Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia.

AIM: To define regional grey-matter abnormalities in schizophrenia patients with poor insight (Insight(-)), relative to patients with preserved clinical insight (Insight(+)), and healthy controls. METHODS: Forty stable schizophrenia outpatients (20 Insight(-) and 20 Insight(+)) and 20 healthy controls underwent whole brain magnetic resonance imaging (MRI). Insight in all patients was assessed using the Birchwood Insight Scale (BIS; a self-report measure). The two patient groups were pre-selected to match on most clinical and demographic parameters but, by design, they had markedly distinct BIS scores. Voxel-based morphometry employed in SPM8 was used to examine group differences in grey matter volumes across the whole brain. RESULTS: The three participant groups were comparable in age [F(2,57) = 0.34, P = 0.71] and the patient groups did not differ in age at illness onset [t(38) = 0.87, P = 0.39]. Insight(-) and Insight(+) patient groups also did not differ in symptoms on the Positive and Negative Syndromes scale (PANSS): Positive symptoms [t(38) = 0.58, P = 0.57], negative symptoms [t(38) = 0.61, P = 0.55], general psychopathology [t(38) = 1.30, P = 0.20] and total PANSS scores [t(38) = 0.21, P = 0.84]. The two patient groups, as expected, varied significantly in the level of BIS-assessed insight [t(38) = 12.11, P < 0.001]. MRI results revealed lower fronto-temporal, parahippocampal, occipital and cerebellar grey matter volumes in Insight(-) patients, relative to Insight(+) patients and healthy controls (for all clusters, family-wise error corrected P < 0.05). Insight(+) patient and healthy controls did not differ significantly (P > 0.20) from each other. CONCLUSION: Our findings demonstrate a clear association between poor clinical insight and smaller fronto-temporal, occipital and cerebellar grey matter volumes in stable long-term schizophrenia patients.

Is it me? Verbal self-monitoring neural network and clinical insight in schizophrenia.

Self-monitoring, defined as the ability to distinguish between self-generated stimuli from other-generated ones, is known to be impaired in schizophrenia. This impairment has been theorised as the basis for many of the core psychotic symptoms, in particular, poor clinical insight. This study aimed to investigate verbal self-monitoring related neural substrates of preserved and poor clinical insight in schizophrenia. It involved 40 stable schizophrenia outpatients, 20 with preserved and 20 with poor insight, and 20 healthy participants. All participants underwent functional magnetic resonance imaging with brain coverage covering key areas in the self-monitoring network during a verbal self-monitoring task. Healthy participants showed higher performance accuracy and greater thalamic activity than both preserved and poor insight patient groups. Preserved insight patients showed higher activity in the putamen extending into the caudate, insula and inferior frontal gyrus, compared to poor insight patients, and in the anterior cingulate and medial frontal gyrus, compared to healthy participants. Poor insight patients did not show greater activity in any brain area compared to preserved insight patients or healthy participants. Future studies may pursue therapeutic avenues, such as meta-cognitive therapies to promote self-monitoring or targeted stimulation of relevant brain areas, as means of enhancing insight in schizophrenia.

Preservation and compensation: the functional neuroanatomy of insight and working memory in schizophrenia.

BACKGROUND: Poor insight in schizophrenia has been theorised to reflect a cognitive deficit that is secondary to brain abnormalities, localized in the brain regions that are implicated in higher order cognitive functions, including working memory (WM). This study investigated WM-related neural substrates of preserved and poor insight in schizophrenia. METHOD: Forty stable schizophrenia outpatients, 20 with preserved and 20 with poor insight (usable data obtained from 18 preserved and 14 poor insight patients), and 20 healthy participants underwent functional magnetic resonance imaging (fMRI) during a parametric 'n-back' task. The three groups were preselected to match on age, education and predicted IQ, and the two patient groups to have distinct insight levels. Performance and fMRI data were analysed to determine how groups of patients with preserved and poor insight differed from each other, and from healthy participants. RESULTS: Poor insight patients showed lower performance accuracy, relative to healthy participants (p=0.01) and preserved insight patients (p=0.08); the two patient groups were comparable on symptoms and medication. Preserved insight patients, relative to poor insight patients, showed greater activity most consistently in the precuneus and cerebellum (both bilateral) during WM; they also showed greater activity than healthy participants in the inferior-superior frontal gyrus and cerebellum (bilateral). Group differences in brain activity did not co-vary significantly with performance accuracy. CONCLUSIONS: The precuneus and cerebellum function contribute to preserved insight in schizophrenia. Preserved insight as well as normal-range WM capacity in schizophrenia sub-groups may be achieved via compensatory neural activity in the frontal cortex and cerebellum.

Cognitive insight in psychosis: the relationship between self-certainty and self-reflection dimensions and neuropsychological measures.

Cognitive insight in schizophrenia encompasses the evaluation and reinterpretation of distorted beliefs and appraisals. We investigated the neuropsychological basis of cognitive insight in psychosis. It was predicted that, like clinical insight, cognitive insight would be associated with a wide range of neuropsychological functions, but would be most strongly associated with measures of executive function. Sixty-five outpatients with schizophrenia or schizoaffective disorder were assessed on tests of intelligence quotient (IQ), executive function, verbal fluency, attention and memory, and completed the Beck Cognitive Insight Scale, which includes two subscales, self-certainty and self-reflection. Higher self-certainty scores reflect greater certainty about being right and more resistant to correction (poor insight), while higher self-reflection scores indicate the expression of introspection and the willingness to acknowledge fallibility (good insight). The self-certainty dimension of poor cognitive insight was significantly associated with lower scores on the Behavioural Assessment of Dysexecutive Syndrome; this relationship was not mediated by IQ. There were no relationships between self-reflection and any neuropsychological measures. We conclude that greater self-certainty (poor cognitive insight) is modestly associated with poorer executive function in psychotic individuals; self-reflection has no association with executive function. The self-certainty and self-reflection dimensions of cognitive insight have differential correlates, and probably different mechanisms, in psychosis.

Functional MRI of verbal self-monitoring in schizophrenia: performance and illness-specific effects.

Previous small-sample studies have shown altered frontotemporal activity in schizophrenia patients with auditory hallucinations and impaired monitoring of self-generated speech. We examined a large cohort of patients with schizophrenia (n = 63) and a representative group of healthy controls (n = 20) to disentangle performance, illness, and symptom-related effects in functional magnetic resonance imaging-detected brain abnormalities during monitoring of self- and externally generated speech in schizophrenia. Our results revealed activation of the thalamus (medial geniculate nucleus, MGN) and frontotemporal regions with accurate monitoring across all participants. Less activation of the thalamus (MGN, pulvinar) and superior-middle temporal and inferior frontal gyri occurred in poorly performing patients (1 standard deviation below controls' mean; n = 36), relative to the combined group of controls and well-performing patients. In patients, (1) greater deactivation of the ventral striatum and hypothalamus to own voice, combined with nonsignificant activation of the same regions to others' voice, associated positively with negative symptoms (blunted affect, emotional withdrawal, poor rapport, passive social avoidance) regardless of performance and (2) exaggerated activation of the right superior-middle temporal gyrus during undistorted, relative to distorted, feedback associated with both positive symptoms (hallucinations, persecution) and poor performance. A further thalamic abnormality characterized schizophrenia patients regardless of performance and symptoms. We conclude that hypoactivation of a neural network comprised of the thalamus and frontotemporal regions underlies impaired speech monitoring in schizophrenia. Positive symptoms and poor monitoring share a common activation abnormality in the right superior temporal gyrus during processing of degraded speech. Altered striatal and hypothalamic modulation to own and others' voice characterizes emotionally withdrawn and socially avoidant patients.

Association between a longer duration of illness, age and lower frontal lobe grey matter volume in schizophrenia.

The frontal lobe has an extended maturation period and may be vulnerable to the long-term effects of schizophrenia. We tested this hypothesis by studying the relationship between duration of illness (DoI), grey matter (GM) and cerebro-spinal fluid (CSF) volume across the whole brain. Sixty-four patients with schizophrenia and 25 healthy controls underwent structural MRI scanning and neuropsychological assessment. We performed regression analyses in patients to examine the relationship between DoI and GM and CSF volumes across the whole brain, and correlations in controls between age and GM or CSF volume of the regions where GM or CSF volumes were associated with DoI in patients. Correlations were also performed between GM volume in the regions associated with DoI and neuropsychological performance. A longer DoI was associated with lower GM volume in the left dorsomedial prefrontal cortex (PFC), right middle frontal cortex, left fusiform gyrus (FG) and left cerebellum (lobule III). Additionally, age was inversely associated with GM volume in the left dorsomedial PFC in patients, and in the left FG and CSF excess near the left cerebellum in healthy controls. Greater GM volume in the left dorsomedial PFC was associated with better working memory, attention and psychomotor speed in patients. Our findings suggest that the right middle frontal cortex is particularly vulnerable to the long-term effect of schizophrenia illness whereas the dorsomedial PFC, FG and cerebellum are affected by both a long DoI and aging. The effect of illness chronicity on GM volume in the left dorsomedial PFC may be extended to brain structure-neuropsychological function relationships.

Neurological basis of poor insight in psychosis: a voxel-based MRI study.

BACKGROUND: As a reflection of poor insight, people with schizophrenia often disagree with carers and clinicians about whether (a) their experiences are abnormal, (b) they are mentally ill, and (c) they need treatment. METHODS: This study used voxel-based morphometry to identify the associations between total and regional grey matter volumes and self-reported and observer-rated insight in 52 patients with schizophrenia or schizoaffective disorder. Thirty healthy participants were also studied. RESULTS: There were positive associations in patients between (i) the ability to recognise experiences as abnormal and the total and right superior temporal gyrus grey matter volumes, (ii), awareness of problems ('something wrong') and the left precuneus grey matter volume and (iii) awareness of symptoms and attributing them to illness and grey matter volumes in the left superior-middle temporal gyrus and the right inferior temporal and lateral parietal gyri. The 'recognition of the need for medication' dimension did not correlate with total or any regional grey matter volumes. Relative to controls, patients had less total and regional grey matter volumes in the thalamus and middle occipital and superior temporal gyri. CONCLUSIONS: Lower grey matter volumes in the temporal and parietal regions that have been implicated in self-monitoring, working memory and access to internal mental states are associated with poor insight on certain dimensions in psychosis.

Uncontrollable voices and their relationship to gating deficits in schizophrenia.

BACKGROUND: Prepulse inhibition (PPI) of the startle response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect is reduced in a number of disorders known to be associated with impaired gating of sensory, cognitive or motor information. The aim of this study was to investigate PPI deficit in relation to the dimensions of auditory hallucinations in patients with schizophrenia or schizoaffective disorder. METHOD: PPI of the acoustically elicited eye blink startle response was measured electromyographically in 62 patients with schizophrenia (n=55) or schizoaffective disorder (n=7) (26 of 62 with current auditory hallucinations) and 22 healthy participants matched, on average, to age and sex of the patient group. RESULTS: Patients, as a group, showed reduced PPI compared to healthy participants. The presence of auditory hallucinations was associated with a marked PPI deficit if the patients felt that they had no control over their occurrence and that they were unable to dismiss them. Hearing voices with a high degree of negative content was associated with high mean startle amplitude in patients with current auditory hallucinations. CONCLUSIONS: Although auditory hallucinations in patients with schizophrenia are theorised to result from impaired monitoring of inner speech, the inability to consciously ignore them appears to be associated with a gating deficit. Hearing voices with negative content is associated with hyper-startle responding, possibly because such voices are threatening and thus provoke anxiety.

Misattribution bias of threat-related facial expressions is related to a longer duration of illness and poor executive function in schizophrenia and schizoaffective disorder.

BACKGROUND: While it is known that patients with schizophrenia recognize facial emotions, specifically negative emotions, less accurately, little is known about how they misattribute these emotions to other emotions and whether such misattribution biases are associated with symptoms, course of the disorder, or certain cognitive functions. METHOD: Outpatients with schizophrenia or schizoaffective disorder (n=73) and healthy controls (n=30) performed a computerised Facial Emotion Attribution Test and Wisconsin Card Sorting Test (WCST). Patients were also rated on the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients were poor at recognizing fearful and angry emotions and attributed fear to angry and angry to neutral expressions. Fear-as-anger misattributions were predicted independently by a longer duration of illness and WCST perseverative errors. CONCLUSION: The findings show a bias towards misattributing fearful and angry facial emotions. The propensity for fear-as-anger misattribution biases increases as the length of time that the disorder is experienced increases and a more rigid style of information processing is used. This, at least in part, may be perpetuated by subtle fearfulness expressed by others while interacting with people with schizophrenia.

Insight in psychosis: influence of cognitive ability and self-esteem.

BACKGROUND: Insight in psychosis has previously been associated with both depression and cognitive ability. Some studies have found a curvilinear relationship between insight and cognitive ability, but the roles of self-esteem and depression have not been taken into account. AIMS: To investigate the relationships between insight and IQ, depression, and self-esteem. METHOD: Correlations between self-reported and observer-rated insight, and measures of IQ, depression and self-esteem were examined in 67 people with psychosis. RESULTS: Better self-reported insight was associated with higher IQ and poorer self-esteem, but not depression. There was some evidence for a curvilinear relationship between IQ and self-reported insight, specifically the ;awareness of illness' dimension, which survived correction for symptom variables. CONCLUSIONS: The relationship between insight and IQ might reflect both the basis of insight in intellectual ability and the influence of a psychological mechanism that preserves self-esteem.