Corpus callosum size and diffusion tensor anisotropy in adolescents and adults with schizophrenia.

The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age- and sex-matched healthy controls. The corpus callosum was manually traced on each participant׳s MRI, and the DTI scan was co-registered to the MRI. The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that the initial stages of the illness are characterized by deficiencies in frontal connections, and the chronic phase is characterized by deficits in the posterior corpus callosum; or, alternatively, adolescent-onset schizophrenia may represent a different or more severe form of the illness.

Age and diffusion tensor anisotropy in adolescent and adult patients with schizophrenia.

Findings of white matter pathology as indicated by diffusion tensor anisotropy values in schizophrenia are well established, but the differences in this measure between the onset of the disease and the chronic state are not well known. To investigate the differences between these states in the progression of the disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on 35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents having their first psychotic episode, and age and sex matched controls (33 adults and 15 adolescents). Regions of interest in major cortical white matter tracts chosen as salient to the prefrontal executive deficit in schizophrenia were assessed using stereotaxic coordinates from the Talairach and Tournoux atlas. Regions of each tract along anterior-posterior and/or inferior-superior directions in both hemispheres were evaluated in multiway ANOVA. Tracts between the frontal lobe and other brain regions, but not temporal, occipital and interhemispheric tracts, showed a differential aging pattern in normals and patients indicating that the white matter pathology in these regions is not stable between the onset and the chronic state in schizophrenia. This suggests that tracts involved in the connectivity of the temporal lobe white matter deficits were already well in place in adolescent patients, while frontal lobe pathology continues to develop from adolescence to adulthood.

FDG-PET in never-previously medicated psychotic adolescents treated with olanzapine or haloperidol.

We acquired Positron emission tomography with 18-F-deoxyglucose (FDG-PET) and anatomical MRI in 30 never-previously medicated psychotic adolescents (ages 13-20). (FDG-PET) was obtained at baseline and after 8-9 weeks of a randomized double-blind trial of either olanzapine or haloperidol. Neuropsychological tests of executive function were also obtained. Patients carried out the serial verbal learning task, a modification of the California Verbal Learning Test, during the uptake of the FDG. PET scans were coregistered with spoiled gradient MRI (TR=24, TE=5, flip angle 40 degrees, slice thickness 1.2 mm, field of view 230 mm) for accurate anatomical identification of regions of interest traced on the MRI. Twenty-two of the thirty patients completed the second PET and clinical evaluation. Individuals treated with olanzapine increased relative metabolic rates in the frontal lobe more than the occipital lobe while patients treated with haloperidol failed to increase frontal metabolic rates and did not show an anteroposterior gradient in medication response. Haloperidol increased striatal metabolic rate more than olanzapine. Both drugs increased thalamic metabolic rates and this increase was significantly larger in younger (age 13-15) than older (16-21) patients.

Diffusion tensor anisotropy in adolescents and adults.

We acquired diffusion tensor images on 33 normal adults aged 22-64 and 15 adolescents aged 14-21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.

Neuropsychological functioning in first-break, never-medicated adolescents with psychosis.

The purpose of the current study was to examine neuropsychological functioning in a group of never-medicated first-break adolescents with psychosis. It is the first report of cognition in a sample of adolescents with psychosis in which all patients were drug-naive. Twenty-nine adolescent patients (mean age = 16.07; SD = 2.00; 15 male and 14 female patients) experiencing their first psychotic episode and 17 age-matched and sex-matched normal volunteers (mean age = 16.88; SD = 2.39; 9 male and 8 female subjects) were recruited and assessed with a neuropsychological battery. Measures of attention, memory, language, executive functioning, perceptual motor processing, and motor speed were obtained. Psychiatric symptomatology, estimated verbal IQ, and parental socioeconomic status were also determined. Patients with psychosis were significantly more impaired than normal volunteers; effect sizes were greatest in the areas of executive functioning, attention, and memory, and significantly smaller in areas of language, perceptual motor processing, and motor speed. The pattern was not altered when differences in verbal IQ and parental socioeconomic status were controlled. Sex and age interactions indicated that younger male patients were particularly impaired. The findings demonstrate neuropsychological deficits in adolescents with psychosis and suggest that cognitive deficits are core symptoms in psychotic disorders.