Neurodevelopmental risk factors in schizophrenia

Lobato, Maria Inês Rodrigues; Belmonte-de-Abreu, Paulo; Knijnik, Daniela Zippin; Teruchkin, Betina; Ghisolfi, Eduardo S.; Henriques, Alexandre Annes

doi:10.1590/s0100-879x2001000200002

Cited by 16 publications

(8 citation statements)

References 60 publications

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“…Moreover, Mlc1 expression in the ependyma could play a role in ependymal cell functioning as a cellular or axonal guidance system. Interestingly, both MLC and schizophrenia are thought to reflect neurodevelopmental disorders (van der Knaap et al, 1995; Lobato et al, 2001; Wassmer et al, 2001; Lewis and Levitt, 2002), further supporting the notion of a critical role of Mlc1 during development.…”

Section: Discussionmentioning

confidence: 91%

The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain

Schmitt

Gofferje

Weber

et al. 2003

Glia

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The human MLC1 gene (also known as KIAA0027 and WKL1) and its murine orthologue (Mlc1) encode a putative transmembrane protein expressed primarily in brain. Recessive mutations within human MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), whereas a missense mutation resulting in a methionine substitution within a transmembrane leucine string of MLC has been implicated in catatonic schizophrenia in a large pedigree. To gain insight into the function of the MLC protein and to elucidate the pathophysiology of these severe neurodegenerative disorders, information on the cellular and regional distribution of the murine Mlc1, as well as the developmental pattern of Mlc1 expression in brain, is required. Using in situ hybridization (ISH), Mlc1 mRNA was exclusively detected in glial cells of the adult murine brain, such as astrocytes, Bergmann glia, and ependymal cells. ISH, Northern blot analysis, and quantitative real-time polymerase chain reaction (PCR) demonstrated that Mlc1 mRNA is broadly distributed in the adult mouse brain, with highest concentrations of expression in the cerebellum and olfactory bulb. Furthermore, differential expression patterns during brain development were revealed. Overall brain Mlc1 mRNA concentrations exhibited a substantial increase in the perinatal period reaching adult concentrations at postnatal day 5. At the cellular level, highest Mlc1 expression was found during the pre- and perinatal period in multipotential neural precursor cells, especially in the subventricular zone of the lateral ventricle, whereas in adulthood highest Mlc1 mRNA concentrations were revealed in Bergmann glia cells. Because the temporal expression profile of Mlc1 indicates that, in contrast to developing and mature astrocytes, oligodendrocytes are devoid of Mlc1 expression, white matter tract abnormalities observed in these disorders may result from a primary astrocytic defect. Detailed information on Mlc1 expression in brain is likely to lead to a better understanding of Mlc1 involvement in the pathogenesis of both MLC and catatonic schizophrenia.

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Section: Discussionmentioning

confidence: 91%

The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain

Schmitt

Gofferje

Weber

et al. 2003

Glia

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“…Dermatoglyphic features are relatively stable and cosmetically insignificant epidermal ridge patterns that form prints on the fingers, hands, and soles. DAs are thought to represent, in part, the impact of prenatal insults, thus providing a window into the timing and nature of early development (Cummins and Midlo, 1961; Davis and Bracha, 1996; Lobato et al, 2001). The development of dermatoglyphics overlaps temporally with neuronal migration (Bracha et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

The presentation of dermatoglyphic abnormalities in schizophrenia: A meta-analytic review

Golembo-Smith

Walder

Daly

et al. 2012

Schizophrenia Research

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Within a neurodevelopmental model of schizophrenia, prenatal developmental deviations are implicated as early signs of increased risk for future illness. External markers of central nervous system maldevelopment may provide information regarding the nature and timing of prenatal disruptions among individuals with schizophrenia. One such marker is dermatoglyphic abnormalities (DAs) or unusual epidermal ridge patterns. Studies targeting DAs as a potential sign of early developmental disruption have yielded mixed results with regard to the strength of the association between DAs and schizophrenia. The current study aimed to resolve these inconsistencies by conducting a meta-analysis examining the six most commonly cited dermatoglyphic features among individuals with diagnoses of schizophrenia. Twenty-two studies published between 1968 and 2012 were included. Results indicated significant but small effects for total finger ridge count and total A-B ridge count, with lower counts among individuals with schizophrenia relative to controls. Other DAs examined in the current meta-analysis did not yield significant effects. Total finger ridge count and total A-B ridge count appear to yield the most reliable dermatoglyphic differences between individuals with and without schizophrenia.

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“…The neurodevelopmental hypothesis is further confirmed by the presence of neural cell adhesion molecules and growthassociated protein-43 in the brains of patients suffering from schizophrenia 29,30 . Abnormal sulci and gyri which present in the brain of postmortem patients with schizophrenia confirm the possibility of maldevelopment of brain, because the sulci and gyri are developed during 16-29th weeks of fetal life [31][32][33] . High incidence of craniofacial malformation in patients with Schizophrenia also confirms neurodevelopmental hypothesis, in particular dysmorphology which present in the structures with ectodermal origin 34 .…”

Section: Journal Of Psychiatry • January 2014mentioning

confidence: 85%

Morphometric characteristics of craniofacial features in patients with schizophrenia

Ahmad¹

2014

J Psychiatry

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Background: High incidence of craniofacial dysmorphology in patients with schizophrenia confirms the developmental disruptions during embryonic period. Anthropometry of head and face can give us several clues regarding the maldevelopment of brain. The aim of this study was to assess various dimensions of skull in Schizophrenics. Methods: One hundred and one (101) male and female patients that have been diagnosed with chronic schizophrenia were selected from a psychiatric hospital and 101 healthy controls, which were mostly the paramedical staff of another hospital, were included in the study. The age for both the groups was between 20 to 60 years. The head length, width and height and coronal, axial and sagittal arc lengths, and also body height and weight and BMI of participants were measured. Results: Mean anthropometric measurements of head length, width and height were 18.92, 14.08 and 12.69 in patients and 18.90, 13.89 and 13.38 centimeter in control, also axial, coronal and sagittal arc lengths were 55.85, 35.21 and 33.00 in patients and 55.70, 34.54 and 32.19 centimeter in control group, respectively. Compared to controls the patients had significantly increased coronal (P< 0.022) and Sagittal (P< 0.001) arc lengths. The patients also showed significantly lesser head height (P< 0.001) as compared with controls. Conclusion: The linear measurements of skull in patients with Schizophrenia do not significantly differ from normal populations and/or have slightly differences. Future studies may investigate whether head can be an anatomical marker for patients with schizophrenia.

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Neurodevelopmental risk factors in schizophrenia

Cited by 16 publications

References 60 publications

The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain

The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain

The presentation of dermatoglyphic abnormalities in schizophrenia: A meta-analytic review

Morphometric characteristics of craniofacial features in patients with schizophrenia

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