Background: In previous functional magnetic resonance imaging (fMRI) studies, participants with schizophrenia showed decreased language lateralisation, resulting from increased activation of the right hemisphere compared with controls, Aim: To determine whether decreased lateralisation and increased right cerebral language activation constitute genetic predispositions for schizophrenia. Method: Language activation was measured using fMRI in 12 right-handed monozygotic twin pairs discordant for schizophrenia and 12 healthy right-handed monozygotic twin pairs who were matched for gender, age and education. Results: Language lateralisation was decreased in discordant twin pairs compared with the healthy twin pairs. The groups did not differ in activation of the language-related areas of the left hemisphere, but language-related activation in the right hemisphere was significantly higher in the discordant twin pairs than in the healthy pairs. Within the discordanttwin pairs, language lateralisation was not significantly different between patients with schizophrenia and their co-twins. Conclusions: Decreased language lateralisation may constitute a genetic predisposition for schizophrenia. ... Read more

Background Whole brain tissue volume decreases in schizophrenia have been related to both genetic risk factors and disease-related (possibly nongenetic) factors; however, whether genetic and environmental risk factors in the brains of patients with schizophrenia are differentially reflected in gray or white matter volume change is not known. Methods Magnetic resonance imaging (1.5 T) brain scans of 11 monozygotic and 11 same-gender dizygotic twin pairs discordant for schizophrenia were acquired and compared with 11 monozygotic and 11 same-gender dizygotic healthy control twin pairs. Results Repeated-measures volume analysis of covariance revealed decreased whole brain volume in the patients with schizophrenia as compared with their co-twins and with healthy twin pairs. Decreased white matter volume was found in discordant twin pairs compared with healthy twin pairs, particularly in the monozygotic twin pairs. A decrease in gray matter was found in the patients compared with their co-twins and compared with the healthy twins. Conclusions The results suggest that the decreases in white matter volume reflect the increased genetic risk to develop schizophrenia, whereas the decreases in gray matter volume are related to environmental risk factors. Study of genes involved in the (maintenance) of white matter structures may be particularly fruitful in schizophrenia. ... Read more

Evidence is accumulating that developmental abnormalities, poor neuromotor function, and increased problem behavior precede the manifestation of schizophrenia itself. Information on school performance and behavioral development was obtained for 49 pairs of twins in which at least one twin suffered from schizophrenia (20 monozygotic [MZ], 29 dizygotic [DZ]) and for 43 pairs of healthy control twins (25 MZ, 18 DZ). Cox regression was used to analyze the contribution of schizophrenia, zygosity, sex, and year of birth to the age at which developmental divergence occurred. In both MZ and DZ twin pairs with schizophrenia, divergence in school performance occurred about 7.5 years earlier than it did in control twins, at 12 years of age, preceding the onset of psychosis by 10 years. This suggests that the first prodromal signs of schizophrenia manifest themselves as cognitive symptoms at the onset of puberty. Underperformance at school might therefore be considered one of the first signs of an until then latent vulnerability for schizophrenia. ... Read more

Twin studies are important to investigate genetic influences on variation in human brain morphology in health and disease. However, the twin method has been criticized for its alleged non-generalizability due to differences in the intrauterine and family environment of twins, compared with singletons. To test whether twin-singleton differences complicate interpretation of genetic contributions on variation in brain volume, brains from 112 pairs of twins and 34 of their siblings with a mean (standard deviation) age of 30.7 (9.6) years were scanned using MRI. The influence of birth order, zygosity and twin-sibling differences on brain volume measures was analysed using maximum-likelihood model fitting. Variances were homogeneous across birth order, zygosity and twin-singleton status. Irrespective of zygosity, intracranial volume was smaller in second-born twins compared with first-born twins and compared with siblings. Grey matter volume was smaller in second-born twins compared with first-born twins. White matter was smaller in twins compared with siblings. Differences in grey and white matter between these groups were no longer significant after correction for intracranial volume. Total brain, and lateral and third ventricle volumes were comparable in twins and single-tons. In conclusion, second-born twins have a smaller intracranial volume than their first-born co-twins and siblings. This suggests aberrant early brain development in second-born twins, which is consistent with the sub-optimal pre- and perinatal environment related to birth order in twins. Since other brain volume measures were comparable between the groups, twin studies can provide reliable estimates of heritabilities in brain volume measures and these can be generalized to the singleton population. ... Read more

Patients with schizophrenia show a loss of sensory (motor) gating, which is reflected in a reduced prepulse inhibition (PPI) of the startle reflex. Furthermore, patients with schizophrenia habituate less than healthy subjects. From previous studies, it is clear that typical antipsychotics have little or no effect on either sensorimotor gating or habituation, while only limited data is available on the effects of atypical antipsychotics on these processes. Forty-four schizophrenic patients (27 stable on typical and 17 stable on atypical antipsychotics) and 35 healthy control subjects were tested in a PPI paradigm. The prepulse and startle stimuli were pure tones of 1500 Hz (duration 40ms, intensity 80 dB and 110 dB respectively), with a fixed interstimulus interval of 120 milliseconds. Block effects in PPI and startle amplitude to the pulse alone trials (habituation) were analyzed over the three groups, using comedication (i.e., benzodiazepines) as a covariate. Main effect for block was found for startle amplitude (habituation), while main effects for group and block were found for percentage PPI. Further analysis displayed significant differences in PPI between the patients treated with typical antipsychotics and the healthy control group, while patients treated with atypical antipsychotics did not differ from either the healthy control group, or the patients treated with typical antipsychotics. Furthermore, post-hoc division of the patients treated with atypical antipsychotics in patients treated with clozapine and risperidone revealed that this superiority from atypical antipsychotics over typical antipsychotics appeared to be mainly based on the effects of clozapine. Patients with schizophrenia who are treated with atypical antipsychotics appear to have levels of sensorimotor gating that are more consistent with healthy controls than patients who are treated with typical antipsychotics. Furthermore, within the class of atypical antipsychotics, clozapine appears most potent in restoring this process. ... Read more

Background: The study was designed to examine the relative contributions of genetic and nongenetic factors to structural brain abnormalities in schizophrenia and subjects at risk to develop the disorder. Methods: The brains of 15 monozygotic and 14 samesex dizygotic twins discordant for schizophrenia (patients) and 29 healthy twins pair-wise matched for zygosity, sex, age, and birth order were studied using high-resolution magnetic resonance imaging scans. Results: Intracranial and whole-brain corrected frontal lobe volumes were smaller (4.6% and 2.7%, respectively) in discordant monozygotic twins as compared with healthy monozygotic twins. Irrespective of zygosity, discordant twins had smaller whole-brain (2%), parahippocampal (9%), and hippocampal (8%) volumes than healthy twins. Moreover, patients had smaller whole-brain volumes (2.2%) than their nonschizophrenic cotwins, who in turn had smaller brains (1%) than healthy twins. Lateral and third-ventricle volumes were increased in discordant dizygotic twins as compared with healthy dizygotic twins (60.6% and 56.6%, respectively). Finally, within discordant twins, lateral ventricles were larger (14.4%) in patients than in their nonschizophrenic cotwins. Conclusions: Smaller intracranial volumes in the monozygotic patients and their cotwins suggest that increased genetic risk to develop schizophrenia is related to reduced brain growth early in life. The additional reduction in whole-brain volume found in the patients suggests that the manifestation of the disorder is related to (neurodegenerative) processes that are most likely nongenetic in origin. ... Read more

Both the skin and the brain develop from the same ectoderm and it is thought, therefore, that dermatoglyphics are informative for early disturbances in brain development in schizophrenia. This study was aimed at investigating the differences in both digital and palmar dermatoglyphic indices between twins discordant for schizophrenia and control twins. Furthermore, the significance of dermatoglyphic indices in relation to other determinants of brain development with regard to the susceptibility to schizophrenia was investigated. Data on dermatoglyphic indices of the hand and the palm were obtained from 21 same-sex discordant and 37 same-sex control twins. For 19 discordant and 25 control twins, there was also data available on brain volumes. Non-genetic intra-uterine circumstances early in pregnancy (10-13 weeks of gestation) are associated with a susceptibility to schizophrenia, since both the twins with schizophrenia and the unaffected co-twins showed more fluctuating asymmetry of the finger ridges (P <0.01), and marginally higher absolute finger ridge counts (P = 0.06) than control twin pairs. Fluctuating asymmetry of the finger ridges was as important as whole brain and left hippocampal volumes in differentiating twins with a high susceptibility to schizophrenia from those with a low susceptibility. © 2001 Elsevier Science B.V. All rights reserved. ... Read more

The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high resolution magnetic resonance imaging scans. Structural equation modeling was used to quantify the genetic and environmental contributions to phenotypic (co)variance in whole brain, gray and white matter volume of the cerebrum, lateral ventricle volume and associated variables such as intracranial volume and height. Because the cerebral cortex makes up more that two-thirds of the brain mass and almost three-quarters of its synapses, our data predominantly concerns the telencephalon. Genetic factors accounted for most of the individual differences in whole brain (90%), gray (82%) and white (88%) matter volume. Individual differences in lateral ventricle volume were best explained by a model containing common (58%) and unique (42%) environmental factors, indicating genes to be of no or minor influence. In our sample, genetic or environmental influences were not different for males and females. The same genes influenced brain volumes and intracranial volume and almost completely explained their high phenotypic correlation. Genes influencing gray and white matter overlapped to a large extent and completely determined their phenotypic correlation. The high heritability estimates that were found indicate that brain volumes may be useful as intermediate phenotypes in behavioral genetic research. ... Read more

The etiology of schizophrenia has not been elucidated yet. Since the concordance in monozygotic twins (48%) is higher than in dizygotic twins (17%), a genetic component seems to be involved. Family studies in schizophrenia suggest that this genetic component also plays a part in the etiology of personality disorders, that resemble mild schizophrenia. Moderate concordance between monozygotic twins with respect to the higher concordance between dizygotic twins as compared to siblings who are not pan of a twin, suggest non-genetic factors to be of importance in the etiology of the syndrome as well. Studies on non-genetic risk factors for schizophrehia show the pre- and perinatal period to be clinical in the etiology of the disease. None of these risk factors have been really established to be important in the etiology of schizophrenia. ... Read more