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Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations.
We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0–18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity.
We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04–1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98–1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10–1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54–0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05–1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77–1.08).
The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.
There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).
Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Persistent negative symptoms are associated with worse outcome in both first-episode and chronic subjects with schizophrenia. The identification of these symptoms in recent-onset subjects is still controversial as retrospective data are often unavailable. The prospective assessment of persistence of negative symptoms might represent a valid alternative but the length of the persistence is still to be established. The present study investigated the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline in a large cohort of patients in the early stage of a schizophrenia-spectrum disorder, recruited to the OPTiMiSE trial. Persistent unconfounded negative symptoms were assessed at 4, 10 and 22 weeks of treatment. Symptomatic remission, attrition rate and psychosocial functioning was evaluated in subjects with short-term (4 weeks) persistent negative symptoms (PNS) and in those with negative symptoms that did not persist at follow-up and/or were confounded at baseline (N-PNS). Negative symptoms of moderate severity were observed in 59% of subjects at baseline and were associated to worse global functioning. PNS were observed in 7.9% of the cohort, unconfounded at both baseline and end of 4-week treatment. PNS subjects showed lower remission and higher attrition rates at the end of all treatment phases. Fifty-six percent of subjects completing phase 3 (clozapine treatment) had PNS, and 60% of them were non-remitters at the end of this phase. The presence of short-term PNS during the first phases of psychosis was associated with poor clinical outcome and resistance to antipsychotic treatment, including clozapine.
Prof Mucci has been a consultant and/or advisor to or has received honoraria from Gedeon Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer and Pierre Fabre.
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.
High potency cannabis has been associated with greater risk, and earlier onset of psychosis. However, its effect on brain structure, particularly white matter (WM), has never been explored.
Objectives and Aims
To elucidate the interplay between cannabis potency, pattern of use (frequency and age of first use) and CC microstructure; in patients with first-episode psychosis (FEP) and healthy controls.
56 FEP and 43 healthy controls underwent Diffusion-Tensor Imaging combined with WM mapping-tractography. CC was virtually dissected and segmented to calculate Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD) and Radial Diffusivity (RD) for each CC segment.
High potency cannabis users had higher Total CC MD and Total CC AD than both low potency users and those who never used (p=0.009 and p=0.02 respectively). Daily users also had higher Total CC MD and Total CC AD than both occasional users and those who never used (p=0.02 and p=0.01 respectively). Furthermore, daily/highpotency users had higher Total CC MD than those who never used or used weekly [F(2,57)=4.7, p=0.01]. There was no effect of diagnosis or diagnosis X potency/patterns of use interactions; neither differences between users who started before the age of 15 and those who started later were detected, in any diffusivity measures.
Frequent use of high-potency cannabis significantly affects callosal microstructure, regardless of the presence of a psychotic disorder. Given the increased availability and use of high potency preparations in Europe, raising awareness about some of their detrimental effects is an important avenue to pursue.
The impact of cannabis use on brain structure, particularly white matter (WM), is poorly understood. The CC is the largest WM structure in the brain. Abnormalities revealed in the CC may underlie functional anomalies of cannabis use. This is the largest study to explore the effect of cannabis on callosal WM connectivity among first episode psychosis (FEP) and controls.
To investigate the relationship between cannabis use and WM micro-structural integrity of the CC, in FEP and healthy controls.
We evaluated 56 FEP patients (67% current cannabis users), and 43 healthy controls (44% current cannabis users). We used Diffusion Tensor Imaging combined with a WM mapping-tractography technique to investigate the microstructural integrity of the CC.
Total CC Fractional anisotropy (FA) was lower in patients than controls (p=0.05). Cannabis-using patients had lower FA of the total CC than cannabis-using controls (p=0.04). There were no differences in FA between cannabis-using patients and those who had never used. However, cannabis-using patients had higher mean diffusivity (MD) of total CC (p= 0.02), Rostral-Body (p=0.003), Anterior Mid-Body (p=0.03) and the Splenium (p=0.06) than patients who never used cannabis. There were no differences in MD between patient users who started before the age of 16 and those who started later.
Cannabis is associated with a significant effect on callosal WM integrity only in patients with psychosis. Disturbed callosal connectivity may explain some of the abnormalities with regard to the functional and clinical outcomes in FEP cannabis users, including measures of cognitive impairment.
Response to treatment and long-term outcome following the first-episode of psychosis are very heterogeneous. Therefore, the early identification of individuals destined to have a worse illness course is of crucial importance, since it can reduce disability, healthcare costs, and eventually improve long-term outcome.
We have used structural Magnetic Resonance Imaging in patients at their first psychotic episode and followed them up clinically to identify neuroanatomical predictors of outcome.
We evaluated patients (n=260) at their first psychotic episode and followed them up for periods varying from 3 months to 5-6 years. We used a number of imaging approaches to study neuroanatomical predictors of outcome, including Support Vector Machine.
At onset, brain alterations of likely neurodevelopmental origin (reduced frontal and temporal gyrification and altered white matter microstructure of interconnecting tracts) were present in individuals with poorer early outcome (all p<0.05 corrected); furthermore, smaller volumes were predictive of subsequent illness episodes with significant accuracy (70% correctly classified; p=0.005). However, brain changes were also observed after illness onset. Among these, hippocampal volume increase (present in 29% of patients) was predictive of better clinical, functional and cognitive outcomes at 6 years (all p<0.03).
In combination with other neuroimaging and clinical measures, neuroanatomical data could considerably help patient stratification in psychiatry, ultimately allowing individualised patient management from the time of the first presentation to services.
In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear.
To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis.
Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist–hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients.
A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. β = 0.36, P = 0.01), higher leptin levels (Std. β = 0.34, P = 0.02), higher waist–hip ratio (Std. β = 0.32, P = 0.04) and lower testosterone levels (Std. β = −0.44, P = 0.002). In contrast, in females, SFQ scores were not associated with any of these factors.
While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist–hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.
Evidence indicates that migrant and ethnic minority groups have an elevated risk of psychosis in a number of countries. Social disadvantage is one of the hypotheses put forward to explain these findings. The aim of this study is to investigate main effects, association and synergism between social disadvantage and migration on odds of psychotic experiences. We collected information on social disadvantage and migration from 332 patients and from 301 controls recruited from the local population in South London. Two indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analyzed. We found evidence that the odds of reporting psychotic experience were higher in those who experienced social disadvantage in childhood (OR= 2.88, 95% CI 2.03-4.06), social disadvantage in adulthood (OR= 9.06, 95% CI 5.21–15.74) and migration (OR = 1.46, 95% CI 1.05–2.02). When both social disadvantage and migration were considered together, the association with psychosis was slightly higher for social disadvantage in childhood and migration (OR 3.46, 95% CI 2.12–5.62) and social disadvantage in adulthood and migration (OR 9.10, 95% CI 4.63-17.86). Migrant cases were not more likely than non-migrant cases to report social disadvantage (p = 0.71) and no evidence of an additive interaction between migration and social disadvantage was found (ICR 0.32 95% CI -4.04–4.69). Preliminary results support the hypothesis that the association between social disadvantage and psychosis is independent of migration status.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
A growing body of evidence suggests that indicators of social disadvantage are associated with an increased risk of psychosis. However, only a few studies have specifically looked at cumulative effects and long-term associations. The aims of this study are: To compare the prevalence of specific indicators of social disadvantage at, and prior to, first contact with psychiatric services in patients suffering their first episode of psychosis and in a control sample. To explore long-term associations, cumulative effects, and direction of effects.
We collected information on social disadvantage from 332 patients and from 301 controls recruited from the local population in South London. Three indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analysed.
Across all the domains considered, cases were more likely to report social disadvantage than were controls. Compared with controls, cases were approximately two times more likely to have had a parent die and approximately three times more likely to have experienced a long-term separation from one parent before the age of 17 years. Cases were also more likely than controls to report two or more indicators of adult social disadvantage, not only at first contact with psychiatric services [odds ratio (OR) 9.5], but also at onset of psychosis (OR 8.5), 1 year pre-onset (OR 4.5), and 5 years pre-onset (OR 2.9).
Greater numbers of indicators of current and long-term exposure are associated with progressively greater odds of psychosis. There is some evidence that social disadvantage tends to cluster and accumulate.
Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.
This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.
Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).
For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations.
A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively.
Both ‘bad’ and ‘enjoyable’ experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population.
These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more ‘bad’ and ‘enjoyable’ experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms.
The use of cannabis with higher Δ9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users.
The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment.
Across the whole sample, users of high-potency cannabis had higher total CC MD and higher total CC AD than both low-potency users and those who never used (p = 0.005 and p = 0.004, respectively). Daily users also had higher total CC MD and higher total CC AD than both occasional users and those who never used (p = 0.001 and p < 0.001, respectively). However, there was no effect of group (patient/individuals without psychosis) or group x potency interaction for either potency or frequency of use. The within-group analysis showed in fact that the effects of potency and frequency were similar in FEP users and in users without psychosis.
Frequent use of high-potency cannabis is associated with disturbed callosal microstructural organization in individuals with and without psychosis. Since high-potency preparations are now replacing traditional herbal drugs in many European countries, raising awareness about the risks of high-potency cannabis is crucial.
The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients.
This study involved 236 FEP cases aged 18–65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire.
Childhood sexual abuse [β = 0.96, 95% confidence interval (CI) 0.40–1.52], childhood physical abuse (β = 0.48, 95% CI 0.03–0.93) and parental separation (β = 0.60, 95% CI 0.10–1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (β = 0.36, 95% CI 0.08–0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions.
A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA–psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.
A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change.
Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests.
Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis.
Diagnoses other than schizophrenia should to be regarded as potentially provisional.