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BACKGROUND: Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. METHODS: Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. RESULTS: The PRS [odds ratio (OR) 1.6 (1.1-2.3)], childhood trauma [OR 4.5 (2.3-8.8)], and regular cannabis use [OR 8.3 (2.1-32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03-0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1-10.4)]. CONCLUSION: The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.

Background Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. Methods Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. Results The PRS [odds ratio (OR) 1.6 (1.1-2.3)], childhood trauma [OR 4.5 (2.3-8.8)], and regular cannabis use [OR 8.3 (2.1-32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03-0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1-10.4)]. Conclusion The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.

Background Impaired memory is among the most profound cognitive deficits observed in patients with schizophrenia. Evidence from twin studies suggests that memory is mainly influenced by genetics. Moreover, a few twin studies have demonstrated genetic overlap between specific memory functions and schizophrenia. Memory deficits in schizophrenia seem to involve abnormalities in frontal cortical areas and the middle temporal lobe, particularly the hippocampus. In the general population, twin studies have consistently demonstrated genetic influences on brain volumes, however, evidence from twin pairs discordant for schizophrenia suggests that hippocampus volumes may be more susceptible to environmental effects in patients. Methods Twin pairs concordant or discordant for a diagnosis in the schizophrenia spectrum were recruited nation-wide by linking The Danish Twin Register and The Danish Psychiatric Central Research Register. Both monozygotic (MZ) and dizygotic (DZ) proband pairs as well as healthy control (HC) pairs were identified. A total of 216 twins participated in this study consisting of 32 complete MZ and 24 complete DZ proband pairs, 29 complete MZ and 20 complete DZ HC pairs, and six twins from proband pairs were included without their sibling. Verbal memory was assessed using the list learning task from the Brief Assessment of Cognition in Schizophrenia (BACS), visual memory using the Rey Complex Figure Test (RCFT) and associative memory using 15 word pairs. Structural brain scans were acquired with T1-weighted sequence on a Philips 3.0 T Achieva MRI scanner with a 32-channel SENSE head coil. Images were processed using FreeSurfer (version 5.3) and the Desikan-Killiany atlas was used to extract the volumes of bilateral hippocampi, superior frontal, rostral and caudal middle frontal cortices as well as the whole brain volume. Structural equation modelling was applied to examine the genetic and environmental contributions to the variability in memory an

Background Memory performance is heritable and shares partial genetic etiology with schizophrenia. How the genetic overlap between memory and schizophrenia is related to intelligence (IQ) and brain volumes has not been formally tested using twin modeling. Methods A total of 214 twins were recruited nationwide by utilization of the Danish registers, including monozygotic and dizygotic twin pairs concordant or discordant for a schizophrenia spectrum disorder and healthy control pairs. Memory/IQ assessments and MRI scans were performed and structural equation modeling was applied to examine the genetic and environmental effects and to quantify associations with schizophrenia liability. Results Significant heritability estimates were found for verbal, visual and working memory. Verbal and visual memory were associated with schizophrenia, and for visual memory the association was due to overlapping genetics. IQ was highly heritable, but only performance IQ was associated with schizophrenia. Genetic factors also contributed to total brain, right superior frontal, left rostral middle frontal and hippocampal volumes. Smaller total brain and hippocampal volumes were associated with schizophrenia, and for the left hippocampus this association was due to overlapping genetic factors. All 3 memory measures were associated with IQ, but only visual memory was associated with total brain and hippocampal volumes. Discussion Specific memory measures and brain volumes were moderately heritable and showed overlap with schizophrenia liability, suggesting partially shared etiological influences. Our findings further suggest that factors impacting IQ also influence memory, whereas memory impairments and brain volume abnormalities appear to represent separate pathological processes in the pathway to schizophrenia.