Background Individuals with schizophrenia (SCZ) and bipolar disorder (BD) display cognitive impairments, but the impairments in those with SCZ are more prominent, supported by genetic overlap between SCZ and cognitive impairments. However, it remains unclear whether cognitive performances differ between individuals at high and low genetic risks for SCZ or BD. Methods Using the latest Psychiatric Genomics Consortium (PGC) data, we calculated PGC3 SCZ-, PGC3 BD-, and SCZ v. BD polygenic risk scores (PRSs) in 173 SCZ patients, 70 unaffected first-degree relatives (FRs) and 196 healthy controls (HCs). Based on combinations of three PRS deciles, individuals in the genetic SCZ, genetic BD and low genetic risk groups were extracted. Cognitive performance was assessed by the Brief Assessment of Cognition in Schizophrenia. Results SCZ-, BD-, SCZ v. BD-PRSs were associated with case–control status (R2 = 0.020–0.061), and SCZ-PRS was associated with relative–control status (R2 = 0.023). Furthermore, individuals in the highest decile for SCZ PRSs had elevated BD-PRSs [odds ratio (OR) = 6.33] and SCZ v. BD-PRSs (OR = 1.86) compared with those in the lowest decile. Of the three genetic risk groups, the low genetic risk group contained more HCs, whereas the genetic BD and SCZ groups contained more SCZ patients (p < 0.05). SCZ patients had widespread cognitive impairments, and FRs had cognitive impairments that were between those of SCZ patients and HCs (p < 0.05). Cognitive differences between HCs in the low genetic risk group and SCZ patients in the genetic BD or genetic SCZ groups were more prominent (Cohen's d > −0.20) than those between HCs and SCZ patients in the no genetic risk group. Furthermore, SCZ patients in the genetic SCZ group displayed lower scores in verbal fluency and attention than those in the genetic BD group (d > −0.20). Conclusions Our findings suggest that cognitive impairments in SCZ are partially mediated through genetic loadings for SCZ but not BD.

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Background: Bipolar disorder (BD) and schizophrenia (SZ) are genetic psychotic disorders (PSY) with maternal inheritance. Some studies have investigated whether genetic variants in the mitochondrial chromosome are associated with BD and SZ. However, the genetic variants identified as being associated are not identical among studies, and the participants were limited to individuals of European ancestry. Here, we investigate associations of genome-wide genetic variants in the mitochondrial chromosome with BD, SZ, and PSY in a Japanese population. Methods: After performing quality control for individuals and genetic variants, we investigated whether mitochondrial genetic variants [minor allele frequency (MAF)>0.01, n=45 variants) are associated with BD, SZ, and PSY in 420 Japanese individuals consisting of patients with BD (n=51), patients with SZ (n=172), and healthy controls (HCs, n=197). Results: Five mitochondrial genetic variants (rs111033358, rs200165736, rs200478835, rs200044200, and rs28359178), two genetic variants (rs199713564 and rs200478835), and five genetic variants (rs199713564, rs200999343, rs200478835, rs28359178, and rs201250154) appeared to be associated with BD, SZ and PSY, respectively (Puncorr<0.05). Of these variants, three (rs200478835, rs200044200 and rs28359178 on or near NADH dehydrogenase) and one (rs200478835) were significantly associated with BD and PSY, respectively, even after correcting for multiple comparisons (PGC=0.045–4.9×10-3). In particular, individuals with the minor G-allele of rs200044200, a missense variant, were only observed among patients with BD (MAF=0.059) but not HCs (MAF=0) (odds ratio=∞). Three patients commonly had neuropsychiatric family histories. Conclusions: We suggest that mitochondrial genetic variants in NADH dehydrogenase-related genes may contribute to the pathogenesis of BD and PSY in the Japanese population through dysfunction of energy production.

Objective: Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute. Methods: To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants. Results: We found a significant difference in olfactory identification ability among the diagnostic groups ( p = 7.65 × 10−16). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen’s d = −0.57, p = 3.13 × 10−6) and healthy controls ( d = −1.00, p = 2.19 × 10−16). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls ( d = −0.29, p = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness ( r = −0.41, p = 1.88 × 10−8) and negative symptoms ( r = −0.28, p = 1.99 × 10−4) in schizophrenia patients, although the correlation with the duration of illness was affected by aging ( r = −0.24). Conclusions: Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.