Cognitive Function In Schizophrenia Research Articles

Association between DBH 19 bp insertion/deletion polymorphism and cognition in schizophrenia with and without tardive dyskinesia

Long-term antipsychotic treatment for schizophrenia is associated with the development of tardive dyskinesia (TD), which is involved in increased cognitive impairment. Dopamine beta-hydroxylase (DBH) gene associated with dopamine and norepinephrine systems influences cognition. Schizophrenia with TD have higher DBH activity than those without TD. This study examined whether DBH5′-insertion/deletion (-Ins/Del) polymorphism could influence cognitive function in schizophrenia with and without TD. The presence of DBH5′-Ins/Del polymorphism was determined in 345 schizophrenia with TD and 397 schizophrenia without TD. The Abnormal Involuntary Movement Scale and Repeatable Battery for Assessment of Neuropsychological Status (RBANS) were used to assess TD severity and cognition. The allele and genotype frequencies of DBH5′-Ins/Del polymorphism did not differ between patients with and without TD (both p>0.05). RBANS total score and subscales did not differ by DBH5′-Ins/Del genotype groups in patients with TD (all p>0.05). However, attention score significantly differed by DBH5′-Ins/Del genotype groups in those without TD (p<0.05). Patients without TD who were Del homozygous had significantly lower attention score than those without TD who were Ins alleles (p<0.05). Immediate memory and attention scores were lower in patients with TD than without TD (both p<0.05). This study indicated that DBH5′-Ins/Del polymorphism may not play a role in the susceptibility to TD and cognitive deficits in schizophrenia with TD, but it may influence cognitive function in schizophrenia with non-TD. Moreover, schizophrenia with TD experienced greater cognitive deficits than those with non-TD, especially in immediate memory and attention.

Increased plasma asymmetric dimethylarginine is associated with cognitive deficits in patients with schizophrenia.

Cognitive deficits are a core feature of schizophrenia. Previous studies have shown that plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, was increased in patients with schizophrenia. This study aimed to investigate the association of ADMA with cognitive deficits in schizophrenia. Forty-seven patients with schizophrenia and 45 healthy control subjects were recruited in present study. Cognitive function was assessed with a neuropsychological battery including 7 neurocognitive tests. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale and plasma ADMA concentration was measured by HPLC. We found that patients with schizophrenia exhibited poorer performances in nearly all of the cognitive tests except for the visual memory index compared with healthy controls. Plasma ADMA levels were significantly increased in patients with schizophrenia when compared to normal controls, and the mean ADMA concentration in patients with multiple episode schizophrenia was much higher than that of patients with first episode schizophrenia. For the patients, ADMA was negatively associated with attention, working memory and executive function in schizophrenia. These results suggest that ADMA may be involved in the pathophysiology of schizophrenia-associated cognitive impairments, and plasma ADMA could be a peripheral biomarker for evaluation of cognitive function in schizophrenia.

A review of Indian research on cognitive remediation for schizophrenia.

Cognitive deficits play a central role in recovery from Schizophrenia (SZ). Cognitive remediation (CR) is increasingly being examined to improve cognitive functions in SZ. It is becoming an inevitable component of treatment for this debilitating illness. This review article presents the current status of research on CR for SZ in India. In contrast to the numerous studies reported from across the globe, there are only five studies on CR for SZ published from India. Of the five, only two are randomized controlled trials, two are non-randomized studies and one is a series of case reports. With different strategies used for CR and a variety of tools and measurements as outcome measures, combined analysis of the data was not feasible. Improvement in cognitive functions and sustenance of the improvement observed at follow-up period ranging from 2 to 6 months duration was underscored by all the four studies. Indigenous methods such as home-based CR techniques and Yoga therapy as an adjunct CR technique have been researched upon. Established method of CR such as the Integrated Psychological Therapy (IPT) has been used with modifications made to suit the cultural scenario. Other treatment methods such as family therapy have been added along with CR for chronic patients. The limited number of research studies has tried to encompass various dimensions. However, there is a dire need for studies with larger sample size with stringent research methods. Culturally feasible CR technique and multi-centric studies with larger sample size can be the next way forward.

Effects of Bupropion on Cognitive Function in Schizophrenia: A Double Blind Randomized Controlled Trial

&lt;p&gt;Smoking habits are common in schizophrenic patients. Nicotine can suppress negative symptoms and cognitive impairments. The aim of this study was to determine the efficacy of bupropion on cognitive function in schizophrenic patients.&lt;strong&gt; &lt;/strong&gt;This study is a double blind randomized controlled trial in a large referral psychiatric university hospital in Iran. Ninety smoker schizophrenic patients were randomly allocated (based on DSM -IV TR criteria) in two groups (46 patients for case group and 44 patients in control group). They get risperidone up to 6 mg/d and bupropion up to 400 mg/d .clinical assessment (Positive and Negative Syndrome Scale (PANSS), Brief psychiatric rating scale (BPRS) were taken in beginning of study, 14&lt;sup&gt;th&lt;/sup&gt; and 28&lt;sup&gt;th&lt;/sup&gt; days of study. Cognitive assessment (Stroop, Digit Span, and Wechsler, Wisconsin) were taken in begging of study, the days 2&lt;sup&gt;nd&lt;/sup&gt;, 7&lt;sup&gt;th&lt;/sup&gt;, 14&lt;sup&gt;th&lt;/sup&gt;, 28&lt;sup&gt;th&lt;/sup&gt;. All data were analyzed by SPSS Ver. 17 with analytic and descriptive tests. Mean age of patients was 37.66±1.01. Mean duration of disorder was 11.63±.98 years. The scores were significantly lower at the day 28&lt;sup&gt;th&lt;/sup&gt; compared to the beginning of the study in both groups in Wechsler, Stroop color word , Stroop word , Stroop color , BPRS, PANSS p value ≤0.05 .The difference between the two treatments was not significant as indicated by the effect of group, the between-subjects factor&lt;strong&gt; &lt;/strong&gt;&lt;strong&gt;p &lt;/strong&gt;value ≥0.05. In this study, the side effects were examined and there was no significant difference between the two groups p value ≥0.05.&lt;strong&gt; &lt;/strong&gt;Augmentation of bupropion to routine treatment improves cognitive symptoms of schizophrenia in abstinence of tobacco.&lt;/p&gt;

Determinants of cerebral hemodynamics during the Trail Making Test in schizophrenia

Patients with schizophrenia show deficits in cognitive functioning, and studies on cerebral hemodynamics have revealed aberrant patterns of mean cerebral blood flow velocity (MFV), an equivalent of cerebral blood flow (CBF). Therefore, we carried out a controlled study that assessed MFV in schizophrenia during a well-known neuropsychological task, the Trail Making Test (TMT). We measured MFV in the middle cerebral arteries using functional transcranial Doppler sonography in 15 schizophrenia patients and 15 healthy subjects. In comparison to healthy subjects, patients performed poorer on the TMT-A and the TMT-B, and there was increased cerebral blood flow velocity during the TMT-B. A comparison of subgroups of patients and controls matched in performance on the TMT-B revealed that these patients still showed significantly increased cerebral blood flow velocity. Increased MFV in schizophrenia suggests specific alterations of cerebral hemodynamics during the Trail Making Test, Part B, which are not detectable during visuomotor activity, and which are independent of performance. These findings emphasize the pathophysiological importance of cognitive functioning in schizophrenia, but cast doubts whether performance in this particular test plays a relevant role for CBF abnormalities in schizophrenia.

Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample.

Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds (NAAc, N-acetylaspartate plus N-acetyl-aspartyl-glutamate), a marker of neuronal viability, can be quantified with proton magnetic resonance spectroscopy (1H-MRS). We used 1H-MRS imaging to assess Glx and NAAc, as well as total-choline (glycerophospho-choline plus phospho-choline), myo-inositol and total-creatine (creatine plus phosphocreatine) from an axial supraventricular slab of gray matter (GM, medial-frontal and medial-parietal) and white matter (WM, bilateral-frontal and bilateral-parietal) voxels. Schizophrenia subjects (N = 104) and healthy controls (N = 97) with a broad age range (16 to 65) were studied. In schizophrenia, Glx was increased in GM (P < .001) and WM (P = .01), regardless of age. However, with greater age, NAAc increased in GM (P < .001) but decreased in WM (P < .001) in schizophrenia. In patients, total creatine decreased with age in WM (P < .001). Finally, overall cognitive score correlated positively with WM neurometabolites in controls but negatively in the schizophrenia group (NAAc, P < .001; and creatine [only younger], P < .001). We speculate the results support an ongoing process of increased glutamate metabolism in schizophrenia. Later in the illness, disease progression is suggested by increased cortical compaction without neuronal loss (elevated NAAc) and reduced axonal integrity (lower NAAc). Furthermore, this process is associated with fundamentally altered relationships between neurometabolite concentrations and cognitive function in schizophrenia.

A randomised controlled trial of adjunctive yoga and adjunctive physical exercise training for cognitive dysfunction in schizophrenia.

Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking. Aims A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study. Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of 'attention' in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm. Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (p<0.036, effect size 0.51). In the PE group, 'accuracy index of attention domain showed greater improvement than TAU alone at 6-month follow-up (p<0.025, effect size 0.61). For several other cognitive domains, significant improvements were observed with YT or PE compared with TAU alone (p<0.05, effect sizes 0.30-1.97). Both YT and PE improved attention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.

Repetitive Noninvasive Brain Stimulation to Modulate Cognitive Functions in Schizophrenia: A Systematic Review of Primary and Secondary Outcomes.

Despite many years of research, there is still an urgent need for new therapeutic options for the treatment of cognitive deficits in schizophrenia. Noninvasive brain stimulation (NIBS) has been proposed to be such a novel add-on treatment option. The main objective of this review was to systematically evaluate the cognitive effects of repetitive NIBS in schizophrenia. As most studies have not been specifically designed to investigate cognition as primary outcome, we have focused on both, primary and secondary outcomes. The PubMed/MEDLINE database (1985-2015) was systematically searched for interventional studies investigating the effects of repetitive NIBS on schizophrenia symptoms. All interventional clinical trials using repetitive transcranial stimulation, transcranial theta burst stimulation, and transcranial direct current stimulation for the treatment of schizophrenia were extracted and analyzed with regard to cognitive measures as primary or secondary outcomes. Seventy-six full-text articles were assessed for eligibility of which 33 studies were included in the qualitative synthesis. Of these 33 studies, only 4 studies included cognition as primary outcome, whereas 29 studies included cognitive measures as secondary outcomes. A beneficial effect of frontal NIBS could not be clearly established. No evidence for a cognitive disruptive effect of NIBS (temporal lobe) in schizophrenia could be detected. Finally, a large heterogeneity between studies in terms of inclusion criteria, stimulation parameters, applied cognitive measures, and follow-up intervals was observed. This review provides the first systematic overview regarding cognitive effects of repetitive NIBS in schizophrenia.

Improving Facial Emotion Recognition in Schizophrenia: a Controlled Study Comparing Specific and Attentional Focused Cognitive Remediation.

Cognitive impairments associated with schizophrenia are very frequent. They concern both neurocognition and social cognition, including facial emotion recognition. These impairments have a negative impact on the daily functioning, in particular the social and vocational rehabilitation of people with schizophrenia. Previous studies in this area clearly demonstrated the interest of cognitive remediation to improve neurocognitive and social cognitive functioning in schizophrenia. They also established clear links between facial emotion recognition skills and attentional processes. The present study compares the GAÏA s-face program (GAÏA arm), which focuses on facial emotion recognition processes, with the RECOS program (RECOS arm), a neurocognitive remediation therapy focusing on selective attention. Forty people with schizophrenia were randomly distributed between each study arm and assessed pre- (T1) and post- (T2) therapy. The single-blind assessment focused on facial emotion recognition (the main criteria), symptoms, social and subjective functioning, and neurocognitive and social cognitive performance. Both programs were conducted by nurses after a 3-day training session. The study showed a significant improvement in facial emotion recognition performance in both groups, with a significantly larger effect in the GAÏA arm. Symptoms and social functioning also improved in the GAÏA arm, and certain neurocognitive and social cognitive processes improved in both study arms. Further studies are recommended, with larger population samples and a follow-up assessing the long-term preservation of these improvements.

Association between actigraphy-derived physical activity and cognitive performance in patients with schizophrenia.

An association between low levels of physical activity and impaired cognitive performance in schizophrenia has been proposed, but most studies have relied on self-report measures of activity. This study examined the association between actigraphy-derived physical activity and cognitive performance adjusting for multiple covariates in patients with schizophrenia. Patients with schizophrenia (n = 199) were recruited from chronic psychiatric wards, and 60 age-, sex- and body mass index-matched comparison participants were recruited from the staff of two hospitals and universities. Physical activity was assessed objectively for 7 days using an ActiGraph. Cognitive performance was assessed with the Cognitrone test from the Vienna Test System and the Grooved Pegboard Test. Demographic variables, metabolic parameters, positive and negative symptoms, duration of illness and hospitalization, and medication use were included as covariates. Pearson correlations and multivariable linear regressions were conducted to examine the associations between physical activity levels and cognitive performance. Patients with schizophrenia were less physically active and had poorer performance on attention/concentration and speed of processing than the comparison group. Patients with schizophrenia who spent more time in light physical activity showed better performance on attention/concentration (β = 0.198, p = 0.020) and speed of processing (β= -0.169, p = 0.048) tasks than those who were less active. Cognitive performance was also associated with moderate-vigorous physical activity, but the effect was no longer significant once light physical activity had been taken into account. This study provides evidence for a positive association between objectively measured light physical activity and cognitive performance in people with schizophrenia, after adjustment for multiple confounders.

The association among smoking, HSV-1 exposure, and cognitive functioning in schizophrenia, bipolar disorder, and non-psychiatric controls

Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV-1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was −0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning.

PM441. Long term atypical antipsychotic treatment improves cognitive performance in schizophrenia but not surpassing conventional antipsychotic drugs effects.

PM441. Long term atypical antipsychotic treatment improves cognitive performance in schizophrenia but not surpassing conventional antipsychotic drugs effects.

A Serious Game to Improve Cognitive Functions in Schizophrenia: A Pilot Study.

Cognitive deficits in schizophrenia impair everyday functioning and instrumental daily living activities. These disabilities can be partly responsible for chronicity and institutionalization. We present here a virtual reality (VR) tool in which patients with schizophrenia performed a virtual game in an imaginary town during a 3-month program. In a pilot study, seven patients with schizophrenia (DSM-5), institutionalized for many years, attended weekly 1-h-and-a-half sessions organized by two clinicians. During the first sessions, they listed together the difficulties they experienced in everyday organization and planning. After being familiarized with the joystick and the VR environment, they navigated in the town, and planned actions that were difficult for them to carry out in their usual life (e.g., shopping, memorizing the way to the supermarket or being on time at a meeting point). They had to look for alternative routes and practice a switch from a 2D Map to the 3D Map. They also gathered their efforts to share strategies for each action, or discussed the action plan they could generate to solve concrete problems. The pre/post-neuropsychological evaluations showed attention, working memory, prospective, and retrospective memory benefits, but no improvement in planning as assessed by the Zoo map test and the action program subtest of Behavioral Assessment of the Dysexecutive Syndrome. Patients also clinically and functionally improved, gaining autonomy. Pragmatically, they reported a strong energy to elaborate concrete plans to search for jobs, or return to activities in the community. Qualitative assessments showed a benefit in sparing time, planning better, enriched relatedness, and better management of their housework. This VR game opens avenue to rehabilitation for patients with schizophrenia experiencing chronicity in their life, less attendance in daycare units, and a better community living. This program might reduce neurocognitive difficulties and might evolve into a true method for cognitive remediation (trial n° 2011-A00988-33).

White matter abnormalities in the fornix are linked to cognitive performance in SZ but not in BD disorder: An exploratory analysis with DTI deterministic tractography

BackgroundIn psychosis, white matter (WM) microstructural changes have been detected previously; however, direct comparisons of findings between bipolar (BD) and schizophrenia (SZ) patients are scarce. In this study, we employed deterministic tractography to reconstruct WM tracts in BD and SZ patients. MethodsDiffusion tensor imaging (DTI) data was carried out with n=32 euthymic BD type I patients, n=26 SZ patients and 30 matched healthy controls. Deterministic tractography using multiple indices of diffusion (fractional anisotropy (FA), tract volume (Vol), tract length (Le) and number of tracts (NofT)) were obtained from the fornix, the cingulum, the anterior thalamic radiation, and the corpus callosum bilaterally. ResultsWe showed widespread WM microstructural changes in SZ, and changes in the corpus callosum, the left cingulum and the fornix in BD. Fornix fiber tracking scores were associated with cognitive performance in SZ, and with age and age at disease onset in the BD patient group. LimitationsAlthough the influence of psychopharmacological drugs as biasing variables on morphological alterations has been discussed for SZ and BD, we did not observe a clear influence of drug exposure on our findings. ConclusionsThese results confirm the assumption that SZ patients have more severe WM changes than BD patients. The findings also suggest a major role of WM changes in the fornix as important fronto-limbic connections in the etiology of cognitive symptoms in SZ, but not in BD.

L’insight neurocognitif dans la schizophrénie

ObjectivesGiven the extent, magnitude and functional significance of the neurocognitive deficits of schizophrenia, growing attention has been paid recently to patients’ self-awareness of their own deficits. Thus far, the literature has shown either that patients fail to recognize their cognitive deficits or that the association between subjective and objective cognition is weak in schizophrenia. The reasons for this lack of consistency remain unexplained but may have to do, among others, with the influence of potential confounding clinical variables and the choice of the scale used to measure self-awareness of cognitive deficits. In the current study, we sought to examine the relationships between subjective and objective cognitive performance in schizophrenia, while controlling for the influence of sociodemographic and psychiatric variables. MethodsEighty-two patients with a schizophrenia-spectrum disorder (DSM-IV criteria) were recruited. Patients’ subjective cognitive complaints were evaluated with the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), the most frequently used scale to measure self-awareness of cognitive deficits in schizophrenia. Neurocognition was evaluated with working memory, planning and visual learning tasks taken from Cambridge Neuropsychological Tests Automated Battery. The Stroop Color-Word test was also administered. Psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. The relationships between subjective and objective cognition were evaluated with multivariate hierarchic linear regression analyses, taking into consideration potential confounders such as sociodemographic and psychiatric variables. Finally, a factor analysis of the SSTICS was performed. ResultsFor the SSTICS total score, the regression analysis produced a model including two predictors, namely visual learning and Stoop interference performance, explaining a moderate portion of the variance. Visual learning performance was the most consistent predictor of most SSTICS subscores (e.g. episodic memory, attention, executive functioning, language and praxis). Modest associations were found between the PANSS cognitive factor and objective cognition (e.g. Stroop interference, visual learning, and working memory). Finally, the factor analysis revealed a 6-factor solution that echoes the classification of the items of the SSTICS based on the neuropsychological literature. ConclusionsUsing a scale having good internal validity, as shown by the factor analysis, the current study highlighted modest associations between subjective and objective cognitive performance, which suggests that schizophrenia patients are only partially aware of their own cognitive deficits. The results also showed a lack of correspondence between the impaired cognitive domain and the domain of cognitive awareness. It should be noted that clinicians were not better than patients at evaluating their cognitive deficits. Future research will need to determine if the observations reported here are schizophrenia-specific or not.

Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology.

Background:We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms.Methods:Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [123I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined.Results:Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016).Conclusions:Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms.

Neurocognitive insight and objective cognitive functioning in schizophrenia

Neurocognitive impairment is a core component of schizophrenia affecting everyday functioning; the extent to which individuals with schizophrenia show awareness of neurocognitive impairment (neurocognitive insight) is unclear. This study investigated neurocognitive insight and examined the cross-sectional relationships between neurocognitive insight and objective neurocognition and functional capacity performance in a large outpatient sample.214 participants with schizophrenia-spectrum disorders completed measures of neurocognition, functional capacity, and self-reported neurocognitive problems. Latent profile analysis classified participants with regard to neuropsychological performance and self-report of neurocognitive problems. The resulting classes were then compared on executive functioning performance, functional capacity performance, and psychiatric symptom severity.More than three quarters of the sample demonstrated objective neurocognitive impairment (global deficit score≥0.50). Among the participants with neurocognitive impairment, 54% were classified as having “impaired” neurocognitive insight (i.e., reporting few neurocognitive problems despite having objective neurocognitive impairment). Participants with impaired vs. intact neurocognitive insight did not differ on executive functioning measures or measures of functional capacity or negative symptom severity, but those with intact neurocognitive insight reported higher levels of positive and depressive symptoms.A substantial portion of individuals with schizophrenia and objectively measured neurocognitive dysfunction appear unaware of their deficits. Patient self-report of neurocognitive problems, therefore, is not likely to reliably assess neurocognition. Difficulty self-identifying neurocognitive impairment appears to be unrelated to executive functioning, negative symptoms, and functional capacity. For those with intact neurocognitive insight, improving depressive and psychotic symptoms may be a valuable target to reduce illness burden.

Cognitive function in schizophrenia: conflicting findings and future directions.

Schizophrenia is a severe mental disorder with multiple psychopathological domains being affected. Several lines of evidence indicate that cognitive impairment serves as the key component of schizophrenia psychopathology. Although there have been a multitude of cognitive studies in schizophrenia, there are many conflicting results. We reasoned that this could be due to individual differences among the patients (i.e. variation in the severity of positive vs. negative symptoms), different task designs, and/or the administration of different antipsychotics. We thus review existing data concentrating on these dimensions, specifically in relation to dopamine function. We focus on most commonly used cognitive domains: learning, working memory, and attention. We found that the type of cognitive domain under investigation, medication state and type, and severity of positive and negative symptoms can explain the conflicting results in the literature. This review points to future studies investigating individual differences among schizophrenia patients in order to reveal the exact relationship between cognitive function, clinical features, and antipsychotic treatment.

Resilience Improves Neurocognition and Treatment Outcomes in Schizophrenia: A Hypothesis

There has been a revolutionary advance in the treatment and management of schizophrenia from a clinical aspect yet the social and functional outcomes remain poor. Cognitive function is impaired in schizophrenia and shows various domains of dysfunction like verbal memory, processing speed and working memory. It is also known to be a factor associated with poor outcome in schizophrenia. Resilience is a new concept psychobiological concept which is defined as individual’s ability to adapt swiftly to adverse life events and bounces back to normalcy. Resilience has genetic, neurobiological, neurochemical and psychological underpinnings. It is the ability to effectively deal with psychosocial stressors and appears to be one of the many factors associated with favourable outcomes in schizophrenia. Besides several neurobiological abnormalities associated with resilience, neucognitive functions are of particular interest. Persistent psychosocial stressors also lead to significant neurobiological changes which may be synergetic to poor outcome due to cognitive changes. Though there has been extensive research in the field of cognitive function in schizophrenia, the trajectory of its pathway of poor outcome remains undetermined. Resilience being a protective factor may be one of the psychobiological functions which modulate the effect of neurocognition on the outcome of schizophrenia. There has been some success with interventions aimed at improving cognitive function in schizophrenia whether pharmacological or non pharmacological. In this paper, we discuss a hypothesis that resilience may be a “linkage” between cognition and outcome. There is a need for interventions aimed at increasing resilience in patients with schizophrenia and we hypothesize giving evidence that this may in turn improve outcome and neurocognitive functioning in schizophrenia.

Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia.

In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=−5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=−0.247; P=0.004) and Hopkins total (r=−0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations.