Verbal fluency is a classic test of language production that requires the subject to generate words, beginning with a particular letter or within a particular semantic category. Functional MRI studies have reported disturbed patterns of left hemisphere dominance of language processing in verbal fluency in patients with schizophrenia [51], showing increased activity in right hemisphere, with bilateral activation of Broca’s area during word generation tasks. The results in healthy relatives are similar, but few studies have looked at this (Supplementary Table 1.D). Two studies [52, 53 ·], using verb and word generation tasks, reported increased right VLPFC activation in healthy twins discordant for schizophrenia compared to normal control twins, reproducing the same pattern observed in patients. Despite several reports suggesting a modulation of verbal fluency circuits by schizophrenia risk genes [54–62], none of these studies show genetic modulation of right VLPFC activation, which has most consistently been reported as an intermediate phenotype during verbal fluency paradigms (Supplementary Table 2.D; Figure 2.D). An exception was found with NRG1 [55], although it is impossible to exclude a medication effect on gene modulation since the gene effect was only found in patients with schizophrenia.
