Duration of illness and treatment effects on hippocampal volume in male patients with schizophrenia

Background Reduced hippocampal volume is a consistently described structural abnormality in schizophrenia but its cause and timing are not known. Aims To examine the relationship of duration of schizophrenic illness and treatment effects with hippocampal volumes. Method Quantitative 1.5 T magnetic resonance imaging brain scans of young male patients in the early stage of schizophrenic illness were compared with those of chronically ill older patients. Scans were also acquired for controls matched to both patient groups for age and handedness. Duration of illness was recorded and severity of symptoms assessed with the Positive and Negative Syndrome Scale. Results The patients with schizophrenia had smaller hippocampal volumes than the controls. The volume reduction was larger in older patients than in young, compared with age-matched controls. In the early illness group atypical antipsychotics rather than haloperidol were associated with larger hippocampal volumes even after controlling for differences in illness severity Conclusions The greater reduction of hippocampal volume in people with chronic v. early illness, after controlling for illness severity and age, supports the hypothesis of progressive hippocampal reduction in males with schizophrenia. Atypical antipsychotics early in illness may protect against this.

[1]  C. Pantelis,et al.  Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study. , 1999, Archives of general psychiatry.

[2]  Jeffrey A. Lieberman,et al.  Hippocampus-amygdala volumes and psychopathology in chronic schizophrenia , 1993, Biological Psychiatry.

[3]  R. Hen,et al.  Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants , 2003, Science.

[4]  J. Lieberman,et al.  Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. , 2003, The American journal of psychiatry.

[5]  J. Lieberman,et al.  Cortical Bcl-2 protein expression and apoptotic regulation in schizophrenia , 2000, Biological Psychiatry.

[6]  Zin Z. Khaing,et al.  BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs , 2001, The European journal of neuroscience.

[7]  L. DeLisi,et al.  Anomalous lateral sulcus asymmetry and cognitive function in first-episode schizophrenia. , 1992, Schizophrenia bulletin.

[8]  G. Duncan,et al.  Comparison of the effects of clozapine, risperidone, and olanzapine on ketamine-induced alterations in regional brain metabolism. , 2000, The Journal of pharmacology and experimental therapeutics.

[9]  G. Moore,et al.  Neuroplasticity and cellular resilience in mood disorders , 2000, Molecular Psychiatry.

[10]  F. Gage,et al.  Neurogenesis in the adult human hippocampus , 1998, Nature Medicine.

[11]  J. Olney,et al.  Glutamate receptor dysfunction and schizophrenia. , 1995, Archives of general psychiatry.

[12]  Eric J. Nestler,et al.  Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[13]  R. Kikinis,et al.  Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging , 1992, Journal of magnetic resonance imaging : JMRI.

[14]  Oliver T Wolf,et al.  MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation , 1999, Psychiatry Research: Neuroimaging.

[15]  R. Murray,et al.  Meta-analysis of regional brain volumes in schizophrenia. , 2000, The American journal of psychiatry.

[16]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[17]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[18]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[19]  F. Gage,et al.  Activity-dependent regulation of neuronal plasticity and self repair. , 2000, Progress in brain research.