Wednesday, January 28, 2009
schizophrenia
Abstract and Introduction
Abstract
Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.
Introduction
The study of adolescents with first-episode psychosis is of great interest for understanding the pathogenesis of psychosis because younger patients are less confounded by environmental factors such as substance abuse, disease duration, education years, and treatment effects, thus representing a more homogenous patient group. Brain volume abnormalities have been consistently described early in the course of psychosis. Reduction in whole brain and in gray matter (GM) volume, primarily in the frontal and temporal lobes, and enlargement of the lateral ventricles[1-4] are among the most replicated findings in cross-sectional studies of adult patients with first psychotic episodes compared with healthy controls, in line with those typically described in chronic schizophrenia.[5,6] Moreover, early onset psychosis (EOP, first episode before 18 years of age) has been associated with brain changes similar to those reported in chronic schizophrenia.[7-10]
The nature, timing, and course of these structural abnormalities need to be elucidated in order to understand the pathological processes underlying psychosis, in the context of the neurodevelopmental or the neurodegenerative hypothesis.[11] The essential question concerns whether brain abnormalities observed at an early stage are static or progress with time.
Evidence of progressive brain changes during the initial years of psychosis is still not conclusive. Whereas some follow-up studies of first-episode schizophrenia have found progressive reduction of GM volume in the total brain,[12] frontal,[13] parietal and temporal lobes,[14] and enlargement of the lateral ventricles,[12,15] others have failed to detect such longitudinal changes.[16-19] Greater volume decline has been found at follow-up in first-episode schizophrenia patients compared with chronic patients,[13] suggesting that brain changes are more pronounced during the early stages of the illness. Longitudinal brain changes observed in patients with childhood-onset schizophrenia include greater GM loss and larger increase in ventricular volume than controls.[20-23] GM loss in these patients appears to start in the parietal cortex, subsequently spreading through the temporal, frontal, and prefrontal cortices,[24] and frontal atrophy seems to be progressive during adolescence.[25] On the other hand, the only longitudinal study of adolescent-onset schizophrenia showed no progressive changes over a 2- to 3-year period in the prefrontal GM deficit, and in the ventricular enlargement observed relative to control subjects.[26,27]
Most longitudinal studies of first-episode psychosis comprise both adolescents and adults,[12,14,15,19] making it difficult to disentangle the influence of normal development on findings. Longitudinal studies of early onset schizophrenia (with the exception of James et al[26,27]) have included mostly treatment-resistant patients with a considerable duration of illness at baseline scanning.[20-25]
To avoid these confounding factors and minimize the impact of illness and medication on baseline and follow-up conditions, this longitudinal study followed a cohort of psychotic patients with very recent onset of psychosis (under 6 months), short duration of disease, and short antipsychotic treatment prior to scanning. The study includes a matched comparison group of healthy adolescents to control for age-related changes, and all subjects were followed for the same period of 2 years. The cohort of patients is particularly suited for a longitudinal study because it showed structural changes relative to controls,[10] in line with known changes in adults. Based on previous research, we hypothesized that the pattern of change over time would be different between psychotic patients and control subjects, with the former having greater loss of GM. In exploratory analyses, we also sought to determine if volume changes would be different in patients with schizophrenia compared with patients with other psychotic disorders and to assess the influence of clinical status on brain volumes.
