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Cross-sectional studies indicate that hippocampal function is abnormal across stages of psychosis. Neural theories of psychosis pathophysiology suggest that dysfunction worsens with illness stage. Here, we test the hypothesis that hippocampal function is impaired in the early stage of psychosis and declines further over the next 2 years.
We measured hippocampal function over 2 years using a scene processing task in 147 participants (76 individuals in the early stage of a non-affective psychotic disorder and 71 demographically similar healthy control individuals). Two-year follow-up was completed in 97 individuals (50 early psychosis, 47 healthy control). Voxelwise longitudinal analysis of activation in response to scenes was carried out within a hippocampal region of interest to test for group differences at baseline and a group by time interaction.
At baseline, we observed lower anterior hippocampal activation in the early psychosis group relative to the healthy control group. Contrary to our hypothesis, hippocampal activation remained consistent and did not show the predicted decline over 2 years in the early psychosis group. Healthy controls showed a modest reduction in hippocampal activation after 2 years.
The results of this study suggest that hippocampal dysfunction in early psychosis does not worsen over 2 years and highlight the need for longer-term longitudinal studies.
Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and identifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. Twenty-six patients with schizophrenia and 21 healthy subjects underwent functional magnetic resonance imaging scanning during performance of two- and four-choice reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between two- and four-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia. (JINS, 2013, 19, 1–10)
The recent development of an isometric instrument for
the precise quantification of hand force persistence has
created a novel opportunity for the evaluation of potential
motor asymmetries in schizophrenia and their response to
treatment. A study of asymmetries in the unmedicated state
may provide insight into the pathogenesis of schizophrenia,
whereas alterations of asymmetries in response to antipsychotic
medication could assist the delineation of a cerebral mechanism
for the effects of pharmacotherapy. The hand force persistence
of 21 unmedicated patients with schizophrenia was compared
to 21 age, gender, and handedness matched normal controls.
The effect of neuroleptic treatment on hand force persistence
was then evaluated on a subset of 10 patients after at
least 30 days of treatment. The anticipated asymmetry was
evident in the unmedicated sample that showed impaired
right hand force persistence compared to the normal control
sample. The prospective comparison showed an alleviation
of the asymmetry resulting from an improvement of right
hand force persistence with treatment. In addition to providing
further support to a primary left hemisphere cerebral involvement
in schizophrenia, the present results suggest that prior
investigations of motor asymmetry may have been compromised
by the study of medicated patients. The apparently paradoxical
improvement of motor skill may relate to the substantial
number of patients treated with 2nd generation neuroleptic
medications which may implicate an improvement in left
hemisphere physiology in the cognitive advantages of the
novel treatments. (JINS, 2001, 7, 606–614.)
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