Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Psychotic disorders often cause a drastic change in the life situation of the affected individual. Personality is an aspect that can affect the symptoms and social function in psychotic disorders.

No study has examined stability of personality traits exceeding five years in patients with schizophrenia. The aim of this study was to investigate the stability of personality traits over a 13-year period among patients with psychotic disorder and healthy individuals and to evaluate case-control differences.

At three occasions during a 13-year period patients with psychotic disorders (n=28) and non-psychotic individuals (n=57) completed Swedish universities Scales of Personality (SSP). For all the individuals within- and between-subject analyses were performed at three occasions for all 13 subscales and the three overall factors of SSP. Correlations, means and SDs were calculated.

Tests of within-subject correlations showed differences in two subscales: Lack of Assertiveness, which were influenced by age and Physical Trait Aggression, where patients ratings were stable, whereas controls rated themselves less aggressive at higher age. Between-subjects correlations showed differences regarding any of the parameters diagnosis, time, age, gender or age x gender in nine of the 13 subscales as well as in factor Neuroticism.

Long term follow-up showed a generally high stability of personality traits measured with SSP, especially among patients. Between-subject analyses over the 13 years showed that patients differed compared to controls for the SSP factor Neuroticism as well as the subscale Detachment, which is in accordance with previous studies.

Newborn infants can suffer permanent brain damage as a result of birth asphyxia (ASP), a severe obstetric complication (OC). However, effects of OCs on cognitive abilities and brain structure in schizophrenia (SZ) are unknown.

The main goals of this study were to investigate putative effects of a history of OCs on adult cognition and brain structure in SZ.

We utilized prospective data from the Medical Birth Registry of Norway to identify incidences of severe OCs in adult healthy controls (HC; n = 622) and patients with SZ (n = 607). IQ was assessed, and a subset of participants (n= 414) underwent magnetic resonance imaging.

Severe OCs (27%) and ASP (14%) were equally common in SZ and HC. SZ patients with OCs had lower IQ than patients without OCs, a difference not found in HC (p = .023). Having experienced more than one co-occurring severe OC was associated with lower IQ in both groups, wherein 81% of co-occurring OCs involved ASP. ASP was related to smaller intracranial volume and brain volumes in both groups. Smaller caudate volumes were found in SZ patients with ASP compared to patients without ASP, a difference not found in HC (p = .009).

Our findings give support for an effect of birth ASP on brain development in both patients with SZ and HC. OC history specifically impacts IQ in SZ. Smaller caudate volumes might be particularly related to disease development. These results warrant replication in an independent sample.

No significant relationships.

To investigate associations between schizophrenia candidate gene polymorphisms and regional cortical thickness and volume in patients with schizophrenia and healthy control subjects.

Genotyping was performed using PCR and pyrosequencing techniques. Cortical morphology was analyzed by processing magnetic resonance brain images with the FreeSurfer software package. General linear model analysis was used to study associations between gene variants and cortical thickness in patients and controls, respectively. Regional cortical volumes were defined from automatic cortical parcellations. Our first studies from 96 patients with schizophrenia and 104 healthy control subjects demonstrate that polymorphisms in the brain derived neurotrophic factor (BDNF) gene may be associated with variation in frontal lobe morphology. Associations seem to be stronger in patients with schizophrenia than in healthy controls.

A majority of the studies on cognition in schizophrenia have been conducted in drug-treated patients. In healthy subjects, administration of antipsychotic medication has been found to have a negative impact on cognitive performance in domains such as speed of processing and attention. Antipsychotic drugs occupy the D2-dopamine receptor, a receptor subtype that has been related to cognitive function. Studies employing Positron Emission Tomography have shown that poor performance in several cognitive domains is associated to low D2-receptor binding. It is therefore crucial to examine cognition in drug-naïve patients with schizophrenia.

In FES patients: To examine the profile of cognitive impairments in the absence of antipsychotic medication and compare with the cognitive profile of patients who are on antipsychotic medication.

To study cognition in FES.

The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery was administered to 60 patients with early schizophrenia and 30 healthy controls, 50% of the patients were drug-naïve. This research is ongoing and a part of the Karolinska Schizophrenia Project (KaSP), a multidisciplinary research consortium that examines the pathophysiology of schizophrenia.

Preliminary findings show that patients perform worse than healthy controls in all cognitive domains, with no significant differences between drug-naïve and medicated patients. Attention and Visual memory were the domains with the greatest impairments. The results are compared with our previous meta-analytic findings in drug-naïve patients.

These preliminary findings confirm the existence of cognitive impairments at the early stage of schizophrenia in the absence of antipsychotic medication.

Neuroimaging studies indicate that auditory hallucinations are associated with smaller grey matter volume in the auditory cortex in schizophrenia patients. However, reduced cortical volume can be the result of reduction in either cortical thickness or cortical surface area, and these two components may reflect different pathophysiological processes.

To measure cortical thickness and surface area of auditory cortex in schizophrenia spectrum patients and healthy controls and investigate putative association of cortical characteristics with auditory hallucinations.

To determine how thickness and surface area of the auditory cortex relate to auditory hallucinations in schizophrenia patients.

Schizophrenia spectrum patients and healthy controls from the Thematically Organized Psychosis study, Oslo, Norway, underwent 1.5 T MRI. General linear models were used to compare cortical thickness and surface area (obtained with FreeSurfer) in transverse temporal gyrus (TTG), planum temporale (PT), and lateral superior temporal gyrus (STG) between hallucinating (score > 3 on Positive and Negative Syndrome Scale, PANSS, item P3; n=82), non-hallucinating (n=139) schizophrenia spectrum patients, and healthy controls (n=323).

Both patient groups had thinner cortex bilaterally in PT and STG, as well as larger left STG surface area compared to controls. The hallucinating group showed reduced thickness in left TTG and trend reduction in left PT compared to non-hallucinating patients. No cortical surface area differences were found between hallucinating and non-hallucinating patients.

Our results indicate that auditory cortex volume reductions associated with auditory hallucinations in schizophrenia patients are driven by reductions in cortical thickness.

Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood trauma, cognitive function, and brain abnormalities in psychoses. Serotonin transporter gene (5-HTTLPR) variants and childhood trauma were also investigated together with cognitive function in psychosis.

A total of 323 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited. A history of childhood trauma was obtained using the Childhood Trauma Questionnaire. BDNF val66met, 5-HTTLPR, and BDNF RNA were analyzed using standardized procedures. A subsample of n=108 underwent MRI scanning, and the FreeSurfer was used to obtain measures of hippocampal subfield. Cognitive function was assessed through a comprehensive, standardized neuropsychological test battery.

Additive effects were observed between a history of childhood trauma and BDNF val66met, in the direction of met carriers with high levels of childhood trauma having the lowest BDNF mRNA levels. Moreover, met carriers reporting high levels of childhood trauma had significantly reduced hippocampal subfield volumes of CA2/3 and CA4 dentate gyrus, as well as reduced cognitive function. Lastly, we observed a significant interaction between homozygotic s-carriers of the serotonin transporter gene 5-HTTLPR variants exposed to high levels of childhood trauma and poorer cognitive functioning, compared to patients with low trauma and ll- or sl- carriers.

Our results need replication but underline the importance of investigating childhood trauma and its interaction with genetic markers when studying cognitive abnormalities in psychotic disorders.

First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a one-year period compared to healthy controls, and if putative changes correlated with clinical characteristics and outcome.

MRIs of 79 FEP (SCID-I verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (SD 7.7), 66% male) and 82 healthy controls (age 29.3 (SD 7.2) 66% male) were acquired from the same 1.5T scanner at baseline and one-year follow up as part of the TOP study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer. General linear models were used to analyze longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations to clinical characteristics.

FEP and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use, and remission at follow-up were not related to longitudinal brain change.

We found no longitudinal brain changes over a one-year period in FEP compared to controls. Our results do not support early progressive brain changes in psychotic disorders.

Schizophrenia patients with a history of community violence constitute a sub-group of schizophrenia patients (SCZ) that receive much public attention. While brain structural abnormalities are established in SCZ, there are few studies of brain morphology in violent SCZ.

To conduct a pilot study of brain morphology in a SCZ cohort with a history of severe community violence from a high security forensic psychiatric unit.

Investigate differences in hippocampal, ventricular, thalamic, and amygdala volumes in violent SCZ, SCZ, and healthy controls (HC).

Structural 3T MRI scans were acquired of 47 subjects (violent SCZ n=11, mean age 33.2 years (SD 9.0), 91% male; SCZ n= 17, 34.3 years (7.4), 94% male; HC n=19, 33.2 years (9.1), 90% male). Violent offence included murder, attempted murder, or severe assault (with or without weapon) towards other people. The FreeSurfer 5.3.0 software was used to obtain subcortical brain volumes. Effects of age, sex, and intracranial volume were controlled for, and Bonferroni correction was applied.

Violent SCZ had smaller right hippocampal volumes (F(2,42)=4.11, p= .024) compared to HC (padj= .028) and SCZ (pnom= .046). On a trend level, violent SCZ had larger right lateral ventricles than HC (pnom =.032) and SCZ (pnom=.049), and smaller left hippocampus than HC (pnom =.027). No differences in thalamus and amygdala volumes were found.

Violent SCZ may be associated with more pronounced brain abnormalities than non-violent SCZ. Future studies are needed to verify the observed abnormalities and determine the pathophysiological mechanisms and functional consequences.

Smaller auditory cortex volume in schizophrenia patients with auditory hallucinations (AH) may be a result of reduced cortical surface area and/or cortical thickness. A neuro–imaging study from our group demonstrated that adult schizophrenia spectrum patients with AH had significantly thinner cortex in the left side Heschl's gyrus (HG), compared to patients without AH, and healthy controls (HC).

This study aims to investigate if adolescents with early-onset psychosis (EOP) and AH demonstrate thinner cortices in HG, as found in Mørch-Johnsen et al. in 2016, compared to EOP patients without AH, and HC.

EOP patients (schizophrenia spectrum, psychotic disorder not otherwise specified) (n = 29) underwent MRI. Mean volume, cortical thickness and surface area in auditory cortex regions (HG, superior temporal gyrus [STG]) were compared between patients with AH (n = 20) and without AH (n = 9), measured with item P3 from the Positive And Negative Syndrome Scale (PANSS), and 48 HC.

Preliminary results show no significant differences between patients with and without AH and HC in mean volume, cortical thickness, or surface area in HG or STG. There were no significant side differences across hemispheres for these structures.

AH in EOP were not related to smaller volume, thinner cortex or reduced surface area in auditory cortex regions. To overcome the limitation of having a relatively small sample size, the sample will be expanded with other EOP cohorts. Investigations into HG structure variation in relation to AH in EOP will also be conducted.

The authors have not supplied their declaration of competing interest.

The ENIGMA-EOP collaboration aims to identify structural phenotypic markers that robustly discriminate adolescents with early-onset psychosis (EOP) from healthy controls through mega- or meta-analysis of magnetic resonance imaging (MR) data. Through larger samples we will obtain sufficient power to detect the brain structural correlates, overcome some of the clinical heterogeneity and characterize the developmental trajectories.

Multiple linear regression was used to investigate structural brain differences in two Scandinavian adolescent EOP cohorts (altogether 50 patients; ages 12.1-18.3 years (mean 16.4 years), 60% female; 68 controls; ages 12.0-18.8 years (mean 16.2 years), 62% female) acquired on two different 3 T GE MRI scanners. The statistical analysis included site as a covariate in addition to age, sex and intracranial volume (ICV). The results are presented by p-values, Cohens's-d effect size and with an indication of directionality. MRI scans were processed following the ENIGMA (http://enigma.ini.usc.edu/) structural image processing protocols using FreeSurfer (Fischl 2012) version 5.3.0 to measure subcortical brain volumes.

Preliminary results show significant or trend-significant group effects on right amygdala (P = 0.001, d = 0.33, patients < controls), total grey matter volume (P = 0.037, d = 0.21, patients < controls), ICV (P = 0.028, d = 0.22, patients < controls) and third ventricle (P = 0.067, d = 0.19, patients > controls). Sub-analyses in the two individual groups show overlapping findings in right amygdala. Previously reported enlarged lateral and 4th ventricles, and caudate, from a similar Scandinavian adolescent EOP cohort (Juuhl-Langseth, 2012) were not replicated.

There is a need for larger subject samples in EOP to better capture disease mechanisms. Research groups interested in participating can join ENIGMA-EOP through: http://enigma.ini.usc.edu/ongoing/enigma-eop-working-group/.

The authors have not supplied their declaration of competing interest.

Cortical brain abnormalities are frequently observed in adults with psychotic disorders, but few studies have investigated adolescents with early-onset psychosis (EOP). A previous magnetic resonance imaging (MRI) study from the NORMENT group in Norway, found widespread cortical thinning and smaller subcortical volumes in adult patients with psychotic disorders, particularly schizophrenia, compared to healthy controls.

Participants from the ongoing NORMENT adolescent EOP-study, 30 patients (age: 13.3–18.3 years, mean age: 16.5, 66% female) and 45 healthy adolescents (age: 13.6–18.8 years, mean age: 16.2, 58% female), underwent 3 T MRI on the same scanner. Surface-based morphometric analyses were performed using FreeSurfer version 5.3.0. Group differences in vertex-wise cortical volume, thickness and surface area were investigated by fitting general linear models at each vertex on the surface. Age, sex and group were entered as covariates, and a non-parametric cluster-wise correction method for multiple comparisons was applied and cluster-forming and cluster-wise threshold set at 0.05.

Preliminary results show thinner cortex in the left medial frontal lobe and smaller surface area in the left temporoparietal junction in EOP patients compared to healthy controls after correction for multiple comparisons.

Surface-based analysis is sensitive to alterations in cortical morphology in an adolescent EOP sample. The regions exhibiting reduced cortical thickness and area in EOP overlap with findings in an adult psychosis sample. Large-scale studies are warranted to better identify the pattern of abnormalities and clarify effects of age, diagnosis and medication.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.