Clinical Neuroscience

[Multilocus genetic analysis implicates neurodevelopment and immune system in the etiology of schizophrenia]

PULAY Attila József1, KOLLER Júlia2, NAGY László3, MOLNÁR Mária Judit1, RÉTHELYI János1,4

MARCH 30, 2017

Clinical Neuroscience - 2017;70(03-04)

DOI: https://doi.org/10.18071/isz.70.0115

[Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives - The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multilocus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods - Associations of single nucleotide and indel markers were transferred to gene- and geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results - After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xq13 cytobands were found (p_corr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (P_rep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses. ]

AFFILIATIONS

  1. Semmelweis Egyetem, Pszichiátriai és Pszichoterápiás Klinika, Budapest
  2. Semmelweis Egyetem, Genomikai Medicina és Ritka Betegségek Intézete, Budapest
  3. Debreceni Egyetem, Biokémiai és Molekuláris Biológiai Intézet, Debrecen
  4. MTA-SE NAP-B Molekuláris Pszichiátriai és in vitro Betegségmodellezési Kutatócsoport, Budapest

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Children with autism spectrum disorder (ASD) show altered learning and memory. A number of recent studies have debated whether procedural learning in ASD is intact or not. Our aim was to further assess the question of whether the implicit, non-conscious form of procedural learning in ASD children is intact or not, furthermore, how shifts towards a more explicit, attention-demanding task setting can alter this performance. We administered a modified version of the Alternating Serial Reaction Time (ASRT) Task to children with ASD and IQ- and age-matched typically developing (TD) children. The task consisted of alternating blocks of cued (explicit) and uncued (implicit probe) blocks, and was repeated after a 16-hour delay. We found that ASD and TD children showed similar sequence-specific learning in cued explicit blocks, however, on the uncued probe blocks ASD children performed better compared to TD children. After the 16-hour delay both groups showed retention of the previously acquired knowledge. Finally, when we investigated the performance in different parts of the blocks, we found that ASD children did not show an effect of fatigue by the second part of the blocks. Our results suggest that children with ASD have increased implicit procedural learning skills compared to TD children. Differences in cued (explicit) and uncued (implicit) settings indicate that children with ASD are not affected by the lack of explicit instructions in probe blocks, suggesting a resistance for changes in task settings. These findings can help in a more thorough planning of cognitive therapeutic setups for ASD children.

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Electrophysiological alterations and general toxic signs obtained by subacute administration of titanium dioxide nanoparticles to the airways of rats

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Introduction and aims - Particles of titanium dioxide (TiO2) with typical size below 100 nm have gained a broad range of application by now, partly involving direct human exposure. Their known properties - high specific surface, mobility within the organism, induction of oxidative stress, release of inflammation mediators etc. - raise the possibility of nervous system damage but the available data regarding this are scarce and contradictory. Based on that, and the experiences with other metal oxide nanoparticles, the aim of the present study was to investigate certain general end nervous system toxic effects of TiO2 nanoparticles applied in the airways of rats. Materials and methods - Young adult Wistar rats (5 groups of 10 rats each) received, daily for 28 days, intratracheal instillations of titanium dioxide nanoparticles of ca. 10 nm diameter, suspended in 1% hydroxyethyl cellulose dissolved in phosphate-buffered saline, in the doses of 1, 3, and 10 mg/kg b. w. Vehicle controls received the suspension medium and there was also an untreated control group. During treatment, the rats’ body weight was measured, and their clinical state observed, daily. After the 28 days, spontaneous cortical activity, sensory evoked potentials and tail nerve action potential was recorded in urethane anesthesia, then the rats were dissected and tissue samples were taken for Ti level determination and biochemical measurements of some oxidative stress indicators. Results - The two higher doses reduced the rate of body weight gain significantly. Sensory evoked potentials and tail nerve action potential were significantly slowed, but the change in the spectrum of spontaneous cortical activity was not significant. Correlation of moderate strength was found between certain evoked potential parameters and brain Ti level and oxidative stress data. Conclusion - Our results underlined the possible neurotoxicity of TiO2 NPs but also the need for further investigations.

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Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical and neuroradiological syndrome which may appear at any age and characterized by headache, altered consciousness, seizures, and cortical blindness. The exact incidence is still unknown. The most commonly identified causes include hypertensive encephalopathy, eclampsia, and some cytotoxic drugs. Vasogenic edema related subcortical white matter lesions, hyperintense on T2A and FLAIR sequences, in a relatively symmetrical pattern especially in the occipital and parietal lobes can be detected on cranial MR imaging. These findings tend to resolve partially or completely with early diagnosis and appropriate treatment. Here in, we present a rare case of unilateral PRES developed following the treatment with pazopanib, a testicular tumor vascular endothelial growth factor (VEGF) inhibitory agent.

Clinical Neuroscience

[Relationship between sport and traumatic brain injury - risks and sequelaes]

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[Traumatic brain injury represents major public health problem worldwide. A typical form of brain injuries is the injury suffered during sports, which according to severity ranges from mild injuries to fatal damages. The significance of the sport related minor head injuries derives form the high incidence, the excessive involvement of the younger age groups, and their potential repetitive nature. The repeated mild head injuries may accumulate, leading to complex structural, neurochemical, neuroendocrine, and psychological alterations, which in long term may result in changes of the patients quality of life and in significant deterioration of participation in the everyday activity. Actually we neither have enough knowledge about the ne-gative consequences, nor the way of prevention, or protection against the harmful long term results. With this study summary we would like to draw attention to the potential hazards emerging from sport injuries, moreover we would like to emphasize the importance of study participation and follow up of articles in this field.]

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