Characterizing the experience of auditory verbal hallucinations and accompanying delusions in individuals with a diagnosis of bipolar disorder: A systematic review.

OBJECTIVES: The aim of the current study was to inform ongoing attempts to identify clinically meaningful subcategories of auditory verbal hallucination (AVH), and to evaluate evidence that might pertain to the suitability of current psychological interventions for people with bipolar disorder (BD) who experience psychotic symptoms. METHODS: A comprehensive synthesis of findings on the phenomenology of AVH and delusions in BD is included, alongside a critical review of clinical and cognitive correlates. Studies published in the previous 20 years, until December 2016, were retrieved from the following databases: Embase, CINAHL, MEDLINE, PsycINFO and Web of Science. Thirty-two articles were reviewed after applying a set of predetermined inclusion criteria. RESULTS: Psychotic symptoms were common in both manic and depressive phases, although higher frequencies were indicated in mania. Few detailed characterizations of AVH phenomenology were identified. Delusions with persecutory, grandiose and referential themes were the most common in BD. AVHs were associated with delusions and there was evidence to suggest that delusion subtype may vary according to mood state and type of AVH. Data on clinical correlates of AVH in BD were sparse. However, the results indicated that cognitive appraisals or interpretations of voices might be different in BD from those established to be predictive of clinical outcomes in schizophrenia spectrum disorders. CONCLUSIONS: Clear gaps exist in our current understanding of the first-person experience of AVH in BD and the potential relationship to co-occurring symptoms, including delusions. Further research into cognitive interpretations of AVH in BD might inform adapted psychological interventions for psychotic symptoms in this population.

Misattributing speech and jumping to conclusions: a longitudinal study in people at high risk of psychosis.

Biases in cognition such as Jumping to Conclusions (JTC) and Verbal Self-Monitoring (VSM) are thought to underlie the formation of psychotic symptoms. This prospective study in people with an At Risk Mental State (ARMS) for psychosis examined how these cognitive biases changed over time, and predicted clinical and functional outcomes. Twenty-three participants were assessed at clinical presentation and a mean of 31 months later. Performance on a JTC and VSM tasks were measured at both time points. Relationships to symptom severity, level of function and the incidence of psychotic disorder were then examined. The levels of symptoms, function and VSM all improved over time, while JTC was stable. Five participants (22%) developed a psychotic disorder during the follow-up period, but the risk of transition was not related to performance on either task at baseline, or to longitudinal changes in task performance. JTC performance correlated with symptom severity at baseline and follow-up. Similarly, performance on the two tasks was not related to the level of functioning at follow-up. Thus, while the ARMS is associated with both VSM and JTC biases, neither predict the onset of psychosis or the overall functional outcome.

Delusional ideation, manic symptomatology and working memory in a cohort at clinical high-risk for psychosis: a longitudinal study.

We followed up a cohort (n=35) of clients with an "At Risk Mental State" (ARMS) for almost 2 years (mean 21.3 months). At baseline, these clients had taken part in research looking at the relationship between reasoning biases, memory, personality styles and delusional ideation. During the follow-up period, clients underwent a package of intervention from a specialist early detection team. Eighty percent (n=28) of these clients were successfully re-interviewed. There was improvement across the cohort as a whole, however five participants (17.9%) had made the transition to psychosis at follow-up. Those who had become psychotic had lower levels of manic symptomatology at baseline than those who did not enter the first episode. Further, across the cohort, impaired working memory and delusional ideation at baseline combined to predict 45% of the delusional ideation at follow-up. These preliminary findings suggest that working memory impairments may be linked to the persistence of delusional ideation and that manic symptoms in someone with an ARMS may suggest that such an individual is less likely to develop a frank psychotic episode.

Prefrontal function at presentation directly related to clinical outcome in people at ultrahigh risk of psychosis.

BACKGROUND: The prodromal phase of psychosis is characterized by impaired executive function and altered prefrontal activation. The extent to which the severity of these deficits at presentation predicts subsequent clinical outcomes is unclear. METHODS: We employed functional magnetic resonance imaging in a cohort of subjects at clinical risk for psychosis and in healthy controls. Images were acquired at clinical presentation and again after 1 year, using a 1.5-T Signa MRI scanner while subjects were performing a verbal fluency task. SPM5 was used for the analysis of imaging data. Psychopathological assessment of the "at-risk" symptoms was performed by using the Comprehensive Assessment for the At-Risk Mental State (CAARMS) and the Positive and Negative Symptom Scale (PANSS). RESULTS: In the at-risk mental state (ARMS) group, between presentation and follow-up, the CAARMS (perceptual disorder and thought disorder subscales) and the PANSS general scores decreased, while the Global Assessment of Functioning (GAF) score increased. Both the ARMS and control groups performed the verbal fluency task with a high degree of accuracy. The ARMS group showed greater activation in the left inferior frontal gyrus but less activation in the anterior cingulate gyrus than controls. Within the ARMS group, the longitudinal normalization of neurofunctional response in the left inferior frontal gyrus was positively correlated with the improvement in severity of hallucination-like experiences. CONCLUSIONS: The normalization of the abnormal prefrontal response during executive functioning is associated with 12-month psychopathological improvement of prodromal symptoms.

Altered brain function directly related to structural abnormalities in people at ultra high risk of psychosis: longitudinal VBM-fMRI study.

BACKGROUND: Several studies have indicated that people with prodromal signs of psychosis show alterations in the structure and function of the brain when they first present to clinical services. However, the longitudinal course of these abnormalities, and how they relate to subsequent clinical and functional outcome is relatively unclear. METHODS: A cohort of subjects at ultra high risk of psychosis were studied using functional magnetic resonance imaging (fMRI) in conjunction with the N-Back task, and volumetric MRI at first clinical presentation and again after one year. Levels of psychopathology and global functioning were assessed at the same time points using the CAARMS, PANSS, and the GAF scale. RESULTS: At baseline, the high risk group showed reduced activation during the task in the left middle frontal gyrus, supramarginal gyrus and inferior parietal lobule, and reduced gray matter volume in the left middle and medial frontal gyri, left insula and the right anterior cingulate gyrus. Within the high-risk group, there was a positive correlation between the magnitude of the functional and structural alterations in the left middle frontal gyrus. Between presentation and follow up, the severity of perceptual disorder and thought disorder (rated by the CAARMS), and of general psychopathology (rated by the PANSS general score) decreased, and the level of global functioning improved. This clinical and functional improvement was associated with a longitudinal increase in activation in the anterior cingulate and right parahippocampal gyrus. The change in anterior cingulate response was directly correlated with the improvement in the GAF score. CONCLUSIONS: In subjects presenting with prodromal signs of psychosis, reduced prefrontal activation during a working memory task is associated with a reduction in gray matter volume in the same area. Changes in anterior cingulate activation were correlated with functional improvement in this group, consistent with the role of this region in multiple cognitive and social processes.

Spatial working memory in individuals at high risk for psychosis: longitudinal fMRI study.

BACKGROUND: Neurocognitive impairments in executive and mnemonic domains are already evident in the pre-psychotic phases. The longitudinal dynamic course of the neurofunctional abnormalities underlying liability to psychosis and their relation to clinical outcomes is unknown. METHODS: In this study we used functional magnetic resonance imaging (fMRI) in a cohort of subjects at ultra high clinical risk for psychosis (with an "At Risk Mental State", ARMS) and in healthy controls. Images were acquired at baseline and again after one year on a 1.5 Tesla Signa, while patients were performing a visuospatial working memory task. Psychopathological assessment of the prodromal symptoms was conducted at the same time points by using the CAARMS and the PANSS instruments. RESULTS: There were no significant differences between the ARMS and control groups with respect to age or IQ. Although both groups performed the PAL task with a high degree of accuracy, the ARMS showed an increased latency in answers during the most demanding level of the task. At baseline, such cognitive impairment was associated with reduced activation in the left precuneus, left superior parietal lobule, right middle temporal gyrus in the ARMS as compared to controls. In addition, the ARMS failed to activate parietal areas with increasing difficulty of the task. Between presentation and follow-up the overall clinical status of the ARMS sample improved, despite 2 out of the 15 subjects having developed a full-blown psychosis: the CAARMS (perceptual disorder and thought disorder subscales) and the PANNS general scores decreased, while the GAF score increased. Such clinical amelioration was associated with a longitudinal compensatory increase in occipitoparietal regions. CONCLUSIONS: The prodromal phase of psychosis is associated with functional alterations in parietal and temporal networks subserving visuospatial working memory which are more evident under high cognitive loads. The clinical improvement at one year is associated with a compensatory increase in occipitoparietal regions.

Neural correlates of visuospatial working memory in the 'at-risk mental state'.

BACKGROUND: Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. METHOD: fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age-matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. RESULTS: In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. CONCLUSIONS: Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis.

Neural correlates of movement generation in the 'at-risk mental state'.

OBJECTIVE: People with 'prodromal' symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at-risk mental state (ARMS) while they performed a random movement generation task. METHOD: Cross-sectional comparison of individuals with an ARMS (n = 17), patients with first episode schizophreniform psychosis (n = 10) and healthy volunteers (n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm. RESULTS: During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group. CONCLUSION: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe.

Impaired verbal self-monitoring in individuals at high risk of psychosis.

BACKGROUND: Cognitive models suggest that auditory verbal hallucinations arise through defective self-monitoring and the external attribution of inner speech. We used a paradigm that engages verbal self-monitoring (VSM) to examine whether this process is impaired in people experiencing prodromal symptoms, who have a very high risk of developing psychosis. METHOD: We tested 31 individuals with an At-Risk Mental State (ARMS) and 31 healthy volunteers. Participants read single adjectives aloud while the source and pitch of the online auditory verbal feedback was manipulated, then immediately identified the source of the speech they heard (Self/Other/Unsure). Response choice and reaction time were recorded. RESULTS: When reading aloud with distorted feedback of their own voice, ARMS participants made more errors than controls (misidentifications and unsure responses). ARMS participants misidentified the source of their speech as 'Other' when the level of acoustic distortion was severe, and misidentification errors were inversely related to reaction times. CONCLUSIONS: Impaired VSM is evident in people with an ARMS, although the deficit seems to be less marked than in patients with schizophrenia. Follow-up of these participants may clarify the extent to which the severity of this impairment predicts the subsequent onset of psychosis and development of positive symptoms.

Economic impact of early intervention in people at high risk of psychosis.

BACKGROUND: Despite the increasing development of early intervention services for psychosis, little is known about their cost-effectiveness. We assessed the cost-effectiveness of Outreach and Support in South London (OASIS), a service for people with an at-risk mental state (ARMS) for psychosis. METHOD: The costs of OASIS compared to care as usual (CAU) were entered in a decision model and examined for 12- and 24-month periods, using the duration of untreated psychosis (DUP) and rate of transition to psychosis as key parameters. The costs were calculated on the basis of services used following referral and the impact on employment. Sensitivity analysis was used to test the robustness of all the assumptions made in the model. RESULTS: Over the initial 12 months from presentation, the costs of the OASIS intervention were pound1872 higher than CAU. However, after 24 months they were pound961 less than CAU. CONCLUSIONS: This model suggests that services that permit early detection of people at high risk of psychosis may be cost saving.

The role of metacognitive beliefs in determining the impact of anomalous experiences: a comparison of help-seeking and non-help-seeking groups of people experiencing psychotic-like anomalies.

BACKGROUND: Current psychological models of psychotic symptoms suggest that metacognitive beliefs impact on an individual's appraisal of anomalous experiences, and thereby influence whether these lead to distress and become clinical symptoms. This study examined the relationship between maladaptive metacognitive beliefs, anomalous experiences, anomaly-related distress, anxiety and depression and diagnostic status. METHOD: The Metacognitions Questionnaire (MCQ), Symptom Checklist 90 - Revised, and Appraisals of Anomalous Experiences interview were administered to 27 people diagnosed with a psychotic disorder, 32 people meeting At Risk Mental State (ARMS) criteria, 24 people with psychotic-like experiences but no need for care, and 32 healthy volunteers. RESULTS: The two clinical groups scored higher than non-patient controls and individuals experiencing psychotic-like anomalies with no need for care on most subscales of the MCQ, particularly the 'general negative beliefs about thoughts' (NEG) subscale. However, most group differences became non-significant when anxiety and depression were controlled for. Few relationships were found between the MCQ subscales and psychotic-like anomalies and anomaly-related distress. Cognitive/attentional difficulty was the only type of anomaly to be significantly associated with maladaptive metacognitive beliefs. Anomaly-related distress was associated with only the NEG subscale of the MCQ. CONCLUSIONS: Maladaptive metacognitive beliefs, as measured by the MCQ, appear to be related more to elevated levels of general psychopathology in psychotic and at-risk groups than to the presence of, and distress associated with, psychotic experiences. Processes by which metacognitions may impact upon the need for care are discussed.

Appraisals of Anomalous Experiences Interview (AANEX): a multidimensional measure of psychological responses to anomalies associated with psychosis.

BACKGROUND: Cognitive models of psychosis suggest that whether anomalous experiences lead to clinically relevant psychotic symptoms depends on how they are appraised, the context in which they occur and the individual's emotional response. AIMS: To develop and validate a semi-structured interview (the Appraisals of Anomalous Experiences Interview; AANEX) to assess (a) anomalous experiences and (b) appraisal, contextual and response variables. METHOD: Following initial piloting, construct validity was tested via cross-sectional comparison of data from clinical and non-clinical samples with anomalous experiences. Interrater reliability was also assessed. RESULTS: Scores from AANEX measuring appraisals, responses and social support differentiated the clinical and nonclinical groups. Interrater reliability was satisfactory for 65 of the 71 items. Six items were subsequently amended. CONCLUSIONS: The AANEX is a valid multidimensional instrument that provides a detailed assessment of psychotic-like experiences and subjective variables relevant to the development of a need for clinical care.

Delusion formation and reasoning biases in those at clinical high risk for psychosis.

BACKGROUND: Cognitive models propose that faulty appraisal of anomalous experiences is critical in developing psychosis, particularly delusions. A data gathering bias may be fundamental to abnormal appraisal. AIMS: To examine whether there is a data gathering bias in people at high risk of developing psychosis. METHOD: Individuals with an at-risk mental state (n=35) were compared with a matched group of healthy volunteers (n=23). Participants were tested using a modified version of the 'beads' reasoning task with different levels of task difficulty. RESULTS: When task demands were high, the at-risk group made judgements on the basis of less information than the control group (P<0.05). Within both groups, jumping to conclusions was directly correlated with the severity of abnormal beliefs and intolerance of uncertainty (P<0.05). In the at-risk group it was also associated with impaired working memory (P<0.05), whereas in the control group poor working memory was associated with a more conservative response style (P<0.05). CONCLUSIONS: People with an at-risk mental state display a jumping to conclusions reasoning style, associated with impaired working memory and intolerance of uncertainty. This may underlie a tendency to develop abnormal beliefs and a vulnerability to psychosis.

Ecological validity of measures of executive functioning.

OBJECTIVES: This study aimed to ascertain the ecological validity of the Hayling and Brixton tests of executive functioning, by investigating whether cognitive 'impairment' detected by these measures was associated with assessment of 'disability' and 'handicap'. DESIGN AND METHOD: A correlational design was employed to evaluate the degree of association between the executive test results, and behavioural and community integration measures. Participants were 53 people with brain injuries participants who were selected from neuropsychology patient lists and their 'significant other'. The brain-injured participant was given the executive tests, together with behavioural and community integration questionnaires, while their 'significant other' was given an equivalent behavioural questionnaire and structured interview. RESULTS: There were moderate relationships between scores on the tests and measures of everyday functioning, suggesting that the tests have modest ecological validity. CONCLUSIONS: The tests contribute to understanding the impact of executive impairment on everyday functioning, but they should be interpreted in combination with other measures of executive functioning.

The continuity of psychotic experiences in the general population.

Schizophrenia is a severe mental illness that affects 1% of the population. The diagnosis is made according to current diagnostic systems of DSM-IV (American Psychiatric Association, 1994) and ICD-10 (World Health Association, 1992) on the basis of characteristic 'positive' and 'negative' symptoms. The traditional medical model assumes a categorical view of the schizophrenia syndrome and its core symptoms, in which differences between psychotic symptoms and their normal counterparts are considered to be qualitative. An alternative, dimensional approach assumes that schizophrenia is not a discrete illness entity, but that psychotic symptoms differ in quantitative ways from normal experiences and behaviours. This paper reviews evidence for the continuity of psychotic symptoms with normal experiences, focusing on the symptoms of hallucinations and delusions. It concludes by discussing the theoretical and treatment implications of such a continuum.

Verbal self-monitoring and auditory verbal hallucinations in patients with schizophrenia.

BACKGROUND: Contemporary cognitive models of auditory verbal hallucinations propose that they arise through defective self-monitoring. We used a paradigm that engages verbal self-monitoring to investigate this theory in patients with schizophrenia. METHODS: Ten patients with auditory verbal hallucinations and delusions (hallucinators), eight patients with delusions but no hallucinations (non-hallucinators), and 20 non-psychiatric control subjects were tested. Participants read single adjectives aloud, under the following randomized conditions: reading aloud; reading aloud with acoustic distortion of their own voice; reading aloud with alien feedback (someone else's voice); and reading aloud with distorted alien feedback. Immediately after articulating each word, participants identified the source of the speech they heard ('self'/'other'/'unsure'), via a button press. Response choice and reaction time were recorded. RESULTS: When reading aloud with distorted feedback of their own voice, patients in both groups made more errors than controls; they either misidentified its source or were unsure. Hallucinators were particularly prone to misattributing their distorted voice to someone else, and were more likely to make errors when the words presented were derogatory. Both patient groups made faster decisions than controls about the source of distorted or alien speech, but faster responses were only associated with errors in the former condition. CONCLUSIONS: Impaired verbal self-monitoring was evident in both hallucinators and non-hallucinators. As both groups had delusions, the results suggest an association between delusions and impaired judgements about ambiguous sensory stimuli. The specific tendency of hallucinators to misattribute their distorted voice to someone else may reflect impaired awareness of internally generated verbal material.