Patients with first-episode psychosis (FEP) exhibit considerable heterogeneity in subcortical brain volumes. We sought to compare ventricle and basal ganglia volumes in FEP patients (n = 50) with those in unaffected relatives (n = 21) and healthy controls (n = 24). Participants were assessed with a semistructured interview and underwent structural magnetic resonance imaging (MRI). Patients had significantly larger left lateral, right lateral and third ventricle volumes than their siblings and larger third ventricle volumes than controls. Additionally, they showed a trend toward significance by having larger right caudate nuclei than controls. Moreover, FEP patients showed lower caudate and putamen laterality indexes (leftward shifts) than healthy controls but not regarding their siblings. Besides, negative dimension was directly associated with lateral and third ventricle volumes and positive dimension with thalamus and ventral diencephalon nuclei. Our findings added evidence to the associations between early enlargement of brain ventricles and negative symptoms, and between early enlargement of thalamic and ventral-diencephalon nuclei and positive symptoms. Moreover, the cumulative exposition to antipsychotics in FEP patients might be related to enlargement of certain subcortical structures, such as the right nucleus accumbens and third ventricle.