ProtocadherinX/Y, a Candidate Gene-Pair for Schizophrenia and Schizoaffective Disorder: A DHPLC Investigation of Gonomic Sequence

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warran

Factor structure and familiality of first-rank symptoms in sibling pairs with schizophrenia and schizoaffective disorder

Background Since their introduction as diagnostic criteria by Schneider in 1937, nuclear symptoms have played a key role in concepts of schizophrenia, but their relationship to each other and to genetic predisposition has been unclear. Aims To ascertain the factor structure and familiality of nuclear symptoms. Methods Nuclear (Schneiderian) symptoms were extracted from case notes and interviews in a study of 103 sibling pairs with DSM-III-R schizophrenia or schizoaffective disorder. Results Principal components analysis demonstrated two major factors : one, accounting for about 50% of the variance, groups thought withdrawal, insertion and broadcasting, with delusions of control ; and the second, accounting for <20% of the variance, groups together third-person voices, thought echo and running commentary. Factor I was significantly correlated within sibling pairs. Conclusions The correlation within sibling pairs suggests that, contrary to the conclusion of some previous studies, some nuclear symptoms do show a degree of familiality and therefore perhaps heritability

Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review

With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis

Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls

The central nervous system and the immune system are closely related. Psychiatric illness is often associated with a dysregulation of the immune response. In an attempt to expand on previously reported immune abnormalities in patients with depressive illness, we compared several immune measures in a group of hospitalized depressed patients and healthy normal controls. Depressed patients had significantly higher percentages of circulating neutrophils, significantly lower percentages of circulating lymphocytes and significantly lower in vitro lymphocyte responses to mitogenic stimulation than normal controls. Basal plasma cortisol and circulating levels of the complement components C3 and C4 were also higher in the depressed group. We also found a significant association between cortisol values and the traffic of leukocytes on the one hand, and complement levels and the lymphocyte mitogenic activities on the other. These findings expand previously reported evidence of immune abnormalities in depressive illness and provide a partial explanation for some of these findings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65846/1/j.1600-0447.1989.tb01316.x.pd

The XVth World Congress of Psychiatric Genetics, October 7–11, 2007: Rapporteur summaries of oral presentations

The World Congress of Psychiatric Genetics (WCPG) has become an annual event since the early 1990's sponsored by the International Society of Psychiatric Genetics (ISPG). Each year the latest published and unpublished findings are aired for discussion by representatives of the majority of research programs on this topic world-wide. The 2007 congress was held in New York City and attracted over 1000 researchers. The topics emphasized included results from whole genome association studies, the significance of copy number variation and the important contributions of epigenetic events to psychiatric disorders. There were over 20 oral sessions devoted to these and other topics of interest. Young investigator recipients of travel awards served as rapporteurs to summarize sessions and these summaries follow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58040/1/30711_ftp.pd

Genetic counselling for psychiatric disorders: accounts of psychiatric health professionals in the United Kingdom

Genetic counselling is not routinely offered for psychiatric disorders in the United Kingdom through NHS regional clinical genetics departments. However, recent genomic advances, confirming a genetic contribution to mental illness, are anticipated to increase demand for psychiatric genetic counselling. This is the first study of its kind to employ qualitative methods of research to explore accounts of psychiatric health professionals regarding the prospects for genetic counselling services within clinical psychiatry in the UK. Data were collected from 32 questionnaire participants, and 9 subsequent interviewees. Data analysis revealed that although participants had not encountered patients explicitly demanding psychiatric genetic counselling, psychiatric health professionals believe that such a service would be useful and desirable. Genomic advances may have significant implications for genetic counselling in clinical psychiatry even if these discoveries do not lead to genetic testing. Psychiatric health professionals describe clinical genetics as a skilled profession capable of combining complex risk communication with much needed psychosocial support. However, participants noted barriers to the implementation of psychiatric genetic counselling services including, but not limited to, the complexities of uncertainty in psychiatric diagnoses, patient engagement and ethical concerns regarding limited capacity

Brain size and brain/intracranial volume ratio in major mental illness

<p>Abstract</p> <p>Background</p> <p>This paper summarizes the findings of a long term study addressing the question of how several brain volume measure are related to three major mental illnesses in a Colorado subject group. It reports results obtained from a large N, collected and analyzed by the same laboratory over a multiyear period, with visually guided MRI segmentation being the primary initial analytic tool.</p> <p>Methods</p> <p>Intracerebral volume (ICV), total brain volume (TBV), ventricular volume (VV), ventricular/brain ratio (VBR), and TBV/ICV ratios were calculated from a total of 224 subject MRIs collected over a period of 13 years. Subject groups included controls (C, N = 89), and patients with schizophrenia (SZ, N = 58), bipolar disorder (BD, N = 51), and schizoaffective disorder (SAD, N = 26).</p> <p>Results</p> <p>ICV, TBV, and VV measures compared favorably with values obtained by other research groups, but in this study did not differ significantly between groups. TBV/ICV ratios were significantly decreased, and VBR increased, in the SZ and BD groups compared to the C group. The SAD group did not differ from C on any measure.</p> <p>Conclusions</p> <p>In this study TBV/ICV and VBR ratios separated SZ and BD patients from controls. Of interest however, SAD patients did not differ from controls on these measures. The findings suggest that the gross measure of TBV may not reliably differ in the major mental illnesses to a degree useful in diagnosis, likely due to the intrinsic variability of the measures in question; the differences in VBR appear more robust across studies. Differences in some of these findings compared to earlier reports from several laboratories finding significant differences between groups in VV and TBV may relate to phenomenological drift, differences in analytic techniques, and possibly the "file drawer problem".</p

Systematic mutation analysis of KIAA0767 and KIAA1646 in chromosome 22q-linked periodic catatonia

BACKGROUND: Periodic catatonia is a familial subtype of schizophrenia characterized by hyperkinetic and akinetic episodes, followed by a catatonic residual syndrome. The phenotype has been evaluated in two independent genome-wide linkage scans with evidence for a major locus on chromosome 15q15, and a second independent locus on chromosome 22q(tel). METHODS: In the positional and brain-expressed candidate genes KIAA0767 and KIAA1646, we searched for variants in the complete exons and adjacent splice-junctions as well as in parts of the 5'- and 3'-untranslated regions by means of a systematic mutation screening in individuals from chromosome 22q-linked pedigrees. RESULTS: The mutation scan revealed 24 single nucleotide polymorphisms, among them two rare codon variants (KIAA0767: S159I; KIAA1646: V338G). However, both were neither found segregating with the disease in the respective pedigree nor found at a significant frequency in a case-control association sample. CONCLUSION: Starting from linkage signals at chromosome22q(tel )in periodic catatonia, we screened two positional brain-expressed candidate genes for genetic variation. Our study excludes genetic variations in the coding and putative promoter regions of KIAA0767 and KIAA1646 as causative factors for periodic catatonia

Deficits in Implicit Attention to Social Signals in Schizophrenia and High Risk Groups: Behavioural Evidence from a New Illusion

Background An increasing body of evidence suggests that the apparent social impairments observed in schizophrenia may arise from deficits in social cognitive processing capacities. The ability to process basic social cues, such as gaze direction and biological motion, effortlessly and implicitly is thought to be a prerequisite for establishing successful social interactions and for construing a sense of "social intuition." However, studies that address the ability to effortlessly process basic social cues in schizophrenia are lacking. Because social cognitive processing deficits may be part of the genetic vulnerability for schizophrenia, we also investigated two groups that have been shown to be at increased risk of developing schizophrenia-spectrum pathology: first-degree relatives of schizophrenia patients and men with Klinefelter syndrome (47,XXY). Results We compared 28 patients with schizophrenia, 29 siblings of patients with schizophrenia, and 29 individuals with Klinefelter syndrome with 46 matched healthy control subjects on a new paradigm. This paradigm measures one's susceptibility for a bias in distance estimation between two agents that is induced by the implicit processing of gaze direction and biological motion conveyed by these agents. Compared to control subjects, patients with schizophrenia, as well as siblings of patients and Klinefelter men, showed a lack of influence of social cues on their distance judgments. Conclusions We suggest that the insensitivity for social cues is a cognitive aspect of schizophrenia that may be seen as an endophenotype as it appears to be present both in relatives who are at increased genetic risk and in a genetic disorder at risk for schizophrenia-spectrum psychopathology. These social cue-processing deficits could contribute, in part, to the difficulties in higher order social cognitive tasks and, hence, to decreased social competence that has been observed in these groups