Neurocognitive Deficits In Schizophrenia Research Articles

Cognitive remediation for schizophrenia: Clinician perspectives on implementation barriers and facilitators.

Neurocognitive deficits in schizophrenia have a major impact on functioning; however, they remain poorly targeted by available treatment offerings. Cognitive remediation (CR) is effective in improving neurocognition and functioning. Despite clinical guidelines for schizophrenia recommending CR, it is still not readily available in clinical services and sizeable attrition rates are reported in clinical trials. To elucidate the barriers and facilitators of CR access and engagement, we conducted a mixed methods qualitative-dominant study with 12 clinicians in Australia, in 2021, with 1 hr interviews and additional rating scales completed. Thematic analysis highlighted four themes (cognitive symptoms, CR intervention, motivation and engagement in CR, and CR implementation), and 14 subthemes. Clinicians emphasized the broad impact of cognitive deficits and outlined pros and cons of different CR approaches. Several factors were suggested as impacting engagement, including motivation assessments/techniques, neurocognitive insight, illness, and demographic factors. Lack of routine implementation in Australia was unanimously espoused and partly explained by a need for cost-effectiveness analyses, remote and flexible delivery, and increasing service resource provision and staff training in CR. This study offers key insights into CR access, while recommending methods for optimizing CR implementation and dissemination to improve recovery outcomes of people diagnosed with schizophrenia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gender-related Characteristics of Oxidative Stress Severity and Cognitive Impairment in Patients With Schizophrenia.

The gender specificity of the clinical and psychopathological features of schizophrenia is an important factor in this disease. Gender features of neurocognitive deficit in schizophrenia and associated functional and structural disorders of the brain activity are of particular interest to researchers. There are several potential pathogenetic factors of this disease associated with gender, one of which is considered to be oxidative stress. Stress-induced cell death in the prefrontal and anterior frontal regions and reduced brain volume in these regions lead to cognitive and executive decline in patients with schizophrenia. Despite the great interest in the gender factor in schizophrenia pathogenesis, there are currently very few studies on gender differences in the severity of redox imbalance in patients with schizophrenia and their association with neurocognitive deficit.The aim of the study was to reveal the gender specificity of oxidative stress severity in patients with schizophrenia and assess its association with the severity of neurocognitive deficit.The study included 125 patients with schizophrenia and 75 sex- and age-matched healthy volunteers. Sociodemographic and clinical data were studied. Cognitive functions were evaluated using BACS. Blood samples were taken for biochemical studies of the levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) in erythrocyte hemolysate, malonic dialdehyde (MDA), aldehyde-2,4-dinitrophenylhydrazones (ADNPH), ketone-2,4-dinitrophenylhydrazones (KDNPH) in plasma. Levels of oxidative stress markers were assessed by spectrophotometric method.In a sample of patients with schizophrenia, a statistically significantly higher activity of CAT was revealed among women compared to men (T=2.25; p=0.025), however, it was lower than in healthy volunteers. But, at the same time, a higher concentration of protein peroxidation products was found in the peripheral blood of women than in men (ADNPH MCO: T=2.52; p=0.013; KDNPH MCO: Z=-2.26; p=0.017). In the group of healthy volunteers, in contrast to patients with schizophrenia, gender differences in markers of oxidative stress were not found. In women with schizophrenia, single correlations were found between the level of the lipid peroxidation product MDA and the test scores for verbal memory (R=-0.36; p=0.006) and working memory (R=-0.36; p=0.006), antioxidant enzyme activity SOD and motor skills (R=-0.26; p=0.047). In men, on the contrary, multiple correlations of both antioxidants and, mainly, products of lipid and protein peroxidation with cognitive functions assessed using BACS were found.Despite the fact that oxidative stress is more pronounced in women than in men with schizophrenia, associations of redox imbalance with neurocognitive deficit in women is much less pronounced than in men.

Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST) as a screening tool for evaluation of cognitive deficits in schizophrenia

Cognitive deficit is one of the core features of schizophrenia and is associated with poor functional outcomes. There is a lack of validated criteria to screen and monitor cognitive deficits in schizophrenia. This study aimed to evaluate the concurrent validity and sensitivity of MoCA (Montreal Cognitive Assessment) and DSST (Digit Symbol Substitution Test) in identifying cognitive deficits in Schizophrenia comparing with a comprehensive MCCB [MATRICS (Measurement And Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery] equivalent battery. We did clinical and cognitive assessments on 30 patients with schizophrenia and 30 age and gender-matched healthy controls. The Cronbach's Alpha of MoCA was 0.839, and on adding the DSST, it increased to 0.859. In stepwise binary logistic regression, adding DSST to MoCA improved the prediction of cognitive impairment as defined by a comprehensive battery with 86.7% classification accuracy. Receiver operating characteristic curve analysis suggested a score of 25 of MoCA and 59 of DSST as an optimal cut-off in identifying severe cognitive deficits with an additional MoCA cut-off of 27 for identifying mild cognitive deficits. Combined MoCA and DSST is a sensitive and quick method to screen for neurocognitive deficits in schizophrenia.

P.0890 A systematic review on relationship between EEG indices and neurocognitive deficits in schizophrenia

P.0890 A systematic review on relationship between EEG indices and neurocognitive deficits in schizophrenia

Dynamics and synchronization control in schizophrenia for EEG signals

Cognitive dysfunction may be central to neurocognitive deficits in schizophrenia. To further explore brain network dynamics and synchronization in first-episode schizophrenia, we exploited pinning control theory to adjust and control the brain regions interacting with each other in schizophrenia to make their network synchronization stability consistent with that of healthy individuals. Our results revealed that in a short-term memory task, the right frontal lobe was abnormal in schizophrenia, resulting in higher synchronous oscillation behavior of the entire brain networks compared with the healthy participants. And the synchronization was positively correlated with each participant’s response time (RT) and negatively correlated with their response accuracy (ACC). In the healthy participants, the frontal lobe facilitated a higher brain synchronization state, whereas in the schizophrenia patients, the parietal-occipital lobe facilitated a higher brain synchronization state. These data provide new evidence for task-relevant dynamic interactions between brain regions in schizophrenia and provide theoretical methods for the adjustment and control of brain networks.

Специфика нарушений процессов зрительного восприятия и мышления и их взаимосвязь с функциональным состоянием магно-и парвоцеллюлярных нейронных систем при шизофрении

The article examines the relationship between cognitive processes of perception and thinking in schizophrenia. An analysis of the functional state of the magnocellular and parvocellular visual systems, the specificity of their interaction was carried out. New data were obtained on the relationship between the mechanisms of global and local analysis of visual information and cognitive impairments in schizophrenia. The contribution of magnocellular and parvocellular systems (mechanisms of global and local analysis) in the implementation of the thinking processes has been discovered. It has been established that the activity of the magnocellular system is associated with the processes of abstraction and generalization. However, hyperactivation of the magnocellular system leads to a violation of the selectivity and goal setting in the thinking process. A decrease in the activity of the parvocellular system in patients with schizophrenia leads to distortions of the generalization process, an increase in the number of “latent” signs in the thinking process. The study obtained results that allow us to state that early sensory deficits are closely interrelated with the level and nature of the functioning of more highly organized cognitive processes. Sensory deficits identified in schizophrenia lead to higher-level cognitive deficits and are a key link in the structure of neurocognitive deficits in schizophrenia.

P.552 Acylcarnitine levels in paranoid schizophrenia with metabolic syndrome during treatment of second-generation antipsychotics

Individuals with schizophrenia have been found to display neurocognitive deficits on the order of 1 standard deviation below the mean of healthy controls on a range of cognitive domains, with no clear pattern of deficits that characterizes the majority of individuals with schizophrenia. Such findings have led some to suggest that schizophrenia is characterized by a “generalized” neurocognitive deficit, implying that a common underlying etiology impacts all cognitive domains. Central nervous system accounts of the generalized deficit have been proposed (e.g., NMDA and GABA interneuron receptor dysfunction); however, there may also be more diffuse “general systems” abnormalities that affect brain function. The current study evaluated the role of one type of general systems abnormality, metabolic dysfunction, on global cognitive functioning in a sample of outpatients with schizophrenia (n = 27) and demographically matched healthy controls (n = 33). Participants completed a battery of neuropsychological tests, as well as metabolic measurements to assess blood glucose, blood pressure, and abdominal obesity. Results indicated that higher pulse pressure predicted the generalized neurocognitive deficit in schizophrenia, but not healthy controls; however, blood glucose and abdominal obesity did not predict cognitive performance in either group. These findings provide support for the role of metabolic abnormalities in the generalized neurocognitive deficit in schizophrenia, and suggest that treatment of hypertension may be a novel adjunctive treatment target for remediating cognitive deficits in schizophrenia.

The impact of neurocognition on mentalizing in euthymic bipolar disorder versus schizophrenia

ABSTRACT Introduction: Theory of mind (ToM) or mentalizing deficits have been found in schizophrenia (SZ) and bipolar disorder (BD), but their relationships to patients’ coexistent neurocognitive deficits are still unclear. The present study aimed to explore the possible differential involvement of neurocognitive deficits in ToM impairments in SZ and euthymic BD. Methods: Fifty-three euthymic patients with BD type I, 54 clinically stable patients with SZ, and 53 healthy participants were assessed with an advanced ToM task (Faux Pas Recognition Test) which measures cognitive and affective ToM components, and a comprehensive battery of neuropsychological measures. The three groups were matched for gender, age and education. Results: Patients with BD showed significant impairment, comparable to that in SZ, only in the cognitive facet of ToM, whereas SZ patients had significantly poorer performance than both BD patients and healthy participants in overall and affective ToM. In both SZ and euthymic BD, ToM performance was related to deficits in particular cognitive functions. After controlling for coexistent neurocognitive deficits, overall and affective ToM in SZ were still impaired whereas the cognitive ToM impairment in BD and SZ did not remained statistically significant. Conclusions: Our findings suggest a different profile of ToM deficits between SZ and BD and an independence of ToM dysfunction from concurrent neurocognitive deficits in SZ but not in BD.

Lateralized evoked responses in parietal cortex demonstrate visual short-term memory deficits in first-episode schizophrenia

Working memory dysfunction may be central to neurocognitive deficits in schizophrenia. Maintenance of visual information in working memory, or visual short-term memory (vSTM), is linked to general cognitive dysfunction and predicts functional outcome. Lateralized change-detection tasks afford investigation of the contralateral delay activity (CDA), a useful tool for investigating vSTM dysfunction. Previous work suggests “hyperfocusing” of attention in schizophrenia, such that CDA is increased when a single item is maintained in vSTM but reduced for multiple items. If observed early in the disease, vSTM dysfunction may be a key feature of schizophrenia or target for intervention. We investigated CDA during lateralized vSTM of one versus three items using sensor-level electroencephalography and source-level magnetoencephalography in 26 individuals at their first episode of schizophrenia-spectrum psychosis (FESz) and 26 matched healthy controls. FESz were unable to modulate CDA with increased memory load – high-load CDA was reduced and low-load CDA was increased compared to controls. Further, sources of CDA in posterior parietal cortex were reduced in FESz and indices of working memory were correlated with neurocognitive deficits and symptom severity. These results support working memory maintenance dysfunction as a central and early component to the disorder. Targeted intervention focusing on vSTM deficits may be warranted to alleviate downstream effects of this disability.

A new look at the genetics of neurocognitive deficits in schizophrenia

The article presents current literature data on genetic studies of neurocognitive deficit in schizophrenia, including the genes of neurotransmitter systems (dopaminergic, glutamatergic, and serotonergic); genes analyzed in genome-wide association studies (GWAS), as well as other genetic factors related to the pathophysiological mechanisms underlying schizophrenia and neurocognitive disorders.

Functional network connectivity impairments and core cognitive deficits in schizophrenia.

Cognitive deficits contribute to functional disability in patients with schizophrenia and may be related to altered functional networks that serve cognition. We evaluated the integrity of major functional networks and assessed their role in supporting two cognitive functions affected in schizophrenia: processing speed (PS) and working memory (WM). Resting-state functional magnetic resonance imaging (rsfMRI) data, N = 261 patients and 327 controls, were aggregated from three independent cohorts and evaluated using Enhancing NeuroImaging Genetics through Meta Analysis rsfMRI analysis pipeline. Meta- and mega-analyses were used to evaluate patient-control differences in functional connectivity (FC) measures. Canonical correlation analysis was used to study the association between cognitive deficits and FC measures. Patients showed consistent patterns of cognitive and resting-state FC (rsFC) deficits across three cohorts. Patient-control differences in rsFC calculated using seed-based and dual-regression approaches were consistent (Cohen's d: 0.31 ± 0.09 and 0.29 ± 0.08, p < 10-4 ). RsFC measures explained 12-17% of the individual variations in PS and WM in the full sample and in patients and controls separately, with the strongest correlations found in salience, auditory, somatosensory, and default-mode networks. The pattern of association between rsFC (within-network) and PS (r = .45, p = .07) and WM (r = .36, p = .16), and rsFC (between-network) and PS (r = .52, p = 8.4 × 10-3 ) and WM (r = .47, p = .02), derived from multiple networks was related to effect size of patient-control differences in the functional networks. No association was detected between rsFC and current medication dose or psychosis ratings. Patients demonstrated significant reduction in several FC networks that may partially underlie some of the core neurocognitive deficits in schizophrenia. The strength of connectivity-cognition relationships in different networks was strongly associated with network's vulnerability to schizophrenia.

Procognitive effects of transcranial magnetic stimulation in the light of neurocognitive deficit in schizophrenia

Transcranial magnetic stimulation (TMS) is a relatively new method of non-invasive therapy of mental and neurological diseases that has great potential of therapeutic and diagnostic application. In schizophrenia, TMS may exert a positive effect on cognitive deficit. However this issue remains open. The authors analyze recent studies focused on the dynamics of neurocognitive deficit in TMS therapy and consider clinical effects of TMS in schizophrenia. The analysis has shown that TMS is successfully implemented in treatment of auditory positive symptoms and studies on its effect on negative symptoms of schizophrenia are perspective. Procognitive effect was found in working memory domain, and partially in perception domain within the perception of faces and facial expressions. The data on regulative functions, attention, speech, and nondeclarative memory remains controversial. It has been concluded that further research is needed to clarify the place of TMS in schizophrenia therapy.

21.2 FAMILIAL RISK FOR SCHIZOPHRENIA

BackgroundLarry Seidman, Ph.D. was a key contributor to the Consortium on the Genetics of Schizophrenia (COGS) with its focus on understanding the genetic substrates of quantitative endophenotypes in schizophrenia patients. With his deep knowledge of neurocognition related to psychosis, Larry was able to help steer the COGS-1 family study of over 300 families. The subsequent COGS-2 case-control study used the same well curated, quality controlled extensive battery of testing with 1411 schizophrenia patients and 1500 extensively tested healthy control subjects. Larry was first author on the 2015 paper “Factor structure and heritability of endophenotypes and schizophrenia: findings from the Consortium on the Genetics of Schizophrenia.” It is important to note that related association studies examined the relationship of quantitative endophenotypes and genetic loci, and this is complementary to but distinct from case-control studies. These COGS studies identified a 42-gene network with a NRGL-ERBB4 hub underlying schizophrenia neurocognitive deficits. Thus, these Ns, modest for case-control studies, are quite powerful for gene finding using quantitative endophenotypic markers related to core “thought disorder” neurocognitive deficits in schizophrenia. These quantitative measures are up to 100 X more efficient and 10 X more powerful for gene finding than case-control studies as explained by Blangero, Williams and Almasy as early as 2005. Genes for SZ overlap with genes for key functionally important quantitative endophenotypes as shown by many groups, including COGENT and COGS, so case-control and endophenotype studies are best viewed as complementary in nature.MethodsSeidman et al (2015) examined 12 heritable neurocognitive and neurophysiological domains (including the Penn CNB Battery), as well as three neurophysiological measures reflecting inhibitory reprocessing from EEG and eye movements. Seidman et al’s analysis revealed five distinct factors in the composite COGS battery. These were 1-episodic memory, 2-working memory, 3-perceptual vigilance, 4-visual abstraction and 5-inhibitory processing. The five factors had similar structures across probands, siblings and controls. Also, heritability was significant for all 5 factors. These composite endophenotype factors will be used to enhance our neurobiological and genetic understanding of schizophrenia and its treatment as we move forward, and are related to the Biotype concept of psychosis. Larry Seidman was also an important contributor to the COGS mission as described below.ResultsThe COGS PsychChip GWAS of quantitative endophenotypes has now identified six regions of association with quantitative neurocognitive measures exceeding genome-wide significance (e.g. NRGL3-Abstaction and Mental Flexibility on the CNB). In addition, many associations between endophenotypes and specific loci exceed the suggestive threshold for further investigation.DiscussionThese data will be presented implicating synaptic plasticity and other crucial CNS processes in endophenotype dysfunction in SZ. NB: COGS interrogates the genetic architecture of endophenotypes associated with SZ and its functional outcome, not schizophrenia per se. Still, there is much overlap between risk genes for SZ and neurocognitive endophenotypes. Also neurocognitive endophenotypes are endorsed by the FDA and MATRICS as treatment targets for schizophrenia itself. This allows for data-guided drug and sensory-cognitive remediation of neurocognitive deficits to improve functional outcome in schizophrenia. Using this genomic information to enhance precision based selection of treatment options now seems to be an exciting and viable new treatment pathway.

Neurocognitive effects of an omega-3 fatty acid and vitamins E+C in schizophrenia: A randomised controlled trial

There is need for more efficient treatment of neurocognitive deficits in schizophrenia. In this 16 weeks randomised, placebo-controlled trial, we examined neurocognitive effects of adding ethyl-eicosapentaenoate 2g/day and/or vitamins E 364mg/day + C 1000mg/day to antipsychotics in 53 patients aged 18–39 years with acute schizophrenia. For the sake of validating neurocognitive tests, healthy subjects, not taking trial drugs, were also included in the study. Ethyl-EPA given alone to patients with low baseline RBC polyunsaturated fatty acids (PUFA), and Vitamins E+C given alone to high PUFA patients, impaired sustained attention (Continuous Performance Test, CPT-IP d prime score), standardised effect sizes d = 0.78 and d = 0.69, respectively. These adverse effects were paralleled by excessive increases in long-chain PUFA and serum alpha-tocopherol, respectively. They were counteracted by combining ethyl-EPA and vitamins, d = 0.80 and d = 0.74 in low and high PUFA patients, respectively. No other neurocognitive tests yielded significant results. Plausible mechanisms of harmful effects are oxidative stress and lipid raft disruption.

Affective symptoms in schizophrenia are strongly associated with neurocognitive deficits indicating disorders in executive functions, visual memory, attention and social cognition

The aim of this study was to assess the neurocognitive correlates of affective symptoms in schizophrenia. Towards this end, 40 healthy controls and 80 schizophrenia patients were investigated with six tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing spatial working memory, paired-association learning, one touch stocking, rapid visual information (RVP), emotional recognition test and intra/extradimensional set shifting. The Hamilton Depression (HDRS) and Anxiety (HAMA) Rating Scales and the Calgary Depression Scale for Schizophrenia (CDSS) as well as the Positive and Negative Syndrome Scale (PANSS) were also used.There were highly significant associations between all 6 CANTAB tests and HDRS, HAMA and CDSS (except RVP) scores. The most significant items associating with neurocognitive impairments in schizophrenia were self-depreciation (CDSS), fatigue, psychomotor retardation and agitation, psychic and somatic anxiety (HDRS), fears, cognitive symptoms, somatic-muscular, genito-urinary and autonomic symptoms and anxious behavior (HAMA). The selected HDRS and HAMA symptoms indicate fatigue, fears, anxiety, agitation, retardation, somatization and subjective cognitive complaints (SCC) and are therefore labeled “FAARS”. Up to 28.8% of the variance in the 6 CANTAB measurements was explained by FAARS, which are better predictors of neurocognitive impairments than the PANSS negative subscale score. Neurocognitive deficits in schizophrenia are best predicted by FAARS combined with difficulties in abstract thinking.In conclusion, depression and anxiety symptoms accompanying the negative and positive symptoms of schizophrenia are associated with neurocognitive deficits indicating disorders in executive functions, attention, visual memory, and social cognition. Neurocognitive deficits in schizophrenia reflect difficulties in abstract thinking and FAARS, including subjective cognitive complaints.

Intranasal Oxytocin May Improve High-Level Social Cognition in Schizophrenia, But Not Social Cognition or Neurocognition in General: A Multilevel Bayesian Meta-analysis.

While there is growing interest in the potential for intranasal oxytocin (IN-OT) to improve social cognition and neurocognition (ie, nonsocial cognition) in schizophrenia, the extant literature has been mixed. Here, we perform a Bayesian meta-analysis of the efficacy of IN-OT to improve areas of social and neurocognition in schizophrenia. A systematic search of original research publications identified randomized controlled trials (RCTs) of IN-OT as a treatment for social and neurocognitive deficits in schizophrenia for inclusion. Standardized mean differences (SMD) and corresponding variances were used in multilevel Bayesian models to obtain meta-analytic effect-size estimates. Across a total of 12 studies (N = 273), IN-OT did not improve social cognition (SMD = 0.07, 95% credible interval [CI] = [-0.06, 0.17]) or neurocognition (SMD = 0.12, 95% CI = [-0.12, 0.34]). There was moderate between study heterogeneity for social cognition outcomes(τs=0.12). Moderator analyses revealed that IN-OT had a significantly larger effect on high-level social cognition (ie, mentalizing and theory of mind) compared to low-level social cognition (ie, social cue perception) (b = 0.19, 95% CI = [0.05, 0.33]). When restricting our analysis to outcomes for high-level social cognition, there was a significant effect of IN-OT (SMD = 0.20, 95 % CI = [0.05, 0.33]) but the effect was not robust to sensitivity analyses. The present analysis indicates that IN-OT may have selective effects on high-level social cognition, which provides a more focused target for future studies of IN-OT.

Neurocognitive deficits in schizophrenia. Are we making mountains out of molehills?

Most original studies and all meta-analyses conducted to date converge on the conclusion that patients with schizophrenia display rather generalized neurocognitive deficits. For the present study, we reopen this seemingly closed chapter and examine whether important influences, such as lack of motivation and negative attitudes towards cognitive assessment, result in poorer secondary neuropsychological performance. A sample of 50 patients with an established diagnosis of schizophrenia were tested for routine neurocognitive assessment and compared to 60 nonclinical volunteers. Before and after the assessment, subjective momentary influences were examined (e.g. motivation, concerns about assessment, fear about poor outcome) for their impact on performance using a new questionnaire called the Momentary Influences, Attitudes and Motivation Impact (MIAMI) on Cognitive Performance Scale. As expected, patients performed significantly worse than controls on all neurocognitive domains tested (large effect size, on average). However, patients also displayed more subjective momentary impairment, as well as more fears about the outcome and less motivation than controls. Mediation analyses indicated that these influences contributed to (secondary) poorer neurocognitive performance. Differences in neurocognitive scores shrank to a medium effect size, on average, when MIAMI scores were accounted for. The data argue that performance on measures of neurocognition in schizophrenia are to a considerable extent due to secondary factors. Poor motivation, fears and momentary impairments distinguished patients from controls and these variables heavily impacted performance. Before concluding that neurocognitive deficits in psychiatric patients are present, clinicians should take these confounding influences into account. Although patients with schizophrenia achieved, on average, worse test scores than controls, a large subgroup displayed spared performance.

Reality monitoring impairment in schizophrenia reflects specific prefrontal cortex dysfunction.

Reality monitoring impairment is often reported in schizophrenia but the neural basis of this deficit is poorly understood. Difficulties with reality monitoring could be attributable to the same pattern of neural dysfunction as other cognitive deficits that characterize schizophrenia, or might instead represent a separable and dissociable impairment. This question was addressed through direct comparison of behavioral performance and neural activity associated with reality monitoring and working memory in patients with schizophrenia and matched healthy controls. Participants performed a word-pair reality monitoring task and a Sternberg working memory task while undergoing fMRI scanning. Distinct behavioral deficits were observed in the patients during performance of each task, which were associated with separable task- and region-specific dysfunction in the medial anterior prefrontal cortex for reality monitoring and dorsolateral prefrontal cortex for working memory. The results suggest that reality monitoring impairment is a distinct neurocognitive deficit in schizophrenia. The findings are consistent with the presence of a range of dissociable cognitive deficits in schizophrenia which may be associated with variable functional and structural dysconnectivity in underlying processing networks.

Severity of hypertension predicts the generalized neurocognitive deficit in schizophrenia

Individuals with schizophrenia have been found to display neurocognitive deficits on the order of 1 standard deviation below the mean of healthy controls on a range of cognitive domains, with no clear pattern of deficits that characterizes the majority of individuals with schizophrenia. Such findings have led some to suggest that schizophrenia is characterized by a “generalized” neurocognitive deficit, implying that a common underlying etiology impacts all cognitive domains. Central nervous system accounts of the generalized deficit have been proposed (e.g., NMDA and GABA interneuron receptor dysfunction); however, there may also be more diffuse “general systems” abnormalities that affect brain function. The current study evaluated the role of one type of general systems abnormality, metabolic dysfunction, on global cognitive functioning in a sample of outpatients with schizophrenia (n=27) and demographically matched healthy controls (n=33). Participants completed a battery of neuropsychological tests, as well as metabolic measurements to assess blood glucose, blood pressure, and abdominal obesity. Results indicated that higher pulse pressure predicted the generalized neurocognitive deficit in schizophrenia, but not healthy controls; however, blood glucose and abdominal obesity did not predict cognitive performance in either group. These findings provide support for the role of metabolic abnormalities in the generalized neurocognitive deficit in schizophrenia, and suggest that treatment of hypertension may be a novel adjunctive treatment target for remediating cognitive deficits in schizophrenia.

Potential Role of Oestrogen Modulation in the Treatment of Neurocognitive Deficits in Schizophrenia.

Cognitive deficits are prevalent in schizophrenia, and these deficits represent a disabling aspect of the illness for which there are no current effective treatments. Recent work has shown that sex hormone levels correlate with brain activity and cognitive abilities differentially in patients with schizophrenia relative to healthy control groups. There is emerging evidence suggesting that oestrogen-based therapies may be useful in reversing the cognitive deficits associated with schizophrenia. To date, the results from clinical trials using oestrogen-based therapies to reverse cognitive impairment in schizophrenia have shown that the selective oestrogen receptor modulator raloxifene may be useful to improve attention, memory, learning and the associated brain activity in chronically ill men and women with schizophrenia or schizoaffective disorder. While these findings of cognitive enhancement with a selective oestrogen receptor modulator in people with schizophrenia are encouraging, additional studies will be required to replicate the initial results, assess the time frame of treatment effects, identify biomarkers in subsets of patients who may be more likely to optimally respond to treatment, and identify a more precise mechanism of action, which may include anti-inflammatory effects of oestrogen-based treatments.