Original Articles
Trajectories of change in depression severity during treatment with antidepressants
- R. Uher, B. Muthén, D. Souery, O. Mors, J. Jaracz, A. Placentino, A. Petrovic, A. Zobel, N. Henigsberg, M. Rietschel, K. J. Aitchison, A. Farmer, P. McGuffin
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- Published online by Cambridge University Press:
- 29 October 2009, pp. 1367-1377
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Background
Response and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change.
MethodGrowth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses.
ResultsThe final two-piece growth mixture model categorized participants into a majority (75%) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results.
ConclusionsLatent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.
The functional neuroanatomy of blood-injection-injury phobia: a comparison with spider phobics and healthy controls
- X. Caseras, V. Giampietro, A. Lamas, M. Brammer, O. Vilarroya, S. Carmona, M. Rovira, R. Torrubia, D. Mataix-Cols
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- Published online by Cambridge University Press:
- 13 May 2009, pp. 125-134
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Background
Most neuroimaging studies of specific phobia have investigated the animal subtype. The blood-injection-injury (BII) subtype is characterized by a unique biphasic psychophysiological response, which could suggest a distinct neural substrate, but direct comparisons between phobia types are lacking.
MethodThis study compared the neural responses during the presentation of phobia-specific stimuli in 12 BII phobics, 14 spider (SP) phobics and 14 healthy controls using functional magnetic resonance imaging (fMRI).
ResultsSubjective ratings showed that the experimental paradigm produced the desired symptom-specific effects. As in many previous studies, when viewing spider-related stimuli, SP phobics showed increased activation in dorsal anterior cingulate and anterior insula, compared to BII phobics and healthy controls. However, when viewing images of blood-injection-injuries, participants with BII phobia mainly showed increased activation in the thalamus and visual/attention areas (occipito-temporo-parietal cortex), compared with the other two groups. The degree of provoked anxiety and disgust by phobia-relevant images was strongly associated with activation in several common regions across the two phobia groups (thalamus, cerebellum, occipito-temporal regions) but only correlated with activation in the dorsal anterior cingulate gyrus and the anterior insula in the SP phobics.
ConclusionsThese results suggest partially distinct neurobiological substrates of animal and BII phobias and support their current classification as two distinct subtypes in the DSM-IV-TR. Further research is needed to better understand the precise neurobiological mechanisms in BII phobia and particularly the fainting response.
Item response modeling of DSM-IV mania symptoms in two representative US epidemiological samples
- A. Agrawal, J. I. Nurnberger, Jr., M. T. Lynskey
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- Published online by Cambridge University Press:
- 02 December 2009, pp. 1549-1558
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Background
There is considerable debate surrounding the effective measurement of DSM-IV symptoms used to assess manic disorders in epidemiological samples.
MethodUsing two nationally representative datasets, the National Epidemiological Survey of Alcohol and Related Conditions (NESARC, n=43 093 at wave 1, n=34 653 at 3-year follow-up) and the National Comorbidity Survey – Replication (NCS-R, n=9282), we examined the psychometric properties of symptoms used to assess DSM-IV mania. The predictive utility of the mania factor score was tested using the 3-year follow-up data in NESARC.
ResultsCriterion B symptoms were unidimensional (single factor) in both samples. The symptoms assessing flight of ideas, distractibility and increased goal-directed activities had high factor loadings (0.70–0.93) with moderate rates of endorsement, thus providing good discrimination between individuals with and without mania. The symptom assessing grandiosity performed less well in both samples. The quantitative mania factor score was a good predictor of more severe disorders at the 3-year follow-up in the NESARC sample, even after controlling for a past history of DSM-IV diagnosis of manic disorder.
ConclusionsThese analyses suggest that questions based on some DSM symptoms effectively discriminate between individuals at high and low liability to mania, but others do not. A quantitative mania factor score may aid in predicting recurrence for patients with a history of mania. Methods for assessing mania using structured interviews in the absence of clinical assessment require further refinement.
Using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess the cognitive impact of electroconvulsive therapy on visual and visuospatial memory
- D. W. Falconer, J. Cleland, S. Fielding, I. C. Reid
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- Published online by Cambridge University Press:
- 24 September 2009, pp. 1017-1025
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Background
The cognitive impact of electroconvulsive therapy (ECT) is rarely measured systematically in everyday clinical practice even though patient and clinician acceptance is limited by its adverse affect on memory. If patients are tested it is often with simple paper and pencil tests of visual or verbal memory. There are no reported studies of computerized neuropsychological testing to assess the cognitive impact of ECT on visuospatial memory.
MethodTwenty-four patients with severe depression were treated with a course of bilateral ECT and assessed with a battery of visual memory tests within the Cambridge Neuropsychological Test Automated Battery (CANTAB). These included spatial and pattern recognition memory, pattern-location associative learning and a delayed matching to sample test. Testing was carried out before ECT, during ECT, within the week after ECT and 1 month after ECT.
ResultsPatients showed significant impairments in visual and visuospatial memory both during and within the week after ECT. Most impairments resolved 1 month following ECT; however, significant impairment in spatial recognition memory remained. This is one of only a few studies that have detected anterograde memory deficits more than 2 weeks after treatment.
ConclusionsPatients receiving ECT displayed a range of visual and visuospatial deficits over the course of their treatment. These deficits were most prominent for tasks dependent on the use of the right medial temporal lobe; frontal lobe function may also be implicated. The CANTAB appears to be a useful instrument for measuring the adverse cognitive effects of ECT on aspects of visual and visuospatial memory.
Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data
- M. Reis, B. Källén
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- Published online by Cambridge University Press:
- 05 January 2010, pp. 1723-1733
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Background
Concerns have been expressed about possible adverse effects of the use of antidepressant medication during pregnancy, including risk for neonatal pathology and the presence of congenital malformations.
MethodData from the Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 were used to identify women who reported the use of antidepressants in early pregnancy or were prescribed antidepressants during pregnancy by antenatal care: a total of 14 821 women with 15 017 infants. Maternal characteristics, maternal delivery diagnoses, infant neonatal diagnoses and the presence of congenital malformations were compared with all other women who gave birth, using the Mantel–Haenszel technique and with adjustments for certain characteristics.
ResultsThere was an association between antidepressant treatment and pre-existing diabetes and chronic hypertension but also with many pregnancy complications. Rates of induced delivery and caesarean section were increased. The preterm birth rate was increased but not that of intrauterine growth retardation. Neonatal complications were common, notably after tricyclic antidepressant (TCA) use. An increased risk of persistent pulmonary hypertension of the newborn (PPHN) was verified. The congenital malformation rate was increased after TCAs. An association between use of paroxetine and congenital heart defects was verified and a similar effect on hypospadias was seen.
ConclusionsWomen using antidepressants during pregnancy and their newborns have increased pathology. It is not clear how much of this is due to drug use or underlying pathology. Use of TCAs was found to carry a higher risk than other antidepressants and paroxetine seems to be associated with a specific teratogenic property.
A twin study of specific bulimia nervosa symptoms
- S. E. Mazzeo, K. S. Mitchell, C. M. Bulik, S. H. Aggen, K. S. Kendler, M. C. Neale
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- Published online by Cambridge University Press:
- 12 October 2009, pp. 1203-1213
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Background
Twin studies have suggested that additive genetic factors significantly contribute to liability to bulimia nervosa (BN). However, the diagnostic criteria for BN remain controversial. In this study, an item-factor model was used to examine the BN diagnostic criteria and the genetic and environmental contributions to BN in a population-based twin sample. The validity of the equal environment assumption (EEA) for BN was also tested.
MethodParticipants were 1024 female twins (MZ n=614, DZ n=410) from the population-based Mid-Atlantic Twin Registry. BN was assessed using symptom-level (self-report) items consistent with DSM-IV and ICD-10 diagnostic criteria. Items assessing BN were included in an item-factor model. The EEA was measured by items assessing similarity of childhood and adolescent environment, which have demonstrated construct validity. Scores on the EEA factor were used to specify the degree to which twins shared environmental experiences in this model.
ResultsThe EEA was not violated for BN. Modeling results indicated that the majority of the variance in BN was due to additive genetic factors. There was substantial variability in additive genetic and environmental contributions to specific BN symptoms. Most notably, vomiting was very strongly influenced by additive genetic factors, while other symptoms were much less heritable, including the influence of weight on self-evaluation. These results highlight the importance of assessing eating disorders at the symptom level.
ConclusionsRefinement of eating disorder phenotypes could ultimately lead to improvements in treatment and targeted prevention, by clarifying sources of variation for specific components of symptomatology.
Neural plasticity in response to attention training in anxiety
- S. Eldar, Y. Bar-Haim
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- Published online by Cambridge University Press:
- 23 July 2009, pp. 667-677
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Background
Behavioral studies show that attention training can alter threat bias, influence vulnerability to stress and reduce clinical anxiety symptoms. The aim of this study was to examine which cognitive functions of attention processing are modulated by attention training, and how a priori anxiety interacts with the attention training procedure. Specifically, we expected modulation in the P1/N1 event-related potential (ERP) complex if early spatial attention was to be affected by training and modulation in later ERP components (P2, N2, P3) had training affected top-down attentional processes.
MethodThirty anxious and 30 non-anxious adults performed a modified probe detection task. Electroencephalograms (EEGs) were recorded throughout for later ERP analyses. Half the participants in each anxiety group were randomly assigned to undergo a training procedure designed to divert their attention away from threat and the other half received placebo training.
ResultsAnxious participants who were trained to avoid threat showed a linear reduction in response time (RT) to targets replacing neutral faces with the progression of training. This change in RT was not observed among non-anxious participants or among anxious participants who were exposed to placebo training. Following training, the anxious participants who were trained to avoid threat showed a reduction in P2 and P3 mean amplitudes and an enhancement in N2 mean amplitude.
ConclusionsAttention training affects anxious participants whereas non-anxious participants seem not to respond to it. The ERP data suggest that attention training modulates top-down processes of attention control rather than processes of early attention orienting.
Randomized trial of reattribution on psychosocial talk between doctors and patients with medically unexplained symptoms
- R. Morriss, L. Gask, C. Dowrick, G. Dunn, S. Peters, A. Ring, J. Davies, P. Salmon
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- Published online by Cambridge University Press:
- 02 July 2009, pp. 325-333
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Background
In reattribution, general practitioners (GPs) request psychosocial information directly and explain medically unexplained symptoms (MUS) using psychosocial information in the consultation. We explored whether reattribution training (RT) increased the communication of psychosocial information and decreased communication about somatic intervention between GPs and their MUS patients.
MethodA cluster randomized controlled trial (RCT) of RT versus usual treatment in GPs from 16 practices and 141 patients with MUS on audio-recorded and transcribed doctor–patient communication in an index consultation. In a secondary data analysis, the Liverpool Clinical Interaction Analysis Scheme (LCIAS) was applied by an experienced rater to each turn of speech in the transcript from the index consultation blind to treatment allocation.
ResultsAfter RT, patients were more likely to disclose and discuss psychosocial problems, and propose psychosocial explanations for symptoms; around 25% of patients discussed psychosocial information extensively. In the RT group, GPs did not seek new psychosocial disclosure but they reduced advocacy for somatic intervention. After RT, GPs suggested, on average, two utterances of psychosocial explanation and six utterances of somatic intervention.
ConclusionsAfter RT, some patients discussed psychosocial issues extensively but GPs did not probe underlying psychosocial issues. They gave mixed psychosocial and somatic messages about MUS, which may have increased patients' concerns about their health. GPs should actively seek the disclosure of underlying psychosocial problems and give clear, unambiguous messages to MUS patients when they are willing to discuss psychosocial issues.
Can pharmacotherapists be too supportive? A process study of active medication and placebo in the treatment of depression
- D. R. Strunk, M. O. Stewart, S. D. Hollon, R. J. DeRubeis, J. Fawcett, J. D. Amsterdam, R. C. Shelton
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- Published online by Cambridge University Press:
- 06 November 2009, pp. 1379-1387
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Background
This study examined therapist–patient interactions during clinical management with antidepressant medication and pill-placebo.
MethodThe sample consisted of 80 patients on active medication and 40 patients in a pill-placebo condition from a randomized controlled trial for moderate to severe depression. Pharmacotherapist–patient interactions were characterized using observer ratings of the therapeutic alliance, pharmacotherapist-offered facilitative conditions, pharmacotherapist adherence to clinical management treatment guidelines and pharmacotherapist competence. Patients, therapists and raters were blind to treatment condition and outcome.
ResultsProvision of greater non-specific support (facilitative conditions) in early sessions predicted less subsequent improvement in depressive symptoms for patients receiving pill-placebo but not those receiving active medications, for which none of the process ratings predicted subsequent change. Early symptom change predicted later alliance and adherence in both conditions and therapist competence in the active condition.
ConclusionsHigher levels of support in early sessions predict poorer subsequent response among placebo patients. It remains unclear whether patients who are likely to be refractory elicit greater non-specific support or whether the provision of such support has a deleterious effect in unmedicated patients. Differences in treatment process variables between conditions late in treatment are likely to be largely a consequence of symptom relief produced by active medications.
Neural correlates of error-related learning deficits in individuals with psychopathy
- A. K. L. von Borries, I. A. Brazil, B. H. Bulten, J. K. Buitelaar, R. J. Verkes, E. R. A. de Bruijn
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- Published online by Cambridge University Press:
- 09 December 2009, pp. 1559-1568
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Background
Psychopathy (PP) is associated with a performance deficit in a variety of stimulus–response and stimulus–reinforcement learning paradigms. We tested the hypothesis that failures in error monitoring underlie these learning deficits.
MethodWe measured electrophysiological correlates of error monitoring [error-related negativity (ERN)] during a probabilistic learning task in individuals with PP (n=13) and healthy matched control subjects (n=18). The task consisted of three graded learning conditions in which the amount of learning was manipulated by varying the degree to which the response was predictive of the value of the feedback (50, 80 and 100%).
ResultsBehaviourally, we found impaired learning and diminished accuracy in the group of individuals with PP. Amplitudes of the response ERN (rERN) were reduced. No differences in the feedback ERN (fERN) were found.
ConclusionsThe results are interpreted in terms of a deficit in initial rule learning and subsequent generalization of these rules to new stimuli. Negative feedback is adequately processed at a neural level but this information is not used to improve behaviour on subsequent trials. As learning is degraded, the process of error detection at the moment of the actual response is diminished. Therefore, the current study demonstrates that disturbed error-monitoring processes play a central role in the often reported learning deficits in individuals with PP.
The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences
- F. Rice, G. T. Harold, J. Boivin, M. van den Bree, D. F. Hay, A. Thapar
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- Published online by Cambridge University Press:
- 29 May 2009, pp. 335-345
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Background
Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers' characteristics and behaviour during pregnancy which are inherited by offspring.
MethodA ‘prenatal cross-fostering’ design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother–child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed.
ResultsAssociations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother–offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother–offspring pairs and therefore was attributable to inherited factors.
ConclusionsGenetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects.
Childhood exposure to sexual abuse and partnership outcomes at age 30
- M. D. Friesen, L. J. Woodward, L. J. Horwood, D. M. Fergusson
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- Published online by Cambridge University Press:
- 05 August 2009, pp. 679-688
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Background
In this study, 30-year longitudinal data from the Christchurch Health and Development Study (CHDS) were used to examine the associations between childhood exposure to sexual abuse and intimate relationship outcomes at age 30. In addition, a broad range of early childhood and family confounding factors were tested, and the role of intervening factors from adolescence was explored.
MethodThe investigation analyzed data from a birth cohort of over 900 New Zealand adults studied to the age of 30. At ages 18 and 21 cohort members reported on any exposure to sexual abuse prior to age 16. This information, along with prospective data gathered in childhood and adolescence, was used to predict partnership outcomes at age 30.
ResultsAfter adjustment for early childhood and family factors, exposure to more severe forms of childhood sexual abuse (CSA) was associated with earlier and more frequent cohabitation, higher rates of perpetrated interpartner violence (IPV), and early parenthood, lower relationship satisfaction and investment. Several factors from adolescence partially or fully mediated these associations, notably a history of early consensual sexual intercourse, higher number of sexual partnerships, substance abuse problems, and self-esteem. After adjustment for intervening factors, exposure to CSA remained significantly associated with IPV.
ConclusionsThe findings support a causal chain process, whereby early childhood and family factors place some individuals at risk for CSA. The extent of CSA exposure is related to adolescent risk taking, which in turn leads to early and more frequent cohabitation, risk of IPV, and lower relationship satisfaction and investment.
Specificity of cognitive biases in patients with current depression and remitted depression and in patients with asthma
- A. Fritzsche, B. Dahme, I. H. Gotlib, J. Joormann, H. Magnussen, H. Watz, D. O. Nutzinger, A. von Leupoldt
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- Published online by Cambridge University Press:
- 01 September 2009, pp. 815-826
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Background
Previous studies have demonstrated a specific cognitive bias for sad stimuli in currently depressed patients; little is known, however, about whether this bias persists after recovery from the depressive episode. Depression is frequently observed in patients with asthma and is associated with a worse course of the disease. Given these high rates of co-morbidity, we could expect to observe a similar bias towards sad stimuli in patients with asthma.
MethodWe therefore examined cognitive biases in memory and attention in 20 currently and 20 formerly depressed participants, 20 never-depressed patients diagnosed with asthma, and 20 healthy control participants. All participants completed three cognitive tasks: the self-referential encoding and incidental recall task, the emotion face dot-probe task and the emotional Stroop task.
ResultsCompared with healthy participants, currently and formerly depressed participants, but not patients with asthma, exhibited specific biases for sad stimuli.
ConclusionsThese results suggest that cognitive biases are evident in depression even after recovery from an acute episode but are not found in never-depressed patients with asthma.
Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1
- A. Sistiaga, I. Urreta, M. Jodar, A. M. Cobo, J. Emparanza, D. Otaegui, J. J. Poza, J. J. Merino, H. Imaz, J. F. Martí-Massó, A. López de Munain
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- Published online by Cambridge University Press:
- 23 July 2009, pp. 487-495
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Background
Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect.
MethodWe examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders.
ResultsPatients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence.
ConclusionsBesides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.
How should DSM-V classify eating disorder not otherwise specified (EDNOS) presentations in women with lifetime anorexia or bulimia nervosa?
- K. T. Eddy, S. A. Swanson, R. D. Crosby, D. L. Franko, S. Engel, D. B. Herzog
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- Published online by Cambridge University Press:
- 05 January 2010, pp. 1735-1744
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Objective
Anorexia nervosa (AN) and bulimia nervosa (BN) are marked by longitudinal symptom fluctuations. DSM-IV-TR does not address how to classify eating disorder (ED) presentations in individuals who no longer meet full criteria for these disorders. To consider this issue, we examined subthreshold presentations in women with initial diagnoses of AN and BN.
MethodA total of 246 women with AN or BN were followed for a median of 9 years; weekly symptom data were collected at frequent intervals using the Longitudinal Interval Follow-up Evaluation of Eating Disorders (LIFE-EAT-II). Outcomes were ED presentations that were subthreshold for ⩾3 months, including those narrowly missing full criteria for AN or BN, along with binge eating disorder (BED) and purging disorder.
ResultsDuring follow-up, most women (77.6%) experienced a subthreshold presentation. Subthreshold presentation was related to intake diagnosis (Wald χ2=8.065, df=2, p=0.018). Individuals with AN most often developed subthreshold presentations resembling AN; those with BN were more likely to develop subthreshold BN. Purging disorder was experienced by half of those with BN and one-quarter of those with AN binge/purge type (ANBP); BED occurred in 20% with BN. Transition from AN or BN to most subthreshold types was associated with improved psychosocial functioning (p<0.001).
ConclusionsSubthreshold presentations in women with lifetime AN and BN were common, resembled the initial diagnosis, and were associated with modest improvements in psychosocial functioning. For most with lifetime AN and BN, subthreshold presentations seem to represent part of the course of illness and to fit within the original AN or BN diagnosis.
Psychological distress and circulating inflammatory markers in healthy young adults
- S. Goldman-Mellor, L. Brydon, A. Steptoe
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- Published online by Cambridge University Press:
- 11 March 2010, pp. 2079-2087
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Background
Although a substantial body of research points to a link between psychological distress and inflammatory responses in middle-aged and older adults, particularly those with cardiovascular disease, the relationship between inflammation and distress in young, healthy individuals has not been established. This study was designed to investigate the cross-sectional association between psychological distress and inflammatory proteins in a young, healthy representative population of English adults.
MethodParticipants were 1338 individuals aged 16–34 years from the 2006 Health Survey for England (HSE). Blood samples to measure plasma fibrinogen and high sensitivity C-reactive protein (hsCRP), as well as measures of psychological distress (using the General Health Questionnaire 12-item scale, GHQ-12) and covariates, were collected during home visits. Linear regression was used to assess the relationship between psychological distress and fibrinogen and hsCRP.
ResultsHigher self-rated distress was positively associated with fibrinogen level in this young population, independently of age, sex, ethnicity, body mass index (BMI), high density lipoprotein (HDL) cholesterol, smoking, and alcohol and medication use (β=0.024, p<0.01). Psychological distress was not related to hsCRP.
ConclusionsPsychological distress may negatively impact inflammatory processes in young adulthood before the onset of chronic health problems such as hypertension and cardiovascular disease. Longitudinal research is needed to elucidate the relationship between distress and inflammation in young adults and its significance for later disease states.
Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer's disease
- B. Schmand, H. M. Huizenga, W. A. van Gool
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- Published online by Cambridge University Press:
- 29 October 2009, pp. 135-145
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Background
Abnormal levels of biomarkers in cerebrospinal fluid (CSF) and atrophy of medial temporal lobe (MTL) structures on magnetic resonance imaging (MRI) are being used increasingly to diagnose early Alzheimer's disease (AD). We evaluated the claim that these biomarkers can detect preclinical AD before behavioural (i.e. memory) symptoms arise.
MethodWe included all relevant longitudinal studies of CSF and MRI biomarkers published between January 2003 and November 2008. Subjects were not demented at baseline but some declined to mild cognitive impairment (MCI) or to AD during follow-up. Measures of tau and beta-amyloid in CSF, MTL atrophy on MRI, and performance on delayed memory tasks were extracted from the papers or obtained from the investigators.
ResultsTwenty-one MRI studies and 14 CSF studies were retrieved. The effect sizes of total tau (t-tau), phosphorylated tau (p-tau) and amyloid beta 42 (aβ42) ranged from 0.91 to 1.11. The effect size of MTL atrophy was 0.75. Memory performance had an effect size of 1.06. MTL atrophy and memory impairment tended to increase when assessed closer to the moment of diagnosis, whereas effect sizes of CSF biomarkers tended to increase when assessed longer before the diagnosis.
ConclusionsMemory impairment is a more accurate predictor of early AD than atrophy of MTL on MRI, whereas CSF abnormalities and memory impairment are about equally predictive. Consequently, the CSF and MRI biomarkers are not very sensitive to preclinical AD. CSF markers remain promising, but studies with long follow-up periods in elderly subjects who are normal at baseline are needed to evaluate this promise.
Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study
- T. Sobanski, G. Wagner, G. Peikert, U. Gruhn, K. Schluttig, H. Sauer, R. Schlösser
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- Published online by Cambridge University Press:
- 08 January 2010, pp. 1879-1886
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Background
With regard to current neurobiological theories, the aim of our study was to examine possible alterations of temporal and frontal lobe volume in panic disorder (PD).
MethodSeventeen in-patients with PD and a group of healthy control subjects (HC) matched for age and gender were investigated by quantitative volumetric magnetic resonance imaging (MRI). Structures of interest were: the temporal lobe, the amygdala–hippocampus complex (AHC) and the frontal lobe. In addition, a voxel-based morphometry (VBM) analysis implemented in Statistical Parametric Mapping 5 (SPM5) was used for a more detailed assessment of possible volume alterations. Modulated grey matter (GM) images were used to test our a priori hypotheses and to present the volumetric results.
ResultsQuantitative volumetric MRI revealed a bilateral reduction in temporal lobe volume in patients with PD compared to HC subjects. The AHC was normal. The right frontal lobe volume was also decreased. Using VBM we detected a significant GM volume reduction in the right middle temporal gyrus [Brodmann area (BA) 21] in patients with PD. In addition, there was a reduction in GM volume in the medial part of the orbitofrontal cortex (BA 11).
ConclusionsOur results of reduced temporal and frontal lobe volume in PD are in agreement with prior studies. By using a recent VBM approach we were able to assess the abnormalities more precisely. The location of GM volume reduction in the right middle temporal gyrus and medial orbitofrontal cortex lends further support to recent aetiological models of PD.
Support for the mutual maintenance of pain and post-traumatic stress disorder symptoms
- A. Liedl, M. O'Donnell, M. Creamer, D. Silove, A. McFarlane, C. Knaevelsrud, R. A. Bryant
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- Published online by Cambridge University Press:
- 08 October 2009, pp. 1215-1223
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Background
Pain and post-traumatic stress disorder (PTSD) are frequently co-morbid in the aftermath of a traumatic event. Although several models attempt to explain the relationship between these two disorders, the mechanisms underlying the relationship remain unclear. The aim of this study was to investigate the relationship between each PTSD symptom cluster and pain over the course of post-traumatic adjustment.
MethodIn a longitudinal study, injury patients (n=824) were assessed within 1 week post-injury, and then at 3 and 12 months. Pain was measured using a 100-mm Visual Analogue Scale (VAS). PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS). Structural equation modelling (SEM) was used to identify causal relationships between pain and PTSD.
ResultsIn a saturated model we found that the relationship between acute pain and 12-month pain was mediated by arousal symptoms at 3 months. We also found that the relationship between baseline arousal and re-experiencing symptoms, and later 12-month arousal and re-experiencing symptoms, was mediated by 3-month pain levels. The final model showed a good fit [χ2=16.97, df=12, p>0.05, Comparative Fit Index (CFI)=0.999, root mean square error of approximation (RMSEA)=0.022].
ConclusionsThese findings provide evidence of mutual maintenance between pain and PTSD.
Separation of genetic influences on attention deficit hyperactivity disorder symptoms and reaction time performance from those on IQ
- A. C. Wood, P. Asherson, J. J. van der Meere, J. Kuntsi
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- Published online by Cambridge University Press:
- 15 September 2009, pp. 1027-1037
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Background
Attention deficit hyperactivity disorder (ADHD) shows a strong phenotypic and genetic association with reaction time (RT) variability, considered to reflect lapses in attention. Yet we know little about whether this aetiological pathway is shared with other affected cognitive processes in ADHD, such as lower IQs or the generally slower responses (mean RTs). We aimed to address the question of whether a shared set of genes exist that influence RT variability, mean RT, IQ and ADHD symptom scores, or whether there is evidence of separate aetiological pathways.
MethodMultivariate structural equation modelling on cognitive tasks data (providing RT data), IQ and ADHD ratings by parents and teachers collected on general population sample of 1314 twins, at ages 7–10 years.
ResultsMultivariate structural equation models indicated that the shared genetic influences underlying both ADHD symptom scores and RT variability are also shared with those underlying mean RT, with both types of RT data largely indexing the same underlying liability. By contrast, the shared genetic influences on ADHD symptom scores and RT variability (or mean RT) are largely independent of the genetic influences that ADHD symptom scores share with IQ.
ConclusionsThe finding of unique aetiological pathways between IQ and RT data, but shared components between mean RT, RT variability and ADHD symptom scores, illustrates key influences in the genetic architecture of the cognitive and energetic processes that underlie the behavioural symptoms of ADHD. In addition, the multivariate genetic model fitting findings provide valuable information for future molecular genetic analyses.