ABSTRACT
BACKGROUND: Imaging studies of patients with schizophrenia have demonstrated that brain abnormalities are largely confined to decreases in gray matter volume and enlargement of the lateral and third ventricles. Global gray matter volume has been reported to progressively decrease in childhood-onset and chronic schizophrenia. Global gray matter volumes have not been examined longitudinally in patients with first-episode schizophrenia. One would expect global gray matter to decrease progressively, particularly in first-episode patients, because clinical deterioration is greatest in the early stages of the disease. METHODS: Patients with first-episode schizophrenia who had taken antipsychotic medication for 0 to 16 weeks (n = 34) and matched healthy comparison subjects (n = 36) were included in the study. For all subjects, magnetic resonance imaging scans of the whole brain were obtained at inclusion and after 1 year (mean [SD], 12.7 [1.1] months). Outcome was measured 2 years after inclusion. To compare morphological changes over time between patients and healthy comparison subjects, multiple repeated-measures analyses of variance were conducted with intracranial volume as a covariate. Outcome and cumulative antipsychotic medication were related to changes in patients' brain volumes. RESULTS: Total brain volume (-1.2%) and gray matter volume of the cerebrum (-2.9%) significantly decreased and lateral ventricle volume significantly increased (7.7%) in patients. The decrease in global gray matter volume significantly correlated with outcome and, independently of that, with higher cumulative dosage of antipsychotic medication. CONCLUSIONS: The loss of global gray matter in schizophrenia is progressive, occurs at an early stage of the illness, and is related to the disease process and antipsychotic medication.
Subject(s)
Brain/pathology , Magnetic Resonance Imaging , Schizophrenia/pathology , Schizophrenic Psychology , Adolescent , Adult , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Dominance, Cerebral/physiology , Echo-Planar Imaging , Female , Follow-Up Studies , Fourier Analysis , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Male , Prospective Studies , Psychiatric Status Rating Scales , Reference Values , Schizophrenia/drug therapyABSTRACT
BACKGROUND: Several studies have shown that the ability to suppress automatic saccadic eye movements is impaired in patients with schizophrenia as well as in their first-degree relatives, and suggest that this impairment is a potential vulnerability marker for schizophrenia. The neurobiological mechanisms underlying normal saccade production and inhibition, revealed in primate studies, indicate that the impairment may result from a failure of the oculomotor system to effectively exert inhibitory control over brainstem structures. Functional localization of the affected brain structure(s) potentially provides a physiological measure for the investigation of vulnerability markers in schizophrenia. METHODS: The hemodynamic response to discrete visual stimuli was measured during prosaccades (saccades toward a peripheral stimulus), antisaccades (saccades toward a position opposite to a peripheral stimulus), and active fixation (holding fixation and ignoring a peripheral stimulus) in 16 patients with schizophrenia receiving atypical neuroleptics and 17 healthy control subjects using an event-related functional magnetic resonance imaging task design. RESULTS: Brain responses were detected in the frontal and parietal regions of the oculomotor system in all 3 tasks. Patients made more errors during inhibition tasks and exhibited a selective failure to activate the striatum during the inhibition of saccades. In other regions that were active during inhibition, specifically the supplementary and frontal eye fields, no difference was found between patients and control subjects. CONCLUSIONS: A frontostriatal network is engaged in the suppression of automatic eye movements. The results indicate that abnormalities in this network, rather than the selective dysfunction of prefrontal brain regions, underlie the saccade inhibition deficit in schizophrenia.
Subject(s)
Brain/abnormalities , Magnetic Resonance Imaging , Neural Inhibition/physiology , Neurons/physiology , Saccades/physiology , Schizophrenia/diagnosis , Schizophrenia/physiopathology , Adult , Brain/blood supply , Brain Stem/blood supply , Brain Stem/physiopathology , Corpus Striatum/blood supply , Corpus Striatum/physiopathology , Electrooculography , Female , Fixation, Ocular/physiology , Frontal Lobe/blood supply , Frontal Lobe/physiopathology , Hemodynamics , Humans , Male , Nerve Net/physiopathology , Photic Stimulation , Prefrontal Cortex/blood supply , Prefrontal Cortex/physiopathology , Visual Fields/physiologyABSTRACT
The effects of transcranial magnetic stimulation (TMS) on hallucination severity and neurocognition were studied in 9 medication-resistant hallucinating patients. A statistically significant improvement was observed on a hallucination scale after 10 days of TMS at the left auditory cortex.
