Asphyxia at birth affects brain structure in patients on the schizophrenia-bipolar disorder spectrum and healthy participants.

BACKGROUND: Uncertainty exists about what causes brain structure alterations associated with schizophrenia (SZ) and bipolar disorder (BD). Whether a history of asphyxia-related obstetric complication (ASP) - a common but harmful condition for neural tissue - contributes to variations in adult brain structure is unclear. We investigated ASP and its relationship to intracranial (ICV), global brain volumes and regional cortical and subcortical structures. METHODS: A total of 311 patients on the SZ - BD spectrum and 218 healthy control (HC) participants underwent structural magnetic resonance imaging. They were evaluated for ASP using prospective information obtained from the Medical Birth Registry of Norway. RESULTS: In all groups, ASP was related to smaller ICV, total brain, white and gray matter volumes and total surface area, but not to cortical thickness. Smaller cortical surface areas were found across frontal, parietal, occipital, temporal and insular regions. Smaller hippocampal, amygdala, thalamus, caudate and putamen volumes were reported for all ASP subgroups. ASP effects did not survive ICV correction, except in the caudate, which remained significantly smaller in both patient ASP subgroups, but not in the HC. CONCLUSIONS: Since ASP was associated with smaller brain volumes in all groups, the genetic risk of developing a severe mental illness, alone, cannot easily explain the smaller ICV. Only the smaller caudate volumes of ASP patients specifically suggest that injury from ASP can be related to disease development. Our findings give support for the ICV as a marker of aberrant neurodevelopment and ASP in the etiology of brain development in BD and SZ.

Cytomegalovirus infection associated with smaller dentate gyrus in men with severe mental illness.

Cytomegalovirus (CMV) infection is usually inapparent in healthy adults but persists for life. Neural progenitor/stem cells are main CMV targets, and dentate gyrus (DG) a major neurogenic niche. Smaller DG volume has been repeatedly reported in severe mental illness (SMI). Considering the suggested immune system, blood-brain barrier and DG disturbances in SMI, we hypothesized that CMV exposure is associated with smaller DG volume in patients, but not healthy controls (HC). Due to the differential male and female immune response to CMV, we hypothesized sex-dependent associations. 381 adult patients with SMI (schizophrenia spectrum or bipolar spectrum disorders) and 396 HC were included. MRI scans were obtained with 1.5T Siemens MAGNETOM Sonata scanner or 3T General Electric Signa HDxt scanner, and processed with FreeSurfer v6.0. CMV immunoglobulin G antibody concentrations were measured by solid phase immunoassay. We investigated main and interaction effects of CMV status (antibody positivity/CMV + vs. negativity/CMV-) and sex on DG in patients and HC. Among patients, there was a significant CMV-by-sex interaction on DG (p = 0.009); CMV + male patients had significantly smaller DG volume than CMV- male patients (p = 0.001, 39 mm3 volume difference) whereas no CMV-DG association was found in female patients. Post-hoc analysis among male patients showed that the CMV-DG association was present in both hemispheres and in both patients with schizophrenia spectrum and bipolar spectrum disorders, and further, that higher CMV antibody titers were associated with smaller DG. No CMV-DG association was found in HC. The results indicate a DG vulnerability to CMV infection in men with SMI.

Cytomegalovirus infection and IQ in patients with severe mental illness and healthy individuals.

Cytomegalovirus (CMV) infection in immunocompetent adults is usually asymptomatic, but results in lifelong latency. Infection occurring congenitally or in immunodeficiency can lead to cognitive impairment. We aimed to investigate the associations between CMV exposure and intelligence quotient (IQ) in patients with schizophrenia spectrum disorders (SZS), bipolar spectrum disorders (BDS) and healthy controls (HC). CMV immunoglobulin G antibody concentrations were measured by immunoassay and expressed as dichotomous measures (seropositive/CMV+ vs. seronegative/CMV-). Based on a significant CMV-by-diagnosis-by-sex interaction on IQ, we investigated main and interaction effects of CMV and sex on IQ in each diagnostic category. Significant CMV-by-sex interactions were found in patient groups. In SZS, CMV+ female patients (n = 50) had significantly lower IQ than CMV- female patients (n = 33), whereas CMV+ (n = 48) and CMV- (n = 45) male patients did not differ in IQ. In BDS, CMV+ (n = 49) and CMV- (n = 37) female patients did not differ in IQ, whereas CMV+ male patients (n = 33) had significantly higher IQ than CMV- male patients (n = 32). Among HC, CMV+ (n = 138) and CMV- (n = 118) male participants as well as CMV+ (n = 125) and CMV- (n = 93) female participants did not differ in IQ. Our findings suggest that CMV exposure may affect IQ in patients with severe mental illness but not HC.

Autoantibodies to the N-Methyl-D-Aspartate Receptor in Adolescents With Early Onset Psychosis and Healthy Controls.

BACKGROUND: Autoantibodies to the N-methyl-D-aspartate receptor (NMDAR-Abs) in autoimmune encephalitis have been associated with prominent psychiatric symptoms. The aims of the present study are to identify the prevalence of NMDAR-Abs in adolescents with early onset psychosis disorders (EOP) and healthy controls (HC) and examine its clinical significance. METHOD: Plasma samples were acquired from 46 adolescent EOP patients and 69 age- and sex matched HC, and assessed for the presence of immunoglobulin G NMDAR-Abs. All participants underwent psychiatric evaluation, neurological examination and head magnetic resonance imaging. RESULTS: NMDAR-Abs were detected in three of 46 (6.5%) EOP patients and in two of 69 (2.9%) HC. One NMDAR-Abs EOP patient presented with unusual psychopathology and minor T1 weighted lesions of vasculopathological origin located bi-frontally and in the basal ganglia, and had a recent diagnosis of a separate autoimmune disease. One NMDAR-Ab HC displayed a T2 weighted FLAIR hyperintensity lesion in the left frontal lobe. The remaining three NMDAR-Ab participants were two EOP patients without neurological or radiological findings, and one HC without any clinical findings. CONCLUSIONS: We report that a small number of EOP patients and HC have NMDAR-Abs with a similar frequency in both groups. The presence of the antibodies was not associated with any distinctive clinical or radiological features. Detection of the antibodies had no diagnostic implication, and a positive NMDAR antibody test must be carefully interpreted and reviewed within the individual clinical context.

Obstetric complications and intelligence in patients on the schizophrenia-bipolar spectrum and healthy participants.

BACKGROUND: Whether severe obstetric complications (OCs), which harm neural function in offspring, contribute to impaired cognition found in psychiatric disorders is currently unknown. Here, we sought to evaluate how a history of severe OCs is associated with cognitive functioning, indicated by Intelligence Quotient (IQ). METHODS: We evaluated the associations of a history of OCs and IQ in 622 healthy controls (HC) and 870 patients on the schizophrenia (SCZ) - bipolar disorder (BIP) spectrum from the ongoing Thematically Organized Psychosis study cohort, Oslo, Norway. Participants underwent assessments using the NART (premorbid IQ) and the WASI (current IQ). Information about OCs was obtained from the Medical Birth Registry of Norway. Multiple linear regression models were used for analysis. RESULTS: Severe OCs were equally common across groups. SCZ patients with OCs had lower performances on both premorbid and current IQ measures, compared to those without OCs. However, having experienced more than one co-occurring severe OC was associated with lower current IQ in all groups. CONCLUSIONS: Severe OCs were associated with lower IQ in the SCZ group and in the BIP and HC groups, but only if they had experienced more than one severe OC. Low IQ might be a neurodevelopmental marker for SCZ; wherein, severe OCs influence cognitive abilities and increase the risk of developing SCZ. Considering OCs as a variable of neurodevelopmental risk for severe mental illness may promote the development of neuroprotective interventions, improve outcome in vulnerable newborns and advance our ability to make clinical prognoses.

[Anti-NMDA-receptor encephalitis]. / Anti-NMDA-reseptorencefalitt.

BACKGROUND In 2007 a clinical disease caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor was described for the first time. Anti-NMDA-receptor encephalitis is a subacute, autoimmune neurological disorder with psychiatric manifestations. The disease is a form of limbic encephalitis and is often paraneoplastic. The condition is also treatable. In this review article we examine the development of the disease, clinical practice, diagnostics and treatment.MATERIAL AND METHOD The article is based on references retrieved from searches in PubMed, and a discretionary selection of articles from the authors' own literature archive.RESULTS The disease most frequently affects young women. It may initially be perceived as a psychiatric condition, as it usually presents in the form of delusions, hallucinations or mania. The diagnosis should be suspected in patients who later develop neurological symptoms such as various movement disorders, epileptic seizures and autonomic instability. Examination of serum or cerebrospinal fluid for NMDA receptor antibodies should be included in the assessment of patients with suspected encephalitis. MRI, EEG and assessment for tumours are important tools in diagnosing the condition and any underlying malignancy.INTERPRETATION If treatment is initiated early, the prognosis is good. Altogether 75 % of patients will fully recover or experience significant improvement. Apart from surgical resection of a possible tumour, the treatment consists of immunotherapy. Because of good possibilities for treatment, it is important that clinicians, particularly those in acute psychiatry, are aware of and alert to this condition.