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Spatial and biological characteristics of structural frontal disconnectivity in schizophrenia remain incompletely understood. Simultaneous streamline count (SC) and fractional anisotropy (FA) analyses may yield relevant complementary information to this end.Using 3T diffusion magnetic resonance imaging both SC and FA were calculated for the tracts linking lateral and medial subregions of prefrontal cortex (PFC) to cingulate, hippocampus, caudate and thalamus in 27 schizophrenia patients (14 first-episodes) and 27 controls. Relationships of these parameters with cognition, symptoms, treatment doses and illness duration were assessed where significant between-groups differences were detected.Patients showed lower SC and FA in the tracts linking lateral and medial PFC to thalamus (likely corresponding to anterior thalamic peduncle) and lower FA in those linking PFC to caudate (likely through internal capsule), right caudal anterior cingulate and left hippocampus (likely corresponding to hippocampal-prefrontal pathway). Moreover, patients showed greater SC values for the tracts linking medial PFC and left caudal anterior cingulate. SC and FA values for the tracts linking PFC and caudal anterior cingulate were positively related to motor speed, executive function, problem solving and completed categories in WCST. FA for the tract linking right lateral PFC and caudate was directly related to positive symptoms and FA for the tract linking left medial PFC and left thalamus was inversely related to negative symptoms. Treatment doses were not associated with SC or FA values in any tract. Illness duration was negatively associated with SC and FA in the tracts linking PFC and subcortical areas.Widespread alterations in frontal structural connectivity of PFC can be found in schizophrenia, and are related to cognition, symptoms and illness duration.We assessed fractional anisotropy and streamline counts for the tracts linking prefrontal cortex with relevant regions.Lower fractional anisotropy were found in schizophrenia patients in most of these anatomical connections.Streamline counts were lower in the patients for the right prefrontal cortico-thalamic tract.These alterations were related with cognition and symptoms.FA and SC were inversely associated to illness duration, but not to treatment doses.