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Background The Semantic Object Retrieval Task (SORT) requires participants to indicate whether word pairs recall a third object. Schizophrenia individuals (SZ) tend to report associations between nonassociated word pairs; this overretrieval is related to formal thought disorder (FTD). Since semantic memory impairments and psychosis are also found in bipolar disorder (BP), we examined whether SORT impairments and their relationship to symptoms are also present in BP. Methods Participants ( n = 239; healthy control subjects [HC] = 133; BP=32; SZ=74) completed SORT while undergoing functional magnetic resonance imaging (fMRI) scanning. Results Retrieval accuracy negatively correlated with negative symptoms and no-retrieval accuracy negatively correlated with FTD severity in SZ but not BP. Retrieval versus no-retrieval trials activated a distributed fronto-parieto-temporal network; bilateral inferior parietal lobule (IPL) activity was larger in HC versus SZ and HC versus BP, with no difference in SZ versus BP. Right IPL activity positively correlated with positive and general psychosis symptoms in SZ but not BP. Conclusions SZ reported more associations between unrelated word pairs than HC; this overretrieval increased with FTD severity. Schizophrenia individuals were also more likely to fail to find associations between related word pairs; this underretrieval increased with negative symptom severity. fMRI symptom correlations in IPL in SZ are consistent with arguments that IPL abnormality relates to loosening of associations in SZ. By comparison, BP showed intermediate impairments on SORT, uncorrelated with symptoms, suggesting that the relationship between SORT performance, fMRI activity, and psychotic symptoms is schizophrenia-specific.

Schizophrenia is a complex genetic disorder, with multiple putative risk genes and many reports of reduced cortical gray matter. Identifying the genetic loci contributing to these structural alterations in schizophrenia (and likely also to normal structural gray matter patterns) could aid understanding of schizophrenia's pathophysiology. We used structural parameters as potential intermediate illness markers to investigate genomic factors derived from single nucleotide polymorphism (SNP) arrays.We used research quality structural magnetic resonance imaging (sMRI) scans from European American subjects including 33 healthy control subjects and 18 schizophrenia patients. All subjects were genotyped for 367 SNPs. Linked sMRI and genetic (SNP) components were extracted to reveal relationships between brain structure and SNPs, using parallel independent component analysis, a novel multivariate approach that operates effectively in small sample sizes.We identified an sMRI component that significantly correlated with a genetic component (r = -.536, p.00005); components also distinguished groups. In the sMRI component, schizophrenia gray matter deficits were in brain regions consistently implicated in previous reports, including frontal and temporal lobes and thalamus (p.01). These deficits were related to SNPs from 16 genes, several previously associated with schizophrenia risk and/or involved in normal central nervous system development, including AKT, PI3K, SLC6A4, DRD2, CHRM2, and ADORA2A.Despite the small sample size, this novel analysis method identified an sMRI component including brain areas previously reported to be abnormal in schizophrenia and an associated genetic component containing several putative schizophrenia risk genes. Thus, we identified multiple genes potentially underlying specific structural brain abnormalities in schizophrenia.

Background The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. Method Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. Results Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. Conclusions Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.