Keith R. Laws

Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies.

Objective:  Hypofrontality is not a well‐replicated finding in schizophrenia either at rest or under conditions of task activation.

Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials

BACKGROUND Although cognitive behavioural therapy (CBT) is claimed to be effective in schizophrenia, major depression and bipolar disorder, there have been negative findings in well-conducted studies and meta-analyses have not fully considered the potential influence of blindness or the use of control interventions. METHOD We pooled data from published trials of CBT in schizophrenia, major depression and bipolar disorder that used controls for non-specific effects of intervention. Trials of effectiveness against relapse were also pooled, including those that compared CBT to treatment as usual (TAU). Blinding was examined as a moderating factor. RESULTS CBT was not effective in reducing symptoms in schizophrenia or in preventing relapse. CBT was effective in reducing symptoms in major depression, although the effect size was small, and in reducing relapse. CBT was ineffective in reducing relapse in bipolar disorder. CONCLUSIONS CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates. It is effective in major depression but the size of the effect is small in treatment studies. On present evidence CBT is not an effective treatment strategy for prevention of relapse in bipolar disorder.

A Meta-analytic Review of Wisconsin Card Sort Studies in Schizophrenia: General Intellectual Deficit in Disguise?

A majority of studies show that schizophrenics perform poorly on so-called tests of executive or frontal lobe function--the paradigmatic case being the Wisconsin Card Sort Test (WCST). Nevertheless, the specific character of this deficit in schizophrenia remains underspecified. In particular, it seems premature to assume that schizophrenia is characterised by an executive dysfunction and/or a disorder of frontal lobe function before determining whether any deficit is: selective; disproportionate to the general level of intellectual functioning; or qualitatively comparable with that of frontal lobe patients. A meta-analysis was conducted on 29 studies comparing the performance of schizophrenics and normal controls on the WCST. This showed that the mean weighted effect size was large for categories achieved (d = 0.91), medium for absolute level of perseveration (d = 0.53), but only small for the proportion of perseverative errors (d = 0.18). By contrast, the effect size for Wechsler Adult Intelligence Scale Intelligence Quotient (WAIS IQ) in a subset of these studies (d = 1.23) was significantly larger than for any WCST measures. This pattern of findings challenges notions that schizophrenia is characterised by an executive dysfunction that is: selective; disproportionate to IQ level; and analogous to that found in frontal lobe patients. Rather, the poor WCST performance of schizophrenics appears to reflect a generalised intellectual deficit.

Semantic priming in schizophrenia: systematic review and meta-analysis

BACKGROUND Increased semantic priming is an influential theory of thought disorder in schizophrenia. However, studies to date have had conflicting findings. AIMS To investigate semantic memory in patients with schizophrenia with and without thought disorder. METHOD Data were pooled from 36 studies comparing patients with schizophrenia and normal controls in semantic priming tasks. Data from 18 studies comparing patients with thought disorder with normal controls, and 13 studies comparing patients with and without thought disorder were also pooled. RESULTS There was no support for altered semantic priming in schizophrenia as a whole. Increased semantic priming in patients with thought disorder was supported, but this was significant only in comparison with normal controls and not in comparison with patients without thought disorder. Stimulus onset asynchrony (SOA) and general slowing of reaction time moderated the effect size for priming in patients with thought disorder. CONCLUSIONS Meta-analysis provides qualified support for increased semantic priming as a psychological abnormality underlying thought disorder. However, the possibility that the effect is an artefact of general slowing of reaction time in schizophrenia has not been excluded.

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.

Illusions of normality: a methodological critique of category-specific naming.

Category-specific disorders are perhaps the archetypal example of domain-specificity--being typically defined by the presence of dissociations between living and nonliving naming ability in people following neurological damage. The methods adopted to quantify naming across categories are therefore pivotal since they provide the criterion for defining whether patients have a category effect and necessarily influence the subsequent direction and the interpretation of testing. This paper highlights a series of methodological concerns relating to how we measure and define category (or any) dissociations. These include the common failure to include control data or the use of control data that is inappropriate e.g. at ceiling, unmatched. A review of past cases shows that the overwhelming majority suffers from these problems and therefore challenges conclusions about the purported empirical demonstrations of dissociations and double dissociations in the category specific literature. This is not a refutation of category deficits, but skepticism about the current existence of any convincing empirical demonstrations of category specific double dissociations. As a potential solution, certain minimal criteria are proposed that might aid with the attempt to document category effects that are more methodologically convincing.

Testing for a deficit in single-case studies : Effects of departures from normality

In neuropsychological single-case research inferences concerning a patients cognitive status are often based on referring the patients test score to those obtained from a modestly sized control sample. Two methods of testing for a deficit (z and a method proposed by Crawford and Howell [Crawford, J. R. & Howell, D. C. (1998). Comparing an individuals test score against norms derived from small samples. The Clinical Neuropsychologist, 12, 482-486]) both assume the control distribution is normal but this assumption will often be violated in practice. Monte Carlo simulation was employed to study the effects of leptokurtosis and the combination of skew and leptokurtosis on the Type I error rates for these two methods. For Crawford and Howells method, leptokurtosis produced only a modest inflation of the Type I error rate when the control sample N was small-to-modest in size and error rates were lower than the specified rates at larger N. In contrast, the combination of leptokurtosis and skew produced marked inflation of error rates for small Ns. With a specified error rate of 5%, actual error rates as high as 14.31% and 9.96% were observed for z and Crawford and Howells method respectively. Potential solutions to the problem of non-normal data are evaluated.

The use of ketamine as an antidepressant: a systematic review and meta-analysis

The current meta‐analysis examines the effects of ketamine infusion on depressive symptoms over time in major depressive disorder (MDD) and bipolar disorder (BD).

The neuropsychology of the schizo-obsessive subtype of schizophrenia: a new analysis

BACKGROUND Interest in the neuro-cognitive profile of patients with schizophrenia and co-morbid obsessive compulsive disorder (schizo-OCD) is rising in response to reports of high co-morbidity rates. Whereas schizophrenia has been associated with global impairment in a wide range of neuro-cognitive domains, OCD is associated with specific deficits featuring impaired performance on tasks of motor and cognitive inhibition involving frontostriatal neuro-circuitry. METHOD We compared cognitive function using the CANTAB battery in patients with schizo-OCD (n=12) and a schizophrenia group without OCD symptoms (n=16). The groups were matched for IQ, gender, age, medication, and duration of illness. RESULTS The schizo-OCD patients made significantly more errors on a task of attentional set-shifting (ID-ED set-shift task). By contrast, no significant differences emerged on the Stockings of Cambridge task, the Cambridge Gamble Task or the Affective Go/NoGo tasks. No correlation emerged between ID-ED performance and severity of schizophrenia, OCD or depressive symptoms, consistent with neurocognitive impairment holding trait rather than state-marker status. Schizo-obsessives also exhibited a trend toward more motor tics emphasizing a neurological contribution to the disorder.ConclusionOur findings reveal a more severe attentional set-shifting deficit and neurological abnormality that may be fundamental to the neuro-cognitive profile of schizo-OCD. The clinical implications of these impairments merit further exploration in larger studies.

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.