IMPORTANCE Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems ...in mediating risk for psychosis have been contentious. OBJECTIVE To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives. DESIGN, SETTING, AND PARTICIPANTS This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study. MAIN OUTCOMES AND MEASURES Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions. RESULTS Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms. CONCLUSIONS AND RELEVANCE First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they represent a putative risk phenotype for psychotic illness.
Future-directed thinking (FDT) is associated with goal directed behaviour and may differ in people with psychosis compared to non-clinical controls. This study investigated whether guided imagery ...could enhance positive FDT in people with psychosis.
Participants were 44 people experiencing a first episode of psychosis. They were assessed for negative and positive symptoms, FDT on the Future Thinking Task (FTT), depression, anxiety, autobiographical memory, verbal fluency and spontaneous use of imagery. They were randomised to either a positive or neutral imagery condition, before being retested on the FTT. Outcomes on the FTT were number of events generated, anticipated likelihood, anticipated affect and a composite score.
Participants in the positive imagery condition generated significantly more positive events on the FTT compared with those in the neutral (F (1, 42) = 19.916, p < .001, ηp2 = 0.322). In both imagery conditions, likelihood ratings of positive events increased post-intervention. Positive and negative events were both perceived as less likely to occur the further into the future they were, and positive events were anticipated to be more positive and negative events more negative, the further into the future they were.
The participants in this study experienced relatively low levels of symptoms, and therefore caution should be used when applying these results to people with greater symptomatology.
Positive guided imagery shows promise for enhancing positive FDT in people with first-episode psychosis. This intervention may offer a simple and effective method of enhancing engagement with the future, with potential implications for goal-directed behaviour.
•Positive imagery increased the number of positive future events generated.•Imagery interventions increased the perceived likelihood of positive future events.•Future events seemed less likely with increasing temporal distance.•Future events seemed more positive or negative with increasing temporal distance.•Improving future-directed thinking may improve goal-directed behaviour.
Objectives
This study employed the Future Thinking Task (MacLeod et al., 2005, Br. J. Clin. Psychol., 44, 495) to investigate whether future‐directed thinking in first‐episode psychosis is ...significantly different from that of matched controls, and to identify its correlates in this patient group.
Design
Cross‐sectional, mixed‐model, case–control design.
Method
Participants were 30 patients with first‐episode psychosis and 27 matched controls. The Future Thinking Task was used to assess future‐directed thinking in both groups. Anxiety and depression were also measured as well as self‐report measures of hopelessness, suicide ideation and a measure of negative symptoms.
Results
Individuals with psychosis were impaired in future‐directed thinking in both positive and negative domains, particularly with respect to the coming year. Increased self‐reported hopelessness was associated with reduced positive future thinking and increased negative future thinking. Increased positive future thinking was also associated with reduced severity of negative symptoms, whilst negative future thinking was associated with suicide ideation.
Conclusions
Individuals with first‐episode psychosis show a reduction in positive future thinking in line with that seen in other clinical groups, but this is accompanied by an unexpected reduction in negative future thinking. The findings suggest a general disengagement with the future in this group that may affect recovery and functioning.
Practitioner points
Individuals with first‐episode psychosis may benefit from interventions to help them engage with their future, in particular in the mid‐range, up to 1 year.
The Future Thinking Task may be a helpful addition to the assessment of suicide risk in those with first‐episode psychosis.
Decreased positive future thinking was associated with increased severity of negative symptoms, indicating a potential new treatment angle for this resistant aspect of psychosis.
The cross‐sectional design of this study does not allow for conclusions about the causal relationship between psychosis and future‐directed thinking.
This study investigated future‐directed thinking in individuals with a range of psychotic illnesses employing a trans‐diagnostic approach; therefore, conclusions cannot be drawn about the nature of future‐directed thinking in individual psychotic disorders.
Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. ...The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy CBT and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis.
We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14–18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433.
Of 101 patients referred to the study, 61 patients (mean age 16·3 years SD 1·3) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 84% participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 82% of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 65% of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight 35% of 23 patients in the combined group, two 13% of 15 in the antipsychotics group, four 24% of 17 in the psychological intervention group, and four 80% of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial.
This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence.
National Institute for Health Research.
Psychosis encompasses a constellation of symptoms that have far-reaching social, physical and functional consequences for sufferers. One of the key clinical concerns in the management of psychotic ...illnesses is the risk of suicide, which is greatest in the early stages of psychosis. Hopelessness is consistently associated with risk for suicide but as a concept it is not well defined and is not specific enough to be of use in prediction of suicide. Future-directed thinking, particularly regarding positive future events, constitutes an aspect of hopelessness that is closely associated with risk for suicide. This study employed the Future Thinking Task to investigate whether future-directed thinking in first episode psychosis is significantly different from that of matched controls in performance or content, and to clarify the nature of its association with suicide risk in this patient group. In addition, the association of future-directed thinking with the negative symptoms of psychosis was investigated. The results showed that individuals with psychosis were impaired in future-directed thinking globally, particularly with respect to the coming year. Specific deficits were shown in the domains of relations with other people and personal development and understanding. Associations were shown between future-directed thinking and suicide, and reduced positive future-directed thinking was shown to be strongly associated with increased severity of negative symptoms. The results suggest avenues for novel interventions to improve hopelessness, suicide risk and the severity of negative symptoms in psychotic illness, and thereby improve functional outcomes.
Psychosis encompasses a constellation of symptoms that have far-reaching social, physical and functional consequences for sufferers. One of the key clinical concerns in the management of psychotic ...illnesses is the risk of suicide, which is greatest in the early stages of psychosis. Hopelessness is consistently associated with risk for suicide but as a concept it is not well defined and is not specific enough to be of use in prediction of suicide. Future-directed thinking, particularly regarding positive future events, constitutes an aspect of hopelessness that is closely associated with risk for suicide. This study employed the Future Thinking Task to investigate whether future-directed thinking in first episode psychosis is significantly different from that of matched controls in performance or content, and to clarify the nature of its association with suicide risk in this patient group. In addition, the association of future-directed thinking with the negative symptoms of psychosis was investigated. The results showed that individuals with psychosis were impaired in future-directed thinking globally, particularly with respect to the coming year. Specific deficits were shown in the domains of relations with other people and personal development and understanding. Associations were shown between future-directed thinking and suicide, and reduced positive future-directed thinking was shown to be strongly associated with increased severity of negative symptoms. The results suggest avenues for novel interventions to improve hopelessness, suicide risk and the severity of negative symptoms in psychotic illness, and thereby improve functional outcomes.
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