ABSTRACT
At what levels of brain organization might pathological change in schizophrenia be anatomically expressed: global, regional or supraregional? We hypothesised that brain structure reflects a set of supra-regional anatomical systems with common developmental influences. We conducted an exploratory analysis to identify supraregional brain systems and to investigate whether abnormal brain architecture in schizophrenia is manifested within one or more of these systems. Magnetic resonance (MR) images were acquired from 27 patients with schizophrenia and 37 control subjects. After segmentation and registration of each individual MRI dataset in the standard space of Talairach and Tournoux, grey matter and ventricular-cerebrospinal fluid (CSF) maps were automatically parcellated into 104 regions. We used principal components analysis of the multiple regional grey matter and ventricular-CSF measurements, on all 64 subjects, to extract the five main normative supra-regional systems. The first two of these components represented global variation in grey matter and ventricular-CSF regional measures. We interpreted the other three components as representing supra-regional systems comprising: a frontal-parietal system, a frontal-temporal system and a frontal-basal ganglia system. Schizophrenic group mean scores on the first component (global grey matter-ventricular contrast) and fourth component (frontal-temporal system) were significantly reduced compared to controls. These results suggest that pathological change in schizophrenia may be expressed at two mutually independent levels of anatomical organization: global change in a grey matter/ventricular system and supra-regional change in a frontal-temporal system.
Subject(s)
Brain/pathology , Schizophrenia/pathology , Adult , Algorithms , Brain/physiopathology , Brain Mapping , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Cerebral Ventricles/pathology , Cerebral Ventricles/physiopathology , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Multivariate Analysis , Schizophrenia/cerebrospinal fluid , Schizophrenia/physiopathologyABSTRACT
Studies of brain changes in schizophrenia have suggested that the disorder is associated with reductions in both global and regional grey matter. In this study, we used structural neuroimaging to differentiate between these two types of change and to examine regional grey matter throughout the whole brain. Grey matter from magnetic resonance images was segmented and transformed into stereotactic space, and patients with schizophrenia and controls were compared with respect to regional grey matter (after compensating for global grey matter differences). In two preliminary analyses to test our methodology, we demonstrated that: (1) in the transformed grey matter maps, voxel values at the location of the caudate nuclei were correlated with region-of-interest measurements of caudate area in native image space, and (2) the technique detected regional grey matter changes resulting from artificial lesions created in the native images. We then used a factorial design to examine data from two studies, comprising a total of 42 schizophrenics and 52 controls. Analysis of the main effect of schizophrenia on regional grey matter revealed significant reductions in (a) the right temporal pole, insula and amygdala, (b) the left temporal pole, insula and dorsolateral prefrontal cortex.
Subject(s)
Brain Mapping , Cerebral Cortex/pathology , Schizophrenia/pathology , Adult , Cerebral Cortex/physiopathology , Female , Functional Laterality , Humans , Magnetic Resonance Imaging , MaleABSTRACT
A boy aged 11 years 11 months, with normal premorbid personality, presented with a severe depressive episode with somatic and psychotic features. A clinical response to amitriptyline was complicated by ECG changes leading to the abrupt withdrawal of amitriptyline, with the development of a withdrawal syndrome. Further trials of antidepressant medication were unsuccessful, including paroxetine (clinical deterioration), lofepramine (ECG changes and clinical deterioration), and trazodone (priapism). Finally, a good clinical response to dothiepin augmented with lithium was achieved. ECG changes were assessed as being idiosyncratic responses to medication, rather than ischaemic in nature. A dose/response relationship with dothiepin was observed. All medication was successfully stopped after 26 months of treatment. Clinical phenomena relevant to the development of guidelines for use of tricyclic antidepressants in childhood and adolescence are discussed.
Subject(s)
Antidepressive Agents, Tricyclic/therapeutic use , Depressive Disorder/drug therapy , Dothiepin/therapeutic use , Lithium Carbonate/therapeutic use , Amitriptyline/adverse effects , Antidepressive Agents, Second-Generation/adverse effects , Child , Depressive Disorder/diagnosis , Drug Monitoring , Drug Therapy, Combination , Electrocardiography , Humans , Lofepramine/adverse effects , Male , Paroxetine/adverse effects , Trazodone/adverse effectsABSTRACT
Many retrospective studies, and an increasing number of prospective studies, have identified subtle abnormalities in preschizophrenics from as early as the first year of life. Premorbid characteristics include development delays, cognitive deficits, and abnormal social interactions. Schizoid personality traits have been a particularly well documented finding, and show some specificity in their association with schizophrenia. Information about the premorbid characteristics of schizophrenia has played a major role in the reorientation of the field, from regarding schizophrenia as an adult onset degenerative disorder, to considering it, at least in part, as a neurodevelopmental condition. However, whether the childhood personality traits are a reflection of an underlying brain lesion, or whether they are independent risk factors for the disorder, is uncertain. In the future, the identification of childhood characteristics may enable us to predict those who are at high risk of developing schizophrenia, and may even be useful in formulating preventive policies. However, at present, the powers of prediction are inadequate for such purposes.
Subject(s)
Schizophrenia/diagnosis , Adult , Child , Child, Preschool , Female , Humans , Male , Risk Factors , Schizophrenic Psychology , Sex Factors , Social PerceptionABSTRACT
Antidepressants are frequently used in the treatment of depressive symptoms associated with schizophrenia. In patients taking clozapine, choice of antidepressant is complicated by additive pharmacodynamic effects and by pharmacokinetic interactions. We predicted that citalopram would not elevate plasma clozapine levels when the two drugs were co-administered because it does not inhibit the relevant enzyme systems. In this preliminary study of five patients given citalopram and clozapine there was no overall change in mean clozapine levels. Based on this limited evidence, citalopram might be the antidepressant of choice in patients taking clozapine.
