Host-parasite interaction associated with major mental illness.

Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have co-morbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-Toxoplasma gondii (T. gondii) antibodies in patients with major mental illnesses, but the underlying mechanism was unclear.

Expression of ZNF804A in human brain and alterations in schizophrenia, bipolar disorder, and major depressive disorder: a novel transcript fetally regulated by the psychosis risk variant rs1344706.

Importance: The single-nucleotide polymorphism rs1344706 in the zinc finger protein 804A gene (ZNF804A) shows genome-wide association with schizophrenia and bipolar disorder. Little is known regarding the expression of ZNF804A and the functionality of rs1344706.

Objectives: To characterize ZNF804A expression in human brain and to investigate how it changes across the life span and how it is affected by rs1344706, schizophrenia, bipolar disorder, and major depressive disorder.

Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.

Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls.

Changed relative to what? Housekeeping genes and normalization strategies in human brain gene expression studies.

Many studies in biological psychiatry compare the abundance of individual messenger RNAs between cases and control subjects or, more recently, between genotype groups. Most utilize some form of normalization procedure, usually expressing the transcript(s) of interest relative to that of a housekeeping gene or genes (also called reference genes), to overcome various sources of experimental error. Indeed, normalization is such a standard procedure that its purpose, principles, and limitations are sometimes overlooked, and some papers lack sufficient information as to its implementation.

The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain.

Disrupted-in-schizophrenia 1 (DISC1) has been genetically associated with schizophrenia, and with brain phenotypes including grey matter volume and working memory performance. However, the molecular and cellular basis for these associations remains to be elucidated. One potential mechanism may be via an altered interaction of DISC1 with its binding partners.

Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder.

Background: Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear because glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synapses. We also measured netrin-G1 and netrin-G2 messenger RNAs because these genes are involved in the formation and plasticity of glutamatergic connections.

Expression of kinase interacting with stathmin (KIS, UHMK1) in human brain and lymphoblasts: Effects of schizophrenia and genotype.

Single nucleotide polymorphisms (SNPs) within the gene encoding the serine/threonine kinase KIS (Kinase Interacting with Stathmin, also known as UHMK1) have recently been associated with schizophrenia. As none of the disease associated SNPs are coding, they may confer susceptibility by altering some facet of KIS expression. Here we have characterised the cellular distribution of KIS in human brain using in situ hybridisation and immunohistochemistry, and quantified KIS protein and mRNA in two large brain series to determine if KIS expression is altered in schizophrenia or bipolar disorder or in relation to a schizophrenia-associated SNP (rs7513662).

Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in schizophrenia and bipolar disorder.

The membrane-bound axon guidance molecules netrin-G1 (NTNG1) and netrin-G2 (NTNG2) play a role in synaptic formation and maintenance. Non-coding single nucleotide polymorphisms (SNPs) in both genes have been reported to be associated with schizophrenia. The main aim of this study was to determine if NTNG1 and NTNG2 mRNA expression is altered in schizophrenia or bipolar disorder, and/or influenced by disease-associated SNPs.

Altered expression of synaptic protein mRNAs in STOP (MAP6) mutant mice.

Stable tubule-only polypeptide (STOP) proteins are a family of microtubule associated proteins (MAPs) important in microtubule stabilization. Data indicating a role for microtubules in synaptic function has come from studies of the STOP null mouse, which exhibits synaptic deficits, in association with behavioural changes that are alleviated by antipsychotic treatment. These findings suggested that STOP mutant mice may be useful in studies of synaptic function, and could be especially relevant to schizophrenia, postulated to be a disorder of the synapse.

Synaptophysin protein and mRNA expression in the human hippocampal formation from birth to old age.

In the human neocortex, progressive synaptogenesis in early postnatal life is followed by a decline in synaptic density, then stability from adolescence until middle age. No comparable data are available in the hippocampus. In this study, the integral synaptic vesicle protein synaptophysin, measured immunoautoradiographically, was used as an index of synaptic terminal abundance in the hippocampal formation of 37 subjects from 5 weeks to 86 yr old, divided into 4 age groups (10 infants, 15 adolescents/young adults, 6 adults, and 6 elderly).

Cellular basis of reduced cortical reelin expression in schizophrenia.

Objective: The authors' goals were to establish the cellular origin of the reduced cortical reelin expression that occurs in schizophrenia and to relate it to markers of synaptic pathology.

Method: In situ hybridization was used to quantify reelin mRNA in the hippocampal formation and dorsolateral prefrontal cortex of brains from 13 subjects with schizophrenia and 12 subjects without schizophrenia. Results were correlated with the expression of three synaptic protein genes in the dentate gyrus.

Anomalies of asymmetry of pyramidal cell density and structure in dorsolateral prefrontal cortex in schizophrenia.

Background: Studies suggest that neuronal density in left dorsolateral prefrontal cortex is increased in schizophrenia.

Aims: To replicate these findings and extend them to both hemispheres.

Method: Neuronal density, size and shape were estimated in the prefrontal cortex (Brodmann area 9) of the left and right hemispheres of brains taken post-mortem from 10 people with schizophrenia and 10 without mental illness (6 men, 4 women in both groups).

Differential expression of calcineurin A subunit mRNA isoforms during rat hippocampal and cerebellar development.

Calcineurin (protein phosphatase 2B) is a calcium-dependent serine-threonine phosphatase. It has diverse roles and is centrally involved in synaptic plasticity. The catalytic A subunit of calcineurin has three isoforms, alpha, beta and gamma.

Does the CAPON gene confer susceptibility to schizophrenia?

Eastwood discusses a new study in that suggests that overexpression of the gene, leading to disruption of NMDA receptor function, may be important in the etiology of severe mental illnesses.

Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia.

Background: Calcineurin (CaN) is a phosphatase involved in synaptic plasticity. A haplotype of the PPP3CC gene, which encodes the gamma isoform of the catalytic subunit (CaN A), has been associated with schizophrenia. However, the distribution of CaN A gamma is not established, nor whether its expression changes in schizophrenia.

The synaptic pathology of schizophrenia: is aberrant neurodevelopment and plasticity to blame?

Synaptic pathology is a feature of the brain in schizophrenia, denoted by alterations in the expression of synaptic proteins. In the absence of data indicative of neurodegenerative processes, the neuropathological features of schizophrenia suggest that the major pathogenic process in the disorder is one of aberrant development. Molecular evidence in support of a neurodevelopmental origin of schizophrenia has come from studies examining the expression of key developmental genes.

Laser-assisted microdissection: methods for the molecular analysis of psychiatric disorders at a cellular resolution.

Gene expression arrays and proteomics together provide a great opportunity to reveal the molecular pathophysiology of psychiatric disorders; however, their potential will not be realized unless due attention is paid to the cellular heterogeneity of the brain and the likely differential neuropathological involvement of specific neuronal and glial cell types. Hence, methods are needed which can procure homogeneous populations of cells as a source of messenger RNA, protein, or DNA. Laser-assisted microdissection techniques provide such a tool.

Glutamate receptors and transporters in the hippocampus in schizophrenia.

Postmortem studies, using various methods and directed at several molecular targets, have provided increasing evidence that glutamatergic neurotransmission is affected in schizophrenia. The bulk of the data are in the hippocampus, wherein there is reduced expression of one or more subunits for all three ionotropic receptors (NMDA, AMPA, and kainate). Presynaptic glutamatergic markers, notably the vesicular glutamate transporter VGLUT1, may also be decreased in schizophrenia, especially in older subjects.