| 1 | Andrologia 2003 Aug 35: 191-9 |
|---|---|
| PMID | 12950402 |
| Title | Are children of older fathers at risk for genetic disorders? |
| Abstract | Genetic risks related to paternal age should be of interest to clinical andrologists counselling older men who wish to father a child. TheoRETically, the number of (pre-meiotic) mitotic cell divisions during spermatogenesis and their remarkable increase with ageing compared with oogenesis would be in favour of genetic risks for the offspring of older men. But for numerical and structural chromosomal anomalies, such an influence of paternal age has not been found. However, in several autosomal dominant disorders affecting three specific genes (fibroblast growth factor receptor 2 and 3, RET proto-oncogene) the risk for a child to be affected increases with paternal age at time of birth. For other autosomal dominant -X chromosomal dominant or recessive disorders, the available data are sufficient to support the concept of a positive relationship between paternal age and de novo gene mutations. Studies analysing gene sequences of affected children and their parents would allow further evaluation of this topic. The impact of paternal age on disorders with a complex genetic background, however, is a matter of debate. A significant effect of paternal age could not be shown for nonfamilial Alzheimer's disease, congenital heart defects, nonfamilial schizophrenia, acute lymphoblastic leukaemia or prostate cancer. |
| SCZ Keywords | schizophrenia |
| 2 | Brain Res. Mol. Brain Res. 2004 Apr 124: 88-95 |
| PMID | 15093689 |
| Title | Alterations in the expressions of mRNA for GDNF and its receptors in the ventral midbrain of rats exposed to subchronic phencyclidine. |
| Abstract | Phencyclidine (PCP) produces schizophrenia-like symptoms in normal humans. This suggests that the dysfunction of glutamatergic neurotransmission may play an important role in the pathology of schizophrenia. However, PCP also exerts its effect on the mesolimbic dopamine (DA) system and modulates DA function in the brain, the abnormality of which is proposed to be a main pathology of schizophrenia. Recently, glial cell-line derived neurotrophic factor (GDNF) has been shown to play a protective role for DA neurons against neurotoxic injuries and maintaining DA function in the brain. We hypothesized that subchronic PCP may alter the function of GDNF in the ventral midbrain, where DA cell bodies are localized. Male Wistar rats were injected intraperitoneally with PCP daily for 10 days at 5 or 10 mg/kg, and their brains were removed 24 h after the last injection. The expressions of GDNF and its receptor (GFRalpha-1 and c-RET) mRNAs in the substantia nigra compacta (SNC) and ventral tegmental area (VTA) were determined by non-radioactive in situ hybridization, and those of GDNF and c-RET mRNA were found to be increased after the PCP subchronic administration. No significant changes, however, were observed in the expressions of GFRalpha-1 and basic fibroblast growth factor. These results suggest that subchronic PCP may modulate the function of the GDNF system, which exerts a trophic action on DA neurons in the ventral midbrain. |
| SCZ Keywords | schizophrenia |
| 3 | Crim Behav Ment Health 2007 -1 17: 300-11 |
| PMID | 18004730 |
| Title | Theory of mind functioning in mentally disordered offenders detained in high security psychiatric care: its relationship to clinical outcome, need and risk. |
| Abstract | Theory of mind (ToM) refers to the cognitive mechanisms that allow us to infer our own mental states and those of others. Whilst ToM deficits are frequently observed among individuals with schizophrenia, little is known about their relationship to functional outcome. Among patients with schizophrenia in a high security hospital, to test whether ToM performance, in relation to other cognitive and clinical variables, is related to measures of subsequent clinical outcome. ToM was assessed using the modified advanced test (MAT) and the revised eyes task (RET). Outcome, including ongoing need and risk, was assessed using the HoNOS secure, CANFOR and HCR-20 respectively three years post ToM assessment. Performance on the RET was the only variable to be significantly correlated with the symptom ratings of the HoNOS secure and the HCR-20 total scores. Performance on the RET also accounted for approximately half of the variance in the CANFOR ratings and a third in the risk management item ratings of the HCR-20. Age, number of years diagnosed with schizophrenia and other aspects of cognition were also significantly correlated with the HoNOS security scale. The results suggest that social perceptual ToM may be a useful prognostic indicator, but also that ToM impairments may represent an unmet need. Replication of the work with larger and more diverse samples of people with schizophrenia is necessary, as well as trials of therapeutic effort directed at improvement of ToM impairments. |
| SCZ Keywords | schizophrenia |
| 4 | Proc. Natl. Acad. Sci. U.S.A. 2010 Jun 107: 10584-9 |
| PMID | 20489179 |
| Title | Strong synaptic transmission impact by copy number variations in schizophrenia. |
| Abstract | schizophrenia is a psychiatric disorder with onset in late adolescence and unclear etiology characterized by both positive and negative symptoms, as well as cognitive deficits. To identify copy number variations (CNVs) that increase the risk of schizophrenia, we performed a whole-genome CNV analysis on a cohort of 977 schizophrenia cases and 2,000 healthy adults of European ancestry who were genotyped with 1.7 million probes. Positive findings were evaluated in an independent cohort of 758 schizophrenia cases and 1,485 controls. The Gene Ontology synaptic transmission family of genes was notably enriched for CNVs in the cases (P = 1.5 x 10(-7)). Among these, CACNA1B and DOC2A, both calcium-signaling genes responsible for neuronal excitation, were deleted in 16 cases and duplicated in 10 cases, respectively. In addition, RET and RIT2, both ras-related genes important for neural crest development, were significantly affected by CNVs. RET deletion was exclusive to seven cases, and RIT2 deletions were overrepresented common variant CNVs in the schizophrenia cases. Our results suggest that novel variations involving the processes of synaptic transmission contribute to the genetic susceptibility of schizophrenia. |
| SCZ Keywords | schizophrenia |
| 5 | Prog Mol Biol Transl Sci 2010 -1 91: 41-52 |
| PMID | 20691958 |
| Title | G protein-coupled receptor heteromers as new targets for drug development. |
| Abstract | We now have a significant amount of experimental evidence that indicates that G protein-coupled receptor (GPCR) oligomerization, including homo- and heteromerization, is a general phenomenon. Receptor heteromers possess unique biochemical characteristics that are demonstrably different from those of its individual units. These properties include allosteric modulation(s) between units, changes in ligand recognition, G protein-coupling and trafficking. The discovery of GPCR oligomers have been related to the parallel discovery and application of a variety of resonance energy transfer (RET) techniques, such as bioluminescence, fluorescence and sequential RET (BRET, FRET and SRET, respectively), time-resolved FRET (T-FRET) and fluorescence recovery after photobleaching (FRAP) microscopy. However, RET techniques are difficult to implement in native tissues. For receptor heteromers, indirect approaches, such as the determination of a unique biochemical characteristic ("biochemical fingerprint"), permit their identification in native tissues and their use as targets for drug development. Dopamine and opioid receptor heteromers are the focus of intense research which is related to the possible multiple applications of their putative ligands in pathological conditions, which include basal ganglia disorders, schizophrenia and drug addiction. |
| SCZ Keywords | schizophrenia |
| 6 | Hippocampus 2015 Nov 25: 1242-9 |
| PMID | 25675878 |
| Title | The importance of the context in the hippocampus and brain related areas throughout the performance of a fear conditioning task. |
| Abstract | The importance context has been broadly studied in the management of phobias and in the drug addiction literature. The way in which changes to a context influence behavior after the simple acquisition of a passive avoidance task remains unclear. The hippocampus has long been implicated in the contextual and spatial processing required for contextual fear, but its role in encoding the aversive component of a contextual fear memory is still inconclusive. Our work tries to elucidate whether a change in context, represented as differences in the load of the stimuli, is critical for learning about the context-shock association and whether this manipulation of the context could be linked to any change in metabolic brain activity requirements. For this purpose, we used an avoidance conditioning task. Animals were divided into three different experimental conditions. In one group, acquisition was performed in an enriched stimuli environment and RETention was performed in a typically lit chamber (the PA-ACQ-CONTX group). In another group, acquisition was performed in the typically lit chamber and RETention was undertaken in the highly enriched chamber (the PA-RET-CONTX group). Finally, for the control group, PA-CN-CONTX, acquisition, and RETention were performed in the enriched stimuli environment. Our results showed that the PA-ACQ-CONTX group had longer escape latencies and poorer RETention than the PA-RET-CONTX and PA-CN-CONTX groups after 24 h of acquisition under contextual changes. To study metabolic brain activity, histochemical labelling of cytochrome c-oxidase (CO) was performed. CO results suggested a neural circuit including the hippocampus, amygdala, thalamus, parahippocampal cortices, and mammillary nuclei that is involved in the learning and memory processes that enable context-dependent behavior. These results highlight how dysfunction in this network may be involved in the contextualization of fear associations that underlie several forms of psychopathology, including post-traumatic stress disorder, schizophrenia, and substance abuse disorders. |
| SCZ Keywords | schizophrenia |