Pituitary volume reduction in schizophrenia following cognitive behavioural therapy.

Cognitive behavioural therapy (CBT) for psychosis (CBTp) aims to lower the stress of psychotic symptoms. Given that the pituitary is involved in stress regulation, CBT-led stress reduction may be accompanied by a change in pituitary volume. This study aimed to determine whether CBTp reduces pituitary volume in schizophrenia. The relation between pre-therapy memory and CBTp-led pituitary volume change was also examined given that poor memory relates to a blunted cortisol awakening response, denoting impaired stress response, in schizophrenia. Pituitary volume was measured at baseline in 40 schizophrenia or schizoaffective disorder patients and 30 healthy participants before therapy. Pituitary volume was measured again 6-9months after patients had either received CBTp in addition to standard care (CBTp+SC, n=24), or continued with standard care alone (SC, n=16). CBTp+SC and SC groups were compared on pituitary volume change from baseline to follow-up. Pre-therapy memory performance (Hopkins Verbal Learning and Wechsler Memory Scale - Logical memory) was correlated with baseline-to-follow-up pituitary volume change. Pituitary volume reduced over time in CBTp+SC patients. Additionally, pre-therapy verbal learning correlated more strongly with longitudinal pituitary volume reduction in the CBTp+SC group than the SC group. To conclude, CBTp reduces pituitary volume in schizophrenia most likely by enhancing stress regulation and lowering the distress due to psychotic symptoms.

Mapping Depression in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Depressive symptoms are common in schizophrenia, often left untreated, and associated with a high relapse rate, suicidal ideation, increased mortality, reduced social adjustment and poor quality of life. The neural mechanisms underlying depression in psychosis are poorly understood. Given reports of altered brain response to negative facial affect in depressive disorders, we examined brain response to emotive facial expressions in relation to levels of depression in people with psychosis. Seventy outpatients (final N= 63) and 20 healthy participants underwent functional magnetic resonance imaging during an implicit affect processing task involving presentation of facial expressions of fear, anger, happiness as well as neutral expressions and a (no face) control condition. All patients completed Beck Depression Inventory (BDI-II) and had their symptoms assessed on the Positive and Negative Syndrome Scale (PANSS). In patients, depression (BDI-II) scores associated positively with activation of the left thalamus, extending to the putamen-globus pallidus, insula, inferior-middle frontal and para-post-pre-central gyri during fearful expressions. Furthermore, patients with moderate-to-severe depression had significantly higher activity in these brain regions during fearful expressions relative to patients with no, minimal, or mild depression and healthy participants. The study provides first evidence of enhanced brain response to fearful facial expressions, which signal an uncertain source of threat in the environment, in patients with psychosis and a high level of self-reported depression.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis.

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness.

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.

Sensorimotor gating and clinical outcome following cognitive behaviour therapy for psychosis.

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. PPI provides an operational index of sensorimotor gating and is reduced, on average, in people with schizophrenia, relative to healthy people. Given the variable response to Cognitive Behaviour Therapy for psychosis (CBTp) and positive associations between pre-therapy brain and cognitive functions and CBT outcome across disorders, we examined whether pre-therapy level of PPI is associated with clinical outcome following CBTp. METHOD: Fifty-six outpatients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBTp in addition to their usual treatment were assessed on acoustic PPI. Subsequently, 28 patients received CBTp (CBTp+treatment-as-usual, 23 completers) for 6-8months and 28 continued with their treatment-as-usual (TAU-alone, 17 completers). Symptoms were assessed (blindly) at entry and follow-up. RESULTS: The CBTp+TAU and TAU-alone groups did not differ demographically, clinically or in PPI at baseline. The CBTp+TAU group showed improved symptoms relative to the TAU-alone group, which showed no change, at follow-up. Pre-therapy PPI level correlated positively with post-CBTp symptom improvement. CONCLUSIONS: Relatively intact sensorimotor gating is associated with a good clinical response following a 6-8months course of NICE compliant CBTp in schizophrenia. Pharmacological or psychological interventions capable of improving PPI may enhance the effectiveness of CBTp in people with schizophrenia, particularly in those who fail to show clinical improvement with currently available antipsychotic drugs and adjunctive CBTp.

Neural changes following cognitive behaviour therapy for psychosis: a longitudinal study.

A growing body of evidence demonstrates that persistent positive symptoms, particularly delusions, can be improved by cognitive behaviour therapy for psychosis. Heightened perception and processing of threat are believed to constitute the genesis of delusions. The present study aimed to examine functional brain changes following cognitive behaviour therapy for psychosis. The study involved 56 outpatients with one or more persistent positive distressing symptoms of schizophrenia. Twenty-eight patients receiving cognitive behaviour therapy for psychosis for 6-8 months in addition to their usual treatment were matched with 28 patients receiving treatment as usual. Patients' symptoms were assessed by a rater blind to treatment group, and they underwent functional magnetic resonance imaging during an affect processing task at baseline and end of treatment follow-up. The two groups were comparable at baseline in terms of clinical and demographic parameters and neural and behavioural responses to facial and control stimuli. The cognitive behaviour therapy for psychosis with treatment-as-usual group (22 subjects) showed significant clinical improvement compared with the treatment-as-usual group (16 subjects), which showed no change at follow-up. The cognitive behaviour therapy for psychosis with treatment-as-usual group, but not the treatment-as-usual group, showed decreased activation of the inferior frontal, insula, thalamus, putamen and occipital areas to fearful and angry expressions at treatment follow-up compared with baseline. Reduction of functional magnetic resonance imaging response during angry expressions correlated directly with symptom improvement. This study provides the first evidence that cognitive behaviour therapy for psychosis attenuates brain responses to threatening stimuli and suggests that cognitive behaviour therapy for psychosis may mediate symptom reduction by promoting processing of threats in a less distressing way.

Functional magnetic resonance imaging of a parametric working memory task in schizophrenia: relationship with performance and effects of antipsychotic treatment.

RATIONALE: Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls. OBJECTIVES: We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group. METHOD: We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task. RESULTS: Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area. CONCLUSIONS: Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics.

Coping styles predict responsiveness to cognitive behaviour therapy in psychosis.

The study aimed to determine the clinical and neuropsychological predictors of responsiveness to cognitive behavioural therapy for psychosis (CBTp). Sixty patients with schizophrenia or schizoaffective disorder and 25 healthy individuals took part in the study. Thirty patients (25 protocol completers) received CBTp in addition to standard care (SC); 30 patients (18 protocol completers) received SC only. All patients were assessed on symptoms using the Positive and Negative Syndrome Scale (PANSS) and clinical and neuropsychological function before and after CBTp. Symptoms and self-esteem improved to a greater extent in the CBTp+SC than SC control group. Greater pre-therapy coping ability and the self-reflectiveness dimension of cognitive insight at baseline predicted improvement in symptoms in the CBTp+SC group, but not the SC control group, explaining up to 21% of the variance in symptom improvement. Pre-therapy neuropsychological function, duration of illness, clinical insight and gender did not predict CBTp responsiveness. Being able to have a range of coping strategies and reflect on one's experiences while refraining from overconfidence in one's interpretations before therapy is conducive to better CBTp responsiveness.

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.

N-acetyl aspartate concentration in the anterior cingulate cortex in patients with schizophrenia: a study of clinical and neuropsychological correlates and preliminary exploration of cognitive behaviour therapy effects.

This study investigated the clinical and neuropsychological correlates of N-acetyl aspartate (NAA) concentration in the anterior cingulate cortex (ACC) in schizophrenia, and explored whether ACC NAA concentration is sensitive to symptom change following cognitive behaviour therapy for psychosis (CBTp). Participants comprised 30 patients and 15 healthy controls who underwent magnetic resonance spectroscopy of the ACC and were assessed on frontal lobe based neuropsychological tasks. Twenty-four (of 30) patients were followed-up; 11 subsequently received 8-9 months of CBTp in addition to standard care (CBTp+SC) and 13 received SC only. At baseline (i) NAA and Cr concentrations were lower in patients compared to controls, (ii) in patients, NAA concentration correlated inversely with positive symptoms and general psychopathology (positive symptoms explained 21% of the variance; total variance explained=25%) and Cho concentration correlated inversely with positive symptoms, and (iii) in controls, NAA concentration correlated positively with working and short-term memory and Cr concentration inversely with executive function. NAA concentration tended to increase in CBTp+SC patients at follow-up (n=7 with usable data) concomitant with improvement in positive symptoms. NAA concentration may be more closely associated with symptoms and symptom change than frontal lobe based neuropsychological function in schizophrenia, perhaps because the latter is relatively stable during the long-term illness course.

Beyond dopamine: functional MRI predictors of responsiveness to cognitive behaviour therapy for psychosis.

Despite the favourable effects of antipsychotics on positive symptoms of schizophrenia, many patients continue to suffer from distressing symptoms. Additional benefits of cognitive behaviour therapy for psychosis (CBTp) have been reported for approximately 50% of such patients. Given the role of left hemisphere-based language processes in responsiveness to CBT for depression, and language pathway abnormalities in psychosis, this study examined whether pre-therapy brain activity during a verbal monitoring task predicts CBTp responsiveness in schizophrenia. Fifty-two outpatients, stable on antipsychotics with at least one persistent distressing positive symptom and wishing to receive CBTp adjunctive to their treatment-as-usual, and 20 healthy participants underwent fMRI during monitoring of self- and externally-generated (normal and distorted) speech. Subsequently, 26 patients received CBTp for 6-8 months adjunctive to their treatment-as-usual (CBTp + TAU, 20 completers), and 26 continued with their treatment-as-usual (TAU-alone, 18 completers). Symptoms were assessed (blindly) at entry and follow-up. The CBTp + TAU and TAU-alone groups had comparable demographic characteristics, performance and baseline symptoms. Only the CBTp + TAU group showed improved symptoms at follow-up. CBTp responsiveness was associated with (i) greater left inferior frontal gyrus (IFG) activity during accurate monitoring, especially of own voice, (ii) less inferior parietal deactivation with own, relative to others', voice, and (iii) less medial prefrontal deactivation and greater thalamic and precuneus activation during monitoring of distorted, relative to undistorted, voices. CBTp + TAU patients, on average, displayed left IFG and thalamic hypo-activation (

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.

Structural magnetic resonance imaging predictors of responsiveness to cognitive behaviour therapy in psychosis.

BACKGROUND: Responsiveness to cognitive behaviour therapy (CBT) in psychosis may have a neurological basis. This study aimed to determine whether improvement in symptoms following CBT for psychosis (CBTp) in people with schizophrenia is positively associated with pre-therapy grey matter volume in brain regions involved in cognitive processing. METHODS: Sixty outpatients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBTp in addition to their standard care (SC), and 25 healthy participants underwent magnetic resonance imaging. Subsequently, 30 patients received CBTp (CBTp+SC; 25 completers) for 6-8 months and 30 continued with their standard care (SC; 19 completers). Symptoms in all patients were assessed (blindly) at entry and follow-up. RESULTS: The CBTp+SC and SC groups did not differ clinically at baseline, and only the CBTp+SC group showed improved symptoms at follow-up. Severity of baseline symptoms was not associated with CBTp responsiveness. Reduction with CBTp in positive symptoms was associated with greater right cerebellum (lobule VII) grey matter volume, in negative symptoms with left precentral gyrus and right inferior parietal lobule grey matter volumes, and in general psychopathology with greater right superior temporal gyrus, cuneus and cerebellum (Crus I) grey matter volumes. Grey matter volume in these brain areas did not correlate with the severity of baseline symptoms. CONCLUSION: Grey matter volume of the frontal, temporal, parietal and cerebellar areas that are known to be involved in the co-ordination of mental activity, cognitive flexibility, and verbal learning and memory predict responsiveness to CBTp in patients with psychosis.

Rumination and negative symptoms in schizophrenia.

Rumination is thought to be an important maintaining factor in depression. Depressive symptomatology is also a prominent feature in schizophrenia. However, little is known about the relationship between rumination and symptoms, such as depression and negative symptoms, in schizophrenia. The present study examined associations between rumination and symptoms in a group of 37 stable medicated patients with schizophrenia. All participants were clinically assessed on their symptoms and completed self-reported measures of depression and rumination. The findings showed that negative symptoms, especially emotional withdrawal and stereotyped thinking, but not depressive symptomatology, were associated with rumination in the present sample of patients with schizophrenia. If the findings are replicated, interventions that reduce rumination and rigid thinking might be helpful to reduce some negative symptoms of psychosis.

Dorsolateral prefrontal cortex activity predicts responsiveness to cognitive-behavioral therapy in schizophrenia.

BACKGROUND: Given the variable response to cognitive-behavioral therapy (CBT) when added to antipsychotic medication in psychosis and the evidence for a role of pretherapy level of frontal lobe-based cognitive function in responsiveness to CBT in other disorders, this study examined whether pretherapy brain activity associated with working memory neural network predicts clinical responsiveness to CBT in schizophrenia. METHODS: Fifty-two outpatients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBT in addition to their usual treatment and 20 healthy participants underwent functional magnetic resonance imaging during a parametric n-back task. Subsequently, 26 patients received CBT for psychosis (CBT+treatment-as-usual [TAU], 19 completers) for 6-8 months, and 26 continued with TAU alone (17 completers). Symptoms in both patient groups were assessed (blindly) at entry and follow-up. RESULTS: The CBT+TAU and TAU-alone groups did not differ clinically or in performance at baseline. The CBT+TAU group showed significant improvement in relation to the TAU-alone group, which showed no change, at follow-up. Stronger dorsolateral prefrontal cortex (DLPFC) activity (within the normal range) and DLPFC-cerebellum connectivity during the highest memory load condition (2-back > 0-back) were associated with post-CBT clinical improvement. CONCLUSIONS: DLPFC activity and its connectivity with the cerebellum predict responsiveness to CBT for psychosis in schizophrenia. These effects may be mediated by PFC-cerebellum contributions to executive processing.

The self or the voice? Relative contributions of self-esteem and voice appraisal in persistent auditory hallucinations.

BACKGROUND: Persistent auditory hallucinations are common, disabling and difficult to treat. Cognitive behavioural therapy is recommended in their treatment though there is limited empirical evidence of the role of cognitive factors in the formation and persistence of voices. Low self-esteem is thought to play a causal and maintaining role in a range of clinical disorders, particularly depression, which is prevalent and disabling in schizophrenia. It was hypothesized that low self-esteem is prominent in, and contributes to, depression in voice hearers. METHODS: Beliefs about persistent auditory hallucinations were investigated in 82 patients using the Beliefs About Voices Questionnaire--revised in a cross-sectional design. Self-esteem and depression were assessed using standardized measures. RESULTS: Depression and low self-esteem were prominent as were beliefs about the omnipotence and malevolence of auditory hallucinations. Beliefs about the uncontrollability and dominance of auditory hallucinations and low self-esteem were significantly correlated with depression. Low self-esteem did not mediate the effect of beliefs about auditory hallucinations--both acted independently to contribute to depression in this sample of patients with schizophrenia and persistent auditory hallucinations. CONCLUSIONS: Low self-esteem is of fundamental importance to the understanding of affective disturbance in voice hearers. Therapeutic interventions need to address both the appraisal of self and hallucinations in schizophrenia. Measures which ameliorate low self-esteem can be expected to improve depressed mood in this patient group. Further elucidation of the mechanisms involved can strengthen existing models of positive psychotic symptoms and provide targets for more effective treatments.

Cortical grey matter volume and sensorimotor gating in schizophrenia.

Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable tool to study the known inability of a large proportion of individuals with schizophrenia to effectively screen out irrelevant sensory input. The cortico-striato-pallido-thalamic circuitry is thought to be responsible for modulation of PPI in experimental animals. The involvement of this circuitry in human PPI is supported by observations of deficient PPI in a number of neuropsychiatric disorders that are characterised by abnormalities at some level in this circuitry, and findings of recent functional neuroimaging studies in healthy participants. The current study sought to investigate the structural neural correlates of PPI in a sample of 42 stable male outpatients with schizophrenia. Participants underwent magnetic resonance imaging (MRI) at 1.5T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimised volumetric voxel-based morphometry implemented in SPM2 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120msec) to regional grey matter (GM) volumes. Significant positive correlations were obtained between PPI and GM volume in the dorsolateral prefrontal, middle frontal and the orbital/medial prefrontal cortices. Our findings are consistent with (a) previous suggestions of susceptibility of PPI to cognitive processes controlled in a 'top down' manner by the cortex and (b) the hypothesis that compromised neural resources in the frontal cortex contribute to reduced PPI in schizophrenia.

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.