Insight: its relationship with cognitive function, brain volume and symptoms in schizophrenia.

BACKGROUND: Lack of insight is frequently observed in schizophrenia. Relationships have been noted between poor insight, clinical symptoms and cognitive impairments but the findings are inconsistent. There have been some recent attempts to relate poor insight to neuro-anatomical measures. METHOD: We assessed insight, positive and negative symptoms of schizophrenia, cognitive performance, and whole brain volumes in a sample of 78 DSM-IV male schizophrenics and 36 normal male comparison subjects matched for age and IQ. Subjects underwent a dual-echo MRI brain scan to establish grey, white and whole brain volumes. RESULTS: Poor Wisconsin Card Sorting Test performance inversely correlated with insight in schizophrenic patients, as did the symptoms alogia, anhedonia, avolition/apathy, affective flattening, inappropriate affect, thought disorder and delusions. The presence of inappropriate affect, delusions and thought disorder, showed the most significant impact on insight levels. There were no significant correlations between whole brain, white and grey matter volume and degree of insight. CONCLUSIONS: The results suggest that poor insight is significantly related to schizophrenic psychopathology, and confirm that there is a relationship between insight and executive performance. Awareness of illness is not related to any global brain measures, suggesting future investigations should pay attention to more specific cortical regions such as the frontal cortex.

Corpus callosum area and functioning in schizophrenic patients with auditory--verbal hallucinations.

Auditory--verbal hallucinations (AVH) are a characteristic feature of schizophrenia. Patients with AVHs have been found to differ from non-hallucinating patients in volumes of certain asymmetrical brain structures on MRI, and on certain neuropsychological measures. There is also evidence of corpus callosum (CC) abnormalities in schizophrenia, and it has been proposed that abnormalities of inter-hemispheric transmission may underlie hallucinations and other symptoms. The aim of this study was to examine whether patients with AVHs have smaller corpora callosa than those without AVH, and whether CC size is related to performance on neuropsychological tests of functional cerebral asymmetry. Seventy-one DSM-IV male schizophrenics were recruited on the basis of their hallucination history plus 33 matched normal controls. Twenty-nine patients had no history of AVH, and 42 had a strong history of AVH. The mid-sagittal surface area and longitudinal length of the CC were measured from T(1)-weighted spin echo images. Callosal area was divided into four sections. There were no significant differences in any of the measurements between the two patient groups, or between patients with schizophrenia and controls. There was no association between CC measures and handedness, or performance on dichotic listening or finger tapping tasks. The results of this study do not lend support for there being a major morphological abnormality of the corpus callosum in schizophrenic patients, or for a specific relationship to AVH. However, a significant association between CC area and overall grey and white matter volumes was noted in the hallucinating patients and, to a lesser extent, in the non-hallucinators, which may point to differing influences on brain development or degeneration in such patients compared with normal controls.

Are auditory hallucinations the consequence of abnormal cerebral lateralization? A morphometric MRI study of the sylvian fissure and planum temporale.

BACKGROUND: Auditory verbal hallucinations (AVHs) are a characteristic feature of schizophrenia. Patients with schizophrenia have been found to have reduced volumes of a variety of brain structures as well as a reduction in right-left asymmetries, using postmortem and magnetic resonance imaging (MRI) measures. There is also evidence that patients with AVHs differ in these structural asymmetries, relative to those patients who do not hallucinate. The aim of this study was to examine whether patients with and without a prominent history of AVHs differ, both from each other and in comparison with normal subjects, in the asymmetry of the sylvian fissure (SF) and planum temporale (PT). METHODS: We recruited 74 DSM-IV male patients with schizophrenia (on the basis of their AVH history) and 32 matched normal control subjects. Thirty patients had no history of AVHs and 44 had a strong definitive history of AVHs. The SF length and PT area and volume were measured on a three-dimensional MRI spoiled GRASS volume sequence. Absolute measures and laterality coefficients were calculated. RESULTS: : All groups had the normal leftward asymmetry in both the SF and PT. Planum temporale volume and surface area and SF length were all larger in the left hemisphere. There were no significant differences in any measures between the two patient groups or between schizophrenic patients and control subjects. Greater leftward asymmetry of the SF correlated with hallucinations and thought disorder within the prominent hallucinator group. An association was found between handedness and brain size, but this did not interact with diagnosis. CONCLUSIONS: The results of this study do not confirm reports, based on smaller samples, of reduced structural asymmetries of either the SF or PT in schizophrenia, nor do they indicate a specific relationship to a propensity to experience AVHs. A modest correlation between leftward asymmetry of the SF and some positive symptomatology was found.

Is semantic fluency differentially impaired in schizophrenic patients with delusions?

The study of cognitive deficits in schizophrenia has recently focused upon semantics: the study of meaning. Delusions are a plausible manifestation of abnormal semantics because by definition they involve changes in personal meaning and belief. A symptom-based approach was used to investigate semantic and phonological fluency in a group of schizophrenic patients subdivided into those with delusions and those with no current delusions. The results demonstrated that deluded patients only were differentially impaired on a test of semantic fluency in comparison to phonological fluency. All subjects showed the same decline in performance over the time course of both tests indicating that retrieval speed in schizophrenia is no different from that of normal controls. Further analysis of word associations in two semantic categories (animals and body parts), revealed that deluded subjects have a more idiosyncratic organisation for animals. The findings of reduced semantic fluency production and poor logical word associations may represent a disorganised storage of semantic information in deluded patients, which in turn affects efficient access.

The planum temporale: a systematic, quantitative review of its structural, functional and clinical significance.

The planum temporale (PT) is a triangular area situated on the superior temporal gyrus (STG), which has enjoyed a resurgence of interest across several disciplines, including neurology, psychiatry and psychology. Traditionally, the planum is thought to be larger on the left side of the brain in the majority of normal subjects [N. Geschwind, W. Levitsky, Human brain: left-right asymmetries in temporal speech regions, Science 161 (1968) 186-87.]. It coincides with part of Wernicke's area and it is believed to consist cytoarchitectonically of secondary auditory cortex. Consequently, it has long been thought to be intimately involved in language function. The PT is, therefore, of relevance to disorders where language function is impaired, such as schizophrenia and dyslexia. The gross anatomical boundaries remain in dispute, and only recently has its cytoarchitecture begun to be studied again after 60 years silence, and finally its functional significance is only now being explored. In the first part of this review the structural aspects and anatomical boundaries of the PT in the normal brain from post mortem and magnetic resonance imaging (MRI) and methods of measurement are discussed. In the second part, studies of the functional significance of the PT in the normal brain are reviewed critically. Finally a meta-analysis of MRI measurements of the distribution of planum anatomy in normal subjects is presented. Comparison is made with clinical populations, including schizophrenia and dyslexia, and the influence of handedness and gender on such measurements is quantified. Although there are many ways of defining and measuring the PT with a wide variety of results, overall there is a significant leftward asymmetry in normals, which is reduced in left handers and females. The leftward asymmetry is much reduced in patients with schizophrenia due to a relatively larger right PT than normal controls. The review is intended to guide future researchers in this area.

Sentence verification and delusions: a content-specific deficit.

BACKGROUND: A sentence verification task was developed to investigate semantic memory in schizophrenia. METHODS: The test consisted of three types of sentence (true, unlikely and nonsense) and seven different types of content (neutral, persecutory, grandiose, political, religious, relationships and somatic) representing common delusional themes present in schizophrenic patients. Sixty-three schizophrenic patients and 66 matched control subjects were asked to make true/false judgements to 143 sentences. RESULTS: Overall accuracy was similar across the two groups; sentences with some emotional themes and sentences of the unlikely type produced the most violations. Significant differences between the two subject groups were found specifically on nonsense sentences with persecutory and religious themes. Patients made significantly more incorrect responses (acceptance) to nonsense sentences that had an emotional content congruent with their delusional beliefs, past or present, and also on unlikely sentences (incorrect rejections) whose content was not congruent with their delusions. Further analysis of response bias in the patients showed, overall, that there were more incorrect rejections (a reflection of the large number of unlikely sentence errors) and more incorrect responses to sentences congruent with patients delusions. Furthermore, analysis of those patients currently experiencing delusions revealed more incorrect responses to sentences congruent with their delusional ideas compared with patients not currently deluded. CONCLUSIONS: These findings are indicative of cognitive bias in schizophrenia towards certain emotional themes that may underlie illogical semantic connections and delusions.

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

OBJECTIVE: The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. METHOD: Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. RESULTS: Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. CONCLUSIONS: These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Successful treatment of tardive dystonia with clozapine and clonazepam.

BACKGROUND: Tardive dystonia is an uncommon complication of neuroleptic treatment which is frequently disabling and poorly responsive to treatment. METHOD: The case is reported of a 28-year-old patient with schizophrenia who developed severe, generalised tardive dystonia after five years of neuroleptic treatment. Stopping neuroleptic medication and treatment with tetrabenazine, an anticholinergic and a benzodiazepine were ineffective. Treatment with clozapine and then the novel combination of clozapine plus clonazepam was instituted. RESULTS: Treatment with clozapine alone brought about limited improvement. Addition of clonazepam resulted in virtually complete disappearance of all abnormal movements. This remission has been sustained for nearly two years. CONCLUSIONS: This report adds to two other cases suggesting that the combination of clozapine and clonazepam may be an effective treatment for tardive dystonia.

Neuropsychological function in manic-depressive psychosis. Evidence for persistent deficits in patients with chronic, severe illness.

BACKGROUND: While neuropsychological deficits are recognised to occur in manic-depressive psychosis during episodes of depression and to reverse with clinical recovery, it is uncertain whether they can ever be seen outside episodes of illness. METHOD: Forty-five patients meeting DSM-III-R criteria for major depression or bipolar disorder were screened using tests of memory, executive function and overall intellectual function. All testing was carried out during remission of affective symptoms. RESULTS: None of 24 young patients and 11 elderly patients scored in the impaired range on any of the tests. However, five of ten patients with chronic, severe affective disorder were impaired on one or more of the measures. On more detailed neuropsychological investigation, these five patients were found to show a variable pattern of impairment, ranging from memory and executive deficits in relative isolation, to widespread poor performance. CONCLUSIONS: Enduring neuropsychological deficits may be a feature of chronic, severe manic-depressive illness.

The Cambridge Neurological Inventory: a clinical instrument for assessment of soft neurological signs in psychiatric patients.

A schedule (the Cambridge Neurological Inventory) has been constructed for standardized neurological assessment of psychiatric patients. Normative data and data resulting from its application to a group of patients with schizophrenia are reported. The instrument is comprehensive, reliable, and easy to administer. In conjunction with other forms of clinical assessment, it may be useful for identifying soft neurological signs and other patterns of neurological impairment relevant to neurobiological localization and prognosis in schizophrenia and other psychiatric disorders.