Key Elements of a Family Intervention for Schizophrenia: A Qualitative Analysis of an RCT.

Schizophrenia is a complex biopsychosocial condition in which expressed emotion in family members is a robust predictor of relapse. Not surprisingly, family interventions are remarkably effective and thus recommended in current treatment guidelines. Their key elements seem to be common therapeutic factors, followed by education and coping skills training. However, few studies have explored these key elements and the process of the intervention itself. We conducted a qualitative and quantitative analysis of the records from a pioneering family intervention trial addressing expressed emotion, published by Leff and colleagues four decades ago. Records were analyzed into categories and data explored using descriptive statistics. This was complemented by a narrative evaluation using an inductive approach based on emotional markers and markers of change. The most used strategies in the intervention were addressing needs, followed by coping skills enhancement, advice, and emotional support. Dealing with overinvolvement and reframing were the next most frequent. Single-family home sessions seemed to augment the therapeutic work conducted in family groups. Overall the intervention seemed to promote cognitive and emotional change in the participants, and therapists were sensitive to the emotional trajectory of each subject. On the basis of our findings, we developed a longitudinal framework for better understanding the process of this treatment approach.

What do We Know about Family Interventions for Psychosis at the Process Level? A Systematic Review.

The evidence regarding effectiveness of family interventions for psychosis (FIP) is strong and consistent. However, there is a gap in the research on the process of these interventions, and little is known about their active ingredients. This review aims to identify the active ingredients of FIP. We conducted a systematic literature review, focusing on qualitative research, and analyzed 22 papers in total. We found a single study comprehensively exploring the process of FIP. All other studies focused on particular aspects of process-related variables. The key elements of FIP seem to be the so-called "common therapeutic factors", followed by education about the illness and coping skills training. This review supports the value of a stepped model of intervention according to the needs of the families. However, the evidence reviewed also reveals a gap in the research findings based on the limited research available. FIP are complex, psychosocial interventions with multiple components, and more intensive, qualitative research is needed to establish linkages between process and outcome.

Computer-assisted therapy for medication-resistant auditory hallucinations: proof-of-concept study.

BACKGROUND: One in four patients with schizophrenia responds poorly to antipsychotic medication, continuing to hear persecutory auditory hallucinations. Patients who are able to sustain a dialogue with their persecutor feel much more in control. AIMS: To develop a computerised system that enables the patient to create an avatar of their persecutor. To encourage them to engage in a dialogue with the avatar, which the therapist is able to control so that the avatar progressively yields control to the patient. METHOD: Avatar therapy was evaluated by a randomised, single blind, partial crossover trial comparing the novel therapy with treatment as usual (TAU). We used three main outcome measures: (a) the Psychotic Symptom Rating Scale (PSYRATS), hallucinations section; (b) the Omnipotence and Malevolence subscales of the Revised Beliefs About Voices Questionnaire (BAVQ-R); and (c) the Calgary Depression Scale (CDS). RESULTS: The control group showed no change over time in their scores on the three assessments, whereas the novel therapy group showed mean reductions in the total PSYRATS score (auditory hallucinations) of 8.75 (P = 0.003) and in the BAVQ-R combined score of omnipotence and malevolence of the voices of 5.88 (P = 0.004). There was no significant reduction in the CDS total score for depression. For the crossover control group, comparison of the period of TAU with the period of avatar therapy confirmed the findings of the previous analysis. The effect size of the therapy was 0.8. CONCLUSIONS: Avatar therapy represents a promising treatment for medication-resistant auditory hallucinations. Replication with a larger sample is required before roll-out to clinical settings.

Assessment of posttraumatic symptoms in patients with first-episode psychosis.

Posttraumatic stress disorder is common among patients with psychotic disorders. The present study examined the internal reliability and comparability of the Impact of Event Scale (IES) in a sample of 38 patients with first-episode psychosis and 47 controls exposed to severe physical and/or sexual abuse. The IES total score and both subscales showed high internal consistency in both groups (Cronbach's alpha coefficients of approximately 0.9 or higher). Given their equivalent trauma reporting, the lack of differences in IES scores between patients and controls seems to indicate that patients are likely to report accurately and neither exaggerate nor minimize their posttraumatic symptoms. Overall, the findings suggest that the IES can be used to assess symptoms of posttraumatic stress in patients with psychotic disorders as in other populations.

Insight, grey matter and cognitive function in first-onset psychosis.

BACKGROUND: Several studies have suggested that neuropsychological and structural brain deficits are implicated in poor insight. Few insight studies however have combined neurocognitive and structural neuroanatomical measures. AIMS: Focusing on the ability to relabel psychotic symptoms as pathological, we examined insight, brain structure and neurocognition in first-onset psychosis. METHOD: Voxel-based magnetic resonance imaging data were acquired from 82 individuals with psychosis and 91 controls assessed with a brief neuropsychological test battery. Insight was measured using the Schedule for the Assessment of Insight. RESULTS: The principal analysis showed reduced general neuropsychological function was linked to poor symptom relabelling ability. A subsequent between-psychosis group analysis found those with no symptom relabelling ability had significant global and regional grey matter deficits primarily located at the posterior cingulate gyrus and right precuneus/cuneus. CONCLUSIONS: The cingulate gyrus (as part of a midline cortical system) along with right hemisphere regions may be involved in illness and symptom self-appraisal in first-onset psychosis.

Gender differences in the association between childhood abuse and psychosis.

BACKGROUND: Studies demonstrating an association between childhood trauma and psychosis in adulthood have not systematically explored gender differences. AIMS: To investigate gender differences in the prevalence of childhood sexual and physical abuse among people with psychosis in comparison with healthy controls. METHOD: The Childhood Experiences of Care and Abuse Questionnaire was completed to elicit experiences of sexual and physical abuse during childhood in first-episode psychosis cases and population-based controls. RESULTS: Among women, those in the cases group were twice as likely to report either physical or sexual abuse compared with controls following adjustment for all confounders. In particular, the effect of physical abuse in women was stronger and more robust than that for sexual abuse. A similar trend was found for psychotic-like experiences in the female control group. No association was found in men. CONCLUSIONS: Reports of severe childhood physical or sexual abuse were associated with psychosis in women but not in men.

The lessons I learned as a psychiatrist from my transcultural work in low- and middle-income countries.

Transcultural observations offer an opportunity to study attitude to mental illness in different societies and family structures. The disparity between industrialised and lower-income societies reflects greater tolerance due to the ability of extended families to compensate for the patient's limitations.

Sexually dimorphic changes in the amygdala in relation to delusional beliefs in first episode psychosis.

BACKGROUND: Few attempts have been made to examine the relationship between amygdala abnormalities and specific symptoms in psychosis. The present study explored the relationship between amygdala morphology and mood congruent and mood incongruent delusional beliefs. METHODS: Amygdala volumes were measured in 43 patients presenting with delusional beliefs in the context of their first episode of psychosis and 43 healthy volunteers matched for age and gender. RESULTS: Left-greater-than-right-asymmetry of the amygdala varied as a function of gender and mood congruence of delusional beliefs, due to asymmetrical enlargement of the left amygdala in women presenting with predominantly mood incongruent delusions. However, there was no difference in amygdala volumes across groups. CONCLUSIONS: Amygdala abnormalities in women may be associated with aberrant emotional processing that could contribute to the development of mood incongruent delusional beliefs. Sexually dimorphic changes in the amygdala may contribute to differential phenotypic illness expression in men and women.

AVATAR therapy for auditory verbal hallucinations in people with psychosis: a single-blind, randomised controlled trial.

BACKGROUND: A quarter of people with psychotic conditions experience persistent auditory verbal hallucinations, despite treatment. AVATAR therapy (invented by Julian Leff in 2008) is a new approach in which people who hear voices have a dialogue with a digital representation (avatar) of their presumed persecutor, voiced by the therapist so that the avatar responds by becoming less hostile and concedes power over the course of therapy. We aimed to investigate the effect of AVATAR therapy on auditory verbal hallucinations, compared with a supportive counselling control condition. METHODS: We did this single-blind, randomised controlled trial at a single clinical location (South London and Maudsley NHS Trust). Participants were aged 18 to 65 years, had a clinical diagnosis of a schizophrenia spectrum (ICD10 F20-29) or affective disorder (F30-39 with psychotic symptoms), and had enduring auditory verbal hallucinations during the previous 12 months, despite continued treatment. Participants were randomly assigned (1:1) to receive AVATAR therapy or supportive counselling with randomised permuted blocks (block size randomly varying between two and six). Assessments were done at baseline, 12 weeks, and 24 weeks, by research assessors who were masked to therapy allocation. The primary outcome was reduction in auditory verbal hallucinations at 12 weeks, measured by total score on the Psychotic Symptoms Rating Scales Auditory Hallucinations (PSYRATS-AH). Analysis was by intention-to-treat with linear mixed models. The trial was prospectively registered with the ISRCTN registry, number 65314790. FINDINGS: Between Nov 1, 2013, and Jan 28, 2016, 394 people were referred to the study, of whom 369 were assessed for eligibility. Of these people, 150 were eligible and were randomly assigned to receive either AVATAR therapy (n=75) or supportive counselling (n=75). 124 (83%) met the primary outcome. The reduction in PSYRATS-AH total score at 12 weeks was significantly greater for AVATAR therapy than for supportive counselling (mean difference -3·82 [SE 1·47], 95% CI -6·70 to -0·94; p<0·0093). There was no evidence of any adverse events attributable to either therapy. INTERPRETATION: To our knowledge, this is the first powered, randomised controlled trial of AVATAR therapy. This brief, targeted therapy was more effective after 12 weeks of treatment than was supportive counselling in reducing the severity of persistent auditory verbal hallucinations, with a large effect size. Future multi-centre studies are needed to establish the effectiveness of AVATAR therapy and, if proven effective, we think it should become an option in the psychological treatment of auditory verbal hallucinations. FUNDING: Wellcome Trust.

Duration of untreated psychosis and neuropsychological function in first episode psychosis.

PURPOSE: We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD: 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS: Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS: Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study.

CONTEXT: Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE: To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN: Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING: Southeast London, Nottingham, and Bristol, England. PARTICIPANTS: One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES: The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis. RESULTS: All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS: There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Duration of prodromal phase and severity of volumetric abnormalities in first-episode psychosis.

BACKGROUND: First-episode psychosis is typically preceded by a prodrome in which there is deterioration in global and social functioning. AIMS: To examine whether the duration of the prodromal phase influences grey and white matter volumes at the onset of psychosis. METHODS: Eighty-two people were scanned using magnetic resonance imaging when they developed a first episode of psychosis. The duration of the prodromal phase was estimated from detailed interviews and medical records. Voxel-based morphometry was used to assess neuroanatomical abnormalities. RESULTS: A long prodromal phase was associated with smaller grey matter volumes in the cingulate, frontal and left insular cortex, and with less white matter volume bilaterally in the superior longitudinal and uncinate fasciculi and the cingulum. CONCLUSIONS: The severity of volumetric abnormalities in first-episode psychosis was greater in those with a long prodrome.

Grey matter abnormalities in first-episode schizophrenia and affective psychosis.

BACKGROUND: Grey matter and other structural brain abnormalities are consistently reported in first-onset schizophrenia, but less is known about the extent of neuroanatomical changes in first-onset affective psychosis. AIMS: To determine which brain abnormalities are specific to (a) schizophrenia and (b) affective psychosis. METHOD: We obtained dual-echo (proton density/T2-weighted) magnetic resonance images and carried out voxel-based analysis on the images of 73 patients with first-episode psychosis (schizophrenia n=44, affective psychosis n=29) and 58 healthy controls. RESULTS: Both patients with schizophrenia and patients with affective psychosis had enlarged lateral and third ventricle volumes. Regional cortical grey matter reductions (including bilateral anterior cingulate gyrus, left insula and left fusiform gyrus) were evident in affective psychosis but not in schizophrenia, although patients with schizophrenia displayed decreased hippocampal grey matter and increased striatal grey matter at a more liberal statistical threshold. CONCLUSIONS: Both schizophrenia and affective psychosis are associated with volumetric abnormalities at the onset of frank psychosis, with some of these evident in common brain areas.

The most important things I have learnt in my career as a psychiatrist.

This paper is something of a patchwork, incorporating many issues that have intrigued me during 34 years of research. I have included the importance of maintaining a solid base in clinical work, alongside research activities, and being alert to the possibility of a somatic condition contributing to psychiatric symptoms. I stress the value of careful observation of patients, their response to treatments and reasons for dropping out. In addition, I have included 14 more lessons, learned from my experience of research, which I hope will be of use to those readers who aspire to become researchers.

Gray matter abnormalities associated with duration of untreated psychosis.

PURPOSE: A long duration of untreated psychosis (DUP) is associated with relatively poor clinical and social outcomes. In order to identify whether an anatomically mediated mechanism may give rise to poorer outcomes, it is important to identify whether a long DUP is associated with greater brain structural abnormalities. METHOD: 81 patients with first-episode psychosis (schizophrenia, affective, and other psychoses) were scanned using high resolution Magnetic Resonance Imaging. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with mental health services. High-resolution MRI images and voxel-based methods of image analysis were used to investigate brain structure in these patients. RESULTS: Longer DUP was associated with gray matter reductions in left middle and inferior temporal, left occipital and left fusiform cortices, and with gray matter excess of the left basal ganglia. All findings remained significant when co-varying for exposure to antipsychotic treatment. CONCLUSIONS: Temporal gray matter reductions are more marked in patients with a long DUP. This could reflect a progressive pathological process that is active prior to treatment. Alternatively, these abnormalities could be associated with a more insidious onset of illness and a later presentation to services.

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study.

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p< 0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study.

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

Outcomes for long-term patients one year after discharge from a psychiatric hospital.

OBJECTIVES: The purpose of this study was to evaluate effects associated with moving patients from hospital to community-based settings, to compare persons who left the hospital with those who remained in the hospital, and to address the question of whether discharge reverses institutionalism in a sample of elderly long-stay psychiatric inpatients. METHODS: The hypotheses were that, compared with the control group of patients who stayed in the hospital, those who left would have significantly better mental states, social functioning, and social networks at follow-up; that community settings would provide a significantly better quality of environment than the hospital; and that discharged patients would express a preference for community care after discharge from the hospital. The study was a prospective nonrandomized controlled trial at Cane Hill, Friern, and Claybury Hospitals in England. Sixty long-term patients with schizophrenia who were discharged to community care were compared over time with matched controls (N=131). RESULTS: No overall differences were detected in the pattern or severity of symptoms between patients who were discharged from the hospital and those who were not, and no significant changes over time were noted. Significant improvements in social networks, patients' preference for community settings, and quality of clinical environment were noted. CONCLUSIONS: These results give qualified support for moving long-stay psychiatric patients from hospital to community settings.

Confronting Auditory Hallucinations Using Virtual Reality: The Avatar Therapy.

The AVATAR therapy is a computer-based intervention which aims to reduce the frequency and severity of voices. The approach is based on computer technology which enables each patient to create an avatar of the entity (human or non-human) that they believe is talking to them. The therapist promotes a dialogue between the patient and the avatar in which the avatar progressively comes under the patient's control. Using real-time voice conversion delivery software, the therapist can modify the relationship between the patient and his/her voice. The innovation of this new intervention is discussed in the present paper as well as the advantages of using a computer based system. The subjective view of the technology from a participant's point of view is also presented.