Original Articles
The link between mental health-related discrimination and suicidality: service user perspectives
- S. Farrelly, D. Jeffery, N. Rüsch, P. Williams, G. Thornicroft, S. Clement
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- Published online by Cambridge University Press:
- 13 February 2015, pp. 2013-2022
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Background
Suicide is a major global public health issue. Mental illness is a risk factor for suicide, but as many individuals with a diagnosed mental health problem do not experience suicidal ideation or attempt suicide, other individual and societal factors must be considered. Mental illness-related discrimination is one potential risk factor.
MethodUsing mixed methods, the influence of discrimination on suicidality amongst 194 individuals diagnosed with depression, bipolar or schizophrenia spectrum disorders was investigated. Qualitative interviews with a sub-sample of 58 individuals who reported a link between experience of discrimination and suicidality were analysed using framework analysis. Quantitative methods were used to examine the model derived from qualitative analyses.
ResultsResults indicate that the experience of discrimination led 38% of the overall sample of 194 participants, to suicidal feelings and 20% reported that it contributed to making a suicide attempt. The qualitative model derived from interviews with a sub-sample of 58 participants suggested that the experience of discrimination is experienced as a stressor that exceeds coping resources, leading to a negative self-image and a perception of decreased supportive networks/social structure. The anticipation of further negative events and treatment, and the perception of a lack of supportive networks led individuals in this study to feelings of hopelessness and suicidality. Quantitative analyses provided support for the model.
ConclusionsThese data suggest that both psychological therapies aimed at improving coping skills and population-level anti-stigma interventions that reduce the occurrence of discrimination may provide some protection against suicide amongst individuals with mental health problems.
Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity
- R. M. Reynolds, A.-K. Pesonen, J. R. O'Reilly, S. Tuovinen, M. Lahti, E. Kajantie, P. M. Villa, H. Laivuori, E. Hämäläinen, J. R. Seckl, K. Räikkönen
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- Published online by Cambridge University Press:
- 28 January 2015, pp. 2023-2030
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Background
Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus.
MethodWe studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11β-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies.
ResultsIn adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01–0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01–0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2–3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses).
ConclusionsOur findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.
Theory of mind in the early course of schizophrenia: stability, symptom and neurocognitive correlates, and relationship with functioning
- J. Ventura, A. Ered, D. Gretchen-Doorly, K. L. Subotnik, W. P. Horan, G. S. Hellemann, K. H. Nuechterlein
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- 03 February 2015, pp. 2031-2043
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Background
Numerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning.
MethodRecent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants’ descriptions of scenes depicting abstract visual stimuli ‘interacting’ in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed.
ResultsOn the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms.
ConclusionsThe ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning.
Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up study
- R. G. Karam, V. Breda, F. A. Picon, D. L. Rovaris, M. M. Victor, C. A. I. Salgado, E. S. Vitola, K. L. Silva, P. O. Guimarães-da-Silva, N. R. Mota, A. Caye, P. Belmonte-de-Abreu, L. A. Rohde, E. H. Grevet, C. H. D. Bau
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- 23 January 2015, pp. 2045-2056
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Background
Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.
MethodA 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.
ResultsRetention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54–25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04–1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).
ConclusionsDespite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.
Emotional response inhibition in children with attention-deficit/hyperactivity disorder: neural and behavioural data
- S. López-Martín, J. Albert, A. Fernández-Jaén, L. Carretié
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- 24 February 2015, pp. 2057-2071
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Background
Although both emotion and response inhibition are thought to be important in attention-deficit/hyperactivity disorder (ADHD), little is known about the neural mechanisms that underlie the interaction between these two processes in patients with this disorder. This study aimed at examining how emotional contexts affect inhibitory control in children with ADHD.
MethodA total of 24 ADHD children and 24 healthy comparison subjects performed a modified go/no-go task during three different emotionally laden contexts: negative, neutral and positive. To explore the timing and the underlying neural substrates of emotion-modulated response inhibition, event-related potentials were measured and further analysed both at the scalp and at the voxel level.
ResultsPatients with ADHD showed greater activation of inhibition-related neural mechanisms (i.e. no-go P3 amplitudes and orbitofrontal cortex activity) to maintain a similar level of performance as healthy comparison subjects, especially during the emotionally arousing contexts (negative and positive).
ConclusionsThis study provides plausible neural mechanisms for the difficulty that ADHD children have in controlling their behaviour in highly emotional situations. Such emotional contexts might increase the need for top-down inhibitory control and put ADHD children at greater risk for impulsive behaviours and emotional dysregulation.
A comparison of depression and anxiety symptom trajectories between women who had an abortion and women denied one
- D. G. Foster, J. R. Steinberg, S. C. M. Roberts, J. Neuhaus, M. A. Biggs
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- 28 January 2015, pp. 2073-2082
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Background
This study prospectively assesses the mental health outcomes among women seeking abortions, by comparing women having later abortions with women denied abortions, up to 2 years post-abortion seeking.
MethodWe present the first 2 years of a 5-year telephone interview study that is following 956 women who sought an abortion from 30 facilities throughout the USA. We use adjusted linear mixed-effects regression analyses to assess whether symptoms of depression and anxiety, as measured by the Brief Symptom Inventory-short form and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, differ over time among women denied an abortion due to advanced gestational age, compared with women who received abortions.
ResultsBaseline predicted mean depressive symptom scores for women denied abortion (3.07) were similar to women receiving an abortion just below the gestational limit (2.86). Depressive symptoms declined over time, with no difference between groups. Initial predicted mean anxiety symptoms were higher among women denied care (2.59) than among women who had an abortion just below the gestational limit (1.91). Anxiety levels in the two groups declined and converged after 1 year.
ConclusionsWomen who received an abortion had similar or lower levels of depression and anxiety than women denied an abortion. Our findings do not support the notion that abortion is a cause of mental health problems.
Impulsive choice predicts short-term relapse in substance-dependent individuals attending an in-patient detoxification programme
- L. Stevens, A. E. Goudriaan, A. Verdejo-Garcia, G. Dom, H. Roeyers, W. Vanderplasschen
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- 02 February 2015, pp. 2083-2093
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Background
Impulsivity is a hallmark characteristic of substance use disorders. Recently, studies have begun to explore whether increased impulsivity in substance-dependent individuals (SDIs) is associated with a greater propensity to relapse following treatment. Despite growing recognition of its multidimensional nature, however, most studies have treated impulsivity unilaterally. Accordingly, it remains unclear whether certain facets of impulsivity are more relevant to relapse than others. The aim of the current study was to examine the relationship between multiple facets of impulsivity and short-term relapse in SDIs. As a secondary aim, we explored the role of treatment retention in this relationship.
MethodA personality-based impulsivity questionnaire (UPPS) and three neurocognitive tasks of impulsivity [stop-signal task (SST), delay discounting task (DDT) and Iowa gambling task (IGT)] were administered in a heterogeneous sample of 70 SDIs shortly following their entry in an in-patient detoxification programme. Mediation analyses were performed to explore whether the effects of impulsivity on relapse were mediated by treatment retention.
ResultsPerformance on two neurocognitive indices of impulsive choice (i.e. delay discounting and impulsive decision-making) significantly predicted short-term relapse. The effects of delay discounting and impulsive decision-making on relapse propensity were mediated by treatment retention.
ConclusionsNeurocognitive indices of impulsivity may be more sensitive to the prediction of relapse than trait-based self-report questionnaires. Post-treatment relapse in SDIs may be reduced by targeting the processes involved in impulsive choice and by improving treatment retention in SDIs with inflated impulsivity.
Clinical effectiveness of cognitive therapy v. interpersonal psychotherapy for depression: results of a randomized controlled trial
- L. H. J. M. Lemmens, A. Arntz, F. Peeters, S. D. Hollon, A. Roefs, M. J. H. Huibers
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- 02 February 2015, pp. 2095-2110
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Background
Although both cognitive therapy (CT) and interpersonal psychotherapy (IPT) have been shown to be effective treatments for major depressive disorder (MDD), it is not clear yet whether one therapy outperforms the other with regard to severity and course of the disorder. This study examined the clinical effectiveness of CT v. IPT in a large sample of depressed patients seeking treatment in a Dutch outpatient mental health clinic. We tested whether one of the treatments was superior to the other at post-treatment and at 5 months follow-up. Furthermore, we tested whether active treatment was superior to no treatment. We also assessed whether initial depression severity moderated the effect of time and condition and tested for therapist differences.
MethodDepressed adults (n = 182) were randomized to either CT (n = 76), IPT (n = 75) or a 2-month waiting list control (WLC) condition (n = 31). Main outcome was depression severity, measured with the Beck Depression Inventory – II (BDI-II), assessed at baseline, 2, 3, and 7 months (treatment phase) and monthly up to 5 months follow-up (8–12 months).
ResultsNo differential effects between CT and IPT were found. Both treatments exceeded response in the WLC condition, and led to considerable improvement in depression severity that was sustained up to 1 year. Baseline depression severity did not moderate the effect of time and condition.
ConclusionsWithin our power and time ranges, CT and IPT appeared not to differ in the treatment of depression in the acute phase and beyond.
Anorexia nervosa and body dysmorphic disorder are associated with abnormalities in processing visual information
- W. Li, T. M. Lai, C. Bohon, S. K. Loo, D. McCurdy, M. Strober, S. Bookheimer, J. Feusner
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- 05 February 2015, pp. 2111-2122
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Background
Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted body image and are frequently co-morbid with each other, although their relationship remains little studied. While there is evidence of abnormalities in visual and visuospatial processing in both disorders, no study has directly compared the two. We used two complementary modalities – event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) – to test for abnormal activity associated with early visual signaling.
MethodWe acquired fMRI and ERP data in separate sessions from 15 unmedicated individuals in each of three groups (weight-restored AN, BDD, and healthy controls) while they viewed images of faces and houses of different spatial frequencies. We used joint independent component analyses to compare activity in visual systems.
ResultsAN and BDD groups demonstrated similar hypoactivity in early secondary visual processing regions and the dorsal visual stream when viewing low spatial frequency faces, linked to the N170 component, as well as in early secondary visual processing regions when viewing low spatial frequency houses, linked to the P100 component. Additionally, the BDD group exhibited hyperactivity in fusiform cortex when viewing high spatial frequency houses, linked to the N170 component. Greater activity in this component was associated with lower attractiveness ratings of faces.
ConclusionsResults provide preliminary evidence of similar abnormal spatiotemporal activation in AN and BDD for configural/holistic information for appearance- and non-appearance-related stimuli. This suggests a common phenotype of abnormal early visual system functioning, which may contribute to perceptual distortions.
Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses
- S. Metzler, D. Dvorsky, C. Wyss, M. Müller, M. Gerstenberg, N. Traber-Walker, S. Walitza, A. Theodoridou, W. Rössler, K. Heekeren
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- 02 February 2015, pp. 2123-2134
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Background
Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period.
MethodData were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d. = 1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory.
ResultsNeurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations.
ConclusionsOur data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness.
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Concepts and methods when considering negative symptom course
- W. T. Carpenter, B. Kirkpatrick
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- 25 February 2015, pp. 2135-2136
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Original Articles
Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study
- M. Virtanen, M. J. Shipley, G. D. Batty, M. Hamer, C. L. Allan, G. D. Lowe, K. P. Ebmeier, T. N. Akbaraly, H. Alenius, R. Haapakoski, A. Singh-Manoux, M. Kivimäki
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- Published online by Cambridge University Press:
- 20 February 2015, pp. 2137-2144
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Background
Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear.
MethodWe examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress.
ResultsRelative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06–1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03–1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution.
ConclusionsIL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.
Axonal myelin increase in the callosal genu in depression but not schizophrenia
- M. R. Williams, P. Sharma, K. L. Fung, R. K. B. Pearce, S. R. Hirsch, M. Maier
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- Published online by Cambridge University Press:
- 25 February 2015, pp. 2145-2155
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Background
Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.
MethodUsing high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.
ResultsCases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.
ConclusionThe results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
Altered mesocorticolimbic functional connectivity in psychotic disorder: an analysis of proxy genetic and environmental effects
- S. C. T. Peeters, E. H. B. M. Gronenschild, V. van de Ven, P. Habets, R. Goebel, J. van Os, M. Marcelis, for Genetic Risk and Outcome of Psychosis (G.R.O.U.P.)
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- 25 March 2015, pp. 2157-2169
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Background
Altered dopaminergic neurotransmission in the mesocorticolimbic (MCL) system may mediate psychotic symptoms. In addition, pharmacological dopaminergic manipulation may coincide with altered functional connectivity (fc) ‘in rest’. We set out to test whether MCL-fc is conditional on (familial risk for) psychotic disorder and/or interactions with environmental exposures.
MethodResting-state functional magnetic resonance imaging data were obtained from 63 patients with psychotic disorder, 73 non-psychotic siblings of patients with psychotic disorder and 59 healthy controls. With the nucleus accumbens (NAcc) as seed region, fc within the MCL system was estimated. Regression analyses adjusting for a priori hypothesized confounders were used to assess group differences in MCL connectivity as well as gene (group) × environmental exposure interactions (G × E) (i.e. to cannabis, developmental trauma and urbanicity).
ResultsCompared with controls, patients and siblings had decreased fc between the right NAcc seed and the right orbitofrontal cortex (OFC) as well as the left middle cingulate cortex (MCC). Siblings showed decreased connectivity between the NAcc seed and lentiform nucleus compared with patients and controls. In addition, patients had decreased left NAcc connectivity compared with siblings in the left middle frontal gyrus. There was no evidence for a significant interaction between group and the three environmental exposures in the model of MCL-fc.
ConclusionsReduced NAcc–OFC/MCC connectivity was seen in patients and siblings, suggesting that altered OFC connectivity and MCC connectivity are vulnerability markers for psychotic disorder. Differential exposure to environmental risk factors did not make an impact on the association between familial risk and MCL connectivity.
Heritable influences on behavioural problems from early childhood to mid-adolescence: evidence for genetic stability and innovation
- G. J. Lewis, R. Plomin
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- Published online by Cambridge University Press:
- 13 March 2015, pp. 2171-2179
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Background
Although behavioural problems (e.g. anxiety, conduct, hyperactivity, peer problems) are known to be heritable both in early childhood and in adolescence, limited work has examined prediction across these ages, and none using a genetically informative sample.
MethodWe examined, first, whether parental ratings of behavioural problems (indexed by the Strengths and Difficulties questionnaire) at ages 4, 7, 9, 12, and 16 years were stable across these ages. Second, we examined the extent to which stability reflected genetic or environmental effects through multivariate quantitative genetic analysis on data from a large (n > 3000) population (UK) sample of monozygotic and dizygotic twins.
ResultsBehavioural problems in early childhood (age 4 years) showed significant associations with the corresponding behavioural problem at all subsequent ages. Moreover, stable genetic influences were observed across ages, indicating that biological bases underlying behavioural problems in adolescence are underpinned by genetic influences expressed as early as age 4 years. However, genetic and environmental innovations were also observed at each age.
ConclusionThese observations indicate that genetic factors are important for understanding stable individual differences in behavioural problems across childhood and adolescence, although novel genetic influences also facilitate change in such behaviours.
Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity
- P. O. Monahan, T. Stump, W. H. Coryell, J. Harezlak, G. A. Marcoulides, H. Liu, C. M. Steeger, P. B. Mitchell, H. C. Wilcox, L. A. Hulvershorn, A. L. Glowinski, Bipolar Disorder Genome Study (BiGS) Consortium, Bipolar High Risk Study Group, P. A. Iyer-Eimerbrink, M. McInnis, J. I. Nurnberger, Jr
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- 31 March 2015, pp. 2181-2196
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Background
The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders.
MethodA cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998–2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA.
ResultsThe two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives.
ConclusionsThe BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.
The effectiveness of psychoeducational family intervention for patients with schizophrenia in a 14-year follow-up study in a Chinese rural area
- M.-S. Ran, C. L.-W. Chan, S.-M. Ng, L.-T. Guo, M.-Z. Xiang
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- Published online by Cambridge University Press:
- 17 February 2015, pp. 2197-2204
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Background
It is unclear if the impact of psychoeducational family intervention for patients with schizophrenia can be sustained over 10 years. In this study, we explored the 14-year effect of psychoeducational family intervention for patients with schizophrenia in a Chinese rural area.
MethodThe data from a cluster randomized control trial (CRCT) study of psychoeducational family intervention in a 14-year follow-up was analyzed. All patients with schizophrenia (n = 326) who participated in the CRCT drawn from six townships in Xinjin County of Chengdu in 1994, of whom 238 (73.0%) who were still alive, and their informants were followed up in 2008. The Patients Follow-up Scale, the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning were used in the follow-up study.
ResultsThere were no significant differences of marital status, mean scores of PANSS positive symptoms, negative symptoms, general mental health, and total scores among the psychoeducational family intervention, medication, and control groups in 2008. The psychoeducational family intervention group had a significantly higher rate of antipsychotic medication and a higher level of work ability than other two groups. The control group had a significantly higher rate of never-treated (26.0%) than psychoeducational family intervention group (6.5%).
ConclusionPsychoeducational family intervention might be still effective in the 14-year follow-up, especially in patients’ treatment adherence/compliance and social functioning. Psychoeducational family intervention might be more effective in places where family members frequently participated in patients’ care and had a lower level of knowledge on mental illness. Family intervention should be considered when making mental health policy and planning mental health services.
Association of older paternal age with earlier onset among co-affected schizophrenia sib-pairs
- S. H. Wang, C. M. Liu, H. G. Hwu, C. K. Hsiao, W. J. Chen
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- Published online by Cambridge University Press:
- 09 March 2015, pp. 2205-2213
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Background
Advanced paternal age is associated with increased risk of schizophrenia. This study aimed to explore whether older paternal age is associated with earlier onset among co-affected schizophrenia sib-pairs with the same familial predisposition.
MethodA total of 1297 patients with schizophrenia from 630 families, which were ascertained to have at least two siblings affected, throughout Taiwan were interviewed using the Diagnostic Interview for Genetic Studies. Both inter-family comparisons, a hierarchical regression model allowing for familial dependence and adjusting for confounders, and within-family comparisons, examining the consistency between onset order and birth order, were performed.
ResultsAn inverted U shape was observed between paternal age and onset of schizophrenia. Affected offspring with paternal age of 20–24 years had the oldest onset. As paternal age increased over 25 years, older paternal age exhibited a linear decrease in the onset of schizophrenia. On average, the onset was lowered by 1.5 years for paternal age of 25–29 years and by 5.5 years for paternal age ⩾50 years (p = 0.04; trend test). The proportion of younger siblings with earlier onset (58%) was larger than that of older siblings with earlier onset (42%) (p = 0.0002).
ConclusionsThese findings indicate that paternal age older than 25 years and younger than 20 years were both associated with earlier onset among familial schizophrenia cases. The associations of advanced paternal age with both increased susceptibility to schizophrenia and earlier onset of schizophrenia are consistent with the rate of increases in spontaneous mutations in sperm as men age.
Familiality and SNP heritability of age at onset and episodicity in major depressive disorder
- P. Ferentinos, A. Koukounari, R. Power, M. Rivera, R. Uher, N. Craddock, M. J. Owen, A. Korszun, L. Jones, I. Jones, M. Gill, J. P. Rice, M. Ising, W. Maier, O. Mors, M. Rietschel, M. Preisig, E. B. Binder, K. J. Aitchison, J. Mendlewicz, D. Souery, J. Hauser, N. Henigsberg, G. Breen, I. W. Craig, A. E. Farmer, B. Müller-Myhsok, P. McGuffin, C. M. Lewis
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- Published online by Cambridge University Press:
- 20 February 2015, pp. 2215-2225
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Background
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
MethodFor investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
ResultsSignificant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
ConclusionsAAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
Direct, indirect and pleiotropic effects of candidate genes on internalizing disorder psychopathology
- J. M. Hettema, X. Chen, C. Sun, T. A. Brown
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- Published online by Cambridge University Press:
- 23 February 2015, pp. 2227-2236
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Background
Twin studies of internalizing disorders suggest that their high co-morbidity is partially explained by shared genetic risk. Few studies have investigated pleiotropic effects of well-validated candidate genes across phenotypes.
MethodSubjects were 928 Caucasian patients who presented to an out-patient clinic specializing in the assessment and treatment of anxiety and mood disorders. We constructed latent dimensional phenotypes across the internalizing spectrum (neuroticism, extraversion, depression, generalized anxiety, panic/agoraphobia, social phobia, post-traumatic stress, and obsessions–compulsions) by combining diagnostic criteria with other clinical indicators. We selected multiple variants in four evidence-based candidate genes (SLC6A4, COMT, GAD1, RGS2) with previously reported effects on several of these phenotypes. We conducted genetic association testing of their direct and indirect effects as well as gene × stress interactions (G × E).
ResultsWe detected 19 nominally significant main effect associations for the 10 polymorphisms tested among the eight phenotypes (24%). These were generally phenotype non-specific, showing pleiotropic effects across multiple domains. The majority of observed sharing was between depression, panic disorder, and post-traumatic stress disorder. Some of these were best explained by mediational models in which genes increase liability for disorders indirectly via their effects on temperament. Limited G × E effects were detected between variants in SLC6A4 and both panic/agoraphobia and post-traumatic stress.
ConclusionsExamining just a few candidate genes for their potential roles in internalizing phenotypes, we found moderate support for the shared effects of several polymorphisms. These findings highlight the richness and complexity by which genes potentially contribute to psychopathology via pleiotropy, moderation by stress, and mediation by temperament.