Neurological soft signs and brain morphology in first-episode schizophrenia

Although minor motor and sensory deficits, or neurological soft signs (NSS), are a well-established finding in schizophrenia, the cerebral changes underlying these signs are only partly understood. We therefore investigated the cerebral correlates of NSS by using magnetic resonance imaging (MRI) in patients with schizophrenia and healthy controls.

Forty-two patients, all receiving atypical neuroleptics, with first-episode schizophrenia or schizophreniform disorder and 22 healthy controls matched for age and gender were included. NSS were examined on the Heidelberg Scale after remission of the acute symptoms before discharge and correlated to density values by using optimized voxel-based morphometry (VBM).

NSS scores were significantly higher in patients than healthy controls. Within the patient group NSS were significantly associated with reduced grey or white-matter densities in the pre- and post-central gyrus, pre-motor area, middle and inferior frontal gyri, cerebellum, caudate nucleus and thalamus. These associations did not apply for the control group, in whom only the associations between NSS and reduced frontal gyri densities could be confirmed.

The pattern of cerebral changes associated with NSS clearly supports the model of 'cognitive dysmetria' with a disrupted cortico-cerebellar-thalamic-cortical circuit in schizophrenia. The variety of sites may correspond with the clinical diversity of NSS, which comprises both motor and sensory signs, and with the putative heterogeneity of the pathogenetic changes involved. That the respective associations did not apply for the healthy control group indicates that NSS in patients and controls refer to different pathogenetic factors.