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1.
BJPsych Open ; 9(6): e193, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37828908

ABSTRACT

BACKGROUND: Excellence is that quality that drives continuously improving outcomes for patients. Excellence must be measurable. We set out to measure excellence in forensic mental health services according to four levels of organisation and complexity (basic, standard, progressive and excellent) across seven domains: values and rights; clinical organisation; consistency; timescale; specialisation; routine outcome measures; research and development. AIMS: To validate the psychometric properties of a measurement scale to test which objective features of forensic services might relate to excellence: for example, university linkages, service size and integrated patient pathways across levels of therapeutic security. METHOD: A survey instrument was devised by a modified Delphi process. Forensic leads, either clinical or academic, in 48 forensic services across 5 jurisdictions completed the questionnaire. RESULTS: Regression analysis found that the number of security levels, linked patient pathways, number of in-patient teams and joint university appointments predicted total excellence score. CONCLUSIONS: Larger services organised according to stratified therapeutic security and with strong university and research links scored higher on this measure of excellence. A weakness is that these were self-ratings. Reliability could be improved with peer review and with objective measures such as quality and quantity of research output. For the future, studies are needed of the determinants of other objective measures of better outcomes for patients, including shorter lengths of stay, reduced recidivism and readmission, and improved physical and mental health and quality of life.

2.
Crim Behav Ment Health ; 31(5): 321-330, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34523174

ABSTRACT

BACKGROUND: Treatment completion difficulties are common in forensic mental health settings and may have a profound impact on recidivism rates. AIMS: To test for associations between measures of risk and of security needs on the one hand and treatment non-completion on the other among male offender-patients in one medium security hospital. METHODS: We conducted a retrospective file study in a Flemish medium security hospital. A random sample of 25 treatment non-completers was compared to a random same-size sample of completers, each rated, blind to outcome, on the DUNDRUM-1 security needs scale from data recorded at the time of admission to the unit. 'Non-completion' was defined as any failure to complete treatment, whether staff-terminated or self-terminated; in Flanders, failure to comply with the judicial conditions of placement can result in re-imprisonment. We used binary logistic regression to test relationships between treatment completion/non-completion and security need, measured with the DUNDRUM-1, together with a range of possible confounding variables. RESULTS: Most patients had psychosis and/or personality disorder and often substance use disorders also. Treatment non-completion was invariably staff ordered because of security breaches. DUNDRUM-1 and PCL-R Facet 4 scores at the time of admission and HCR-20 scores during admission were significantly higher among non-completers than completers, but after binary logistic regression, only the DUNDRUM-1 rating was independently associated with non-completion. CONCLUSIONS: Our study showed that an admission DUNDRUM-1 rating, indicating levels of security need, co-varies only to a small extent with the historical items of the HCR-20, so may be regarded as measuring complementary domains. While conditions in Flanders at the time of the study complicated it in that medium security hospital units offered the highest level of hospital security available, the finding that non-completion of treatment was particularly likely when the DUNDRUM-1 indicated a higher security need than facilities could provide may have implications for all secure hospital services.


Subject(s)
Criminals , Psychotic Disorders , Forensic Psychiatry , Hospitalization , Humans , Male , Retrospective Studies
3.
Int J Law Psychiatry ; 64: 205-210, 2019.
Article in English | MEDLINE | ID: mdl-31122631

ABSTRACT

BACKGROUND: Criteria to determine in which level of security forensic patients should receive treatment are currently non-existent in Belgium. Courts largely rely on the evaluations of the prison psychiatrists and psychologists to form their decision. None of the few available instruments - e.g., the DUNDRUM-1 - is currently used to provide structured clinical judgment when determining security level. METHOD: DUNDRUM-1 scores were collected for 150 forensic patients. Security levels according to DUNDRUM-1 assessment were compared to security levels as decided by the court. RESULTS: There was little agreement between DUNDRUM-1 scores and proposals for secure care made by the court. The DUNDRUM-1 predicted eventual admission to a high security setting, but not a medium security setting. CONCLUSION: The DUNDRUM-1 is an instrument that can help clinicians and judges to make more reliable and transparent decisions regarding secure care. However, further research with regard to practical applicability is needed.


Subject(s)
Criminals/legislation & jurisprudence , Involuntary Commitment/legislation & jurisprudence , Jurisprudence , Adult , Aged , Forensic Psychiatry/methods , Forensic Psychiatry/standards , Humans , Insanity Defense , Involuntary Commitment/standards , Judgment , Male , Middle Aged , Retrospective Studies , Security Measures , Violence , Young Adult
4.
PLoS One ; 12(1): e0166651, 2017.
Article in English | MEDLINE | ID: mdl-28045900

ABSTRACT

BACKGROUND: The alterations in cortical morphology, such as cortical thinning, observed in psychotic disorder, may be the outcome of interacting genetic and environmental effects. It has been suggested that urban upbringing may represent a proxy environmental effect impacting cortical thickness (CT). Therefore, the current study examined whether the association between group as a proxy genetic variable (patients with psychotic disorder [high genetic risk], healthy siblings of patients [intermediate risk] and healthy control subjects [average risk]) and CT was conditional on different levels of the childhood urban environment and whether this was sex-dependent. METHODS: T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 non-psychotic siblings of patients with psychotic disorder and 87 healthy control subjects. Freesurfer software was used to measure CT. Developmental urban exposure was classified as low, medium, and high, reflecting the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. Multilevel regression analyses were used to examine the association between group, sex, and urban upbringing (as well as their interactions) and cortical CT as the dependent variable. RESULTS: CT was significantly smaller in the patient group compared to the controls (B = -0.043, p <0.001), but not in the siblings compared to the controls (B = -0.013, p = 0.31). There was no main effect of developmental urbanicity on CT (B = 0.001, p = 0.91). Neither the three-way group × urbanicity × sex interaction (χ2 = 3.73, p = 0.16), nor the two-way group × urbanicity interaction was significant (χ2 = 0.51, p = 0.77). CONCLUSION: The negative association between (familial risk for) psychotic disorder and CT was not moderated by developmental urbanicity, suggesting that reduced CT is not the outcome of familial sensitivity to the proxy environmental factor 'urban upbringing'.


Subject(s)
Brain/diagnostic imaging , Brain/physiopathology , Cities , Psychotic Disorders/epidemiology , Adolescent , Adult , Belgium/epidemiology , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Netherlands , Population Density , Psychotic Disorders/etiology , Regression Analysis , Risk Factors , Severity of Illness Index , Sex Factors , Siblings , Software , Surveys and Questionnaires , Urban Population , Young Adult
5.
Law Hum Behav ; 41(1): 29-43, 2017 02.
Article in English | MEDLINE | ID: mdl-27936826

ABSTRACT

Recent field studies have questioned the interrater reliability (IRR) and predictive validity regarding (violent) recidivism of the Psychopathy Checklist-Revised (PCL-R). Using a forensic psychiatric sample, the current study investigated discrepancies in scoring between hospital and prison settings, as well as differences in predictive validity across these two settings. PCL-R information was collected from prison and hospital files, resulting in 224 PCL-R total scores and 74 double scores. When examining repeated measurements, large individual differences were found together with an intraclass correlation coefficient (ICCA,1) of .42 for the total score. Discrepant results were found for Factor 2, with repeated scores within the same setting having an ICCA,1 of .28 versus an ICCA,1 of .57 for repeated scores between settings. However, areas under the curve (AUCs) from receiver operating characteristic (ROC) analyses for total, factor and facet scores did not differ between settings. For the whole sample, Factor 2 scores marginally predicted violent and general recidivism after 2 years (AUC = .62 and .63), whereas Factor 1 did not predict (violent) recidivism. Consistent with recent studies from other countries, these results suggest inadequate field reliability and validity in prison and hospital settings in Flanders (Belgium). (PsycINFO Database Record


Subject(s)
Checklist/standards , Hospitals , Mental Disorders/diagnosis , Prisons , Belgium , Forensic Psychiatry , Humans , Reproducibility of Results
6.
J Craniomaxillofac Surg ; 44(8): 1015-24, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27259679

ABSTRACT

PURPOSE: The aim of this study was to evaluate the usefulness of intra-operative visualisation, endoscopic assistance, and CT measurements for estimating the orbital fracture size and complexity. METHODS: Ten human cadaver heads were subjected to thin-slice computed tomography (CT). Standardised fractures were created using piezoelectric surgery in accordance with the Jaquiéry classification system. Four surgeons and one anatomist used six different observation methods to visualise and describe the orbital defects. RESULTS: The intraclass correlation coefficients (ICCs) for the fracture length measurements were relatively low for all observation methods (range, 0.666-0.883). CT measurements of width showed high consistency (ICC, 0.910). The surface area of the defect was highly overestimated by all methods (range, 121-184%). None of the observers was able to accurately estimate the length or width of 95% of the defects within an error range of ±0.75 cm. CONCLUSION: CT measurements are the most consistent and accurate tool for estimating the critical size of orbital factures. In daily practice, a measurement tool in a DICOM viewer could be used, although software packages that allow manual adjustments are advisable. Direct intraoperative visualisation and surgeon experience are of limited value in the estimation of fracture size and complexity, and endoscopy provides no additional advantages.


Subject(s)
Orbital Fractures/diagnosis , Surgeons , Tomography, X-Ray Computed , Cadaver , Endoscopy , Humans , Observer Variation , Orbital Fractures/diagnostic imaging , Orbital Fractures/pathology , Surgery, Computer-Assisted
7.
Int J Law Psychiatry ; 47: 45-52, 2016.
Article in English | MEDLINE | ID: mdl-27084203

ABSTRACT

AIM: To examine the criminal outcome of Flemish forensic psychiatric patients ('internees') after medium security treatment. Also, the effect of conditional release on recidivism of two subgroups (internees under conditional release and internees who received unconditional release) was examined. METHOD: Reconviction rates and revocation rates were collected for all participants. Kaplan-Meier survival analyses were used to investigate recidivism rates while controlling for time at risk. RESULTS: During the 10-year period, 502 offenders were discharged from medium security treatment. Over a follow-up period averaging 3.6years, 7.4% of discharged patients were reconvicted or received a new 'not guilty by reason of insanity' (NGRI) verdict for a violent offence. One-quarter of the population had their conditional release revoked. Part of the study population was granted unconditional release. Reconviction rates were higher after unconditional release in comparison to conditional release. CONCLUSIONS: The results of this study suggest that the court supervision of NGRI patients in Flanders is effective in protecting the community from further offending.


Subject(s)
Commitment of Mentally Ill/legislation & jurisprudence , Insanity Defense/statistics & numerical data , Patient Discharge/legislation & jurisprudence , Patient Discharge/statistics & numerical data , Patient Readmission/legislation & jurisprudence , Patient Readmission/statistics & numerical data , Prisoners/legislation & jurisprudence , Prisoners/statistics & numerical data , Security Measures/legislation & jurisprudence , Violence/legislation & jurisprudence , Violence/psychology , Adolescent , Adult , Aged , Belgium , Dangerous Behavior , Female , Humans , Male , Middle Aged , Organization and Administration , Secondary Prevention , Violence/prevention & control , Young Adult
8.
Arthritis Res Ther ; 17: 209, 2015 Aug 24.
Article in English | MEDLINE | ID: mdl-26268317

ABSTRACT

INTRODUCTION: Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA). METHODS: Platelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity. RESULTS: Platelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcγRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level. CONCLUSIONS: We show for the first time that ACPA can mediate an FcγRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset.


Subject(s)
Arthritis, Rheumatoid/immunology , Autoantibodies/immunology , Citrulline/immunology , Peptides, Cyclic/immunology , Platelet Activation/immunology , Arthritis, Rheumatoid/blood , Autoantibodies/blood , Blood Platelets/immunology , Blood Platelets/metabolism , CD40 Ligand/blood , CD40 Ligand/immunology , CD40 Ligand/metabolism , Female , Flow Cytometry , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , P-Selectin/blood , P-Selectin/immunology , P-Selectin/metabolism
9.
PLoS One ; 10(3): e0120030, 2015.
Article in English | MEDLINE | ID: mdl-25790002

ABSTRACT

BACKGROUND: Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. METHODS: Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. RESULTS: There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. DISCUSSION: Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.


Subject(s)
Gyrus Cinguli/physiopathology , Neural Pathways/physiopathology , Psychotic Disorders/physiopathology , Adult , Case-Control Studies , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Risk , Schizophrenia/diagnosis , Schizophrenia/physiopathology , Siblings
10.
J Appl Res Intellect Disabil ; 28(3): 182-92, 2015 May.
Article in English | MEDLINE | ID: mdl-25175692

ABSTRACT

BACKGROUND: A stable assessment of cognition is of paramount importance for forensic psychiatric patients (FPP). The purpose of this study was to compare repeated measures of IQ scores in FPPs with and without intellectual disability. METHODS: Repeated measurements of IQ scores in FPPs (n = 176) were collected. Differences between tests were computed, and each IQ score was categorized. Additionally, t-tests and regression analyses were performed. RESULTS: Differences of 10 points or more were found in 66% of the cases comparing WAIS-III with RAVEN scores. Fisher's exact test revealed differences between two WAIS-III scores and the WAIS categories. The WAIS-III did not predict other IQs (WAIS or RAVEN) in participants with intellectual disability. DISCUSSION: This study showed that stability or interchangeability of scores is lacking, especially in individuals with intellectual disability. Caution in interpreting IQ scores is therefore recommended, and the use of the unitary concept of IQ should be discouraged.


Subject(s)
Forensic Psychiatry , Intellectual Disability/psychology , Intelligence , Adult , Female , Hospitalization , Hospitals, Psychiatric , Humans , Intellectual Disability/diagnosis , Intelligence Tests/standards , Male , Netherlands , Regression Analysis
11.
Neuroimage Clin ; 9: 607-16, 2015.
Article in English | MEDLINE | ID: mdl-26740914

ABSTRACT

BACKGROUND: Dysconnectivity in schizophrenia can be understood in terms of dysfunctional integration of a distributed network of brain regions. Here we propose a new methodology to analyze complex networks based on semi-metric behavior, whereby higher levels of semi-metricity may represent a higher level of redundancy and dispersed communication. It was hypothesized that individuals with (increased risk for) psychotic disorder would have more semi-metric paths compared to controls and that this would be associated with symptoms. METHODS: Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 unaffected siblings and 72 controls. Semi-metric percentages (SMP) at the whole brain, hemispheric and lobar level were the dependent variables in a multilevel random regression analysis to investigate group differences. SMP was further examined in relation to symptomatology (i.e., psychotic/cognitive symptoms). RESULTS: At the whole brain and hemispheric level, patients had a significantly higher SMP compared to siblings and controls, with no difference between the latter. In the combined sibling and control group, individuals with high schizotypy had intermediate SMP values in the left hemisphere with respect to patients and individuals with low schizotypy. Exploratory analyses in patients revealed higher SMP in 12 out of 42 lobar divisions compared to controls, of which some were associated with worse PANSS symptomatology (i.e., positive symptoms, excitement and emotional distress) and worse cognitive performance on attention and emotion processing tasks. In the combined group of patients and controls, working memory, attention and social cognition were associated with higher SMP. DISCUSSION: The results are suggestive of more dispersed network communication in patients with psychotic disorder, with some evidence for trait-based network alterations in high-schizotypy individuals. Dispersed communication may contribute to the clinical phenotype in psychotic disorder. In addition, higher SMP may contribute to neuro- and social cognition, independent of psychosis risk.


Subject(s)
Brain Mapping/methods , Brain/physiopathology , Genetic Predisposition to Disease , Magnetic Resonance Imaging/methods , Psychotic Disorders/genetics , Psychotic Disorders/physiopathology , Adult , Data Interpretation, Statistical , Female , Humans , Image Processing, Computer-Assisted , Male , Risk Factors , Siblings , Young Adult
12.
PLoS One ; 9(3): e92722, 2014.
Article in English | MEDLINE | ID: mdl-24658422

ABSTRACT

In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs) associated with the stress response, such as FK506-binding protein 5 (FKBP5) and brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target underlying these interactions. Therefore, more detailed modelling of these effects, using appropriate covariates, is required. We examined whether BDNF/FKBP5 and childhood trauma interactions affected two proxies of hippocampal integrity: (i) hippocampal volume and (ii) cognitive performance on a block design (BD) and delayed auditory verbal task (AVLT). We also investigated whether the putative interaction was different for patients with a psychotic disorder (n = 89) compared to their non-psychotic siblings (n = 95), in order to elicit possible group-specific protective/vulnerability effects. SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5) and rs6265 (BDNF). In the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not different for patients and siblings. The omission of drug use and alcohol consumption sometimes yielded false positives, greatly affected explained error and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by childhood trauma interactions on assessments of hippocampal integrity suggests that the effect of these interactions on psychotic symptoms is not mediated by hippocampal integrity. The importance of appropriate statistical designs and inclusion of relevant covariates should be carefully considered.


Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Cognition , Genotype , Hippocampus/pathology , Psychotic Disorders/diagnosis , Psychotic Disorders/etiology , Tacrolimus Binding Proteins/genetics , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Organ Size , Polymorphism, Single Nucleotide , Psychotic Disorders/drug therapy , Risk Factors , Tomography, X-Ray Computed , Young Adult
13.
Schizophr Res ; 146(1-3): 291-300, 2013 May.
Article in English | MEDLINE | ID: mdl-23523694

ABSTRACT

BACKGROUND: There is evidence for microstructural white matter alterations in patients with psychotic disorder, suggesting altered interregional connectivity. Less is known about the presence and role of white matter alterations in well individuals at higher than average genetic risk for psychotic disorder. METHODS: 85 patients with psychotic disorder, 93 non-psychotic siblings of patients with psychotic disorder and 80 healthy controls underwent a diffusion tensor imaging (DTI) scanning protocol. In a whole brain voxel-based analysis using Tract Based Spatial Statistics (TBSS), fractional anisotropy (FA) values were compared between the three groups. Effects of antipsychotic medication and drug use were examined. RESULTS: The patients displayed significantly lower mean FA than the controls in the following regions: corpus callosum (genu, body, splenium), forceps major and minor, external capsule bilaterally, corona radiata (anterior, posterior) bilaterally, left superior corona radiata and posterior thalamic radiation bilaterally. Similar FA differences existed between the patients and siblings; the siblings did not differ from the controls. CONCLUSION: Profound microstructural white matter alterations were found in the corpus callosum and other tracti and fasciculi in the patients with psychotic disorder, but not in siblings and the controls. These alterations may reflect brain pathology associated with the illness, illness-related environmental risk factors, or its treatment, rather than genetic risk.


Subject(s)
Corpus Callosum/pathology , Diffusion Tensor Imaging , Family Health , Leukoencephalopathies/etiology , Psychotic Disorders/complications , Adolescent , Adult , Anisotropy , Brain Mapping , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Leukoencephalopathies/pathology , Longitudinal Studies , Male , Middle Aged , Psychiatric Status Rating Scales , Psychotic Disorders/pathology , Sex Characteristics , Young Adult
14.
PLoS One ; 7(6): e38234, 2012.
Article in English | MEDLINE | ID: mdl-22675527

ABSTRACT

FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8 ± 6.6% (range 1.3-64.0%) (volume) and 2.8 ± 1.3% (1.1-7.7%) (cortical thickness). About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies.The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross-version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable.


Subject(s)
Cerebral Cortex/anatomy & histology , Computers , Software , Adolescent , Adult , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Organ Size , Young Adult
15.
Biol Psychiatry ; 69(5): 487-94, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-20951979

ABSTRACT

BACKGROUND: The etiology of schizophrenia is thought to involve differential-likely genetically mediated-sensitivity to environmental exposures. However, examination of differential sensitivity in models of psychopathologic constructs is subject to bias because psychopathology itself may distort exposure assessment. The use of neuroimaging phenotypes, conversely, may provide unbiased evidence for differential sensitivity to environmental exposures. This study examined the impact of two environmental exposures associated with both schizophrenia and magnetic resonance imaging (MRI) cerebral alterations in models of cerebral cortical thickness. METHODS: T1-weighted MRI scans were acquired from 88 patients with schizophrenia, 98 healthy siblings at higher than average genetic risk for schizophrenia, and 87 control subjects. Freesurfer software was used to measure cortical thickness for 68 brain regions. Associations between 1) cortical thickness and 2) cannabis use and developmental trauma were examined. RESULTS: A significant group × developmental trauma interaction (χ(2) = 9.65, p = .01), as well as a significant group × cannabis interaction (χ(2) = 6.04, p = .05) was apparent, indicating differential sensitivity of the patient group, which displayed stronger reductions of cortical thickness for both exposures. A similar pattern was found in the sibling-control comparison for cannabis. For developmental trauma, siblings did not differ from control subjects, displaying an increase in cortical thickness with higher levels of trauma. CONCLUSIONS: The findings suggest that schizophrenia and its genetic liability are associated with differential cerebral cortical sensitivity to developmental environmental exposures such as cannabis. Gene-environment interactions may underlie some of the brain alterations observed in patients with schizophrenia and their relatives.


Subject(s)
Cerebral Cortex/pathology , Environmental Exposure/statistics & numerical data , Schizophrenia/epidemiology , Schizophrenia/pathology , Adult , Age of Onset , Alcohol Drinking/pathology , Child , Child Abuse/psychology , Diagnostic and Statistical Manual of Mental Disorders , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Marijuana Smoking/pathology , Risk Factors , Schizophrenic Psychology
16.
Circ Res ; 102(7): 849-59, 2008 Apr 11.
Article in English | MEDLINE | ID: mdl-18276916

ABSTRACT

Nppa, encoding atrial natriuretic factor, is expressed in fetal atrial and ventricular myocardium and is downregulated in the ventricles after birth. During hypertrophy and heart failure, Nppa expression is reactivated in the ventricles and serves as a highly conserved marker of heart disease. The Nppa promoter has become a frequently used model to study mechanisms of cardiac gene regulation. Nevertheless, the regulatory sequences that provide the correct developmental pattern and ventricular reactivation during cardiac disease remain to be defined. We found that proximal Nppa fragments ranging from 250 bp to 16 kbp provide robust reporter gene activity in the atria and correct repression in the atrioventricular canal and the nodes of the conduction system in vivo. However, depending on fragment size and site of integration into the genome of mice, the fetal ventricular activity was either absent or present in an incorrect pattern. Furthermore, these fragments did not provide ventricular reactivation in heart disease models. These results indicate that the proximal promoter does not provide a physiologically relevant model for ventricular gene activity. In contrast, 2 modified bacterial artificial chromosome clones with partially overlapping genomic Nppa sequences provided appropriate reactivation of the green fluorescent protein reporter during pressure overload-induced hypertrophy and heart failure in vivo. However, only 1 of these bacterial artificial chromosomes provided correct fetal ventricular green fluorescent protein activity. These results show that distinct distal regulatory sequences and divergent regulatory pathways control fetal ventricular activity and reactivation of Nppa during cardiac disease, respectively.


Subject(s)
Atrial Natriuretic Factor/metabolism , Gene Expression Regulation, Developmental/physiology , Heart Diseases/physiopathology , Animals , Atrial Natriuretic Factor/genetics , Atrioventricular Node/embryology , Atrioventricular Node/metabolism , Disease Models, Animal , Gene Expression Regulation, Developmental/genetics , Heart Atria/embryology , Heart Atria/metabolism , Heart Diseases/genetics , Heart Ventricles/embryology , Heart Ventricles/metabolism , Male , Mice , Mice, Transgenic , Natriuretic Peptide, C-Type/genetics , Natriuretic Peptide, C-Type/metabolism , Promoter Regions, Genetic/genetics , Promoter Regions, Genetic/physiology , Protein Precursors/genetics , Protein Precursors/metabolism
17.
Am J Psychol ; 120(2): 205-18, 2007.
Article in English | MEDLINE | ID: mdl-17650918

ABSTRACT

Previous research using a thought suppression paradigm found that repressors are more skilled in suppressing anxious autobiographical thoughts than low anxious, high anxious, and defensive high anxious people. Another line of research showed that individual differences in working memory capacity are related to the ability to intentionally suppress intrusive thoughts. This study aimed at combining these findings and sought to investigate whether repressors' superior ability to suppress intrusive thoughts is related to a larger working memory capacity. Results indicate that in a thought suppression paradigm, repressors report fewer intrusive thoughts for their most anxious experiences than participants in the 3 other subgroups. Furthermore, the superior ability of repressors to avoid intrusive thoughts can be explained largely by their higher working memory capacity.


Subject(s)
Adaptation, Psychological , Memory, Short-Term , Repression, Psychology , Thinking , Anxiety/diagnosis , Anxiety/psychology , Autobiographies as Topic , Cognition , Humans , Surveys and Questionnaires
18.
J Muscle Res Cell Motil ; 24(2-3): 205-9, 2003.
Article in English | MEDLINE | ID: mdl-14609031

ABSTRACT

Cardiac expression of a transgene is a common approach for determining the role of gene products in the processes underlying cardiomyopathy and heart failure (HF). We have generated transgenic mice that express the 'harmless' yeast transcription factor Gal4 in the heart under control of the alpha-myosin heavy chain promoter and found that expression of this gene causes cardiomyopathy and HF, the severity of which correlated with the number of copies of the transgene integrated into the genome and with the expression level. A line with a single copy of the transgene targeted to the hprt locus correctly expressed the transgene but did not develop cardiomyopathy. Our results indicate that expression of a transgene in the heart may non-specifically cause HF in a dose-dependent manner.


Subject(s)
Cardiomyopathies/genetics , Gene Expression , Myocardium/metabolism , Saccharomyces cerevisiae Proteins/genetics , Transcription Factors/genetics , Animals , Atrial Natriuretic Factor/genetics , Calcium-Transporting ATPases/genetics , Cardiac Myosins/genetics , Cardiomyopathies/pathology , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Connexin 43/genetics , DNA-Binding Proteins , Down-Regulation , Gene Dosage , Gene Expression Regulation, Developmental/genetics , Genetic Vectors/genetics , Heart Atria/chemistry , Heart Atria/metabolism , Heart Failure/genetics , Heart Failure/pathology , In Situ Hybridization , Mice , Mice, Transgenic , Myocardium/chemistry , Myocardium/pathology , Myosin Heavy Chains/genetics , Myosin Light Chains/genetics , Organ Size/genetics , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Sex Factors , Up-Regulation , Ventricular Myosins/genetics
19.
Cardiovasc Res ; 58(2): 246-63, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12757861

ABSTRACT

Fragments of regulatory DNA of cardiac genes drive reporter gene expression in sometimes unexpected subdomains of the heart. These patterns have revealed that the regulatory DNA of genes consists of distinct subfragments (regulatory modules) that are active in different regions of the developing heart. In this review we give an overview of the activity of regulatory modules in vivo. Furthermore, we investigated the relationship between the activity domains of the regulatory modules, the building blocks of the heart and the developmental patterning of the myocardium. Most of the regulatory modules show a domain of activity broader than the morphological boundary of a cardiac compartment and seem to respond to a patterning program along the antero-posterior axis.


Subject(s)
Heart/embryology , Mammals/embryology , Animals , Biological Evolution , Gene Expression Regulation , Humans , Mice , Mice, Transgenic , Morphogenesis/genetics
20.
Anat Rec ; 268(1): 27-37, 2002 Sep 01.
Article in English | MEDLINE | ID: mdl-12209562

ABSTRACT

Key morphogenetic events during heart ontogenesis are similar in different vertebrate species. We report that in primitive vertebrates, i.e., cartilaginous fishes, both the embryonic and the adult heart show a segmental subdivision similar to that of the embryonic mammalian heart. Early morphogenetic events during cardiac development in the dogfish are long-lasting, providing a suitable model to study changes in pattern of gene expression during these stages. We performed a comparative study among dogfish, chicken, rat, and mouse to assess whether species-specific qualitative and/or quantitative differences in myosin heavy chain (MyHC) distribution arise during development, indicative of functional differences between species. MyHC RNA content was investigated by means of in situ hybridisation using an MyHC probe specific for a highly conserved domain, and MyHC protein content was assessed by immunohistochemistry. MyHC transcripts were found to be homogeneously distributed in the myocardium of the tubular and embryonic heart of dogfish and rodents. A difference between atrial and ventricular MyHC content (mRNA and protein) was observed in the adult stage. Interestingly, differences in the MyHC content were observed at the tubular heart stage in chicken. These differences in MyHC content illustrate the distinct developmental profiles of avian and mammalian species, which might be ascribed to distinct functional requirements of the myocardial segments during ontogenesis. The atrial myocardium showed the highest MyHC content in the adult heart of all species analysed (dogfish (S. canicula), mouse (M. musculus), rat (R. norvegicus), and chicken (G. gallus)). These observations indicate that in the adult heart of vertebrates the atrial myocardium contains more myosin than the ventricular myocardium.


Subject(s)
Chick Embryo/metabolism , Dogfish/metabolism , Heart/embryology , Mice/metabolism , Myocardium/metabolism , Myosin Heavy Chains/genetics , Rats/metabolism , Animals , Body Patterning/physiology , Chick Embryo/embryology , Dogfish/embryology , Gene Expression Regulation, Developmental/physiology , Heart/physiology , Heart Atria/embryology , Heart Ventricles/embryology , Immunohistochemistry , Mice/embryology , Molecular Sequence Data , Myosin Heavy Chains/metabolism , Protein Isoforms/genetics , RNA, Messenger/metabolism , Rats/embryology , Sequence Homology, Nucleic Acid
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