Tim M. Gale

Defining remission by cut off score on the MADRS: selecting the optimal value

BACKGROUND Remission from major depression may be conceptualised in terms of a cut-off score on an appropriate rating scale. Candidate values proposed hitherto have not been directly validated. METHOD The relationship between The Clinical Global Impression Scale for Severity (CGI-S) and the Montgomery-Asberg Depression Rating Scale (MADRS) was explored in 684 major depressed patients (1114 observations). The value on the MADRS which had greatest concordance with remission, as defined by the CGI-S, was computed using two models. Concordance between clinician and patient judgements of global illness were also compared. RESULTS AND CONCLUSION The two models yielded optimal definitions of remission of <9 and <10 on the MADRS. Either value offers a workable operationalisation of remission and there is little to choose between them. CLINICAL RELEVANCE The data confirm that MADRS <10 should provide the clinician with a valid, and reasonably objectifiable, target for remission

Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study

This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive–compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n=11) or placebo (n=10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale–Brown Obsessive–Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD.

Greater cognitive deterioration in women than men with Alzheimer's disease: A meta analysis

Studies reporting on the cognitive abilities of men and women with Alzheimers disease (AD) are surprisingly rare. We carried out a meta-analysis of neurocognitive data from 15 studies (n = 828 men; 1,238 women), which revealed a consistent male advantage on verbal and visuospatial tasks and tests of episodic and semantic memory. Moderator regression analyses showed that age, education level, and dementia severity did not significantly predict the male advantage. Reasons posited for this advantage include a reduction of estrogen in postmenopausal women, sex differences in AD pathology, and greater cognitive reserve in men.

When is category specific in Alzheimer's disease?

Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimers disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data). We examined picture naming in Alzheimers patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.

'Normal' semantic-phonemic fluency discrepancy in Alzheimer's disease? A meta-analytic study.

In a meta-analysis of 135 studies involving 6000 patients with Alzheimers disease (AD) and 6057 healthy controls, we examined the relative degree of semantic and phonemic fluency impairment in AD patients. The effect size for semantic fluency (d=2.10: 95%CI 2.22-1.97) was significantly larger than for both phonemic fluency (d=1.46: 95%CI 1.56-1.36) and picture naming (d=1.54: 95%CI 1.66-1.40). In meta-regression analyses we found that studies with greater proportions of female patients and less severe dementia both led to better phonemic fluency; while perhaps surprisingly, increased patient education led to worse semantic fluency. Critically, in 50 studies measuring both semantic and phonemic fluency, the effect size for the semantic-phonemic discrepancy scores did not differ between AD patients and controls; and was unrelated to any of the moderator variables. The latter findings indicate that the semantic-phonemic fluency discrepancy measure often reported as an important distinguishing characteristic of AD patients may be an exaggerated normal tendency.

A meta-analytic review of category naming in Alzheimer's disease

Patients with Alzheimers disease (AD) experience word-finding difficulties that become increasingly pronounced as pathological changes accrue in the brain. One question that has received increasing attention over the last two decades concerns whether the anomia in AD is category-specific, i.e. differentially affects the ability to name living things (LT) and non-living things (NLT). The current meta-analysis systematically reviewed the effect sizes for naming pictures of LT and NLT in comparisons of AD patients and healthy controls in 21 studies with over 1000 participants (557 patients and 509 healthy controls). A random effects model analysis revealed no significant difference in the large weighted effect sizes for naming pictures of LT and NLT (d=1.76 and 1.49, respectively). Moderator variable analyses revealed a significant impact of stimulus colour on the effect size for LT, indicating that using colour stimuli significantly increases the impairment of naming LT in AD patients. Additionally, we found that LT and the NLT effect sizes were larger for samples with proportionally more female patients; smaller samples produced larger LT effect sizes. In contrast, effect sizes were not significantly related to dementia severity, patient age, the number of stimuli, years of education, or the number of matching variables controlled.

Sex differences in cognitive impairment in Alzheimer’s disease

Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimers disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.

Structure and content of risk assessment proformas in mental healthcare

Background: The NSF specifies that mental health service providers should have a locally agreed proforma for assessing risk. Risk assessment proformas (RAPs) currently in use vary considerably in both structure and content. This study describes some similarities and differences. Method: We requested a copy of each provider trusts RAP. These were assessed across a range of structural characteristics, including layout, design, data coding, and were also studied for their content. Results: Some consistency was seen in the themes addressed: suicide/self harm, risk to others (notably violence) and vulnerability were well represented. Several additional themes were notable by their absence. There was general conformity in the way in which data was coded, with most using tick box categories. However, there were striking differences in layout quality and usability and many common problems were identified. Conclusions: RAPs as currently used in NHS mental-health practice vary in structure, content, length and quality. We question (i) the most common approaches in recording risk data in RAPs, and (ii) whether the focus on three domains of risk acts to neglect other, less dramatic, areas. Risk assessment procedures need to be critically evaluated and the introduction of standardized tools would be advantageous in this respect. Declaration of interest: This work was supported by NHS R&D Support funding awarded to Hertfordshire Partnership NHS Trust.

The Hatfield Image Test (HIT) : A new picture test and norms for experimental and clinical use

We present a new corpus of 147 high-quality photographic colour images (the Hatfield Image Test: HIT). Existing sets of pictorial stimuli tend to be line drawn, contain many items that are readily identifiable by healthy participants, and, therefore, have an inherent tendency towards ceiling effects in the normal population. The broad range of item difficulty and range of semantic subcategories in the HIT permits researchers to select stimuli of appropriate difficulty as required. We present naming data from 152 healthy participants. Additionally, we present mean ratings for each item on several widely used psycholinguistic variables: age of acquisition, colour diagnosticity, familiarity, name agreement (and the H statistic), visual complexity, and word frequency. These stimuli provide a useful corpus for experimental and clinical researchers.

VISUAL CROWDING AND CATEGORY SPECIFIC DEFICITS FOR PICTORIAL STIMULI : A NEURAL NETWORK MODEL

This paper describes a series of modular neural network simulations of visual object processing. In a departure from much previous work in this domain, the model described here comprises both supervised and unsupervised modules and processes real pictorial representations of items from different object categories. The unsupervised module carries out bottom-up encoding of visual stimuli, thereby developing a “perceptual” representation of each presented picture. The supervised component then classifies each perceptual representation according to a target semantic category. Model performance was assessed (1) during learning, (2) under generalisation to novel instances, and (3) after lesion damage at different stages of processing. Strong category effects were observed throughout the different experiments, with living things and musical instruments eliciting greater recognition failures relative to other categories. This pattern derives from within-category similarity effects at the level of perceptual representation and our data support the view that visual crowding can be a potentially important factor in the emergence of some category-specific impairments. The data also accord with the cascade model of object recognition, since increased competition between perceptual representations resulted in category-specific impairments even when the locus of damage was within the semantic component of the model. Some strengths and limitations of this modelling approach are discussed and the results are evaluated against some other accounts of category-specific recognition failure.