Scientific abstract

Background

Schizophrenia is one of the most devastating psychiatric disorders to affect adolescents. Although extremely rare before the age of 10, the incidence of schizophrenia rises steadily through adolescence to reach its peak in early adult life. Early-onset schizophrenia (EOS) is associated with poor premorbid functioning and early developmental delays, which is particularly striking for patients with onset before adolescence. Similar developmental, social and neurocognitive impairments in adolescence have been reported in adult-onset schizophrenia, but premorbid impairments appear to be more common and severe in EOS. These deficits may be markers of underlying neuropathological processes. Although the brain abnormalities in EOS patients are beginning to be better characterized by neuroimaging and neurocognitive studies, the number of studies is still low and results inconclusive.

Aim

The main aim of this thesis was to investigate brain abnormalities in EOS using functional, structural and behavioral measures. Three representative methods were applied to provide three different research angels into brain abnormalities of EOS.

Methods

In three papers, the present thesis examines participants from the same sample of patients with EOS and healthy controls applying three different methods. First, fMRI activation during a working-memory task (2-back) was measured for 15 EOS patients compared to 15 healthy controls. Second, a backward-masking task was applied to assess early visual processing in 28 EOS patients compared to 80 healthy controls in a longitudinal study including baseline, one-year and two-year follow-ups. Although the backward-masking study does not include imaging data, early detection of visual stimuli is a psychophysical measure that has well defined neurophysiological correlates. Third, cross-sectional age-related differences in cortical thickness were measured using structural MRI for 23 patients and 32 healthy controls. In addition analyses of age by group interaction effects were performed for parcellations in both hemispheres.

Results

Overall, the thesis demonstrates several differences between EOS patients and healthy controls. The fMRI-study revealed hyper-activation in ventrolateral prefrontal cortex (VLPFC) in EOS patients compared to healthy controls during a 2-back working-memory task. The patients hyperactivated the VLPFC even though they performed at the same level on the working-memory task in the scanner. The backward-masking study showed no difference between EOS patients and healthy controls in masking effect performance. However, the patients did reveal deficit of early visual processing in general by showing a deficit of processing the target in the no-mask condition. In addition there was an effect of development for both EOS and healthy controls. In the investigation of cortical thickness, the EOS patients failed to demonstrate adequate cortical thinning evident in the healthy controls. Also, an age by group interaction effect was shown in some areas in both hemispheres.

Conclusion

In sum this thesis contributes to the description and understanding of neurocognitive functioning and brain functioning in EOS patients. The fMRI-study suggests that the VLPFC hyper-activation in EOS is compensatory in nature. Moreover, it is speculated that patients with EOS use more cognitive effort or a different strategy in performing working-memory tasks. The early visual processing deficit in EOS found in the second study suggests that basic visual processing is an important feature of the illness, and may be related to sensory dysfunction. In the structural MRI study the patient’s failure to demonstrate adequate cortical thinning suggests that EOS patients follow a different developmental pathway than healthy controls.

Publisert 16. mai 2013 15:15