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Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.
Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007).
We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls.
We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. All were recruited as part of the Genetic and Psychosis (GAP) study which studied all patients who presented to the South London and Maudsley Trust.
There was no significant difference in the life-time prevalence of cannabis use or age at first use between cases and controls. However, cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls. The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007).
Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.
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.
Large population based studies demonstrate a link between childhood trauma (CT) and increased prevalence of a wide range of psychiatric disorders, including mood disorders and psychosis. The identification of CT as an environmental risk factor for bipolar disorders (BD) and schizophrenia is of crucial importance to move to GxE interaction studies. In this presentation, we will mainly use the example of bipolar disorders (BD) and draw some parallels with psychosis. First we have demonstrated that CT were associated to BD using case-control studies (with a dose-effect of emotional abuse), as this has been previously demonstrated in psychosis by meta-analytic approaches. We also have shown that CT (mainly emotional and sexual abuses) influenced the clinical expression and course of BD, with associations between CT, earlier age at onset, rapid cycling and suicidal behavior. Some of these associations were also observed in schizophrenia and thus appeared as relatively non-specific. Moreover some cumulative effects of CT and cannabis misuse on the age at onset of BD or on the transition to psychosis have been suggested. Using psychopathological dimensions as outputs, we have been able to demonstrate that CT influence affective regulation and impulsivity-related dimensions, that could mediate the links between CT and clinical categorical outputs. Disentangling these pathways from CT, through dimensions, to clinical expression could shed some light on the clinical and dimensional aspects to could be incorporated in future GenexCT interaction studies. As an example, we will present preliminary data on the interaction between CT and serotonin transporter gene variants but also dysimmunity-related genes variants on the age at onset in BD.
Childhood trauma increases the risk of a range of mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing of emotions among the core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and an increased negativity bias. Here we tested if childhood trauma was associated with differentiation in brain responses to negative and positive stimuli. We also tested if trauma was associated with emotional ratings of negative and positive faces.
We included 101 patients with a DSM schizophrenia spectrum or bipolar spectrum diagnosis. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). Brain activation was measured with functional MRI during presentation of faces with negative or positive emotional expressions. After the scanner session, patients performed emotional ratings of the same faces. Structural MRI was also measured.
Higher levels of childhood trauma were associated with stronger differentiation in brain responses to negative compared to positive faces in clusters comprising the right angular gyrus, supramarginal gyrus, middle temporal gyrus, and the lateral occipital cortex (Cohen's d = 0.72-0.77). In patients with schizophrenia, childhood trauma was associated with reporting negative faces as more negative, and positive faces as less positive (Cohen's d > 0.8).
Along with the observed negativity bias in the assessment of emotional valence of faces, our data suggest stronger differentiation in brain responses between negative and positive faces in patients with childhood trauma.
Disclosure of interest
The author has not supplied his declaration of competing interest.
Background: Inadequate postoperative pain control is common and is associated with negative clinical outcomes. The objective is to identify preoperative predictors of poor postoperative pain control in the adult population undergoing inpatient surgery. Methods: Meta-analysis was performed according to MOOSE guidelines. Studies were included if they evaluated postoperative pain using a validated instrument in adults undergoing inpatient surgery and reported a measure of association between poor postoperative pain control and at least one preoperative predictor. Measures of association were pooled using random effects models. Results: A total of 33 studies representing 59,259 patients were included. Significant preoperative predictors of poor postoperative pain included sleeping difficulties (OR 2.32 [95% CI 1.46-3.69]), history of depressive symptoms (OR 1.71 [95% CI 1.32-2.22]), use of preoperative analgesia (OR 1.54 [95% CI 1.18-2.03]), smoking (OR 1.33 [95% CI 1.09-1.61]), -female sex (OR 1.29 [95% CI 1.17-1.43]), presence of preoperative pain (OR 1.21 [95% CI 1.10-1.32]], history of anxiety symptoms (OR 1.22 [95% CI 1.09-1.36)], younger age (OR 1.18 [95% CI 1.05-1.32)], and higher BMI (OR 1.02 [95% CI 1.01-1.03]). Conclusions: Nine significant predictors of poor postoperative pain control were identified and these should be recognized as important factors when developing pre- and peri-operative strategies to improve pain outcomes.
Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use.
We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case–control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis.
Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset <18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42).
Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.
Background: Idiopathic intracranial hypertension (IIH) is a unique disorder that is characterized by an intractable high intracranial pressure. Several interventions have been in clinical practice upon failure of medical management. Yet, none of the available modalities have been evaluated systematically for an CSF diverion procedure. Methods: We conducted a systematic review in order to compare the therapeutic efficacy of the most two common interventions, namely VPS vs. LPS. The complications rate and incidence of shunt revision were assessed. The electronic database from EMBASE, Medline, Cochrane databases, and references of review articles have been used. Results: A total of five retrospective comparative studies had been included out of 724 articles based on inclusion and exclusion criteria. A 2570 VPS were compared to 1832 LPS with 85% of heterogeneity. Although there was a tendency that suggests better outcome in VPS over LPS but it was not statistically significant [OR=0.91, 95% CI: 0.26-3.24]. Similar tendency was observed as well with shunt obstruction. Conclusions: The overall outcomes for stabilizing visual deterioration and improvement of headaches were similar among VPS and LPS. A large prospective multicenteric randomized controlled trial is needed in order to compare effectiveness of VPS and LPS, and also to establish a treatment guideline for IIH.
Background: Intracranial mycotic aneurysms are rare forms of vascular abnormalities. They are typically fragile and have high tendency to bleed. Even when they are successfully secured upon intervention, the medical management can be challenging in presence of other non-ruptured aneurysms and concomitant cerebral vasospasm. Methods: A 31 year old female was admitted with right sided large intracerebral hemorrhage due to ruptured mycotic MCA aneurysm. She was also known with severe tricuspid regurgitation from drug abuse. Others aneurysms were also located intracranially and extracranially, including subclavian and renal arteries. Results: The MCA aneurysm was successfully clipped during decompressive craniectomy. The non-ruptured left ACA aneurysm was occluded through endovascular intervention. Due to cardiac condition and presence of other non-secured extarcranial aneurysms, we followed the MNI protocol for treating cerebral vasospsam by milrinone infusion. The treatment was successful for over three weeks until another micro-aneurysm had ruptured which had lead to severe and rapid clinical deterioration, that had lead eventually to death. Conclusions: Intracranial mycotic aneurysms remain challenging. Patients should be selected for surgical clipping versus endovascular intervention based on clinical state and radiological features. We suggest using milrinone over induced hypertension therapy for post-intervention cerebral vasospasm in order to lower the risk for rupturing non-secured aneurysms.
We report the case of a 12-year-old boy who presented with acute heart failure due to newly developed mitral valve regurgitation. The boy’s history combined with raised levels of inflammatory markers was suggestive of paediatric eosinophilic granuloma with polyangiitis. The echocardiographic course and rapid response to therapy are presented.
Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD.
A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro.
Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset.
Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.
Childhood trauma increases risk of a range of mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing of emotions among the core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and increased negativity bias. Here, we tested the association between childhood trauma and brain activation during emotional face processing in patients diagnosed with psychosis continuum disorders. In particular, we tested if childhood trauma was associated with the differentiation in brain responses between negative and positive face stimuli. We also tested if trauma was associated with emotional ratings of negative and positive faces.
We included 101 patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM) schizophrenia spectrum or bipolar spectrum diagnosis. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Brain activation was measured with functional magnetic resonance imaging during presentation of faces with negative or positive emotional expressions. After the scanner session, patients performed emotional ratings of the same faces.
Higher levels of total childhood trauma were associated with stronger differentiation in brain responses to negative compared with positive faces in clusters comprising the right angular gyrus, supramarginal gyrus, middle temporal gyrus and the lateral occipital cortex (Cohen's d = 0.72–0.77). In patients with schizophrenia, childhood trauma was associated with reporting negative faces as more negative, and positive faces as less positive (Cohen's d > 0.8).
Along with the observed negativity bias in the assessment of emotional valence of faces, our data suggest stronger differentiation in brain responses between negative and positive faces with higher levels of trauma.
Measurement error in self-reported total sugars intake may obscure associations between sugars consumption and health outcomes, and the sum of 24 h urinary sucrose and fructose may serve as a predictive biomarker of total sugars intake.
The Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) was an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort. Doubly labelled water and 24 h urinary sucrose and fructose were used as biomarkers of energy and sugars intake, respectively. Participants’ diets were assessed by up to three 24 h recalls (88 % had two or more recalls). Procedures were repeated approximately 6 months after the initial visit among a subset of ninety-six participants.
Four centres (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) across the USA.
Men and women (n 477) aged 18–74 years.
The geometric mean of total sugars was 167·5 (95 % CI 154·4, 181·7) g/d for the biomarker-predicted and 90·6 (95 % CI 87·6, 93·6) g/d for the self-reported total sugars intake. Self-reported total sugars intake was not correlated with biomarker-predicted sugars intake (r=−0·06, P=0·20, n 450). Among the reliability sample (n 90), the reproducibility coefficient was 0·59 for biomarker-predicted and 0·20 for self-reported total sugars intake.
Possible explanations for the lack of association between biomarker-predicted and self-reported sugars intake include measurement error in self-reported diet, high intra-individual variability in sugars intake, and/or urinary sucrose and fructose may not be a suitable proxy for total sugars intake in this study population.
Introduction: Degenerative disc disease (DDD) is a common cause of lower back pain. Calcification of the intervertebral disc (IVD) has been correlated with DDD. The role of IVD calcification in the development DDD is unknown. We noticed an increase in ionic calcium content and expression of the extracellular calcium-sensing receptor (CaSR) in the degenerate discs, however, its role in DDD remains unclear. Material and Methods: IVD Cells: Bovine and human NP and AF cells were incubated in culture media supplemented with various concentrations of calcium, and a CaSR agonist IVD Cultures: IVDs from bovine tails were isolated and the vertebral bone was removed. IVDs were cultured for 6 weeks in culture medium supplemented with calcium (1.0, 2.5, or 5.0 mM), or a CaSR agonist. Western blotting was performed on extracts to assess for aggrecan and Col II. Results: The expression of aggrecan and Col II decreased dose-dependently in both NP and AF cells, as well as in the organ culture model following supplementation with calcium or the CaSR agonist. Conclusion: Our results suggest that changes in the local concentrations of calcium are not benign, and that activation of the CaSR may be a contributing factor in IVD degeneration.
To evaluate the safety and effectiveness of radiofrequency dissection in conventional ‘open’ total thyroidectomy.
Thirty-nine patients scheduled for conventional total thyroidectomy were included in a prospective randomised study. Patients were randomly assigned to one of two groups: a radiofrequency dissection method was used in one group, and a knot tying technique was used in the other.
Significantly fewer surgical instruments and materials were required for the radiofrequency dissection group than the knot tying group (p < 0.01). There were no significant differences between the two groups in mean operative time, blood loss, post-operative drainage and pain, recurrent palsy, and hypocalcaemia (p > 0.05).
Radiofrequency dissection is a safe alternative to the knot tying technique, and enables a significant reduction in the number of surgical instruments required for the operation.
Ethnic minority status and childhood trauma are established risk factors for psychotic disorders. Both are found to be associated with increased level of positive symptoms, in particular auditory hallucinations. Our main aim was to investigate the experience and effect of childhood trauma in patients with psychosis from ethnic minorities, hypothesizing that they would report more childhood trauma than the majority and that this would be associated with more current and lifetime hallucinations.
In this cross-sectional study we included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or affective psychotic disorder. Current hallucinations were measured with the Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime hallucinations were assessed with the SCID-I items: auditory hallucinations, voices commenting and two or more voices conversing. Childhood trauma was assessed with the Childhood Trauma Questionnaire, self-report version.
Patients from ethnic minority groups (n = 69) reported significantly more childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had significantly more current hallucinatory behaviour and lifetime symptoms of hearing two or more voices conversing. Regression analyses revealed that the presence of childhood trauma mediated the association between ethnic minorities and hallucinations.
More childhood trauma in ethnic minorities with psychosis may partially explain findings of more positive symptoms, especially hallucinations, in this group. The association between childhood trauma and these first-rank symptoms may in part explain this group's higher risk of being diagnosed with a schizophrenia-spectrum diagnosis. The findings show the importance of childhood trauma in symptom development in psychosis.
We observed Hydroxyl, water, ammonia, carbon monoxide and neutral carbon towards the +50 km s−1 cloud (M−0.02−0.07), the circumnuclear disk (CND) and the +20 km s−1 (M−0.13−0.08) cloud in the Sgr A complex with the VLA, Odin and SEST. Strong OH absorption, H2O emission and absorption lines were seen at all three positions. Strong C18O emissions were seen towards the +50 and +20 km s−1 clouds. The CND is rich in H2O and OH, and these abundances are considerably higher than in the surrounding clouds, indicating that shocks, star formation and clump collisions prevail in those objects. A comparison with the literature reveals that it is likely that PDR chemistry including grain surface reactions, and perhaps also the influences of shocks has led to the observed abundances of the observed molecular species studied here. In the redward high-velocity line wings of both the +50 and +20 km s−1 clouds and the CND, the very high H2O abundances are suggested to be caused by the combined action of shock desorption from icy grain mantles and high-temperature, gas-phase shock chemistry. Only three of the molecules are briefly discussed here. For OH and H2O three of the nine observed positions are shown, while a map of the C18O emission is provided. An extensive paper was recently published with Open Access (Karlsson et al. 2013, A&A 554, A141).
Previous studies of bipolar disorders indicate that childhood abuse and substance abuse are associated with the disorder. Whether both influence the clinical picture, or if one is mediating the association of the other, has not previously been investigated.
A total of 587 patients with bipolar disorders were recruited from Norway and France. A history of childhood abuse was obtained using the Childhood Trauma Questionnaire. Diagnosis and clinical variables, including substance abuse, were based on structured clinical interviews (Structured Clinical Interview for DSM-IV Axis I disorders or French version of the Diagnostic Interview for Genetic Studies).
Cannabis abuse was significantly associated with childhood abuse, specifically emotional and sexual abuse (χ2 = 8.63, p = 0.003 and χ2 = 7.55, p = 0.006, respectively). Cannabis abuse was significantly associated with earlier onset of the illness (z = −4.17, p < 0.001), lifetime history of at least one suicide attempt (χ2 = 11.16, p = 0.001) and a trend for rapid cycling (χ2 = 3.45, p = 0.06). Alcohol dependence was associated with suicide attempt (χ2 = 10.28, p = 0.001), but not with age at onset or rapid cycling. After correcting for possible confounders and multiple testing, a trend was observed for an interaction between cannabis abuse and childhood abuse and suicide attempt (logistic regression: r2 = 0.06, p = 0.039). Significant additive effects were also observed between cannabis abuse and childhood abuse on earlier age at onset (p < 0.001), increased rapid cycling and suicide attempt (logistic regression: r2 = 0.03–0.04, p < 0.001). No mediation effects were observed; childhood abuse and cannabis abuse were independently associated with the disorder.
Our study is the first to demonstrate significant additive effects, but no mediation effects, between childhood abuse and cannabis abuse on increased clinical expressions of bipolar disorders.
To examine the sociodemographic correlates of obesity among Ghanaian women.
The 2003 and 2008 Ghana Demographic and Health Survey data sets were used to examine the sociodemographic characteristics and the BMI of women aged 15–49 years using descriptive statistics, bivariate and multivariate analyses.
Ghana is a West African country which is divided into ten administrative regions. The country is further divided into the northern and southern sectors. The northern sector includes the three northern regions (Northern, Upper East and Upper Westen regions) and the seven remaining regions form the southern sector.
Women aged 15–49 years whose BMI values were available.
The overall prevalence of obesity and overweight increased from 25·5 % in 2003 to 30·5 % in 2008. Obesity varied directly with age from 20 to 44 years. Women with higher education had the highest rate of obesity. Obesity was more common among women from wealthy households compared to women from poor households.
Obesity and overweight were found to be more common among older women, urban women, married women, women with higher education and women from rich households. Adoption of healthy lifestyles and the implementation of policies that promote healthy living can help reduce the prevalence of overweight and obesity.