Longitudinal studies of cognition in first episode psychosis: a systematic review of the literature

Although cognitive deficits are recognized as a core feature in schizophrenia, their evolution over the course of the illness is still debated. Longitudinal studies of cognition in patients after a first episode of psychosis (FEP) provide extremely useful information, in that they include an adequate and realistic baseline measure of cognitive performance, while at the same time minimizing the effect of confounding variables associated with chronicity. The aim of this systematic review was to summarize findings of studies assessing the longitudinal course of neuropsychological deficits in patients with FEP for durations of at least one year. Overall, the neuropsychological deficits that are present following a first episode of psychosis appeared to remain stable over time for periods of up to ten years, the only possible exception being verbal memory deficits, where there is some evidence of further deterioration over the long term. However, further studies are needed to confirm this conclusion, especially in the (somewhat inconsistently defined) domain of executive function. Improvements in psychopathology appear to positively influence the course of cognitive deficits, although the effects of antipsychotic medication are not as clear.     

Suicidality in first episode psychosis

Many studies have confirmed that the risk of suicide is high in the period after first presentation. There is relatively little information about the risk of suicide using illness onset as the starting point. We assessed suicidality in a cohort of 166 individuals from an urban catchment area during the period of untreated psychosis and at 4 year follow up. Nearly 10% of individuals attempted suicide prior to presentation. Four years later 18% had made a suicide attempt and 3% completed suicide. Suicide attempts prior to presentation were associated with a longer duration of untreated psychosis.     

Sexual risk behaviour in young people with first episode psychosis

Aim: Previous studies have consistently reported high rates of risky behaviour for sexually transmitted infections (STIs) amongst individuals with persistent psychosis. Whether such behaviours are evident from the first presentation or relate to a chronic illness course remains largely undetermined, with limited research conducted amongst young people with first episode psychosis. The aim of the current study was to compare engagement in sexual risk behaviour amongst young people with first episode psychosis with their peers. Methods: Sixty-seven sexually active young people with first episode psychosis and 48 healthy control participants (aged 18–29 years) closely matched on sociodemographic characteristics completed a detailed questionnaire assessing a comprehensive range of sexual risk behaviours. Results: There were few differences in the rates of sexual risk behaviour reported by the first episode sample and their peers. Compared with control participants, young people with first episode psychosis reported significantly more inconsistent condom use, less condom-related preparatory behaviour, more concern about HIV/STIs when sex was unprotected, less confidence discussing condom use and increased substance use by their last sexual partner. Conclusions: The sexual behaviour of young people with first episode psychosis appears similar to their peers. However, group differences, particularly increased frequency of unprotected sex amongst the first episode sample, suggest that those with psychosis are at increased STI risk and have distinct needs. The findings support the call for early intervention strategies that target reduction of sexual risk behaviour in the context of persistent mental illness.     

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.     

Brain-derived neurotrophic factor levels in first episode of psychosis: A systematic review

AIM: To systematically review studies measuring peripheric brain-derived neurotrophic factor (BDNF) levels on first-episode psychosis patients and variables related to them. METHODS: A systematic search was made of articles published in the Medline database from 2002 up to June 2014. Included are original studies that report enzyme-linked immunosorbent assay measurement of BDNF levels in serum or plasma in patients with a diagnosis of first episode psychosis (FEP) and age- and gender- matched healthy controls. RESULTS: Of the initially identified 147 articles, only 18 satisfied the inclusion criteria. Of this, 15 found a significant reduction in patients with FEP compared with age- and gender - matched controls. CONCLUSION: Peripheral BDNF levels are generally reduced in FEP patients. There are some factors that may influence BDNF levels that need to be further studied. Furthermore, a future meta-analysis in this topic is needed.     

Neuropsychological status of subjects at high risk for a first episode of psychosis

Thirty-six subjects aged 16 years or older judged at risk for a first episode of psychosis within a North American multi-site study of the schizophrenia prodrome [McGlashan et al., Schizophr. Res. (2003); Miller et al., Schizophr. Res. (2003)] performed at levels intermediate to population norms and data reported for schizophrenia samples on a comprehensive neuropsychological exam. In the context of normal intelligence, this intermediate status suggests that, as a group, these subjects are not fully normal in neuropsychological functioning. Conversely, the finding that they do not show the levels of impairment commonly observed in schizophrenia, including within the first episode, suggests that prodromal interventions might conceivably prevent, delay, or lessen the severity of declines associated with first psychotic episodes.     

Subjective quality of life in subjects at risk for a first episode of psychosis: a comparison with first episode schizophrenia patients and healthy controls

The concept of quality of life (QoL) is of growing relevance in schizophrenia research. However, there is to date no information on subjective QoL in subjects at risk for a first episode of psychosis in comparison to first episode schizophrenia patients (FE) or healthy controls (HC). Therefore 45 subjects in a putatively early initial prodromal state (EIPS), 40 FE and 45 HC were assessed on demographics, symptoms and subjective QoL as measured by the Modular System for Quality of Life. Results indicated that in most areas HC experienced the highest QoL scores followed in hierarchical order by EIPS and FE. EIPS and FE experienced significantly lower QoL than HC in 5 and 6 of 7 QoL domains. EIPS experienced the lowest ratings in affective QoL. Thus the data demonstrates that subjective QoL in subjects at risk for a first episode of psychosis is substantially reduced when compared with HC and suggests that subjective QoL is already compromised prior to the onset of first positive schizophrenia symptoms. These findings support the notion that subjects at risk for a first episode of psychosis constitute a clinical population for which further service and intervention research is indicated.     

Major self-mutilation in the first episode of psychosis

Major self-mutilation (MSM) is a rare but catastrophic complication of severe mental illness. Most people who inflict MSM have a psychotic disorder, usually a schizophrenia spectrum psychosis. It is not known when in the course of psychotic illness, MSM is most likely to occur. In this study, the proportion of patients in first episode of psychosis (FEP) was assessed using the results of a systematic review of published case reports. Histories of patients who had removed an eye or a testicle, severed their penis, or amputated a portion of a limb and were diagnosed with a schizophrenia spectrum psychosis were included. A psychotic illness was documented in 143 of 189 cases (75.6%) of MSM, of whom 119 of 143 (83.2%) were diagnosed with a schizophrenia spectrum psychosis. The treatment status of a schizophrenia spectrum psychosis could be ascertained in 101 of the case reports, of which 54 were in the FEP (53.5%, 95% confidence interval = 43.7%-63.2%). Patients who inflict MSM in FEP exhibited similar symptoms to those who inflict MSM later in their illness. Acute psychosis, in particular first-episode schizophrenia, appears to be the major cause of MSM. Although MSM is extremely uncommon, earlier treatment of psychotic illness may reduce the incidence of MSM.     

Predictors of cognition in first episode psychosis

PurposeCognitive deficits are common in the first episode of psychosis (FEP) and may begin much earlier. While some evidence suggests that the decline in cognition occurs over the untreated symptomatic period, including the prodromal phase, others point to these deficits being present even earlier. We aimed to investigate the differential effect of untreated symptomatic and pre-morbid phases on cognition in a large sample of FEP.MethodsTwo hundred and sixty eight FEP patients, admitted into a specialized early intervention service, were administered neuro-cognitive tests. The Circumstances of Onset and Relapse Schedule (CORS) was administered for measurement of duration of untreated psychosis (DUP), the duration of untreated illness (DUI) and demographic factors. The Pre-morbid Adjustment Scale (PAS) was used to measure different domains of pre-morbid adjustment. Seventy three healthy controls were also recruited for neuro-cognitive comparison.ResultsWe observed no effect of DUP and a minimal effect of DUI on cognitive functioning in FEP. Instead, the early educational pre-morbid adjustment domain was most strongly associated with cognition and predicted both global cognitive and verbal memory outcome in FEP.ConclusionOur results suggest that symptoms associated with the symptomatic phase of a FEP do not influence cognitive functioning in FEP. Instead, cognitive deficits in FEP may predate illness onset and may indicate susceptibility to such illness.     

Correlates of insight in first episode psychosis

Impaired insight is common in schizophrenia and may be related to poor treatment adherence. Few studies have examined the clinical and neurocognitive correlates of insight in early schizophrenia. Early course schizophrenia, schizoaffective, and schizophreniform disorder patients (n=535) were studied. The Positive and Negative Symptom Scale (PANSS) was used to assess psychopathology, and a broad range of neuropsychological functions was assessed. Using hierarchical stepwise multiple regression analyses, we examined the association of clinical, neurocognitive, and premorbid measures with the level of insight. Impaired insight was associated with overall symptomatology, including positive, negative, and general psychopathology and with deficits in cognitive functioning. In descending order of robustness, the significant variables were PANSS general psychopathology (p<0.0001), Rey Auditory Verbal Learning Test (p<0.0004), Clinical Global Impression (p<0.005), PANSS positive (p<0.007), and premorbid adjustment—general subscale (p=0.02). Among the PANSS general psychopathology items, unusual thought content was most robustly associated with impaired insight (p<0.00000). Insight impairment is very common in early schizophrenia, and appears to be associated with a broad range of psychopathology and deficits in multiple cognitive domains. These observations suggest that deficits in insight may be related to a generalized dysfunction of neural networks involved in memory, learning, and executive functions.     

Negative symptoms in first episode non-affective psychosis

OBJECTIVE: To determine the prevalence of negative symptoms and to examine secondary sources of influence on negative symptoms and the role of specific negative symptoms in delay associated with seeking treatment in first episode non-affective psychosis. METHOD: One hundred and ten patients who met Diagnostic Statistical Manual-IV (DSM-IV) criteria for a first episode of schizophrenia spectrum psychoses were rated for assessment of negative, positive, depressive and extrapyramidal symptoms, the premorbid adjustment scale and assessment of demographic and clinical characteristics including duration of untreated psychosis (DUP). RESULTS: Alogia/flat affect and avolition/anhedonia were strongly influenced by parkinsonian and depressive symptoms, respectively. A substantial proportion (26.8%) of patients showed at a least moderate level of negative symptoms not confounded by depression and Parkinsonism. DUP was related only to avolition/anhedonia while flat affect/alogia was related to male gender, diagnosis of schizophrenia, age of onset and the length of the prodrome. CONCLUSION: Negative symptoms that are independent of the influence of positive symptoms, depression and extra pyramidal symptoms (EPS) are present in a substantial proportion of first episode psychosis patients and delay in seeking treatment is associated mainly with avolition and anhedonia.     

Cognitive functioning in first episode psychosis: initial presentation

This first part of a longitudinal study examined the initial cognitive performance of 312 individuals who recently presented with a first episode (FE) of psychosis. All attend a comprehensive first episode program. Deficits on a wide range of cognitive tests were observed, suggesting impairment similar to that seen in those with an established schizophrenia illness. There was no evidence to support differences in cognition among the different schizophrenia spectrum diagnostic groups.