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Background: The structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. More recently, aberrant myelination of frontal fasciculi, especially, cingulum has been proposed to underlie delayed corollary discharges that can affect sense of agency and contribute to delusions of control (Schneiderian delusions). Using the magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated the putative myelin content of cingulum bundle in patients with schizophrenia. Methods: Seventeen clinically stable patients with schizophrenia and 20 controls were recruited for this 7T MRI study. We used a region-of-interest method and extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum bundles and estimated patients v. controls differences. We also related the cingulum MTR values to the severity of Schneiderian delusions. Results: Patients had a significant reduction in the MTR, indicating reduced myelin content, in the cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The reduced MTR of left cingulum was associated with higher severity of Schneiderian delusions (τ = −0.45, p = 0.026) but no such relationship was seen for the right cingulum MTR (τ = −0.136, p = 0.50) among patients. The association between the left cingulum MTR and Schneiderian delusions was not explained by the presence of other delusions, hallucinations, disorganization or negative symptoms. Conclusions: Dysmyelination of the cingulum bundle is seen in a subgroup of patients with schizophrenia and may be involved in the mechanism of Schneiderian delusions. [ABSTRACT FROM AUTHOR]

In 41 patients with schizophrenia, we used neuroanatomical information derived from structural imaging to identify patients with more severe illness, characterised by high symptom burden, low processing speed, high degree of illness persistence and lower social and occupational functional capacity. Cortical folding, but not thickness or volume, showed a high discriminatory ability in correctly identifying patients with more severe illness. [ABSTRACT FROM AUTHOR]

Background: Brain serotonin(2) (5-hydroxytryptamine(2); 5-HT(2)) receptors were considered potential targets for therapeutic efficacy of electroconvulsive therapy (ECT), but pre-clinical studies showed that electroconvulsive shock up-regulates 5-HT(2) receptors in contrast to antidepressant medications, which down-regulate brain 5-HT(2) receptors. Positron emission tomography (PET) studies in individuals with depression confirmed that antidepressant medications reduce brain 5-HT(2) receptors, but the effects of ECT on these receptors in individuals with depression are unknown.Aims: To determine if a course of ECT alters brain 5-HT(2) receptors in individuals with depression and whether such changes correlate with improvement in symptoms.Method: Fifteen people with major depression, refractory to antidepressant therapy and referred for a course of ECT, had an [18F]setoperone scan during baseline drug-free washout period and another after a course of ECT. We assessed changes in brain 5-HT(2) receptors with ECT and their relationship to therapeutic outcome.Results: Widespread reduction in brain 5-HT(2) receptors was observed in all cortical areas with changes slightly more prominent in the right hemisphere. There was a trend for correlation between reduction in brain 5-HT(2) receptors in right parahippocampal gyrus, right lingual gyrus and right medial frontal gyrus, and improvement in depressive symptoms.Conclusions: Unlike in rodents, and similar to antidepressants, ECT reduces brain 5-HT(2) receptors in individuals with depression. The ability of ECT to further down-regulate brain 5-HT(2) receptors in antidepressant non-responsive individuals may explain its efficacy in those people with antidepressant refractory depression. [ABSTRACT FROM AUTHOR]

Background: Although 5-hydroxytryptamine (5-HT) has been implicated in mania, the precise alterations in the 5-HT system remain elusive.Aims: To assess brain 5-HT2 receptors in drug-free individuals experiencing a manic episode in comparison with healthy volunteers using positron emission tomography (PET).Method: Participants (n = 10) with DSM-IV bipolar I disorder-manic episode and healthy controls (n = 10) underwent [18F]-setoperone scans. The differences in 5-HT2 receptor binding potential between the two groups were determined using statistical parametric mapping (SPM) analysis.Results: Age was a significant correlate with 5-HT2 receptor binding potential with a similar magnitude of correlation in both groups. The SPM analysis with age as a covariate showed that the individuals with current mania had significantly lower 5-HT2 receptor binding potential in frontal, temporal, parietal and occipital cortical regions, with changes more prominent in the right cortical regions compared with controls.Conclusions: This study suggests that brain 5-HT2 receptors are decreased in people with acute mania. [ABSTRACT FROM AUTHOR]

The article discusses the study which offered insights into the political culture of the ancient city states in Greece and their reactions to different situations. It proposes that the Megarians had used the inscribed decrees that looked similar but not identical with their Athenian neighbors during the early Hellenistic period. It also emphasizes the usefulness of decree culture which expressed the political culture of the Hellenistic Greek.

Background: Subtle formal thought disorders are difficult to quantify. Their relationship to florid thought disorder is unknown.Aims: To assess the interrater reliability, sensitivity and factor structure of a new assessment instrument, the Thought and Language Index (TLI), and to determine if minor aberrations detectable in the speech of healthy individuals are related to the more severe formal thought disorders characteristic of schizophrenia.Method: Interrater reliability was evaluated by determining the intraclass correlation for the ratings by five assessors. Factor analysis of the TLI scores of 87 patients was performed, and TLI scores in matched patients and controls were compared.Results: The intraclass correlation was good for individual TLI items, and excellent for sub-scale scores. Factor analysis identified three groups of approximately orthogonal disorders. Mild speech aberrations were observed in healthy participants and in patients with schizophrenia. The prevalence of mild aberrations was correlated with the prevalence of definite formal thought disorders.Conclusions: The TLI is reliable and capable of detecting subtle disorders. Some mild aberrations occurring in the speech of healthy individuals appear to be attenuated forms of the florid disorders characteristic of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: In the rating scales commonly used for assessing response to antipsychotic treatment, individual items embrace symptoms that apparently arise from distinguishable pathophysiological processes and might be expected to respond differently to treatment.Aims: To test the reliability, sensitivity to change and factor structure of a new scale for the assessment of the Signs and Symptoms of Psychotic Illness (the SSPI).Method: Interrater reliability was evaluated by determining the intraclass correlation for the ratings of 63 patients. Sensitivity to change was assessed in a longitudinal study of 33 patients. Factor structure was determined from scores for 155 patients.Results: The intraclass correlation was satisfactory for all individual items and excellent for the total score. Scores were sensitive to change. A change in Clinical Global Impression of one unit corresponded to an SSPI total score change of 31%. Factor analysis revealed five clusters of symptoms.Conclusions: The SSPI provides a sensitive and reliable measure of the five major clusters of symptoms that occur commonly in psychotic illness. [ABSTRACT FROM AUTHOR]

Background: The mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown.Aims: To determine the effects of RTD on brain 5-HT(2) receptors using positron emission tomography (PET) and (18)F-labelled setoperone.Method: Ten healthy women under went two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days.Results: The RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT(2) receptor binding in various cortical regions following the RTD session.Conclusions: When taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT(2) receptors, these findings suggest that a decrease in 5-HT(2) binding following RTD might be an adaptive response that provides protection against depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Functional imaging studies indicate that delusions and hallucinations in schizophrenia are associated with overactivity of the left hippocampus and ventral striatum. Hippocampal neuronal firing modulates feedback to cortex via cortico-striato-thalamic loops.Aims: To test the hypothesis that recovery from psychosis is associated with decrease in activity in cortico-striato-thalamic circuits, and, furthermore, that reduction in hippocampal activity predicts the degree of alleviation of delusions and hallucinations.Method: Positron emission tomography (PET) was used to measure the effects of the atypical antipsychotic, risperidone, on glucose metabolism in eight first-episode schizophrenia patients.Results: A single dose of risperidone produced decreases in metabolism in ventral striatum, thalamus and frontal cortex. The magnitude of decreases in left hippocampus predicted subsequent reduction in delusions and hallucinations. After six weeks' treatment with risperidone, the decreases in frontal metabolism were more extensive.Conclusions: The mechanism of antipsychotic action of risperidone entails reduction of hippocampal activity together with reduced feedback via cortico-striato-thalamic loops. [ABSTRACT FROM AUTHOR]

Background: PET studies of verbal fluency in schizophrenia report a failure of 'deactivation' of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying 'functional disconnectivity'.Aim: To test whether these findings provide trait-markers for schizophrenia.Method: We used H2(15)O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls.Results: We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex.Conclusions: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype. [ABSTRACT FROM AUTHOR]

The article comments on the papers "Negative symptoms in schizophrenia: Definition and reliability," by N.C. Andreasen (1982), "Negative v. positive schizophrenia: Definitions and validation," by Andreasen and S. Olsen (1982), and "The molecular pathology of schizophrenia: More than one disease process?," by T.J. Crow (1980). The segragation of schizophrenic symptoms and the relationship between symptoms, cerebral structure and cerebral function are also discussed.

About 10% of women show elation and associated features of hypomania in the first 5 days following childbirth. These symptoms can be detected using a self-rating scale (the 'Highs') based on SADS-L criteria. This phenomenon has been confirmed using the observer-rated Comprehensive Psychopathological Rating Scale, which also revealed a high degree of related irritability. Significantly more women scoring > or = 8 on the Highs scale at 3 days postpartum went on to manifest depression at 6 weeks than did subjects with no psychopathology in the early puerperium. It is suggested that the 'highs' followed by depression may be a mild and common form of bipolar disorder. [ABSTRACT FROM AUTHOR]

Investigation of the relationships between negative schizophrenic symptoms, abnormal involuntary movements and age in 179 chronic schizophrenic patients confirmed that both orofacial and trunk and limb dyskinesia are associated with negative symptoms, but only orofacial dyskinesia showed a significant increase in prevalence with increasing age. Estimation of the mean age of onset of orofacial dyskinesia from the observed variation in prevalence of orofacial dyskinesia with age indicated that patients having negative symptoms tend to develop orofacial dyskinesia at an earlier age. The estimated mean age of onset was 43.6 years in patients with substantial negative symptoms, and 54.6 years in patients without substantial negative symptoms. These findings support the proposal that the pathological process underlying negative symptoms can contribute to the occurrence of both orofacial and trunk and limb dyskinesia, but, in the case of orofacial dyskinesia, there is a synergistic interaction between the pathological process underlying negative symptoms and age-related neuronal changes. [ABSTRACT FROM AUTHOR]

Twenty chronic schizophrenic patients, ten matched normal controls and nine depressed controls performed categorical verbal fluency tasks for three minutes each on five separate occasions. On each occasion the schizophrenic patients generated significantly fewer words than the controls. Comparison of the different occasions showed that the schizophrenic patients had as many words available in their inner lexicons but were inefficient in retrieving them. The schizophrenic patients also generated fewer clusters of related words and more words outside the specified category. Reduced ability to generate words while the lexicon remained intact was more marked in patients with negative features. Patients with incoherence, in contrast, were more likely to produce inappropriate words. We propose that both poverty of speech and incoherence of speech reflect problems in the retrieval of words from the lexicon. To cope with these problems patients with poverty of speech terminate their search prematurely while the patients with incoherence commit errors in selecting words for output. [ABSTRACT FROM AUTHOR]

A battery of neuropsychological tests sensitive to frontal lobe impairment was administered to 43 chronic schizophrenic patients to delineate the abnormality of mental processing associated with the syndromes of psychomotor poverty and disorganisation, which had been identified in a previous study of the segregation of schizophrenic symptoms. Psychomotor poverty was found to be associated with slowness of mental activity, including slowness of generating words. The disorganisation syndrome was associated with impairment in tests in which the subject is required to inhibit an established but inappropriate response. [ABSTRACT FROM AUTHOR]

Confirmation is reported of an earlier finding that the symptoms of patients with chronic schizophrenia segregate into three syndromes: psychomotor poverty (poverty of speech, flatness of affect, decreased spontaneous movement); disorganisation (disorders of the form of thought, inappropriate affect); and reality distortion (delusions and hallucinations). [ABSTRACT FROM AUTHOR]

The article reports on the relationship of negative symptoms, tardive dyskinesia and depression with that of chronic schizophrenia. Psychiatric patients receiving anti-psychotic medication revealed an increase in the sixth decade as association between age and oro-facial dyskinesia is examined. The emergence of tardive dyskinesia during mid-life is assumed as prevalence of tardive dyskinesia in young patients show. Schizophrenic patients with negative symptoms who develop tardive dyskinesia earlier than those without such symptoms, show more susceptibility to the condition.

Out of 194 chronic schizophrenic in-patients, depressed mood (item 23 of the PSE) was present in 25 (13%). When compared with 25 matched controls, the patients with depressed mood had significantly higher scores on the MADRS and the Beck Depression Inventory. Serious suicidal ideas and auditory hallucinations were significantly more common in the depressed group. However, there were no significant differences between the matched groups in terms of negative symptoms, Parkinsonism, tardive dyskinesia, anticholinergic medication, or current dose of antipsychotic drug, which suggests that the depression identified was not related to drug treatment, nor was it a direct manifestation or misinterpretation of negative symptoms. Over three-month follow-up, the MADRS and Beck scores covaried closely with the presence or absence of depressed mood. This depressive syndrome persisted over the three months in the majority of patients originally depressed. [ABSTRACT FROM AUTHOR]

The relationships between symptoms in 40 schizophrenic patients, selected for persistence of symptoms, were examined. The symptoms segregated into three syndromes: psychomotor poverty (poverty of speech, lack of spontaneous movement and various aspects of blunting of affect); disorganisation (inappropriate affect, poverty of content of speech, and disturbances of the form of thought); and reality distortion (particular types of delusions and hallucinations). Both the psychomotor poverty and disorganisation syndromes were associated with social and occupational impairment; in particular, the psychomotor poverty syndrome was associated with impairment of personal relationships, and the disorganisation syndrome with poor self-care and impersistence at work. [ABSTRACT FROM AUTHOR]

The examines the effectiveness regarding the use of Modified Rogers Scale in assessing the complexity schizophrenics and other movement disorders. According to the author, the guidelines of the Rogers scale for rating underactivity include several descriptions of behavior which can also be found on Parkinson's disease such as sitting abnormally still, inert and passive. On the other hand, one study has found the relationship between catatonia and schizophrenic symptoms which remained after correcting effects of chronicity and serverity of the illness. Other results of the studies were also discussed.

Sarró et al report grey matter deficits associated with tardive dyskinesia in schizophrenia. Much evidence suggests that the intrinsic pathophysiology of schizophrenia contributes to predisposition to tardive dyskinesia. The possibility that antipsychotics might play a causal role in the grey matter deficits cannot be excluded, but the evidence is tenuous. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to comments made on the authors' article about tardive dyskinesia.

A letter to the editor is presented in response to a study by Peralta and colleagues in the September 1992 issue about factor analysis of schizophrenia symptoms.

Background: In patients with schizophrenia, distributed abnormalities are observed in grey matter volume. A recent hypothesis posits that these distributed changes are indicative of a plastic reorganisation process occurring in response to a functional defect in neuronal information transmission. We investigated the structural covariance across various brain regions in early-stage schizophrenia to determine if indeed the observed patterns of volumetric loss conform to a coordinated pattern of structural reorganisation., Methods: Structural magnetic resonance imaging scans were obtained from 40 healthy adults and 41 age, gender and parental socioeconomic status matched patients with schizophrenia. Volumes of grey matter tissue were estimated at the regional level across 90 atlas-based parcellations. Group-level structural covariance was studied using a graph theoretical framework., Results: Patients had distributed reduction in grey matter volume, with high degree of localised covariance (clustering) compared with controls. Patients with schizophrenia had reduced centrality of anterior cingulate and insula but increased centrality of the fusiform cortex, compared with controls. Simulating targeted removal of highly central nodes resulted in significant loss of the overall covariance patterns in patients compared with controls., Conclusion: Regional volumetric deficits in schizophrenia are not a result of random, mutually independent processes. Our observations support the occurrence of a spatially interconnected reorganisation with the systematic de-escalation of conventional 'hub' regions. This raises the question of whether the morphological architecture in schizophrenia is primed for compensatory functions, albeit with a high risk of inefficiency.

Background: Whether there are distinct subtypes of schizophrenia is an important issue to advance understanding and treatment of schizophrenia., Aims: To understand and treat individuals with schizophrenia, the aim was to advance understanding of differences between individuals, whether there are discrete subtypes, and how first-episode patients (FEP) may differ from multiple episode patients (MEP)., Method: These issues were analysed in 687 FEP and 1880 MEP with schizophrenia using the Positive and Negative Syndrome Scale for (PANSS) schizophrenia before and after antipsychotic medication for 6 weeks., Results: The seven Negative Symptoms were correlated with each other and with P2 (conceptual disorganisation), G13 (disturbance of volition), and G7 (motor retardation). The main difference between individuals was in the cluster of seven negative symptoms, which had a continuous unimodal distribution. Medication decreased the PANSS scores for all the symptoms, which were similar in the FEP and MEP groups., Conclusions: The negative symptoms are a major source of individual differences, and there are potential implications for treatment., Declaration of Interests: L.P. received speaker fees from Otsuka Canada and educational grant from Janssen Canada in 2017., Copyright and Usage: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

In 41 patients with schizophrenia, we used neuroanatomical information derived from structural imaging to identify patients with more severe illness, characterised by high symptom burden, low processing speed, high degree of illness persistence and lower social and occupational functional capacity. Cortical folding, but not thickness or volume, showed a high discriminatory ability in correctly identifying patients with more severe illness., (© The Royal College of Psychiatrists 2015.)

Background: Patients with schizophrenia have an impaired ability to generate activity that is appropriate to current circumstances and goals., Method: We report a study using functional magnetic resonance imaging (fMRI) to examine cerebral activity during a three-tone auditory oddball target detection task in a sample of 28 patients with schizophrenia and 28 healthy controls., Results: The patients exhibited significantly less activation in response to target stimuli relative to baseline in an extensive set of sites in association neocortex, paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a normal level of activation in the sensorimotor cortex. Comparison of activity elicited by rare target stimuli with that elicited by equally rare novel stimuli makes it possible to distinguish cerebral activity associated with attention to behaviourally salient stimuli from activity associated with attending to other attention-capturing stimuli. This comparison revealed that the patients with schizophrenia also exhibited a deficit in activation of basal forebrain areas that mediate motivation during the processing of behaviourally salient stimuli, including the amygdala, ventral striatum, orbital frontal cortex and rostral anterior cingulate cortex., Conclusion: Patients with schizophrenia have a deficit in function of the brain system concerned with mediating motivation, in addition to a more general deficit in the cerebral response to attention-captivating stimuli.