| 1. |
- Calkova, Tereza, et al.
(författare)
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Cytomegalovirus infection associated with lower IQ in adolescent patients with schizophrenia spectrum disorders : A preliminary report
- 2022
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Ingår i: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 151, s. 571-574
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Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection of immunocompetent hosts is usually inapparent, but typically results in a non-silent chronic latency which is considerably more active than previously considered. In adults with schizophrenia spectrum disorders, CMV latent infection has been associated with cognitive disturbance including lower intelligent quotient (IQ). We hypothesized that the same pattern will be present in adolescent patients with schizophrenia spectrum disorders (early-onset non-affective psychosis). We included 17 adolescents with schizophrenia spectrum disorders (10 patients with schizophrenia, one patient with schizoaffective disorder and six patients with psychosis not otherwise specified), mean age 16.7 years, females 71% and CMV seropositivity 35%. Current IQ was estimated with the Wechsler Abbreviated Scale of Intelligence. CMV immunoglobulin G (IgG) concentrations were measured by solid-phase immunoassays and expressed as dichotomous measures (seropositive/CMV + vs. seronegative/CMV-). CMV + patients (mean IQ 91) had significantly lower full-scale IQ than CMV- patients (mean IQ 110) (20 units difference; p < 0.001). Post-hoc analyses showed that CMV + patients had both lower performance and lower verbal IQ relative to CMV- patients (p = 0.001 and 0.049, respectively). In this preliminary report, we found that CMV IgG seropositivity, reflecting previous CMV infection and current latency, was associated with lower IQ. This may be indicative of an unfavorable impact of CMV infection on general intelligence in early-onset non-affective psychosis.
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| 2. |
- Palmer, Duncan S., et al.
(författare)
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Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
- 2022
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 54:5, s. 541-547
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Tidskriftsartikel (refereegranskat)abstract
- We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.
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| 3. |
- Schwarz, Emanuel, et al.
(författare)
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Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response
- 2018
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Ingår i: Schizophrenia Research. - Amsterdam, Netherlands : Elsevier. - 0920-9964 .- 1573-2509. ; 192, s. 398-403
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Tidskriftsartikel (refereegranskat)abstract
- The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission.
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| 4. |
- Severance, Emily G., et al.
(författare)
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The Gut Microbiota and the Emergence of Autoimmunity : Relevance to Major Psychiatric Disorders
- 2016
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Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 22:40, s. 6076-6086
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Forskningsöversikt (refereegranskat)abstract
- Background: Autoimmune phenotypes are prevalent in major psychiatric disorders. Disequilibria of cellular processes occurring in the gastrointestinal (GI) tract likely contribute to immune dysfunction in psychiatric disorders. As the venue of a complex community of resident microbes, the gut in a homeostatic state equates with a functional digestive system, cellular barrier stability and properly regulated recognition of self and non-self antigens. When gut processes become disrupted as a result of environmental or genetic factors, autoimmunity may ensue. Methods: Here, we review the issues pertinent to autoimmunity and the microbiome in psychiatric disorders and show that many of the reported immune risk factors for the development of these brain disorders are in fact related and consistent with dysfunctions occurring in the gut. We review the few human microbiome studies that have been done in people with psychiatric disorders and supplement this information with mechanistic data gleaned from experimental rodent studies. Results: These investigations demonstrate changes in behavior and brain biochemistry directly attributable to alterations in the gut microbiome. We present a model by which autoantigens are produced by extrinsically-derived food and microbial factors bound to intrinsic components of the gut including receptors present in the enteric nervous system. Conclusion: This new focus on examining activities outside of the CNS for relevance to the etiology and pathophysiology of psychiatric disorders may require new modalities or a re-evaluation of pharmaceutical targets found in peripheral systems.
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