Review Article
Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables
- D. Vancampfort, C. U. Correll, M. Wampers, P. Sienaert, A. J. Mitchell, A. De Herdt, M. Probst, T. W. Scheewe, M. De Hert
-
- Published online by Cambridge University Press:
- 21 November 2013, pp. 2017-2028
-
- Article
- Export citation
-
Background
Individuals with depression have an elevated risk of cardiovascular disease (CVD) and metabolic syndrome (MetS) is an important risk factor for CVD. We aimed to clarify the prevalence and correlates of MetS in persons with robustly defined major depressive disorder (MDD).
MethodWe searched Medline, PsycINFO, EMBASE and CINAHL up until June 2013 for studies reporting MetS prevalences in individuals with MDD. Medical subject headings ‘metabolic’ OR ‘diabetes’ or ‘cardiovascular’ or ‘blood pressure’ or ‘glucose’ or ‘lipid’ AND ‘depression’ OR ‘depressive’ were used in the title, abstract or index term fields. Manual searches were conducted using reference lists from identified articles.
ResultsThe initial electronic database search resulted in 91 valid hits. From candidate publications following exclusions, our search generated 18 studies with interview-defined depression (n = 5531, 38.9% male, mean age = 45.5 years). The overall proportion with MetS was 30.5% [95% confidence interval (CI) 26.3–35.1] using any standardized MetS 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.
ConclusionsThe 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.
Cognitive impairment in depression: a systematic review and meta-analysis
- P. L. Rock, J. P. Roiser, W. J. Riedel, A. D. Blackwell
-
- Published online by Cambridge University Press:
- 29 October 2013, pp. 2029-2040
-
- Article
- Export citation
-
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.
MethodWe 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.
ResultsOur 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.
ConclusionsBoth 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 meta-analysis 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.
Original Articles
Revisiting default mode network function in major depression: evidence for disrupted subsystem connectivity
- F. Sambataro, N. D. Wolf, M. Pennuto, N. Vasic, R. C. Wolf
-
- Published online by Cambridge University Press:
- 31 October 2013, pp. 2041-2051
-
- Article
- Export citation
-
Background
Major depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's ‘resting state’. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.
MethodHere, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.
ResultsWe show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems.
ConclusionsThese data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic targets.
Local cortical thinning links to resting-state disconnectivity in major depressive disorder
- M.-J. van Tol, M. Li, C. D. Metzger, N. Hailla, D. I. Horn, W. Li, H. J. Heinze, B. Bogerts, J. Steiner, H. He, M. Walter
-
- Published online by Cambridge University Press:
- 01 November 2013, pp. 2053-2065
-
- Article
- Export citation
-
Background
Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD.
MethodA total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated.
ResultsLower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity.
ConclusionsAbnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.
Depression is more than the sum score of its parts: individual DSM symptoms have different risk factors
- E. I. Fried, R. M. Nesse, K. Zivin, C. Guille, S. Sen
-
- Published online by Cambridge University Press:
- 02 December 2013, pp. 2067-2076
-
- Article
- Export citation
-
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, using a population cohort that shifts from low to elevated depression levels.
MethodWe assessed the nine DSM-5 MDD criterion symptoms (using the Patient Health Questionnaire; PHQ-9) and seven depression risk factors (personal and family MDD history, sex, childhood stress, neuroticism, work hours, and stressful life events) in a longitudinal study of medical interns prior to and throughout internship (n = 1289). We tested whether risk factors varied across symptoms, and whether a latent disease model could account for heterogeneity between symptoms.
ResultsAll MDD symptoms increased significantly during residency training. Four risk factors predicted increases in unique subsets of PHQ-9 symptoms over time (depression history, childhood stress, sex, and stressful life events), whereas neuroticism and work hours predicted increases in all symptoms, albeit to varying magnitudes. MDD family history did not predict increases in any symptom. The strong heterogeneity of associations persisted after controlling for a latent depression factor.
ConclusionsThe influence of risk factors varies substantially across DSM depression criterion symptoms. As symptoms are etiologically heterogeneous, considering individual symptoms in addition to depression diagnosis might offer important insights obfuscated by symptom sum scores.
Perturbed threat monitoring following a traumatic event predicts risk for post-traumatic stress disorder
- R. Naim, I. Wald, A. Lior, D. S. Pine, N. A. Fox, G. Sheppes, P. Halpern, Y. Bar-Haim
-
- Published online by Cambridge University Press:
- 17 October 2013, pp. 2077-2084
-
- Article
- Export citation
-
Background
Post-traumatic stress disorder (PTSD) is a chronic and difficult to treat psychiatric disorder. Objective, performance-based diagnostic markers that uniquely index risk for PTSD above and beyond subjective self-report markers could inform attempts to improve prevention and early intervention. We evaluated the predictive value of threat-related attention bias measured immediately after a potentially traumatic event, as a risk marker for PTSD at a 3-month follow-up. We measured the predictive contribution of attentional threat bias above and beyond that of the more established marker of risk for PTSD, self-reported psychological dissociation.
MethodDissociation symptoms and threat-related attention bias were measured in 577 motor vehicle accident (MVA) survivors (mean age = 35.02 years, 356 males) within 24 h of admission to an emergency department (ED) of a large urban hospital. PTSD symptoms were assessed at a 3-month follow-up using the Clinician-Administered PTSD Scale (CAPS).
ResultsSelf-reported dissociation symptoms significantly accounted for 16% of the variance in PTSD at follow-up, and attention bias toward threat significantly accounted for an additional 4% of the variance in PTSD.
ConclusionsThreat-related attention bias can be reliably measured in the context of a hospital ED and significantly predicts risk for later PTSD. Possible mechanisms underlying the association between threat bias following a potentially traumatic event and risk for PTSD are discussed. The potential application of an attention bias modification treatment (ABMT) tailored to reduce risk for PTSD is suggested.
Dimensional structure and course of post-traumatic stress symptomatology in World Trade Center responders
- R. H. Pietrzak, A. Feder, C. B. Schechter, R. Singh, L. Cancelmo, E. J. Bromet, C. L. Katz, D. B. Reissman, F. Ozbay, V. Sharma, M. Crane, D. Harrison, R. Herbert, S. M. Levin, B. J. Luft, J. M. Moline, J. M. Stellman, I. G. Udasin, R. El-Gabalawy, P. J. Landrigan, S. M. Southwick
-
- Published online by Cambridge University Press:
- 02 December 2013, pp. 2085-2098
-
- Article
- Export citation
-
Background
Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations.
MethodData were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11.
ResultsCFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time.
ConclusionsResults of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.
Randomized controlled trial and uncontrolled 9-month follow-up of an adjunctive emotion regulation group therapy for deliberate self-harm among women with borderline personality disorder
- K. L. Gratz, M. T. Tull, R. Levy
-
- Published online by Cambridge University Press:
- 28 August 2013, pp. 2099-2112
-
- Article
- Export citation
-
Background
Despite the clinical importance of deliberate self-harm (DSH; also referred to as non-suicidal self-injury) within borderline personality disorder (BPD), empirically supported treatments for this behavior among individuals with BPD are difficult to implement in many clinical settings. To address this limitation, a 14-week, adjunctive emotion regulation group therapy (ERGT) for DSH among women with BPD was developed. The current study examined the efficacy of this ERGT in a randomized controlled trial (RCT) and the durability of treatment gains over a 9-month uncontrolled follow-up period.
MethodFemale out-patients with BPD and recent recurrent DSH were randomly assigned to receive this ERGT in addition to their ongoing out-patient therapy immediately (n = 31) or after 14 weeks (n = 30). Measures of DSH and other self-destructive behaviors, psychiatric symptoms, adaptive functioning and the proposed mechanisms of change (emotion dysregulation/avoidance) were administered pre- and post-treatment or -waitlist (to assess treatment efficacy), and 3 and 9 months post-treatment (to assess durability of treatment gains).
ResultsIntent-to-treat (ITT) analyses (n = 61) revealed significant effects of this ERGT on DSH and other self-destructive behaviors, emotion dysregulation, BPD symptoms, depression and stress symptoms, and quality of life. Analyses of all participants who began ERGT (across treatment and waitlist conditions; n = 51) revealed significant improvements from pre- to post-treatment on all outcomes, additional significant improvements from post-treatment to 9-month follow-up for DSH, emotion dysregulation/avoidance, BPD symptoms and quality of life, and no significant changes from post-treatment to 9-month follow-up on the other measures.
ConclusionsThe results support the efficacy of this ERGT and the durability of treatment gains.
Differential role of visuospatial working memory in the propensity toward uncertainty in patients with obsessive–compulsive disorder and in healthy subjects
- V. Lambrecq, J.-Y. Rotge, N. Jaafari, B. Aouizerate, N. Langbour, B. Bioulac, C. Liégeois-Chauvel, P. Burbaud, D. Guehl
-
- Published online by Cambridge University Press:
- 31 October 2013, pp. 2113-2124
-
- Article
- Export citation
-
Background
Obsessive–compulsive disorder (OCD) is associated with visuospatial working memory deficits. Intolerance of uncertainty is thought to be a core component of OCD symptoms. Recent findings argue for a possible relationship between abilities in visuospatial memory and uncertainty. However, this relationship remains unclear in both OCD patients and healthy subjects. To address this issue, we measured performance in visuospatial working memory and the propensity to express uncertainty during decision making. We assessed their relationship and the temporal direction of this relationship in both OCD patients and healthy subjects.
MethodBaseline abilities in visuospatial working memory were measured with the Corsi block-tapping test. A delayed matching-to-sample task was used to identify explicit situations of certainty, uncertainty and ignorance and to assess continuous performance in visuospatial working memory. Behavioural variables were recorded over 360 consecutive trials in both groups.
ResultsBaseline scores of visuospatial working memory did not predict the number of uncertain situations in OCD patients whereas they did in healthy subjects. Uncertain trials led to reduced abilities in visuospatial working memory to 65% of usual performance in OCD patients whereas they remained stable in healthy subjects.
ConclusionsThe present findings show an opposite temporal direction in the relationship between abilities in working memory and uncertainty in OCD patients and healthy subjects. Poor working memory performance contributes to the propensity to feel uncertainty in healthy subjects whereas uncertainty contributes to decreased continuous performance in working memory in OCD patients.
Predicting response to cognitive behavioral therapy in contamination-based obsessive–compulsive disorder from functional magnetic resonance imaging
- B. O. Olatunji, R. Ferreira-Garcia, X. Caseras, M. A. Fullana, S. Wooderson, A. Speckens, N. Lawrence, V. Giampietro, M. J. Brammer, M. L. Phillips, L. F. Fontenelle, D. Mataix-Cols
-
- Published online by Cambridge University Press:
- 12 November 2013, pp. 2125-2137
-
- Article
- Export citation
-
Background
Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive–compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension.
MethodParticipants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT.
ResultsPatterns of brain activity during symptom provocation were correlated with a decrease on the Yale–Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation.
ConclusionsSuccessful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.
White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study
- L. Emsell, C. Chaddock, N. Forde, W. Van Hecke, G. J. Barker, A. Leemans, S. Sunaert, M. Walshe, E. Bramon, D. Cannon, R. Murray, C. McDonald
-
- Published online by Cambridge University Press:
- 26 November 2013, pp. 2139-2150
-
- Article
- Export citation
-
Background
White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.
MethodDiffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.
ResultsWe detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.
ConclusionsWM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.
P300 waveform and dopamine transporter availability: a controlled EEG and SPECT study in medication-naive patients with schizophrenia and a meta-analysis
- K. C. Chen, I. H. Lee, Y. K. Yang, S. Landau, W. H. Chang, P. S. Chen, R. B. Lu, A. S. David, E. Bramon
-
- Published online by Cambridge University Press:
- 15 November 2013, pp. 2151-2162
-
- Article
- Export citation
-
Background
Reduced P300 event-related potential (ERP) amplitude and latency prolongation have been reported in patients with schizophrenia compared to healthy controls. However, the influence of antipsychotics (and dopamine) on ERP measures are poorly understood and medication confounding remains a possibility.
MethodWe explored ERP differences between 36 drug-naive patients with schizophrenia and 138 healthy controls and examined whether P300 performance was related to dopamine transporter (DAT) availability, both without the confounding effects of medication. We also conducted a random effects meta-analysis of the available literature, synthesizing the results of three comparable published articles and our local study.
ResultsNo overall significant difference was found in mean P300 ERP between patients and controls in latency or in amplitude. There was a significant gender effect, with females showing greater P300 amplitude than males. A difference between patients and controls in P300 latency was evident with ageing, with latency increasing faster in patients. No effect of DAT availability on P300 latency or amplitude was detected. The meta-analysis computed the latency pooled standardized effect size (PSES; Cohen's d) of −0.13 and the amplitude PSES (Cohen's d) of 0.48, with patients showing a significant reduction in amplitude.
ConclusionsOur findings suggest the P300 ERP is not altered in the early stages of schizophrenia before medication is introduced, and the DAT availability does not influence the P300 ERP amplitude or latency. P300 ERP amplitude reduction could be an indicator of the progression of illness and chronicity.
Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis
- V. A. Morgan, J. J. McGrath, A. Jablensky, J. C. Badcock, A. Waterreus, R. Bush, V. Carr, D. Castle, M. Cohen, C. Galletly, C. Harvey, B. Hocking, P. McGorry, A. L. Neil, S. Saw, S. Shah, H. J. Stain, A. Mackinnon
-
- Published online by Cambridge University Press:
- 02 January 2014, pp. 2163-2176
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.
MethodThe 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.
ResultsThe 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.
ConclusionsOur 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.
The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis
- A. Hargreaves, R. Anney, C. O'Dushlaine, K. K. Nicodemus, Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Wellcome Trust Case Control Consortium 2, M. Gill, A. Corvin, D. Morris, Gary Donohoe
-
- Published online by Cambridge University Press:
- 28 November 2013, pp. 2177-2187
-
- Article
- Export citation
-
Background
Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.
MethodIn total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.
ResultsIncreased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1–3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.
ConclusionsThese data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.
Tobacco smoking in schizophrenia: investigating the role of incentive salience
- T. P. Freeman, J. M. Stone, B. Orgaz, L. A. Noronha, S. L. Minchin, H. V. Curran
-
- Published online by Cambridge University Press:
- 01 November 2013, pp. 2189-2197
-
- Article
- Export citation
-
Background
Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations.
MethodTwenty-two smokers diagnosed with schizophrenia and 23 control smokers were assessed for smoking-related attentional bias using a modified Stroop task. Craving, nicotine dependence, smoking behaviour and positive and negative symptoms of schizophrenia were also recorded.
ResultsBoth groups showed similar craving scores and smoking behaviour according to self-report and expired carbon monoxide (CO), although the patient group had higher nicotine dependence scores. Attentional bias, as evidenced by significant interference from smoking-related words on the modified Stroop task, was similar in both groups and correlated with CO levels. Attentional bias was positively related to severity of delusions but not hallucinations or other symptoms in the schizophrenia group.
ConclusionsThis study supports the hypothesis that the development of delusions and the incentive motivational aspects of smoking may share a common biological substrate. These findings may offer some explanation for the elevated rates of smoking and other drug use in people with psychotic illness.
Bullying in elementary school and psychotic experiences at 18 years: a longitudinal, population-based cohort study
- D. Wolke, S. T. Lereya, H. L. Fisher, G. Lewis, S. Zammit
-
- Published online by Cambridge University Press:
- 17 December 2013, pp. 2199-2211
-
- Article
- Export citation
-
Background
Victims of bullying are at risk for psychotic experiences in early adolescence. It is unclear if this elevated risk extends into late adolescence. The aim of this study was to test whether bullying perpetration and victimization in elementary school predict psychotic experiences in late adolescence.
MethodThe current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective community-based study. A total of 4720 subjects with bullying perpetration and victimization were repeatedly assessed between the ages of 8 and 11 years by child and mother reports. Suspected or definite psychotic experiences were assessed with the Psychosis-Like Symptoms semi-structured interview at age 18 years.
ResultsControlling for child's gender, intelligence quotient at age 8 years, childhood behavioural and emotional problems, and also depression symptoms and psychotic experiences in early adolescence, victims [child report at 10 years: odds ratio (OR) 2.4, 95% confidence interval (CI) 1.6–3.4; mother report: OR 1.6, 95% CI 1.1–2.3], bully/victims (child report at 10 years: OR 3.1, 95% CI 1.7–5.8; mother: OR 2.9, 95% CI 1.7–5.0) and bullies (child report at 10 years: OR 4.9, 95% CI 1.3–17.7; mother: OR 1.2, 95% CI 0.46–3.1, n.s.) had a higher prevalence of psychotic experiences at age 18 years. Path analysis revealed that the association between peer victimization in childhood and psychotic experiences at age 18 years was only partially mediated by psychotic or depression symptoms in early adolescence.
ConclusionsInvolvement in bullying, whether as victim, bully/victim or bully, may increase the risk of developing psychotic experiences in adolescence. Health professionals should ask routinely during consultations with children about their bullying of and by peers.
Psychodynamic therapy for adolescents suffering from co-morbid disorders of conduct and emotions in an in-patient setting: a randomized controlled trial
- S. Salzer, C. Cropp, U. Jaeger, O. Masuhr, A. Streeck-Fischer
-
- Published online by Cambridge University Press:
- 12 November 2013, pp. 2213-2222
-
- Article
- Export citation
-
Background
Co-morbid disorders of conduct and emotions can be regarded as childhood antecedents of further negative developments (e.g. manifestation of personality disorders in adulthood). We evaluated a manualized psychodynamic therapy (PDT) for adolescents with these co-morbid disorders.
MethodIn a randomized controlled trial (RCT), 66 adolescents diagnosed with mixed disorders of conduct and emotions (F92 in ICD-10) were randomly assigned to a manualized in-patient PDT group or a waiting list/treatment-as-usual (WL/TAU) control condition. Diagnoses according to DSM-IV were also documented. Patients were compared using rates of remission as the primary outcome. The Global Severity Index (GSI) and the Strengths and Difficulties Questionnaire (SDQ) were used as secondary measures. Assessments were performed at baseline, post-treatment and at the 6-month follow-up.
ResultsThe sample consisted of severely impaired adolescents with high rates of further co-morbid disorders and academic failure. Patients in the treatment group had a significantly higher rate of remission [odds ratio (OR) 26.41, 95% confidence interval (CI) 6.42–108.55, p < 0.001]. Compared with the control group, the PDT group resulted in significantly better outcomes on the SDQ (p = 0.04) but not the GSI (p = 0.18), with small between-group effect sizes (SDQ: d = 0.38, GSI: d = 0.18). However, the scores of patients treated with PDT were post-treatment no longer significantly different from normative data on the GSI and within the normal range on the SDQ. The effects in the treatment group were stable at follow-up. Furthermore, most patients were reintegrated into educational processes.
ConclusionPDT led to remarkable improvement and furthered necessary preconditions for long-term stabilization. In future, PDT should be compared to other strong active treatments.
The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan
- H. Larsson, Z. Chang, B. M. D'Onofrio, P. Lichtenstein
-
- Published online by Cambridge University Press:
- 10 October 2013, pp. 2223-2229
-
- Article
- Export citation
-
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.
MethodInformation 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.
ResultsThe 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).
ConclusionsThis 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.
Association between body mass index and mental health among Scottish adult population: a cross-sectional study of 37272 participants
- Z. Ul-Haq, D. F. Mackay, E. Fenwick, J. P. Pell
-
- Published online by Cambridge University Press:
- 25 November 2013, pp. 2231-2240
-
- Article
- Export citation
-
Background
The evidence is conflicting as to whether body mass index (BMI) is associated with mental health and, if so, to what extent it varies by sex and age. We studied mental health across the full spectrum of BMI among the general population, and conducted subgroup analyses by sex and age.
MethodWe undertook a cross-sectional study of a representative sample of the Scottish adult population. The Scottish Health Survey provided data on mental health, measured by the General Health Questionnaire-12 (GHQ), BMI, demographic and life-style information. Good mental health was defined as a GHQ score <4, and poor mental health as a GHQ score ⩾4. Logistic regression models were applied.
ResultsOf the 37 272 participants, 5739 (15.4%) had poor mental health. Overall, overweight participants had better mental health than the normal-weight group [adjusted odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87–0.99, p = 0.049], and individuals who were underweight, class II or class III obese had poorer mental health (class III obese group: adjusted OR 1.26, 95% CI 1.05–1.51, p = 0.013). There were significant interactions of BMI with sex (p = 0.013) and with age (p < 0.001). Being overweight was associated with significantly better mental health in middle-aged men only. In contrast, being underweight at all ages or obese at a young age was associated with significantly poorer mental health in women only.
ConclusionsThe adverse associations between adiposity and mental health are specific to women. Underweight women and young women who are obese have poorer mental health. In contrast, middle-aged overweight men have better mental health.
Front Cover (OFC, IFC) and matter
PSM volume 44 issue 10 Cover and Front matter
-
- Published online by Cambridge University Press:
- 10 June 2014, pp. f1-f2
-
- Article
-
- You have access Access
- Export citation