This included an association between the rs2007044 (risk allele G) within CACNA1C and poorer working memory performance (increased errors B (95% CI)=0.635-4.535, p=0.012), an effect driven mainly by the psychosis groups.
Our data suggests a minor involvement of CACNA1Crs1006737 in psychosis via conferring susceptibility to white matter microstructural abnormalities in SZ.
A history of suicide attempt was assessed in a sample of 1009 patients with BD, SCZ and related psychosis spectrum disorders, and associations with the joint genetic risk variants for BD and SCZ (rs2239547 (ITIH3/4-region), rs10994359 (ANK3) and rs4765905 (CACNA1C)) were investigated.
Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major depressive disorder.
The pathogenic repeat expansion [GGGGCC]<sub>n</sub> found at the C9orf72 locus is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and has also been documented in patients with psychosis and schizophrenia.
Thalamus degeneration was identified only in bvFTD cases with the C9ORF72 repeat expansion, and to a similar extent in cases with and without psychosis.
Thirty-eight per cent of the patients with C9ORF72 mutations presented with psychosis, with a further 28% exhibiting paranoid, deluded or irrational thinking, whereas <4% of non-mutation bearers presented similarly.
Despite the high frequency of psychiatric symptoms in bvFTD patients and the extremely high prevalence of the C9ORF72 expansion in Finland, pathogenic expansion (>40 repeats) was not detected among the Northern Finland Birth Cohort 1966 individuals with psychosis, indicating that these disorders, especially schizophrenia before the age of 43 years, may not be associated with the C9ORF72 expansion.
Impaired reward processing may be a transdiagnostic phenotype of variation in CACNA1C that could contribute to anhedonia and other clinical features common to both affective and psychotic disorders.
Results revealed: 1) prevalence is approximately 10%, 2) TDP-43 type B and FUS pathologies might have relatively high frequency of psychosis, 3) psychosis in FTD is higher with genetic mutations of C9ORF72 and GRN, 4) imaging researches did not achieve conclusive results, and 5) no treatment for psychosis in FTD is currently available.
Since CACNA1C variants have been associated repeatedly with psychosis at a genome-wide level, and preclinical data provide convergent evidence for the relevance of the CACNA1C gene for hippocampal and frontolimbic plasticity and adaptive regulation of stress, our data suggest a potential pathophysiological mechanism conferred by CACNA1C variants that may mediate risk for symptom dimensions shared among bipolar disorder, major depression, and schizophrenia.
In contrast, C9ORF72-FTLD is predominantly associated with behavioural variant FTD, which often presents with psychosis, most commonly in the form of hallucinations and delusions.
Among participants in a genetic study of psychoses (N=739), two pairs of related individuals had C9orf72 expansions, of whom three were diagnosed with schizophrenia (SZ) / schizoaffective disorder (SZA), but their clinical features did not suggest dementia or ALS.
Second, a balanced polymorphism in the C terminus opposite-paired domain, a key motif in the MED12-mediated transcriptional repression of Wnt signaling, has been associated with increased risk for psychosis.
These findings provide evidence of the important role of early cannabis use and the Val66MetBDNF polymorphism on age at psychosis onset and they point out to sex-specific differences in cannabis use patterns.
No significant differences in the distribution of allele and genotype frequencies of the 5-HTTLPR (p>0.01) and 5-HT2AT102C (p>0.05) were found between patients and controls as well as between the patients' subgroups without and with psychosis.
Finally, we observe that frontal-cortex DNA methylation in the BDNF gene is correlated with genotype at a nearby nonsynonymous SNP that has been previously associated with major psychosis.
To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis.
The strong and robust positive association that was noted between the C allele of HTR2A and psychosis suggests that the HTR2AT102C polymorphism is a significant risk factor for psychosis of AD.