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Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR).
In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview.
At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment.
ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.
Persons at clinical high-risk for psychosis (CHR) are characterised by specific neurocognitive deficits. However, the course of neurocognitive performance during the prodromal period and over the onset of psychosis remains unclear. The aim of this meta-analysis was to synthesise results from follow-up studies of CHR individuals to examine longitudinal changes in neurocognitive performance. Three electronic databases were systematically searched to identify articles published up to 31 December 2021. Thirteen studies met inclusion criteria. Study effect sizes (Hedges' g) were calculated and pooled for each neurocognitive task using random-effects meta-analyses. We examined whether changes in performance between baseline and follow-up assessments differed between: (1) CHR and healthy control (HC) individuals, and (2) CHR who did (CHR-T) and did not transition to psychosis (CHR-NT). Meta-analyses found that HC individuals had greater improvements in performance over time compared to CHR for letter fluency (g = −0.32, p = 0.029) and digit span (g = −0.30, p = 0.011) tasks. Second, there were differences in longitudinal performance of CHR-T and CHR-NT in trail making test A (TMT-A) (g = 0.24, p = 0.014) and symbol coding (g = −0.51, p = 0.011). Whilst CHR-NT improved in performance on both tasks, CHR-T improved to a lesser extent in TMT-A and had worsened performance in symbol coding over time. Together, neurocognitive performance generally improved in all groups at follow-up. Yet, evidence suggested that improvements were less pronounced for an overall CHR group, and specifically for CHR-T, in processing speed tasks which may be a relevant domain for interventions aimed to enhance neurocognition in CHR populations.
Persistent negative symptoms are associated with worse outcome in both first-episode and chronic subjects with schizophrenia. The identification of these symptoms in recent-onset subjects is still controversial as retrospective data are often unavailable. The prospective assessment of persistence of negative symptoms might represent a valid alternative but the length of the persistence is still to be established. The present study investigated the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline in a large cohort of patients in the early stage of a schizophrenia-spectrum disorder, recruited to the OPTiMiSE trial. Persistent unconfounded negative symptoms were assessed at 4, 10 and 22 weeks of treatment. Symptomatic remission, attrition rate and psychosocial functioning was evaluated in subjects with short-term (4 weeks) persistent negative symptoms (PNS) and in those with negative symptoms that did not persist at follow-up and/or were confounded at baseline (N-PNS). Negative symptoms of moderate severity were observed in 59% of subjects at baseline and were associated to worse global functioning. PNS were observed in 7.9% of the cohort, unconfounded at both baseline and end of 4-week treatment. PNS subjects showed lower remission and higher attrition rates at the end of all treatment phases. Fifty-six percent of subjects completing phase 3 (clozapine treatment) had PNS, and 60% of them were non-remitters at the end of this phase. The presence of short-term PNS during the first phases of psychosis was associated with poor clinical outcome and resistance to antipsychotic treatment, including clozapine.
Prof Mucci has been a consultant and/or advisor to or has received honoraria from Gedeon Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer and Pierre Fabre.
Equipping our medical students with as many tools as possible to cope with the challenges that they will inevitably face has never been more important than it is today.
The aim of this study was to examine the effectiveness of a reflective practice (RP) group for medical students, particularly with adaptation to COVID-19 and transition to video.
A pilot programme of RP for 3rd year medical students commencing their clinical placement was run by the Sligo Medical Academy, NUIG in Ireland between January – April 2020. This group for nine students was initially run face-to-face but pivoted to an online group in March 2020 with the COVID-19 pandemic. Data was collected through one-to-one interviews with all student participants and the facilitator (n=10). Interviews were recorded and transcribed. Data were analysed using thematic content analysis.
Our analysis identified four main discussion themes: transition to clinical environment, gender in the workplace, building professional identity and family and support systems. The students who continued the RP group over zoom during the COVID-19 pandemic particularly identified with the theme of support systems and solidarity. The smooth transition to zoom and its effectiveness in a time of social distancing were discussed. Identified challenges related primarily to timing of the RP group, particularly after a full day of placements or time differences for international students overseas.
Reflective practice programmes are not routinely offered to medical students in Ireland currently and this study gives recommendations on implementing and improving experiences of undergraduate training based on RP.
Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis.
Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up.
The association of stress with positive (β = −0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = −2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506).
Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.
Suicide accounts for 2.2% of all years of life lost worldwide. We aimed to establish whether infectious epidemics are associated with any changes in the incidence of suicide or the period prevalence of self-harm, or thoughts of suicide or self-harm, with a secondary objective of establishing the frequency of these outcomes.
In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO and AMED were searched from inception to 9 September 2020. Studies of infectious epidemics reporting outcomes of (a) death by suicide, (b) self-harm or (c) thoughts of suicide or self-harm were identified. A random-effects model meta-analysis for the period prevalence of thoughts of suicide or self-harm was conducted.
In total, 1354 studies were screened with 57 meeting eligibility criteria, of which 7 described death by suicide, 9 by self-harm, and 45 thoughts of suicide or self-harm. The observation period ranged from 1910 to 2020 and included epidemics of Spanish Flu, severe acute respiratory syndrome, human monkeypox, Ebola virus disease and coronavirus disease 2019 (COVID-19). Regarding death by suicide, data with a clear longitudinal comparison group were available for only two epidemics: SARS in Hong Kong, finding an increase in suicides among the elderly, and COVID-19 in Japan, finding no change in suicides among children and adolescents. In terms of self-harm, five studies examined emergency department attendances in epidemic and non-epidemic periods, of which four found no difference and one showed a reduction during the epidemic. In studies of thoughts of suicide or self-harm, one large survey showed a substantial increase in period prevalence compared to non-epidemic periods, but smaller studies showed no difference. As a secondary objective, a meta-analysis of thoughts of suicide and self-harm found that the pooled prevalence was 8.0% overall (95% confidence interval (CI) 5.2–12.0%; 14 820 of 99 238 cases in 24 studies) over a time period of between seven days and six months. The quality assessment found 42 studies were of low quality, nine of moderate quality and six of high quality.
There is little robust evidence on the association of infectious epidemics with suicide, self-harm and thoughts of suicide or self-harm. There was an increase in suicides among the elderly in Hong Kong during SARS and no change in suicides among young people in Japan during COVID-19, but it is unclear how far these findings may be generalised. The development of up-to-date self-harm and suicide statistics to monitor the effect of the current pandemic is an urgent priority.
Psychosis is associated with a reasoning bias, which manifests as a tendency to ‘jump to conclusions’. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.
In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A ‘beads’ task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.
There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.
In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.
Altered neurocognitive function in schizophrenia could reflect both genetic and illness-specific effects.
To use functional magnetic resonance imaging to discriminate between the influences of the genetic risk for schizophrenia and environmental factors on the neural substrate of verbal fluency, a candidate schizophrenia endophenotype using a case control twin design.
We studied 23 monozygotic twin pairs: 13 pairs discordant for schizophrenia and 10 pairs of healthy volunteer twins. Groups were matched for age, gender, handedness, level of education, parental socio-economic status, and ethnicity. Behavioural performance and regional brain activation during a phonological verbal fluency task were assessed.
Relative to healthy control twins, both patients and their non-psychotic co-twins produced fewer correct responses and showed less activation in the medial temporal region and inferior frontal gyrus. Twins with schizophrenia showed greater activation than both their non-psychotic co-twins and controls in right lateral temporal cortex, reflecting reduced deactivation during word generation while their non-psychotic co-twins showed greater activation in the left temporal cortex.
Both genetic vulnerability to schizophrenia and schizophrenia were associated with impaired verbal fluency performance, reduced engagement of the medial temporal region and dorsal inferior frontal gyrus. Schizophrenia was specifically associated with an additional reduction in deactivation in the right temporal cortex.
DTI studies in schizophrenia have consistently reported decreased fractional anisotropy (FA, an index of white matter microstructure) in patients. There is little evidence as to the genetic or environmental determinants of this difference however. Studies of twins with schizophrenia allow us to estimate these influences. We report a cross-sectional case control study of twins with and without schizophrenia.
We recruited mono- and di-zygotic twins concordant and discordant for DSM schizophrenia from across the United Kingdom, referred by their treating psychiatrists. We recruited healthy control twins from the Institute of Psychiatry Volunteer Twin Register and by national media advertisements. Clinical diagnoses were confirmed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (Spitzer and Endicott, 1978). Zygosity was confirmed by DNA analysis. Eleven pairs of monozygotic twins concordant for schizophrenia, 10 pairs of monozygotic and seven pairs of dizygotic twins discordant for schizophrenia, 24 pairs of healthy monozygotic twins and 20 pairs of healthy dizygotic twins were recruited.
Subjects were scanned with an optimized DTI sequence at 1.5T. Scans were warp-corrected, masked, and FA calculated at each voxel. FA maps were then co-registered to a study-specific FA template using SPM2 and group differences calculated on segmented white-matter FA maps using non-parametric XBAM_v3.4.
Results are presented of analyses comparing twins with schizophrenia with their well co-twin, linear trend analyses comparing healthy controls with well di and mono-zygotic co-twins, and a heritability analysis of the healthy controls.
Cannabis is the world's most commonly used illicit substance. Whilst its effects on perception are well documented, little is known about the neural basis of these effects and how they are modulated by two of cannabis sativa's most abundant active ingredients, Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).
We used fMRI to assess the effects of THC and CBD on brain activation during a simple visual and auditory stimulation paradigm in healthy volunteers.
Fourteen right handed male subjects were scanned on 3 occasions. Identical 10mg THC, 600mg CBD and placebo capsules were allocated in a balanced double blinded pseudorandomised crossover design.
Ingestion of THC and CBD led to reliable increases in plasma levels of each substance and for THC concomitant increases in anxiety, intoxication and positive psychotic symptoms; CBD and placebo caused no significant symptoms. Visual and auditory stimulation led to robust activations in occipital and temporal cortices respectively under placebo conditions. Administration of THC led to decreased activation in primary sensory cortices relative to placebo whilst CBD led to an increase in activation in right temporal regions during auditory stimulation and right striate cortex activation during visual stimulation. THC mediated reduction of activation in this area during auditory stimulation correlated with a concomitant rise in psychotic symptoms.
These data indicate that the different psychoactive constituents of cannabis have dissociable effects on sensory processing, often in opposite directions
Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
Cannabis is the world's most widely used illicit drug. It can impair verbal learning and induce psychosis, both acutely and possibly following long term use. But, where cannabis acts in the brain to impair verbal learning and induce psychotic symptoms is unclear. The aim of this study was to clarify how one of the main psychoactive ingredients of cannabis, delta-9-tetrahydrocannabinol (THC) acts on the brain to impair verbal learning and induce psychotic symptoms.
15 healthy males with minimal exposure to cannabis, were studied on 2 occasions approximately 1 month apart, following oral administration of 10mg of THC or placebo 1 hour prior to scanning, in a double-blind design. MR images were acquired on a 1.5T GE camera while subjects performed a Verbal paired associates task with separate encoding followed by retrieval conditions, with the conditions repeated in the same sequence 4 times. We examined the main effects of drug, task and drug- task interactions.
Administration of THC abolished the normal linear decrement in parahippocampal activation across successive encoding blocks and was associated with a trend for impaired word recall. Administration of THC also altered the normal time-dependent change in ventral striatal activation during retrieval of word pairs which was directly correlated with concurrently induced psychotic symptoms.
These results suggest that impairment in learning and verbal memory associated with cannabis use may be mediated through its action in the medial temporal cortex while psychotic symptoms may be induced through its action in the ventral striatum.
Neuroimaging is one of the most promissing avenues for exploring psychiatric disorders in general and schizophrenia in particular both in terms of aetiology but also pathophysiology and treatment response.The aim of this workshop is to discuss possible avenues for Europe-wide collaborative research in neuroimaging and the implications it has for training and general infrastructure
The workshop leaders with discuss at their individual presentations the current vision for more uniform approach to neuroimaging across Europe, steps already taken towards it and plans for the future.
The organisers of the workshop hope that a consensus view will emerge to move neuroimaging research in schizophrenia into a Europe wide platform.
The future rests is collaborative large scale multicentre research.
Executive and mnemonic impairments have been well documented in the high-risk states for development of psychosis and have been pinpointed as a possible core neuropsychological dysfunction. However, their neurofunctional correlates are still not clear.
fMRI was used in 17 patients at risk for developing psychosis (ARMS, “at risk mental state”), 10 patients with a first episode of psychosis (FEP) and 15 age-matched healthy comparison subjects to examine neural responses to increasing difficulty of mnemonic engagement in an object–location paired associate memory task. Groups were matched in terms of age, IQ, gender, and psychopathology ratings. Accuracy and reaction time were recorded during the scan.
As the mnemonic load increased, response latency increased and response accuracy decreased in an approximately linear fashion. No main effect for group was observed. However, a trend towards decreased accuracy in FEP subjects, as compared with controls, was evident. As the task difficulty increased, increased brain activity was observed in the medial frontal cortex and in the medial posterior parietal cortex. Between-groups differences in activation were observed in a cluster spanning the MFG, SFG and SMA and in the right precuneus. However, these neurofunctional abnormalities were more evident in the most demanding level of the task than in the easy level, with the ARMS groups showing less activation than controls and higher activation than FEP.
Abnormal neural activity in medial frontal cortex and posterior parietal cortex during paired associate learning task may represent a neurofunctional substrates of vulnerability to psychosis.
Object working memory performance is abnormal in the early stages of schizophrenia. Such tasks recruit frontal and temporal cortices, possible sites of progressive change over the early illness course. We wanted to clarify if functional changes can be detected in the early stages of schizophrenia, to identify their anatomical location and their relationship to the stage of illness using a functional object working memory task in which the length of memory delay was manipulated.
40 subjects contributed: 10 first episode psychosis (FEp) patients, 16 with an at risk mental state (ARMS) and 14 healthy controls. We collected functional MRI data while the subjects performed a version of the delayed matching to sample (DMTS) task from the Cambridge Automated Neuropsychological Test Battery (CANTAB).
Behaviourally there was a trend to a group by delay interaction, the two patient groups making more errors at longer memory delays. At successful recognition a main effect of group was detected in the medial temporal lobe bilaterally, while a main effect of delay was detected in the left medial temporal lobe. At each length of memory delay the patient groups showed consistently greater activation of medial temporal regions when performing the task accurately.
Both ARMS & FEp groups showed greater activation than controls in the medial temporal cortex across all lengths of memory delay. These differences were not related to poorer task performance, but suggest an inefficiency mechanism that may correlate with the vulnerability to psychosis rather than pychosis per se.
There is considerable interest in the therapeutic potential of Cannabidiol (CBD), the second most abundant component of Cannabis. While delta-9-THC, the main psychoactive ingredient of cannabis, impairs memory and induces anxiety and psychotic symptoms acutely and increases the risk of psychotic disorders in regular cannabis users, CBD does not impair memory, may have anxiolytic and possibly antipsychotic effects. Hence, we compared directly the acute neural effects of these two active ingredients of cannabis, by combining pharmacological challenge with fMRI. Using a double-blind, repeated measures design and oral challenge with 10mg of delta-9-THC, 600mg of CBD or placebo in 15 healthy volunteers, we examined whether delta-9-THC and CBD have opposing effects on the neural substrates of verbal memory and fear processing and whether they also have opposing effects on the neural substrates of anxiety and psychotic symptoms induced by delta-9-THC. Delta-9-THC induced anxiety and psychotic symptoms acutely while there was a trend for a reduction in anxiety but no change in psychotic symptoms with CBD. During the memory task, delta-9-THC attenuated and CBD increased activation in the striatum bilaterally. Effect of delta-9-THC on striatal activation was inversely correlated with the psychotic symptoms induced by it concomitantly. During the processing of fearful faces, delta-9-THC increased and CBD attenuated activation in the amygdala and these effects correlated with their anxiogenic and anxiolytic effects respectively. These opposing effects of CBD on the key neural substrates for psychotic symptoms and anxiety induced by delta-9-THC may suggest its possible therapeutic role in countering these conditions.