Quality of clinical management of cardiometabolic risk factors in patients with severe mental illness in a specialist mental health care setting.

PURPOSE: Cardiometabolic disease in patients with severe mental illness is a major cause of shortened life expectancy. There is sparse evidence of real-world clinical risk prevention practice. We investigated levels of assessments of cardiometabolic risk factors and risk management interventions in patients with severe mental illness in the Norwegian mental health service according to an acknowledged international standard. METHODS: We collected data from 264 patients residing in six country-wide health trusts for: (a) assessments of cardiometabolic risk and (b) assessments of levels of risk reducing interventions. Logistic regressions were employed to investigate associations between risk and interventions. RESULTS: Complete assessments of all cardiometabolic risk variables were performed in 50% of the participants and 88% thereof had risk levels requiring intervention according to the standard. Smoking cessation advice was provided to 45% of daily smokers and 4% were referred to an intervention program. Obesity was identified in 62% and was associated with lifestyle interventions. Reassessment of psychotropic medication was done in 28% of the obese patients. Women with obesity were less likely to receive dietary advice, and use of clozapine or olanzapine reduced the chances for patients with obesity of getting weight reducing interventions. CONCLUSIONS: Nearly nine out of the ten participants were identified as being at cardiometabolic high risk and only half of the participants were adequately screened. Women with obesity and patients using antipsychotics with higher levels of cardiometabolic side effects had fewer adequate interventions. The findings underscore the need for standardized recommendations for identification and provision of cardiometabolic risk reducing interventions in all patients with severe mental illness.

Cortical thickness abnormalities in bipolar disorder patients with a lifetime history of auditory hallucinations.

OBJECTIVES: We aimed to investigate morphometric correlates of auditory hallucinations in bipolar disorder (BD) by comparing cortical thickness and cortical surface area in bipolar disorder patients with (BD+) and without (BD-) a lifetime history of auditory hallucinations. Based on previous findings in schizophrenia patients, we hypothesized that the cortex would be thinner in the auditory cortex in BD+ compared to BD-. METHODS: Bipolar disorder spectrum (n = 157) patients and healthy controls (n = 279) underwent 1.5T magnetic resonance imaging (MRI) scanning. Hypothesis-driven analyses of cortical thickness and surface area in regions of the auditory cortex (Heschl's gyrus [HG], planum temporale and superior temporal gyrus) were conducted comparing BD+ (n = 49) and BD- (n = 108) using linear regression models, covaried for age and sex. Furthermore, we explored vertex-wise group differences in thickness and surface area across the whole cerebral cortex. RESULTS: Hypothesis-driven analyses:BD+ had significantly thicker cortex in the left HG compared to BD- (B = 0.128, P = .0046). The finding was not explained by duration of illness, global functioning, bipolar subtype, IQ or use of antipsychotic, antidepressant or antiepileptic medication, or by lithium. Exploratory analyses: A small region of thicker cortex in BD+ compared to BD- was seen in the left superior parietal lobule (false discovery rate <0.05). There were no significant group differences in cortical surface area. CONCLUSION: A lifetime history of auditory hallucinations in BD was associated with cortical thickness alterations in both the left HG and the superior parietal lobule. Contrary to our hypothesis, BD+ showed thicker, rather than thinner cortex compared to BD-. Replications in independent samples are needed.

Effect of DISC1 SNPs on brain structure in healthy controls and patients with a history of psychosis.

Disrupted-in-Schizophrenia-1 (DISC1) has been suggested as a susceptibility locus for a broad spectrum of psychiatric disorders. Risk variants have been associated with brain structural changes, which overlap alterations reported in schizophrenia and bipolar disorder patients. We used genome-wide genotyping data for a Norwegian sample of healthy controls (n = 171) and patients with a history of psychosis (n = 184), to investigate 61 SNPs in the DISC1 region for putative association with structural magnetic resonance imaging (sMRI) measures (hippocampal volume; mean cortical thickness; and total surface area, as well as cortical thickness and area divided into four lobar measures). SNP rs821589 was associated with mean temporal and total brain cortical thickness in controls (P(adjusted) = 0.009 and 0.02, respectively), but not in patients. SNPs rs11122319 and rs1417584 were associated with mean temporal cortical thickness in patients (P(adjusted) = 0.04 and 0.03, respectively), but not in controls, and both SNPs have previously been highly associated with DISC1 gene expression. There were significant genotype × case-control interactions. There was no significant association between SNPs and cortical area or hippocampal volume in controls, or with any of the structural measures in cases, after correction for multiple comparisons. In conclusion, DISC1 SNPs might impact brain structural variation, possibly differently in psychosis patients versus controls, but independent replication will be needed to confirm our findings.

Psychodynamic case formulations without technical language: a reliability study.

BACKGROUND: To bridge the gap between symptoms and treatment, constructing case formulations is essential for clinicians. Limited scientific value has been attributed to case formulations because of problems with quality, reliability, and validity. For understanding, communication, and treatment planning beyond each specific clinician-patient dyad, a case formulation must convey valid information concerning the patient, as well as being a reliable source of information regardless of the clinician's theoretical orientation. The first aim of the present study is to explore the completeness of unstructured psychodynamic formulations, according to four components outlined in the Case Formulation Content Coding Method (CFCCM). The second aim is to estimate the reliability of independent formulations and their components, using similarity ratings of matched versus mismatched cases. METHODS: This study explores psychodynamic case formulations as made by two or more experienced clinicians after listening to an evaluation interview. The clinicians structured the formulations freely, with the sole constraint that technical, theory-laden terminology should be avoided. The formulations were decomposed into components after all formulations had been written. RESULTS: The results indicated that most formulations were adequately comprehensive, and that overall reliability of the formulations was high (> 0.70) for both experienced and inexperienced clinician raters, although the lower bound reliability estimate of the formulation component deemed most difficult to rate - inferred mechanisms - was marginal, 0.61. CONCLUSIONS: These results were achieved on case formulations made by experienced clinicians using simple experience-near language and minimizing technical concepts, which indicate a communicative quality in the formulations that make them clinically sound. TRIAL REGISTRATION: linicalTrials.gov Identifier: NCT00423462 . https://doi.org/10.1007/s00432-018-2781-7 ., January 18, 2007.

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Auditory Cortex Characteristics in Schizophrenia: Associations With Auditory Hallucinations.

BACKGROUND: Neuroimaging studies have demonstrated associations between smaller auditory cortex volume and auditory hallucinations (AH) in schizophrenia. Reduced cortical volume can result from a reduction of either cortical thickness or cortical surface area, which may reflect different neuropathology. We investigate for the first time how thickness and surface area of the auditory cortex relate to AH in a large sample of schizophrenia spectrum patients. METHODS: Schizophrenia spectrum (n = 194) patients underwent magnetic resonance imaging. Mean cortical thickness and surface area in auditory cortex regions (Heschl's gyrus [HG], planum temporale [PT], and superior temporal gyrus [STG]) were compared between patients with (AH+, n = 145) and without (AH-, n = 49) a lifetime history of AH and 279 healthy controls. RESULTS: AH+ patients showed significantly thinner cortex in the left HG compared to AH- patients (d = 0.43, P = .0096). There were no significant differences between AH+ and AH- patients in cortical thickness in the PT or STG, or in auditory cortex surface area in any of the regions investigated. Group differences in cortical thickness in the left HG was not affected by duration of illness or current antipsychotic medication. CONCLUSIONS: AH in schizophrenia patients were related to thinner cortex, but not smaller surface area of the left HG, a region which includes the primary auditory cortex. The results support that structural abnormalities of the auditory cortex underlie AH in schizophrenia.

Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders.

BACKGROUND: Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB) in early onset schizophrenia spectrum disorders (EOS). To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS. METHODS: Twenty-four patients with EOS and 33 healthy controls (HC) were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables. RESULTS: The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034). There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship. CONCLUSION: Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.

Brain structure characteristics in intellectually superior schizophrenia.

The current study aims to fill a gap in the knowledge base by investigating the structural brain characteristics of individuals with schizophrenia and superior intellectual abilities. Subcortical volumes, cortical thickness and cortical surface area were examined in intellectually normal and intellectually superior participants with schizophrenia and their IQ-matched healthy controls, as well as in intellectually low schizophrenia participants. We replicated significant diagnostic group effects on hippocampal and ventricular size after correction for multiple comparisons. There were no statistically significant effects of intellectual level or of the interaction between diagnostic group and intellectual level. Effect sizes indicated that differences between schizophrenia and healthy control participants were of similar magnitude at both intellectual levels for all three types of morphological data. A secondary analysis within the schizophrenia group, including participants with low intellectual abilities, yielded numerical, but no statistically significant differences on any structural brain measure. The present findings indicate that the brain structure abnormalities in schizophrenia are present at all intellectual levels, and individuals with schizophrenia and superior intellectual abilities have brain structure abnormalities of the same magnitude as individuals with schizophrenia and normal intellectual abilities.

Normal birth weight variation is related to cortical morphology across the psychosis spectrum.

BACKGROUND: Normal birth weight variation affects schizophrenia risk and cognitive performance in schizophrenia patients and healthy controls. Brain cortical anatomy is altered in psychotic disorders and in low birth weight subjects, but if birth weight variation relates to cortical morphology across the psychosis spectrum is not known. METHODS: Magnetic Resonance Imaging brain scans and clinical-, neurocognitive-, and medical birth registry data were collected from 359 adults including patients with a DSM-IV diagnosis of schizophrenia (n = 90, mean age 29.4±10.2 [95% CI], 62% male), bipolar disorder (n = 79, age 29.4±11.8, 39% male) or other psychosis (n = 40, age 26.3±10.0, 56% male), and healthy controls (n = 140, age 30.8±12.0,53% male). We explored the relationship between whole-range birth weight variation and cortical surface area and thickness and their possible associations to cognitive performance. RESULTS: Across all groups, lower birth weight was associated with smaller total surface area (t = 3.87, P = .0001), within specific regions of the temporal, parietal, and frontal cortex bilaterally. There were no associations between birth weight and cortical thickness, and no diagnosis by birth weight interaction effects on cortical thickness or surface area. Smaller cortical area (t = 2.50, P = .013) and lower birth weight (t = 2.53, P = .012) were significantly related to poorer working memory performance in all diagnostic groups except schizophrenia. CONCLUSION: Birth weight relates to adult cortical surface area, but not cortical thickness, in patients across the psychosis spectrum and in healthy controls. Cortical area appears to be a diagnosis-independent general marker of early neurodevelopment, with a dose-response association to normal birth weight variation.

Reduced brain cortical folding in schizophrenia revealed in two independent samples.

The cerebral cortex is highly convoluted, and principal folding patterns are determined early in life. Degree of cortical folding in adult life may index aberrations in brain development. Results from previous studies of cortical folding in schizophrenia are inconsistent. Here we investigated cortical folding patterns in the hitherto largest sample of patients with schizophrenia drawn from two independent cohorts. Magnetic resonance imaging scans were acquired from 207 patients and 206 healthy subjects recruited to two separate research projects in Sweden and Norway. Local gyrification index (lGI) was estimated continuously across the cortex using automated methods. Group differences in lGI were analyzed using general linear models. Patients had lower lGI in three large clusters of the cortex with peak differences found in the left precentral gyrus, right middle temporal gyrus, and right precuneus. Similar, although not completely overlapping results were found when the two cohorts were analyzed separately. There were no significant interaction effects between age and diagnosis and gender and diagnosis. The finding of reduced degree of folding in large regions of the cerebral cortex across two independent samples indicates that reduced gyrification is an inherent feature of the brain pathology in schizophrenia.

ZNF804A and cortical thickness in schizophrenia and bipolar disorder.

ZNF804A SNP rs1344706 confers genome-wide risk for schizophrenia and bipolar disorder. Both disorders affect cortical thickness. To determine if single nucleotide polymorphisms (SNPs) across ZNF804A are associated with cortical thinning, we investigated 63 SNPs (including rs1344706) in 365 psychosis patients and healthy controls. Results show no significant associations.

A 5-year follow-up study of brain cortical and subcortical abnormalities in a schizophrenia cohort.

BACKGROUND: Magnetic resonance imaging studies have demonstrated that patients with schizophrenia have thinner cortex in prefrontal and temporal brain regions, and enlarged lateral ventricles, compared to healthy subjects. Longitudinal studies have shown progressive brain tissue loss and ventricular dilatation among patients, predominantly in the early phase of the illness. Evidence for progression in more chronic phases of schizophrenia is less established. METHODS: Measurements of cortical thickness, cortical volume and subcortical volumes were obtained from 52 patients with long-term treated schizophrenia and 63 healthy subjects who were scanned twice over five years. Differences in brain measurements across time and group were investigated using general linear models. RESULTS: Compared to controls, patients had similar patterns of thinner cortex and smaller cortical volumes in prefrontal and temporal regions at both time points. In the follow-up interval regional cortical volumes decreased and lateral ventricle volumes increased in both groups. There was a trend level interaction effect of group and time for the right lateral ventricle, but not for cortical measurements. This effect was related to higher degree of negative symptoms at follow-up. CONCLUSIONS: Regional differences in cortical thickness and volume between long-term treated patients with schizophrenia and healthy subjects are stable across five years, while right lateral ventricle volumes tend to increase more in the patients. The findings indicate that brain structure abnormalities found in schizophrenia are not progressive in the chronic stage of the disease, but that some progression in subcortical structures may be present in patients with poor outcome.

Cortical volume, surface area, and thickness in schizophrenia and bipolar disorder.

BACKGROUND: Magnetic resonance imaging studies have shown that structural brain abnormalities are present in both schizophrenia and bipolar disorder. Most previous studies have focused on brain tissue volumes, but advances in neuroimaging data processing have made it possible to separate cortical area and cortical thickness. The purpose of the present study was to provide a more complete picture of cortical morphometric differences in schizophrenia and bipolar disorder, decomposing cortical volume into its constituent parts, cortical thickness and cortical area. METHODS: We analyzed magnetic resonance imaging images from a sample of 173 patients with schizophrenia, 139 patients with bipolar disorder, and 207 healthy control subjects. Maps of cortical volume, area, and thickness across the continuous cortical surface were generated within groups and compared between the groups. RESULTS: There were widespread reductions in cortical volume in schizophrenia relative to healthy control subjects and patients with bipolar disorder type I. These reductions were mainly driven by cortical thinning, but there were also cortical area reductions in more circumscribed regions, which contributed to the observed volume reductions. CONCLUSIONS: The current surface-based methodology allows for a distinction between cortical thinning and reduction in cortical area and reveals that cortical thinning is the most important factor in volume reduction in schizophrenia. Cortical area reduction was not observed in bipolar disorder type I and may be unique to schizophrenia.

Common sequence variants in the major histocompatibility complex region associate with cerebral ventricular size in schizophrenia.

BACKGROUND: Because of evidence from genetic linkage and genome-wide association studies, as well as suggested involvement of infection, the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1 has been implicated in the development of schizophrenia. METHODS: Here, we investigated how gene variants across the MHC region are associated with brain structure in a large ethnically homogenous sample (n = 420), including patients with schizophrenia spectrum disorders and other severe mental illness and healthy control subjects. RESULTS: We demonstrate highly significant associations between common gene markers in the MHC region and cerebral ventricular volume specifically in schizophrenia spectrum patients (uncorrected p values between 1.16 × 10⁻4 and 2.00 × 10⁻7). One single nucleotide polymorphism, rs2596532, survives Bonferroni correction for multiple testing across all single nucleotide polymorphisms and brain structure measures (adjusted p value 5.59 × 10⁻4). CONCLUSIONS: The results indicate that MHC variants are implicated in characteristic brain abnormalities of schizophrenia.

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls.

BACKGROUND: Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder. METHODS: MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests. RESULTS: In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group. CONCLUSION: The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.

Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder.

BACKGROUND: Schizophrenia and bipolar disorder are severe psychiatric diseases with overlapping symptomatology. Widespread brain morphologic abnormalities, including cortical thinning and subcortical volume reductions, have been demonstrated in schizophrenia but it is unclear whether similar abnormalities are present in bipolar disorder. The purpose of this study was to compare cortical thickness and subcortical volumes in schizophrenia and bipolar disorder, to assess differences and similarities in cortical and subcortical brain structure. METHODS: We analyzed magnetic resonance images from a sample of 173 patients with schizophrenia spectrum disorder, 139 patients with bipolar disorder, and 207 healthy control subjects. Cortical thickness was compared between the groups in multiple locations across the continuous cortical surface. Subcortical volumes were compared on a structure-by-structure basis. RESULTS: There was widespread cortical thinning in schizophrenia compared with control subjects, in frontal, temporal, occipital, and smaller parietal regions. There was no cortical thinning in bipolar disorder compared with control subjects or in schizophrenia compared with bipolar disorder. However, the subgroup of patients with bipolar disorder Type 1 showed cortical thinning, primarily in the frontal lobes and superior temporal and temporoparietal regions. Both patient groups showed substantial subcortical volume reductions bilaterally in the hippocampus, the left thalamus, the right nucleus accumbens, the left cerebellar cortex, and the brainstem, along with substantial ventricular enlargements. CONCLUSIONS: We found substantial overlap in the underlying brain morphologic abnormalities in schizophrenia and bipolar disorder in subcortical structures, and between schizophrenia and bipolar disorder Type 1 in the cerebral cortex.