predicted by either baseline family stress, burden of care or patient-related variables. Conversely, baseline EOI predicted both family stress and burden of care at 7 months follow-up. Finally, family burden of care at follow-up was a function of baseline EOI and patients' depressive symptoms. Conclusions. This study provides preliminary support to the postulate that EOI and CC may be influenced by separate factors early in the course of psychosis and warrant future research and therapeutic interventions as separate constructs. Implications for family interventions in the early phase of psychosis and the prevention of CC and EOI are discussed. [ABSTRACT FROM AUTHOR]

Schizophrenia is associated with structural brain abnormalities, but the timing of onset and course of these changes remains unclear. Longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive brain volume decreases in patients around and after the onset of illness, although considerable discrepancies exist regarding which brain regions are affected. The anatomical pattern of these progressive changes in schizophrenia is largely unknown. In this study, MRI scans were acquired repeatedly from 16 schizophrenia patients approximately 2 years apart following their first episode of illness, and also from 14 age-matched healthy subjects. Cortical Pattern Matching, in combination with Structural Image Evaluation, using Normalisation, of Atrophy, was applied to compare the rates of cortical surface contraction between patients and controls. Surface contraction in the dorsal surfaces of the frontal lobe was significantly greater in patients with first-episode schizophrenia (FESZ) compared with healthy controls. Overall, brain surface contraction in patients and healthy controls showed similar anatomical patterns, with that of the former group exaggerated in magnitude across the entire brain surface. That the pattern of structural change in the early course of schizophrenia corresponds so closely to that associated with normal development is consistent with the hypothesis that a schizophrenia-related factor interacts with normal adolescent brain developmental processes in the pathophysiology of schizophrenia. The exaggerated progressive changes seen in patients with schizophrenia may reflect an increased rate of synaptic pruning, resulting in excessive loss of neuronal connectivity, as predicted by the late neurodevelopmental hypothesis of the illness. [ABSTRACT FROM AUTHOR]

Objective: Anterior cingulate cortex (ACC) abnormalities are commonly reported in studies of patients with bipolar disorder (BD), but it is unclear whether these precede or follow illness onset. We investigated the evidence for early neurodevelopmental anomalies in the ACC and adjacent paracingulate cortex (PaC) of BD patients by studying cortical folding patterns of the region. Method: Magnetic resonance images were acquired from 54 BD patients and 116 healthy controls. Cortical folding patterns were assessed by classifying the incidence of the paracingulate sulcus (PCS) and interruptions in the course of the cingulate sulcus (CS). Results: Patients were significantly less likely to show a PCS bilaterally. There were no differences in the frequency of CS interruptions. Conclusion: The bilateral reduction observed in our patient sample implicates aberrant pre- or peri-natal developmental processes. To our knowledge, this is the first in vivo evidence for early neurodevelopmental anomaly of the ACC/PaC region in BD. [ABSTRACT FROM AUTHOR]

Preventive strategies can be divided into universal, selective and indicated prevention and early intervention. Universal interventions are directed to the general population. Selective approaches are targeted at people who have risk factors for an illness, but who do not show any current signs. Indicated approaches target high risk individuals with minimal signs or symptoms foreshadowing mental disorder, but who do not meet diagnostic levels at the current time. Early intervention involves treating those with already diagnosable disorder in a timely and optimal manner aiming to decrease the severity of the illness, and reduce secondary morbidity. Although universal and selective interventions are not yet viable strategies, indicated prevention and early intervention are now realistic possibilities in schizophrenia. Development of methods to identify those at risk of psychosis continues to evolve. Promising results in the prevention and delay of transition to psychotic disorder from high risk state have been found. Early intervention in schizophrenia, including promotion of early help-seeking, has been shown to reduce the duration of untreated psychosis, which is known to be associated with poor outcome in schizophrenia. Early intervention programmes which optimise the care of the first episode have been shown to produce better outcomes than routine management. [ABSTRACT FROM AUTHOR]

Although the underlying neurobiology of emerging psychotic disorders is not well understood, evidence from structural imaging and other studies support the notion that schizophrenia arises as a consequence of both an 'early neurodevelopmental' disturbance, as well as 'late neurodevelopmental' changes occurring during the initial stages of a psychotic illness, including around the time of transition to illness. In line with this, our longitudinal MRI findings in individuals at ultra-high risk for developing a psychotic illness show that there are excessive neuroanatomical changes in those who convert to psychosis. These aberrant changes are observed most prominently in medial temporal and prefrontal lobe regions. In a further series of longitudinal studies in first-episode psychosis, we have identified changes in prefrontal regions that indicate an accelerated loss of grey matter in patients compared to healthy control subjects. We suggest that the available evidence is consistent with the presence of subtle regionally and temporally specific neurobiological changes through the course of psychosis (Pantelis et al., 2005), including: (1) evidence for early (pre- and peri-natal) neurodevelopmental anomalies, (2) evidence for progressive grey matter loss involving medial temporal and orbital prefrontal regions around the time of transition to illness, and (3) evidence of late (post-pubertal) neurodevelopmental changes soon after the onset of psychosis, involving an acceleration of normal brain maturational processes, associated with significant loss of grey matter in dorsal prefrontal regions. The pathological processes underlying such changes remain unclear and may reflect anomalies in genetic and/or other endogenous mechanisms responsible for brain maturation, the adverse effects of intense or prolonged stress, or other environmental factors. These findings suggest that early markers of impending illness may prove difficult to define, and that brain changes in psychosis may better be conceptualized as anomalous trajectories of brain development. Further, active changes during transition to illness may present the potential to intervene and ameliorate these changes with potential benefit clinically. [ABSTRACT FROM AUTHOR]

Objective: While rates and correlates of comorbidity have been investigated in the early course of psychosis, little is known about comorbidity in the medium-to-longer term or its relationship with outcome. Method: A total of 182 first-episode psychosis (FEP) patients who met DSM-IV criteria for a current psychotic disorder 8 years after index presentation were grouped according to concurrent comorbidity [no concurrent axis I disorder; concurrent substance use disorder (SUD); other concurrent axis I disorder; concurrent SUD and other axis I disorder]. Outcomes were compared between groups controlling for relevant covariates. Results: As much as 39% met criteria for one or more concurrent axis 1 diagnoses. Comorbidity was associated with greater severity of general psychopathology, but not with measures of functioning, treatment or negative symptoms. Conclusion: Specific combinations of comorbid disorders may influence patterns of psychotic symptomatology. Routine examination of axis I disorders is warranted in the ongoing management of psychosis. [ABSTRACT FROM AUTHOR]

Objective: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. Method: We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. Results: Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. Conclusion: These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP). Method: Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP ( n = 23) with a clinical control condition (psychoeducation, PE; n = 24). Results: There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention. There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time. Conclusion: PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population. [ABSTRACT FROM AUTHOR]

Objective: Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross-sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms. Method: The Early Psychosis Prevention and intervention Centre admitted 786 first-episode psychosis (FEP) patients between 1998 and 2000. Data on SUD and clinical outcome were collected from patients' medical records (MR) of 643 patients who met inclusion criteria. Results: Lifetime prevalence of SUD was 74%, with 62% having a SUD at baseline. This reduced to 36% in those patients who completed 18 months of treatment at the EPPIC program. A Cox regression analysis indicated that a decrease or cessation of substance use significantly increased the probability of remission, whilst persistent SUD substantially reduced the likelihood. In addition, patients who reduced use appeared to have better outcomes at 18 months than those patients who had never used substances. Baseline SUD was not found to have any significant influence on symptom remission. Conclusion: Patients presenting with FEP have high rates of SUD. Effective management of psychosis within a specialized service is associated with reductions in SUD over the course of treatment, although persistent substance use is associated with non-compliance, treatment drop-out and poor remission rates. As such, young people with FEP and comorbid substance use should be offered integrated treatment that addresses both disorders. [ABSTRACT FROM AUTHOR]

Sim K, Swapna V, Mythily S, Mahendran R, Kua EH, McGorry P, Chong SA. Psychiatric comorbidity in first episode psychosis: the Early Psychosis Intervention Program (EPIP) experience. Acta Psychiatr Scand 2004: 109: 23–29. © Blackwell Munksgaard 2004. To determine the prevalence rates of psychiatric comorbidity in a hospitalized Asian patient group with first episode psychosis and examine its clinical correlates. Seventy-nine consecutively admitted patients with first episode psychosis were assessed using the Structured Clinical Interview for DSM-IV-axis I disorders (patient edition), Positive and Negative Symptom Scale (PANSS), Scale to assess Unawareness of Mental Disorders (SUMD) and Global Assessment of Functioning (GAF) scales. Psychiatric comorbidity was present in 36.7% ( n = 29) of the patients. Patients with psychiatric comorbidity were younger ( P < 0.05), had an earlier onset of illness ( P < 0.05) and better insight on social consequences and flat affect items ( P < 0.05) on the SUMD. No significant differences were found between the two groups with and without psychiatric comorbidity in gender, ethnicity, marital status, length of education, employment status, living arrangements, duration of hospitalization and untreated psychosis as well as total PANSS and GAF scores. Psychiatric comorbidity is common thus calling for a greater awareness in clinicians of these conditions, which are often under-recognized, under-diagnosed and untreated. [ABSTRACT FROM AUTHOR]

Objective: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. Method: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. Results: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. Conclusions: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms. [ABSTRACT FROM AUTHOR]

The article discusses a study on the correlation between decreased levels of nervonic acid (NA), a monounsaturated omega-9 fatty acid, and prodromal symptoms and predict conversion to psychosis in young people at high clinical risk for psychosis. The study subjects 81 individuals at ultra-high risk of psychosis. It shows that omega-3 fatty acid supplementation prevents transition to psychosis.

Background: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups.Methods/design: ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration.Discussion: Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry.Trial Registration: Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018. [ABSTRACT FROM AUTHOR]

Introduction Predicting transition from clinical high risk (CHR) to first episode psychosis has proven difficult. Assessment of oxidative stress biomarkers and the niacin skin flush response (NSFR) may improve prediction accuracy. Objectives To predict transition to psychosis based on combined clinical and blood biomarker. Aims To analyse data from patients in placebo group of a 12-week trial of omega-3 fatty acid supplementation in CHR. Transition likelihood ratios (LRs) for baseline historical risks, clinical assessments (PANSS subscales and total, GAF), NSFR and blood markers (nervonic acid, superoxide dismutase, glutathione) were calculated. Variables with the highest positive and lowest negative LRs were included in an odds ratio form of Bayes’ rule transition prediction models. Model accuracy was calculated by area under the receiver operating curves (AUROC) of each model. Results 1-year transition to psychosis was 28% (n=40). Historical data showed no predictability (sensitivity 30%, specificity 100% (AUROC)=0.688, p=0.085). Clinical assessments alone produced a sensitivity of 30% at a specificity of 95% (AUROC=0.83, p<0.0001). The biomarker panel alone predicted transition with 40% sensitivity and 100% specificity (AUROC=0.73, p=0.03). Combining history and clinical assessment provided no improvement above clinical data alone (sensitivity = 30%, specificity = 100%, AUROC=0.85, p< 0.0001). The combination of history, clinical assessment and biomarkers identified transition with a sensitivity of 60% and specificity of 100% (AUROC=0.87, p< 0.0001). Conclusions Probabilistic models combining biomarkers and clinical data are able to target high-risk subgroups within CHR and may help to personalise treatment. [ABSTRACT FROM AUTHOR]

Background: Age at onset of psychosis (AAO) may be younger in patients with cannabis use disorders (CUD) compared to those without CUD (NCUD). Most previous studies did not control for potential confounders, did not report effect sizes and included mostly adult patients from non-representative samples. Methods: Controlling for relevant confounders, differences in AAO between patients with and without lifetime CUD were analysed in a large epidemiologically based cohort of 606 first-episode psychosis (FEP) patients (age 14 to 29 years) admitted within three years to the Melbourne Early Psychosis Prevention and Intervention Centre. Data were collected from medical files using a standardized scale. Results: Overall, AAO was not significantly different in CUD (n=449; 74.1%) compared to NCUD, neither univariate nor when controlling for gender and premorbid functioning. However, AAO was younger in those with early CUD (starting before age 14) compared to NCUD (F(1)=11.3; p=0.001; partial η2 =0.042). When considering the subgroups of early versus late onset psychosis, AAO was even later in early onset psychosis patients with CUD compared to those with NCUD (F(1)=8.4; p=0.004; partial η2=0.072). These findings were consistent for patients with non-affective psychoses, in those with CUD without other substance use disorders and in those with CUD explicitly starting in the pre-psychotic phase. Notably, 89.1% started cannabis before the onset of psychotic symptoms. Conclusions: CUD starting before age 14 was associated with an earlier AAO at a small effect size, but only in adult onset FEP patients. [ABSTRACT FROM AUTHOR]

Objective: Previous studies on the impact of cannabis use disorders (CU) on outcome in psychosis were mostly based on non-representative samples, have often not controlled for confounders and rarely focused on adolescents. Thus, the aims of the present study were to assess; (i) prevalence of CU; (ii) pre-treatment and baseline differences between CU and those without CU (NCU); and (iii) the impact of baseline and course of CU on 18-month outcomes in a representative cohort of adolescents with early onset first episode psychosis (EOP). Method: The sample comprised 99 adolescents (age 14 to 18) with EOP (onset age 14 to 17), admitted to the Early Psychosis Prevention and Intervention Centre in Australia. Data were collected from medical files using a standardized questionnaire. Results: Prevalence of lifetime CU was 65.7%, baseline CU 53.5%, and persistent CU 26.3%. Baseline CU compared to NCU was associated with higher illness-severity, lower functioning, less insight, lower premorbid functioning and longer duration of untreated psychosis. Compared to both NCU and those who decreased or stopped CU during treatment, only persistent CU was linked to worse outcomes and more service disengagement. Effect sizes were medium controlling for relevant confounders. Medication non-adherence did not explain the link between persistent CU and worse outcome. Conclusions: The prevalence of CU in adolescents with EOP is high, while only persistent CU use was associated with worse outcome with medium effect sizes. Specific needs of adolescent patients with respect to cannabis interventions within integrated care settings should be addressed in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Individuals at Ultra High Risk (UHR) for psychosis typically present with attenuated psychotic symptoms. However it is difficult to predict which individuals will later develop frank psychosis when their mental state is rated in terms of individual symptoms. The objective of the study was to examine the phenomenological structure of the UHR mental state and identify symptom profiles that predict later transition to psychosis. Method: Psychopathological data from a large sample of UHR subjects were analysed using latent class cluster analysis. A total of 318 individuals with a UHR for psychosis. Data were collected from two specialised community mental health services for people at UHR for psychosis: OASIS in London and PACE, in Melbourne. Results: Latent class cluster analysis produced 4 classes: Class 1 - Mild was characterized by lower scores on all the CAARMS items. Subjects in Class 2 - Moderate scored moderately on all CAARMS items and was more likely to be in employment. Those in Class 3 - Moderate-Severe scored moderately-severe on negative symptoms, social isolation and impaired role functioning. Class 4 - Severe was the smallest group and was associated with the most impairment: subjects in this class scored highest on all items of the CAARMS, had the lowest GAF score and were more likely to be unemployed. This group was also characterized by the highest transition rate (41%). Conclusions: Different constellations of symptomatology are associates with varying levels of risk to of transition to psychosis. [ABSTRACT FROM AUTHOR]