Showing papers in "Psychological Medicine in 2014"

Cognitive impairment in depression: a systematic review and meta-analysis

Abstract: Background. This review aimed to address the question of whether cognitive impairment should be considered a core feature of depression that may be a valuable target for treatment. Method. We conducted a systematic review and meta-analysis of cognitive function, assessed with a single neuropsychological test battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), in patients with depression during symptomatic and remitted states. Inclusion of studies comparing patients remitted from depression and controls enabled us to investigate whether cognitive impairment persists beyond episodes of low mood in depression. Results. Our meta-analysis revealed significant moderate cognitive deficits in executive function, memory and attention in patients with depression relative to controls (Cohen’s d effect sizes ranging from �0.34 to �0.65). Significant moderate deficits in executive function and attention (Cohen’s d ranging from �0.52 to �0.61) and non-significant small/moderate deficits in memory (Cohen’s d ranging from �0.22 to �0.54) were found to persist in patients whose depressive symptoms had remitted, indicating that cognitive impairment occurs separately from episodes of low mood in depression. Conclusions. Both low mood and cognitive impairment are associated with poor psychosocial functioning. Therefore, we argue that remediation of cognitive impairment and alleviation of depressive symptoms each play an important role in improving outcome for patients with depression. In conclusion, this systematic review and metaanalysis demonstrates that cognitive impairment represents a core feature of depression that cannot be considered an epiphenomenon that is entirely secondary to symptoms of low mood and that may be a valuable target for future interventions.

Barriers to mental health treatment: Results from the WHO World Mental Health surveys

Abstract: The WHO WMH Survey Initiative is supported by the National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864 and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481). The Sao Paulo Megacity Mental Health Survey is supported by the State of Sao Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00 204-3. The ESEMeD project is funded by the European Commission (Contracts QLG5-1999-01 042; SANCO 2 004 123 and EAHC20081308), the Piedmont Region (Italy), Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnologia, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP). The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labor and Welfare. The Lebanese National Mental Health Survey (LEBANON) is supported by the National Institute of Health/Fogarty International Center (R03 TW006481- 01. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H). The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study was funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the NIMH (U01-MH60220), the Robert Wood Johnson Foundation (RWJF; Grant044780)

The global burden of anxiety disorders in 2010

Abstract: Background Despite their high prevalence, the global burden of anxiety disorders has never been calculated comprehensively. The new Global Burden of Disease (GBD) study has estimated burden due to morbidity and mortality caused by any anxiety disorder. Method Prevalence was estimated using Bayesian meta-regression informed by data identified in a systematic review. Years of life lived with disability (YLDs) were calculated by multiplying prevalent cases by an average disability weight based on severity proportions (mild, moderate and severe). Disability-adjusted life years (DALYs) were then calculated and age standardized using global standard population figures. Estimates were also made for additional suicide mortality attributable to anxiety disorders. Findings are presented for YLDs, DALYs and attributable burden due to suicide for 21 world regions in 1990 and 2010. Results Anxiety disorders were the sixth leading cause of disability, in terms of YLDs, in both high-income (HI) and low- and middle-income (LMI) countries. Globally, anxiety disorders accounted for 390 DALYs per 100 000 persons [95% uncertainty interval (UI) 191–371 DALYs per 100 000] in 2010, with no discernible change observed over time. Females accounted for about 65% of the DALYs caused by anxiety disorders, with the highest burden in both males and females experienced by those aged between 15 and 34 years. Although there was regional variation in prevalence, the overlap between uncertainty estimates means that substantive differences in burden between populations could not be identified. Conclusions Anxiety disorders are chronic, disabling conditions that are distributed across the globe. Future estimates of burden could be further improved by obtaining more representative data on severity state proportions.

The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies.

Abstract: Background Longitudinal studies reporting the association between cannabis use and developing depression provide mixed results. The objective of this study was to establish the extent to which different patterns of use of cannabis are associated with the development of depression using meta-analysis of longitudinal studies. Method Peer-reviewed publications reporting the risk of developing depression in cannabis users were located using searches of EMBASE, Medline, PsychINFO and ISI Web of Science. Only longitudinal studies that controlled for depression at baseline were included. Data on several study characteristics, including measures of cannabis use, measures of depression and control variables, were extracted. Odds ratios (ORs) were extracted by age and length of follow-up. Results After screening for 4764 articles, 57 articles were selected for full-text review, of which 14 were included in the quantitative analysis (total number of subjects = 76058). The OR for cannabis users developing depression compared with controls was 1.17 [95% confidence interval (CI) 1.05–1.30]. The OR for heavy cannabis users developing depression was 1.62 (95% CI 1.21–2.16), compared with non-users or light users. Meta-regression revealed no significant differences in effect based on age of subjects and marginal difference in effect based on length of follow-up in the individual studies. There was large heterogeneity in the number and type of control variables in the different studies. Conclusions Cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders. There is need for further longitudinal exploration of the association between cannabis use and developing depression, particularly taking into account cumulative exposure to cannabis and potentially significant confounding factors.

Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials

Abstract: Background Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs). Method We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT). Results Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant. Conclusions HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.

The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies.

Abstract: Background Dementia with Lewy bodies (DLB) is increasingly recognized as a common cause of dementia in older people. However, its true frequency remains unclear, with previous studies reporting a prevalence range from zero to 22.8% of all dementia cases. This review aimed to establish the population prevalence and incidence for DLB and to compare this to its prevalence in secondary care settings. Method A literature review of all relevant population and clinical studies was conducted using PubMed. Additional references from papers found during that process were added to this. Results DLB accounted for 4.2% of all diagnosed dementias in the community. In secondary care this increased to 7.5%. The incidence of DLB was 3.8% of new dementia cases. There was a significant increase in DLB diagnoses when using the revised (2005) International Consensus Criteria (ICC) for DLB compared to the original (1996) criteria. Conclusions DLB currently accounts for around one in 25 dementia cases diagnosed in the community and one in 13 cases in secondary care. The significantly higher rates of DLB in secondary care may reflect enhanced diagnostic accuracy in specialist settings and/or the increased morbidity and carer burden of the DLB syndrome compared to other dementias. However, the true prevalence is likely to be much higher because DLB diagnoses are often missed, although there is evidence that new criteria aid case identification.

The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan

Abstract: Background No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the lifespan with a specific focus on ADHD in adults. Method Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins. Results The best-fitting model revealed a high heritability of ADHD [0.88, 95% confidence interval (CI) 0.83–0.92] for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56–0.84). Conclusions This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.

Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications

Abstract: BACKGROUND Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 s.d. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not. METHOD A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning. RESULTS Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia. CONCLUSIONS These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment.

Cognitive functioning in obsessive-compulsive disorder: a meta-analysis.

Abstract: Background Substantial empirical evidence has indicated impairment in the cognitive functioning of patients with obsessive-compulsive disorder (OCD) despite inconsistencies. Although several confounding factors have been investigated to explain the conflicting results, the findings remain mixed. This study aimed to investigate cognitive dysfunction in patients with OCD using a meta-analytic approach. Method The PubMed database was searched between 1980 and October 2012, and reference lists of review papers were examined. A total of 221 studies were identified, of which 88 studies met inclusion criteria. Neuropsychological performance and demographic and clinical variables were extracted from each study. Results Patients with OCD were significantly impaired in tasks that measured visuospatial memory, executive function, verbal memory and verbal fluency, whereas auditory attention was preserved in these individuals. The largest effect size was found in the ability to recall complex visual stimuli. Overall effect estimates were in the small to medium ranges for executive function, verbal memory and verbal fluency. The effects of potentially confounding factors including educational level, symptom severity, medication status and co-morbid disorders were not significant. Conclusions Patients with OCD appear to have wide-ranging cognitive deficits, although their impairment is not so large in general. The different test forms and methods of testing may have influenced the performance of patients with OCD, indicating the need to select carefully the test forms and methods of testing used in future research. The effects of various confounding variables on cognitive functioning need to be investigated further and to be controlled before a definite conclusion can be made.

A meta-analysis of neuropsychological markers of vulnerability to suicidal behavior in mood disorders.

Abstract: Background Suicidal behavior results from a complex interplay between stressful events and vulnerability factors, including cognitive deficits. However, it is not clear which cognitive tests may best reveal this vulnerability. The objective was to identify neuropsychological tests of vulnerability to suicidal acts in patients with mood disorders. Method A search was made of Medline, EMBASE and PsycINFO databases, and article references. A total of 25 studies (2323 participants) met the selection criteria. A total of seven neuropsychological tests [Iowa gambling task (IGT), Stroop test, trail making test part B, Wisconsin card sorting test, category and semantic verbal fluencies, and continuous performance test] were used in at least three studies to be analysed. Results IGT and category verbal fluency performances were lower in suicide attempters than in patient controls [respectively, g = –0.47, 95% confidence interval (CI) –0.65 to –0.29 and g = –0.32, 95% CI –0.60 to –0.04] and healthy controls, with no difference between the last two groups. Stroop performance was lower in suicide attempters than in patient controls (g = 0.37, 95% CI 0.10–0.63) and healthy controls, with patient controls scoring lower than healthy controls. The four other tests were altered in both patient groups versus healthy controls but did not differ between patient groups. Conclusions Deficits in decision-making, category verbal fluency and the Stroop interference test were associated with histories of suicidal behavior in patients with mood disorders. Altered value-based and cognitive control processes may be important factors of suicidal vulnerability. These tests may also have the potential of guiding therapeutic interventions and becoming part of future systematic assessment of suicide risk.

Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables

Abstract: criteria. Compared with age- and gender-matched control groups, individuals with MDD had a higher MetS prevalence [odds ratio (OR) 1.54, 95% CI 1.21–1.97, p=0.001]. They also had a higher risk for hyperglycemia (OR 1.33, 95% CI 1.03–1.73, p=0.03) and hypertriglyceridemia (OR 1.17, 95% CI 1.04–1.30, p=0.008). Antipsychotic use (p<0.05) significantly explained higher MetS prevalence estimates in MDD. Differences in MetS prevalences were not moderated by age, gender, geographical area, smoking, antidepressant use, presence of psychiatric co-morbidity, and median year of data collection. Conclusions. The present findings strongly indicate that persons with MDD are a high-risk group for MetS and related cardiovascular morbidity and mortality. MetS risk may be highest in those prescribed antipsychotics.

Trajectories of PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study.

Abstract: Background Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders. Method A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks. Results Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories. Conclusions Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.

Depression is related to an absence of optimistically biased belief updating about future life events.

Abstract: BACKGROUND: When challenged with information about the future, healthy participants show an optimistically biased updating pattern, taking desirable information more into account than undesirable information. However, it is unknown how patients suffering from major depressive disorder (MDD), who express pervasive pessimistic beliefs, update their beliefs when receiving information about their future. Here we tested whether an optimistically biased information processing pattern found in healthy individuals is absent in MDD patients. Method MDD patients (n = 18; 13 medicated; eight with co-morbid anxiety disorder) and healthy controls (n = 19) estimated their personal probability of experiencing 70 adverse life events. After each estimate participants were presented with the average probability of the event occurring to a person living in the same sociocultural environment. This information could be desirable (i.e. average probability better than expected) or undesirable (i.e. average probability worse than expected). To assess how desirable versus undesirable information influenced beliefs, participants estimated their personal probability of experiencing the 70 events a second time. RESULTS: Healthy controls showed an optimistic bias in updating, that is they changed their beliefs more toward desirable versus undesirable information. Overall, this optimistic bias was absent in MDD patients. Symptom severity correlated with biased updating: more severely depressed individuals showed a more pessimistic updating pattern. Furthermore, MDD patients estimated the probability of experiencing adverse life events as higher than healthy controls. CONCLUSIONS: Our findings raise the intriguing possibility that optimistically biased updating of expectations about one's personal future is associated with mental health.

The dynamic nature of depression: a new micro-level perspective of mental disorder that meets current challenges

Abstract: The examination of moment-to-moment, 'micro-level' patterns of experience and behaviour using experience sampling methodology has contributed to our understanding of the 'macro-level' development of full-blown symptoms and disorders. This paper argues that the micro-level perspective can be used to identify the smallest building blocks underlying the onset and course of mental ill-health. Psychopathology may be the result of the continuous dynamic interplay between micro-level moment-to-moment experiences and behavioural patterns over time. Reinforcing loops between momentary states may alter the course of mental health towards either a more or less healthy state. An example with observed data, from a population of individuals with depressive symptoms, supports the validity of a dynamic network model of psychopathology and shows that together and over time, this continuous interplay between momentary states may result in the cluster of symptoms we call major depressive disorder. This approach may help conceptualize the nature of mental disorders, and generate individualized insights useful for diagnosis and treatment in psychiatry.

The methods and outcomes of cultural adaptations of psychological treatments for depressive disorders: a systematic review.

Abstract: Results. Twenty studies were included in this review, of which 16 were included in the meta-analysis. The process of adaptation was reported in two-thirds of the studies. Most adaptations were found in the dimensions of language, context and therapist delivering the treatment. The meta-analysis revealed a statistically significant benefit in favor of the adapted treatment [standardized mean difference (SMD) �0.72, 95% confidence interval (CI) �0.94 to �0.49]. Conclusions. Cultural adaptations of PTs follow a systematic procedure and lead primarily to adaptations in the implementation of the treatments rather than their content. Such PTs are effective in the treatment of depressive disorders in populations other than those for whom they were originally developed.

Depression is more than the sum score of its parts: individual DSM symptoms have different risk factors

Abstract: Background For diagnostic purposes, the nine symptoms that compose the DSM-5 criteria for Major Depressive Disorder (MDD) are assumed to be interchangeable indicators of one underlying disorder, implying that they should all have similar risk factors. The present study investigates this hypothesis, utilizing a population cohort that shifts from low to elevated depression levels.

Does asking about suicide and related behaviours induce suicidal ideation? What is the evidence?

Abstract: There is a commonly held perception in psychology that enquiring about suicidality, either in research or clinical settings, can increase suicidal tendencies. While the potential vulnerability of participants involved in psychological research must be addressed, apprehensions about conducting studies of suicidality create a Catch-22 situation for researchers. Ethics committees require evidence that proposed studies will not cause distress or suicidal ideation, yet a lack of published research can mean allaying these fears is difficult. Concerns also exist in psychiatric settings where risk assessments are important for ensuring patient safety. But are these concerns based on evidence? We conducted a review of the published literature examining whether enquiring about suicide induces suicidal ideation in adults and adolescents, and general and at-risk populations. None found a statistically significant increase in suicidal ideation among participants asked about suicidal thoughts. Our findings suggest acknowledging and talking about suicide may in fact reduce, rather than increase suicidal ideation, and may lead to improvements in mental health in treatment-seeking populations. Recurring ethical concerns about asking about suicidality could be relaxed to encourage and improve research into suicidal ideation and related behaviours without negatively affecting the well-being of participants.

Breastfeeding is negatively affected by prenatal depression and reduces postpartum depression

Abstract: This research was supported by FEDER Funds through the Programa Operacional Factores de Competitividade - COMPETE and by National Funds through FCT – Fundacao para a Ciencia e a Tecnologia under the project: PTDC/SAU/SAP/116738/2010, and by a FCT grant to the first author (BSAB/1300656063).

Lessons learned from the psychosis high-risk state: towards a general staging model of prodromal intervention

Abstract: Background The past two decades have seen exponential clinical and research interest in help-seeking individuals presenting with potentially prodromal symptoms for psychosis. However, the epidemiological validity of this paradigm has been neglected, limiting future advancements in the field. Method We undertook a critical review of core epidemiological issues underlying the clinical high-risk (HR) state for psychosis and which model of prodromal intervention is best suited for mental health. Results The HR state for psychosis model needs refining, to bring together population-based findings of high levels of psychotic experiences (PEs) and clinical expression of risk. Traditionally, outcome has been attributed to ‘HR criteria’ alone rather than taking into account sampling strategies. Furthermore, the exclusive focus on variably defined ‘transition’ obscures true variation in the slow and non-linear progression across stages of psychopathology. Finally, the outcome from HR states is variable, indicating that the underlying paradigm of ‘schizophrenia light progressing to schizophrenia’ is inadequate. Conclusions In the general population, mixed and non-specific expression of psychosis, depression, anxiety and subthreshold mania is common and mostly transitory. When combined with distress, it may be considered as the first, diagnostically neutral stage of potentially more severe psychopathology, which only later may acquire a degree of diagnostic specificity and possible relative resistance to treatment. Therefore, rather than creating silos of per-disorder ultra-HR syndromes, an early intervention focus on the broad syndrome of early mental distress, requiring phase-specific interventions, may be more profitable.

A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models

Abstract: Background Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning. Method The neuropsychological functioning of 83 medication-naive boys with well-characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks. Results Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)]. Conclusions The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment.

A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa

Abstract: Background The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, ‘enhanced’ cognitive-behavioral therapy (CBT-E). Method Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). Results Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. Conclusions ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

Sociodemographic, psychiatric and somatic risk factors for suicide: a Swedish national cohort study.

Abstract: Background More effective prevention of suicide requires a comprehensive understanding of sociodemographic, psychiatric and somatic risk factors. Previous studies have been limited by incomplete ascertainment of these factors. We conducted the first study of this issue using sociodemographic and out-patient and in-patient health data for a national population. Method We used data from a national cohort study of 7140589 Swedish adults followed for 8 years for suicide mortality (2001-2008). Sociodemographic factors were identified from national census data, and psychiatric and somatic disorders were identified from all out-patient and in-patient diagnoses nationwide. Results There were 8721 (0.12%) deaths from suicide during 2001-2008. All psychiatric disorders were strong risk factors for suicide among both women and men. Depression was the strongest risk factor, with a greater than 15-fold risk among women or men and even higher risks (up to 32-fold) within the first 3 months of diagnosis. Chronic obstructive pulmonary disease (COPD), cancer, spine disorders, asthma and stroke were significant risk factors among both women and men (1.4-2.1-fold risks) whereas diabetes and ischemic heart disease were modest risk factors only among men (1.2-1.4-fold risks). Sociodemographic risk factors included male sex, unmarried status or non-employment; and low education or income among men. Conclusions All psychiatric disorders, COPD, cancer, spine disorders, asthma, stroke, diabetes, ischemic heart disease and specific sociodemographic factors were independent risk factors for suicide during 8 years of follow-up. Effective prevention of suicide requires a multifaceted approach in both psychiatric and primary care settings, targeting mental disorders (especially depression), specific somatic disorders and indicators of social support. (Less)

Reappraising the Long-term Course and Outcome of Psychotic Disorders: The ÆSOP-10 Study

Abstract: Background Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare. Method AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews. Results At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1–4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London. Conclusions Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.

Cause and effect in studies on unemployment, mental health and suicide : a meta-analytic and conceptual review

Abstract: Background There are ongoing questions about whether unemployment has causal effects on suicide as this relationship may be confounded by past experiences of mental illness. The present review quantified the effects of adjustment for mental health on the relationship between unemployment and suicide. Findings were used to develop and interpret likely causal models of unemployment, mental health and suicide. Method A random-effects meta-analysis was conducted on five population-based cohort studies where temporal relationships could be clearly ascertained. Results Results of the meta-analysis showed that unemployment was associated with a significantly higher relative risk (RR) of suicide before adjustment for prior mental health [RR 1.58, 95% confidence interval (CI) 1.33–1.83]. After controlling for mental health, the RR of suicide following unemployment was reduced by approximately 37% (RR 1.15, 95% CI 1.00–1.30). Greater exposure to unemployment was associated with higher RR of suicide, and the pooled RR was higher for males than for females. Conclusions Plausible interpretations of likely pathways between unemployment and suicide are complex and difficult to validate given the poor delineation of associations over time and analytic rationale for confounder adjustment evident in the revised literature. Future research would be strengthened by explicit articulation of temporal relationships and causal assumptions. This would be complemented by longitudinal study designs suitable to assess potential confounders, mediators and effect modifiers influencing the relationship between unemployment and suicide.

Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis

Abstract: Background: There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities. Method: The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants. Results: The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18-64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence. Conclusions: Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness. Copyright © Cambridge University Press 2013 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence http://creativecommons.org/licenses/by/3.0/.

Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress.

Abstract: In support of the developmental origins of disease hypothesis (Barker, 1998), accumulating evidence links maternal stress to increased risk of psychopathological morbidity in offspring (Khashan et al., 2008a, Li et al., 2010, Khashan et al., 2011, Van Os and Selten, 1998, Ronald et al., 2011, Huttunen and Niskanen, 1978, Rodriguez and Bohlin, 2005). Studies have identified associations with severe, impairing, and costly psychiatric disorders, including autism spectrum disorder (ASD; Ganz, 2007, Beversdorf et al., 2005), attention-deficit/hyperactivity disorder (ADHD; Rodriguez and Bohlin, 2005, Polanczyk et al., 2007, Pelham et al., 2007), and schizophrenia (Jablensky, 2000, Khashan et al., 2008a). Associations with adverse psychopathological outcomes have been reported following maternal exposure to physical stressors, such as famine (Brown et al., 2000, Brown et al., 1995), and psychological stressors, such as bereavement (Khashan et al., 2008a, Khashan et al., 2011, Li et al., 2010), trauma (Brand et al., 2006), war (Van Os and Selten, 1998), and natural disaster (Glynn et al., 2001, King and Laplante, 2005, Kinney et al., 2008a). Assessing the effect of timing of an individual level, objective psychological stress on psychiatric outcomes is particularly important because linkage with a specifically-timed effect increases the likelihood that an association might be causal (Smith, 2008). Previous research suggests that exposure during sensitive critical periods may exist for certain psychiatric disorders. For example, in humans preconception stress may be associated with an increased risk of childhood ADHD (Li et al., 2010) and adult affective disorder (Khashan et al., 2011), but only in male offspring. In rodents, preconception stress is associated with altered adult offspring memory functioning (Schelar et al., 2007) and differences in affective and social behaviour (Shachar-Dadon et al., 2009). In humans, evidence indicates that prenatal maternal stress is associated with psychopathological outcomes across stressors and populations (Khashan et al., 2008a, Li et al., 2010, Khashan et al., 2011, Van Os and Selten, 1998, Ronald et al., 2011, Huttunen and Niskanen, 1978, Rodriguez and Bohlin, 2005, Talge et al., 2007, Bale et al., 2010, O’Connor et al., 2003, Beydoun and Saftlas, 2008, Beversdorf et al., 2005, Kinney et al., 2008a). Additionally, postnatal stress exposure is associated with increased risk of offspring psychiatric outcomes (Brent and Mann, 2006, Heim et al., 2008, Landau et al., 2010, Rosenberg et al., 2007, Mortensen et al., 2003, Epstein et al., 2008, Guinchat et al., 2012, Rai et al., 2012). While associations between early stress exposure and perinatal outcomes show relative consistency (Beydoun and Saftlas, 2008), associations between early maternal stress exposure and major psychopathological outcomes remain inconsistent and need focused and continued exploration for several reasons. First, there is a paucity of evidence for the effect of preconception maternal exposure to severe stress; where these do exist, effect sizes are modest at best (Khashan et al., 2008a, Khashan et al., 2011). Second, replication is needed for a number of reported effects. For example, a meta-analysis did not support an association between prenatal stress and schizophrenia (Selten et al., 2003), and studies predicting autism from prenatal stress also have been inconsistent (Li et al., 2009, Beversdorf et al., 2005, Rai et al., 2012, Ronald et al., 2011). Finally, several important methodological issues limit the quality of much of the evidence to date. For example, measurement difficulties abound, such as the use of retrospective self-reports in small and biased samples (Beversdorf et al., 2005). In famine studies, individuals are exposed to psychological as well as nutritional stressors, while women that conceive and complete pregnancy during famine may represent an unusual group (Dunkel-Schetter and Glynn, 2011, Rodriguez and Bohlin, 2005, Brown et al., 2000, St. Clair et al., 2005). These limitations are of enough concern to render current evidence for robust and/or causal associations between preconception, prenatal, and postnatal maternal stress exposure and offspring psychopathological outcomes inconclusive. We set out to address sample size, measurement, and timing limitations in previous studies by analysing data from Swedish national registers. These data provide one of the largest and most comprehensive population registers currently available for psychiatric research. Utilising the highest quality and largest data set possible was necessary to draw conclusions regarding associations between rare risks and outcomes across several early risk periods in one population. We decided to focus on psychopathological outcomes with the best evidence to date (ASD, ADHD, and schizophrenia), associated outcomes of suicidal behaviour (suicide attempt and completed suicide), and bipolar disorder, which has not been directly examined previously. We defined exposure to maternal stress as the occurrence of the death of a first degree relative of the mother which we considered an objective measure of psychological stress. We also utilised the random nature of the timing of the exposure to bereavement stress in a quasi-experimental design (Academy of Medical Sciences Working Group, 2007), while statistically controlling for measured covariates to help account for alternative explanations. We hypothesised that the findings would support prior positive findings by timing of exposure, as well as reveal novel associations with previously unstudied outcomes. In particular, we hypothesized that preconception bereavement stress would be associated with increased risk for offspring ADHD but not other outcomes (Li et al., 2010, Khashan et al., 2008a, Li et al., 2009). We hypothesized that prenatal bereavement stress would be associated with increased risk for ADHD and schizophrenia (Kinney et al., 2008b, Ronald et al., 2011, Li et al., 2010, Brown et al., 2000, Khashan et al., 2008a, Kinney et al., 2008a), as well as increased risk for bipolar disorder and attempted and completed suicide, but not ASD (Li et al., 2009, Rai et al., 2012). Finally, we hypothesized that postnatal bereavement stress would be associated with increased risk for offspring ASD, ADHD (Epstein et al., 2008, Guinchat et al., 2012, Landau et al., 2010, Rai et al., 2012) and attempted and completed suicide (Williams and Pollock, 2000). We also performed sensitivity analyses to rule out moderation by offspring sex, test the robustness of associations by birth outcomes and parental psychopathology, and explore outcome specificity (Khashan et al., 2008b, Smith et al., 2003, Gluckman and Hanson, 2004, Mittendorfer-Rutz et al., 2004, Lindstrom et al., 2011, Abel et al., 2010, Moster et al., 2008, Hultman et al., 2007, Losh et al., 2011).

Netmums: a phase II randomized controlled trial of a guided Internet behavioural activation treatment for postpartum depression

Abstract: Background Despite the high prevalence of postnatal depression (PND), few women seek help. Internet interventions may overcome many of the barriers to PND treatment use. We report a phase II evaluation of a 12-session, modular, guided Internet behavioural activation (BA) treatment modified to address postnatal-specific concerns [Netmums Helping With Depression (NetmumsHWD)]. Method To assess feasibility, we measured recruitment and attrition to the trial and examined telephone session support and treatment adherence. We investigated sociodemographic and psychological predictors of treatment adherence. Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7, Work and Social Adjustment Scale, Postnatal Bonding Questionnaire, and Social Provisions Scale. Results A total of 249 women were recruited via a UK parenting site, Netmums.com. A total of 83 women meeting DSM-IV criteria for major depressive disorder were randomized to NetmumsHWD (n = 41) or treatment-as-usual (TAU; n = 42). Of the 83 women, 71 (86%) completed the EPDS at post-treatment, and 71% (59/83) at the 6-month follow-up. Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules. Working women and those with less support completed fewer modules. There was a large effect size favouring women who received NetmumsHWD on depression, work and social impairment, and anxiety scores at post-treatment compared with women in the TAU group, and a large effect size on depression at 6 months post-treatment. There were small effect sizes for postnatal bonding and perceived social support. Conclusions A supported, modular, Internet BA programme can be feasibly delivered to postpartum women, offering promise to improve depression, anxiety and functioning.

Cognitive behavioural therapy for psychosis prevention: a systematic review and meta-analysis.

Abstract: Results. Our search produced 1940 titles, out of which we found seven completed trials (six published). The relative risk (RR) of developing psychosis was reduced by more than 50% for those receiving CBT at every time point [RR at 6 months 0.47, 95% confidence interval (CI) 0.27–0.82, p=0.008 (fixed-effects only: six randomized controlled trials (RCTs), n=800); RR at 12 months 0.45, 95% CI 0.28–0.73, p=0.001 (six RCTs, n=800); RR at 18–24 months 0.41, 95% CI 0.23–0.72, p=0.002 (four RCTs, n=452)]. Heterogeneity was low in every analysis and the results were largely robust to the risk of an unpublished 12-month study having unfavourable results. CBT was also associated with reduced subthreshold symptoms at 12 months, but not at 6 or 18–24 months. No effects on functioning, symptom-related distress or quality of life were observed. CBT was not associated with increased rates of clinical depression or social anxiety (two studies). Conclusions. CBT-informed treatment is associated with a reduced risk of transition to psychosis at 6, 12 and 18–24 months, and reduced symptoms at 12 months. Methodological limitations and recommendations for trial reporting are discussed.

Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis.

Abstract: Background. Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulatedby antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-basedmorphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able todistinguish the morphological features of the disease itself from those of treatment.Method. Asystematic search was conductedfor the relevant studies. Effect-size signeddifferential mappingwas appliedto analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regressionwas used to explore the effects of demographics and clinical characteristics.Results. A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusioncriteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal andlimbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, andincreased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regressionanalyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the righthippocampus.Conclusions. By excluding interference from medication effects, the present study identified grey matter reductionin the prefrontal–limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamusvolume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be aneffect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences inepidemiological and clinical aspects of MDD.Received 5 June 2013; Revised 23 January 2014; Accepted 13 February 2014; First published online 21 March 2014Keywords: Effect size signed differential mapping, grey matter, magnetic resonance imaging, major depressive disorder,meta-analyses, voxel-based morphometry.

Cognitive variability in psychotic disorders: a cross-diagnostic cluster analysis.

Abstract: Background. Cognitive dysfunction is a core feature of psychotic disorders; however, substantial variability exists both within and between subjects in terms of cognitive domains of dysfunction, and a clear ‘profile’ of cognitive strengths and weaknesses characteristic of any diagnosis or psychosis as a whole has not emerged. Cluster analysis provides an opportunity to group individuals using a data-driven approach rather than predetermined grouping criteria. While several studies have identified meaningful cognitive clusters in schizophrenia, no study to date has examined cognition in a cross-diagnostic sample of patients with psychotic disorders using a cluster approach. We aimed to examine cognitive variables in a sample of 167 patients with psychosis using cluster methods.Method. Subjects with schizophrenia (n = 41), schizo-affective disorder (n = 53) or bipolar disorder with psychosis (n = 73) were assessed using a battery of cognitive and clinical measures. Cognitive data were analysed using Ward's method, followed by a K-means cluster approach. Clusters were then compared on diagnosis and measures of clinical symptoms, demographic variables and community functioning.Results. A four-cluster solution was selected, including a ‘neuropsychologically normal’ cluster, a globally and significantly impaired cluster, and two clusters of mixed cognitive profiles. Clusters differed on several clinical variables; diagnoses were distributed amongst all clusters, although not evenly.Conclusions. Identification of groups of patients who share similar neurocognitive profiles may help pinpoint relevant neural abnormalities underlying these traits. Such groupings may also hasten the development of individualized treatment approaches, including cognitive remediation tailored to patients' specific cognitive profiles.