ABSTRACT
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Subject(s)
Depression/diagnosis , Depression/therapy , Schizophrenia/diagnosis , Schizophrenia/therapy , Mood Disorders/diagnosis , Mood Disorders/therapy , Neurasthenia/diagnosis , Neurasthenia/therapy , Memory Disorders/diagnosis , Mood Disorders/prevention & controlABSTRACT
BACKGROUND: Functional neuroimaging findings of "hypofrontality" in schizophrenic patients is still controversial, due to the heterogeneity of methods and patient samples. This study tries to prevent some of these concerns by studying neuroleptic-naive (NN) and neuroleptic-free (NF) young female patients both in resting conditions and during a frontal cognitive activation task. METHODS: Regional cerebral blood flow (rCBF) was studied at rest and during the Wisconsin Card Sorting Test (WCST) in 25 young acute unmedicated schizophrenic female patients (14 NN and 11 NF) and 15 female controls, using single photon emission computed tomography. RESULTS: The schizophrenic and control groups did not differ in rCBF during the baseline condition, but the schizophrenic group failed to activate the frontal lobe during the WCST condition. In addition, the left anterior temporal rCBF at rest correlated with the Scale for the Assessment of Positive Symptoms total score. CONCLUSIONS: The results suggest that hypofrontality in young acute unmedicated schizophrenic patients is a result of an inability to activate frontal regions during cognition, rather than a baseline decrease in frontal activity. Furthermore, positive symptoms seem to be associated with left temporal cortex activity.
Subject(s)
Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathology , Adult , Cerebrovascular Circulation/physiology , Female , Humans , Radiopharmaceuticals , Technetium Tc 99m Exametazime , Tomography, Emission-Computed, Single-PhotonABSTRACT
Twenty-two schizophrenic inpatients were treated for 3 weeks with three randomly fixed oral doses of haloperidol (10, 20, or 30 mg). Analysis of the results by a nonlinear regression model revealed a curvilinear relationship between haloperidol levels in plasma and clinical response, as assessed on the Brief Psychiatric Rating Scale (pseudo-R2 = 0.85, F = 17.7, p < 0.001, correlation between coefficients ranged from 0.99 to -0.52). This curve defines roughly three drug level ranges (low, < 5.5 ng/ml; optimal, 5.5 to 14.4 ng/ml; and high or toxic, > 14.4 ng/ml), which are significant for clinical practice. Patients with high levels improve to a lesser extent or even worsen in negative symptoms, showing a nonstatistically significant trend to present more extrapyramidal symptoms. Our data thus support the existence of a therapeutic window for haloperidol. Schizophrenic patients with acute exacerbation and drug levels in this range would have a greater probability of global clinical improvement.
Subject(s)
Haloperidol/administration & dosage , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced/blood , Dyskinesia, Drug-Induced/diagnosis , Female , Haloperidol/adverse effects , Haloperidol/pharmacokinetics , Humans , Male , Psychiatric Status Rating Scales , Schizophrenia/blood , Schizophrenia, Paranoid/blood , Schizophrenia, Paranoid/drug therapy , Schizophrenia, Paranoid/psychologyABSTRACT
Regional cerebral blood flow (rCBF) was measured with single photon emission computed tomography (SPECT) in six neuroleptic-naive, young, acute schizophrenic patients and six normal control subjects. We evaluated rCBF changes in prefrontal areas at rest and during a prefrontal activation task, the Wisconsin Card Sorting Test (WCST). Schizophrenic patients had significantly higher prefrontal blood flow than did control subjects during the resting conditions. During activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. These results suggest that at rest there is no evidence of hypofrontality, whereas hyperfrontality seems to be the most frequent pattern in our selected sample of young acute neuroleptic-naive schizophrenic patients. Furthermore, schizophrenic patients seem to be unable to increase prefrontal blood flow under conditions that challenge the prefrontal cortex.
Subject(s)
Prefrontal Cortex/blood supply , Prefrontal Cortex/diagnostic imaging , Schizophrenia/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Adult , Female , Humans , Prefrontal Cortex/physiopathology , Psychiatric Status Rating Scales , Schizophrenia/diagnosis , Schizophrenia/physiopathologyABSTRACT
UNLABELLED: This study assesses prefrontal and temporal regional cerebral blood flow (rCBF) changes in young, neuroleptic-naive schizophrenic patients with acute disease. METHODS: A selected population of 10 young, never-treated schizophrenic women with acute disease was studied by two hexamethylpropyleneamine oxime (HMPAO) brain SPECT sessions, performed 48 hr apart, both at rest and during a prefrontal activation task using the Wisconsin Card Sort Test (WCST). All patients met Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-revised criteria for schizophrenia or schizophreniform disorder, were neuroleptic-naive and had acute symptoms. RESULTS: Under resting conditions, the schizophrenic group had significantly higher rCBF in the prefrontal regions, mainly in the left side and including the anterior cingulate, than did the controls. In addition, schizophrenic patients showed significant interhemispheric differences in prefrontal and posterior temporal index values at rest (left hyperfrontality and left hypotemporality). During WCST activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. CONCLUSION: These results support a physiologic dysfunction of the prefrontal cortex in schizophrenia that is present at the onset of the illness prior to neuroleptic treatment. Furthermore, both left hyperfrontality and left hypotemporality may indicate a brain lateralization defect in schizophrenia.
Subject(s)
Cerebral Cortex/diagnostic imaging , Cerebrovascular Circulation , Organotechnetium Compounds , Oximes , Schizophrenia/physiopathology , Tomography, Emission-Computed, Single-Photon , Acute Disease , Adult , Cerebral Cortex/physiopathology , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Humans , Rest , Schizophrenia/diagnostic imaging , Schizophrenic Psychology , Technetium Tc 99m Exametazime , Temporal Lobe/diagnostic imaging , Temporal Lobe/physiopathology , ThinkingABSTRACT
1. Clinical response to treatment with haloperidol was studied in 20 schizophrenic inpatients with acute exacerbation (DSM-IIIR). 2. Patients were assigned to fixed doses of haloperidol (10, 20 or 30 mg/day) for three weeks. Clinical assessment was made using scales SAPS, SANS, BPRS and Simpson-Angus Scale for rating of extrapyramidal side effects. 3. Sixteen patients showed forty per cent or more decrease in positive symptoms assessed by SAPS, being considered the group of responders. Six out of the twenty patients showed improvement in negative symptoms assessed by SANS (improvement above 30%). 4. Clinical predictors of response were only identified for SAPS. The group of responders showed higher basal scores in total scale and formal thought disorder. 5. Negative symptoms responsive to treatment were affective flattening and alogia. Improvement in negative symptoms was independent from that in positive ones. 6. Socio-demographic predictors of clinical response were not found. No differences in clinical response were found in relation to the dose administered. 7. The results of our study suggest that negative symptomatology improves in a scheduled treatment with haloperidol. Assessment of negative symptoms may be useful in the evaluation of treatment of acute schizophrenia.
