Konstantine K. Zakzanis

Neurocognitive deficit in schizophrenia: a quantitative review of the evidence.

The neurocognitive literature on test performance in schizophrenia is reviewed quantitatively. The authors report 22 mean effect sizes from 204 studies to index schizophrenia versus control differences in global and selective verbal memory, nonverbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language, and interhemispheric tactile-transfer test performance. Moderate to large raw effect sizes (d > .60) were obtained for all 22 neurocognitive test variables, and none of the associated confidence intervals included zero. The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.

Neurocognitive deficits in cocaine users: a quantitative review of the evidence.

Studies on the neurocognitive effects of cocaine abuse are equivocal with respect to the specific types of deficits observed, although the vast majority of studies indicate that at least some deficits in certain broad functions such as attention, learning and memory, executive functions, and response speed exist. All of these studies based their results on null hypothesis statistical significance testing (NHSST). It is argued that effect size analysis, which provides information about the magnitude of difference, offers a more valid index of cognitive impairments in a population when compared to NHSST. Accordingly, the objective of the current study was to conduct an effect size analysis (or a meta-analysis in cases where the same test measure was utilized in more than one study) to determine the type and the magnitude of the specific cognitive deficits found as a result of cocaine use. Effect sizes were calculated for each test variable across 15 empirical studies that met inclusion criteria. The results from 481 cocaine users and 586 healthy normal controls revealed that cocaine use had the largest effect on several measures of attention (0.40 0.50) were also obtained on tests of visual memory and working memory. Minimal effect sizes (d<0.30) were obtained on tests of verbal fluency and other language functions and sensory-perceptual functions. Tests of executive functioning produced mixed findings and were interpreted in terms of degree rather than nature of impairment. The results are consistent with findings from neuroimaging and neurochemical studies that have found cocaine use to be associated with dysfunctions in the anterior cingulate gyrus and orbitofrontal cortex; these regions are highly implicated in the mediation of attentional and executive functions, respectively. Methodological limitations of the empirical studies included in the analysis are discussed.

Further parameters of insight and neuropsychological deficit in schizophrenia and other chronic mental disease.

Evidence has begun to accumulate which suggests that lack of awareness of illness in schizophrenia is related to and possibly the result of a cognitive deficit involving prefrontal cerebral dysfunction. This study further explores this relationship along with other domains of self-awareness in chronic schizophrenics and other subjects with serious mental disorders. One hundred eight schizophrenics and 21 bipolar subjects from three separate sites in Britain, Germany, and Canada were administered the Wisconsin Card Sorting Test and three measures of self-awareness. Lack of illness awareness and other domains of self-knowledge were significantly more related to poorer neuropsychological performance in schizophrenia patients than in the other subjects. The results support the hypothesis that lack of illness awareness is related to defective frontal lobe functioning as indexed by neuropsychological measures.

Distinct Neurocognitive Profiles in Multiple Sclerosis Subtypes

An effect size analysis was used to review the neuropsychological literature of multiple sclerosis (MS) to determine whether reliable neurocognitive test deficits and differences between chronic-progressive and relapse-remitting subtypes are apparent. Studies dating back to 1983 were gathered and the neuropsychological test results from a total of 1,845 patients with MS, and 1,265 healthy controls, were synthesized using meta-analytic principles. The results indicate that neurocognitive impairment is indeed evident in patients with MS on a number of cognitive tasks and test variables. Secondly, distinct patterns of neurocognitive deficits are evident in chronic-progressive and relapse-remitting subtypes of MS. Finally, relations between neurocognitive impairment and clinical and demographic attributes of patients with MS were revealed.

Memory impairment in abstinent MDMA (“Ecstasy”) users: A longitudinal investigation

To examine the neurotoxic potential of continued MDMA (“Ecstasy”) use in humans and its functional consequences over the course of 1 year, 15 MDMA users participated in a longitudinal study in which they completed a brief neuropsychological test battery composed mainly of retrospective and prospective memory tasks. Subjects were abstinent for 2 weeks on initial and 1-year testing. Continued use of MDMA was associated with progressive decline in terms of immediate and delayed recall.

Incentive motivation deficits in schizophrenia reflect effort computation impairments during cost-benefit decision-making

BACKGROUND Motivational impairments are a core feature of schizophrenia and although there are numerous reports studying this feature using clinical rating scales, objective behavioural assessments are lacking. Here, we use a translational paradigm to measure incentive motivation in individuals with schizophrenia. METHODS Sixteen stable outpatients with schizophrenia and sixteen matched healthy controls completed a modified version of the Effort Expenditure for Rewards Task that accounts for differences in motoric ability. Briefly, subjects were presented with a series of trials where they may choose to expend a greater amount of effort for a larger monetary reward versus less effort for a smaller reward. Additionally, the probability of receiving money for a given trial was varied at 12%, 50% and 88%. Clinical and other reward-related variables were also evaluated. RESULTS Patients opted to expend greater effort significantly less than controls for trials of high, but uncertain (i.e. 50% and 88% probability) incentive value, which was related to amotivation and neurocognitive deficits. Other abnormalities were also noted but were related to different clinical variables such as impulsivity (low reward and 12% probability). These motivational deficits were not due to group differences in reward learning, reward valuation or hedonic capacity. CONCLUSIONS Our findings offer novel support for incentive motivation deficits in schizophrenia. Clinical amotivation is associated with impairments in the computation of effort during cost-benefit decision-making. This objective translational paradigm may guide future investigations of the neural circuitry underlying these motivational impairments.

A Meta-Analysis of Structural and Functional Brain Imaging in Dementia of the Alzheimer's Type: A Neuroimaging Profile

We conducted a quantitative review of the imaging literature using meta-analytic methodology to characterize further the magnitude of hippocampal deficit in probable Alzheimers disease (AD) and to determine whether other neuroanatomic structures in AD can better discriminate the disease from normal aging. Additionally, we parceled the discriminability of neuroanatomic structures by duration of disease to determine those structures most sensitive to AD in its early and late stages. One hundred twenty-one studies published between 1984 and 2000 met criteria for inclusion in the present analysis. In total, structural (i.e., CT and MRI) and functional (i.e., SPECT and PET) neuroimaging results from 3511 patients with AD, and 1632 normal healthy controls were recorded across meta-analyses. Our results include neuroimaging profiles for both early onset and longer duration patients with AD. In sum, these profiles yield a signature of diagnostic markers in both cortical and subcortical neuroanatomic areas. This signature is consistent with the clinical phenomenology of Alzheimers dementia and should aid in the positive identification of AD.

Dopamine D2 densities and the schizophrenic brain

Meta-analytic methods were used to test the D2 dopamine density hypothesis in schizophrenia. Post-mortem as well as in-vivo (i.e., PET and SPECT) neuroimaging studies that met criteria for inclusion into the meta-analysis were gathered from 1980 to 1996. The mean effect size across studies corresponds to an effect size of 1.47 (d). Although large, the effect size obtained does not meet heuristic benchmark criteria that would suggest D2 density increases to be a marker for schizophrenia. That is, roughly 30% of patients with schizophrenia could not be discriminated from normal healthy controls. Based on the findings, it is argued that D2 density receptor increases in patients with schizophrenia, although a reliable finding in many patients (i.e., approximately 70%), is not a specific or consistent marker for schizophrenia.

The effects of cannabis use on neurocognition in schizophrenia: A meta-analysis

Patients with schizophrenia frequently report cannabis use, yet its effects on neurocognitive functioning in this population are still unclear. This meta-analysis was conducted to determine the magnitude of effect of cannabis consumption on cognition in schizophrenia without the confounding effects of other co-morbid substance use disorders. Eight studies met inclusion criteria yielding a total sample of 942. Three hundred and fifty six of these participants were cannabis users with schizophrenia, and 586 were patients with no cannabis use. Neuropsychological tests were grouped into seven domains (general cognitive ability and intelligence; selective, sustained and divided attention; executive abilities; working memory and learning; retrieval and recognition; receptive and expressive language abilities and visuo-spatial and construction abilities). Effect sizes were computed for each cognitive domain between cannabis-using patients and patients with no history of cannabis use. Effect size differences in cognitive performance in the schizophrenia group as a function of cannabis use were in the small to medium range, denoting superior performance in cannabis-using patients. Explanations for these findings are discussed and suggestions for future research in this area are recommended.

Amygdala and hippocampal volume reductions as candidate endophenotypes for borderline personality disorder: A meta-analysis of magnetic resonance imaging studies

Borderline personality disorder (BPD) is a genetically influenced psychiatric illness with disruptions in neural systems supporting cognition and emotion regulation. Volumetric decreases of the hippocampus and amygdala may characterize BPD and serve as putative endophenotypes for the illness. The purpose of the present study was to evaluate whether the magnitude of these volume reductions and their associations with state-of-illness factors and psychiatric disorders which often co-occur with BPD warrant their consideration as potential endophenotypes. Volumetric magnetic resonance imaging results from 11 studies comprising 205 BPD patients and 222 healthy controls were quantitatively synthesized using meta-analytic techniques. Patients showed an average 11% and 13% decrease in the size of the hippocampus and amygdala, respectively. These volumetric differences were not attenuated in patients being treated with psychotropic medications. Comorbid depression, post-traumatic stress disorder, and substance use disorders were unrelated to volumetric decreases in either structure. These findings suggest modest volume reductions of the amygdala and hippocampus bilaterally in BPD which cannot be attributed to illness state or comorbid psychopathology. Decreased volumes of these key limbic structures may hold promise as candidate endophenotypes for BPD.