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Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.
To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.
Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance.
The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months.
We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.
Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention.
We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone.
A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16–25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation.
We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was −4.44 (95% CI −10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm.
We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.
In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate.
In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers.
Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring.
ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.
Alison R. Yung, Professor of Psychiatry,
Kathryn M. Abel, Professor of Psychological Medicine and Director of the Centre for Women's Mental Health (CWMH) at the University of Manchester,
Sarah Cornick, works for the South London
Holly is an 18-year-old student who lives with her mother in an inner-city area. She had been well until about 5 months previously. In spite of being an above-average student, she started having difficulty with schoolwork. She became easily flustered about homework, frequently missed deadlines and cried about how stressed and tired she felt. She started missing school frequently.
Two months later, Holly started having aches and strange feelings all over and inside her body. She started hearing indistinct whispers, which distressed and further distracted her. The whispering gradually became clearer, until she could make out voices telling her she was ugly and really a man. She started to become unsure of her gender, attributing the strange bodily sensations to her changing sex. She later refused to attend school at all and also refused to see the general practitioner (GP).
Holly became increasingly tearful and stopped washing. She locked herself in her room and her GP advised her mother to take Holly to the local hospital for assessment. Holly was subsequently referred to the local community mental health team, which became concerned about her level of distress and the thoughts she was experiencing that life was not worth living. The mental health team identified her as having a psychotic illness and she was admitted to hospital.
Holly had no past history of psychiatric illness and her childhood was uneventful, except that her mother had experienced postnatal depression after Holly's birth. Holly's parents were divorced, but had shared custody. Although Holly had not visited her father for 3 months before admission, she felt she had a loving relationship with both of them. Her personality had been described as ‘bubbly and warm’ until 6 months before admission, when she had become less happy and more anxious than usual.
Holly was an in-patient for 3 weeks. She was treated with antipsychotic medication. She also received a sleeping tablet at night for a short period after her admission and underwent tests to make sure there were no underlying physical reasons for her symptoms.
Holly settled quickly on the ward and had a good rapport with her treatment team (psychiatrists, nurses, psychologist and occupational therapist).
Early intervention in psychosis, while not a new concept, has seen great development over the last 15 years. Growth in this time has occurred in a number of areas and has attracted a broad coalition of researchers, consumers, clinicians, carers and policy makers. In this time the concept of early intervention has moved from the fringes to the mainstream of clinical approaches to psychosis in many places, and is doing so in even more. After a decade and a half, this paper reviews some of the key issues that have been addressed and points to areas where further growth and reform is still required. Some issues that have created controversy are examined here including pre-onset intervention and identification, the relationship of duration of untreated psychosis (DUP) to outcome and whether or not early intervention is an effective and economically viable model. Areas that are only now developing or which require further investigation are considered, including the concept of stages of mental illness and concomitant interventions, closing the efficacy-effectiveness gap and an increased focus on functioning as part of the recovery process. Early intervention in psychosis started as a reformist movement, agitating for change from outside the mainstream. Change has occurred and now early intervention is part of the mainstream approach to psychotic illness. In order to continue to develop, while enjoying the benefits of being a mainstream intervention, early intervention must not stray too far from its reformist roots.
Morphological abnormalities of the superior temporal gyrus have been
consistently reported in schizophrenia, but the timing of their
occurrence remains unclear.
To determine whether individuals exhibit superior temporal gyral changes
before the onset of psychosis.
We used magnetic resonance imaging to examine grey matter volumes of the
superior temporal gyrus and its subregions (planum polare, Heschl's
gyrus, planum temporale, and rostral and caudal regions) in 97
antipsychotic-naive individuals at ultra-high risk of psychosis, of whom
31 subsequently developed psychosis and 66 did not, and 42 controls.
Those at risk of psychosis had significantly smaller superior temporal
gyri at baseline compared with controls bilaterally, without any
prominent subregional effect; however, there was no difference between
those who did and did not subsequently develop psychosis.
Our findings indicate that grey matter reductions of the superior
temporal gyrus are present before psychosis onset, and are not due to
medication, but these baseline changes are not predictive of transition
Grey matter changes have been described in individuals who are pre- and peri-psychotic, but it is unclear if these changes are accompanied by changes in white matter structures.
To determine whether changes in white matter occur prior to and with the transition to psychosis in individuals who are pre-psychotic who had previously demonstrated grey matter reductions in frontotemporal regions.
We used magnetic resonance imaging (MRI) to examine regional white matter volume in 75 people with prodromal symptoms. A subset of the original group (n=21) were rescanned at 12–18 months to determine white matter volume changes. Participants were retrospectively categorised according to whether they had or had not developed psychosis at follow-up.
Comparison of the baseline MRI data from these two subgroups revealed that individuals who later developed psychosis had larger volumes of white matter in the frontal lobe, particularly in the left hemisphere. Longitudinal comparison of data in individuals who developed psychosis revealed a reduction in white matter volume in the region of the left fronto-occipital fasciculus. Participants who had not developed psychosis showed no reductions in white matter volume but increases in a region subjacent to the right inferior parietal lobule.
The reduction in volume of white matter near the left fronto-occipital fasciculus may reflect a change in this tract in association with the onset of frank psychosis.
The origin of cognitive impairments in psychotic disorders is still
unclear. Although some deficits are apparent prior to the onset of frank
illness, it is unknown if they progress
To investigate whether cognitive function declined over the transition to
psychosis in a group of ultra-high risk individuals
Participants consisted of two groups: controls (n = 17)
and individuals at ultra-high risk for development of psychosis
(n = 16). Seven of the latter group later developed
psychosis. Neuropsychological testing was conducted at baseline and again
after at least a 12-month interval
Both the Visual Reproduction sub-test of the Wechsler Memory
Scale-Revised and Trail-Making Test B showed a decline over the follow-up
period that was specific to the group who became psychotic. In addition,
both high-risk groups showed a decline in digit span performance. No
other task showed significant change over time
These preliminary data suggest that as psychosis develops there may be a
specific decline in visual memory and attentional set-shifting,
reflecting impairments in efficient organisation of visual stimuli. This
may be caused by either the illness itself or treatment with
Treating psychotic disorders in their earliest stages has become a key focus
for research and clinical care. This paper reviews evidence of the capacity
to identify those at increased risk for psychotic disorder and to intervene
in the identified, high-risk individuals to ameliorate the course of
disorder. Issues involved in preventive oriented clinical care are
addressed, such as risk/benefit considerations, ethical and safety issues
and the value of stage-specific interventions. Clinical predictors
identified in recent research, promising intervention trials and proposed
clinical practice guidelines are described. An approach based on active
engagement, support and monitoring, yet with a conservative approach to
medication use is advocated at present. Potential neurobiological processes
have been studied and reinforce the sense that this is a critical phase for
active treatment, and may prove helpful in understanding the process of
transition across stages of illness. More research is required in
prediction, neurobiology and treatment
Clinical and research focus has recently shifted from established psychotic disorders to first-episode psychosis and the prepsychotic phase of illness.
To describe the principles, progress and dilemmas associated with the prospective detection, engagement and treatment of young people at risk of developing a psychotic disorder.
Strategies to identify young people at heightened risk of a psychotic disorder are described. Preventive interventions and results of their evaluation are provided.
Well-validated criteria for identifying young people at heightened risk of psychosis have been developed, evidence of the efficacy of various psychological and pharmacological interventions in preventing progression has accumulated and progress towards the identification of clinical and neurobiological predictors of transition to acute psychosis has been made.
The detection, monitoring and treatment of young people in the prepsychotic phase is a growth area in psychiatry. The ethical considerations about treatment options, treatment of minors and provision of information about risk status must be treated with sensitivity if the potential benefit to many young people and their families is to be realised.
Patients with psychosis have activation of the hypothalamic-pituitary-adrenal (HPA) axis during the acute phase of the psychosis. Whether this has any morphological consequences for the pituitary gland is currently unknown.
To examine pituitary volume variation in people at different stages of psychotic disorder.
Pituitary volume was measured using 1.5 mm, coronal magnetic resonance images in 24 people with first-episode psychosis, 51 with established schizophrenia and 59 healthy controls.
Compared with the control group, the people with first-episode psychosis had pituitary volumes that were 10% larger, whereas those with established schizophrenia had pituitary volumes that were 17% smaller. In both of the groups with psychosis, there was no difference in pituitary volume between those receiving typical antipsychotic drugs and those receiving atypical antipsychotics.
The first episode of a psychosis is associated with a larger pituitary volume, which we suggest is due to activation of the HPA axis. The smaller pituitary volume in the group with established schizophrenia could be the consequence of repeated episodes of HPA axis hyperactivity.
Background The identification of people at high risk of becoming psychotic within the near future creates opportunities for early intervention prior to the onset of psychosis to prevent or minimise later ill-health. The present study combines current knowledge about risk factors for schizophrenia with our knowledge of psychotic prodromes in an attempt to identify a group particularly vulnerable to impending psychosis. We wanted to identify people with high likelihood of transition to psychosis within a follow-up period of 12 months, and to determine the rate of transition to psychosis in this group.
Method Various state and trait risk factors for psychosis were used alone and in combination to operationally define a putatively high-risk group. Operationalised criteria for onset of psychosis were established. The individuals were assessed monthly on measures of psychopathology for six months.
Results Eight out of 20 people made the transition to frank psychosis within a six-month follow-up period. Follow-up of this group is still in progress, and the 12 month transition rate might prove to be higher still.
Conclusions We have demonstrated that it is possible to identify individuals with a high likelihood of onset of psychosis within a brief follow-up period. This lays the foundation for early treatment in an attempt to prevent, delay or minimise the severity of first onset of schizophrenia.
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