Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers

Background

Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.

Methods

Three groups (n = 100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2 s & 12 s); sustained attention processing was assessed using the Continuous Performance Task—Identical Pairs version.

Results

SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.

Conclusions

These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.     

Elevated noise power in gamma band related to negative symptoms and memory deficit in schizophrenia

Patients with schizophrenia have low extraversion and high neuroticism. These personality traits affect the everyday life of patients with schizophrenia, making it important to investigate neurobiological basis of personality traits. In healthy people, extraversion is associated with hemodynamic responses in the amygdala and electrophysiological brain activity such as event-related potential and event-related desynchronization during emotional face processing. Patients with schizophrenia show abnormal neural activity during emotional face processing, such as an N170 amplitude reduction. However, few studies to date have reported an association between personality traits and neural activity during emotional face processing in schizophrenia. In the present study, we examined N170 during emotional face processing, and association with personality traits in patients with schizophrenia. Fifteen male patients with chronic schizophrenia and 15 healthy male subjects participated in this study. Patients with schizophrenia had reduced N170 amplitudes (p=0.007). While healthy subjects had increased N170 amplitudes in response to emotional faces compared with neutral faces (p=0.003), patients with schizophrenia showed no difference in N170 amplitudes between emotional and neutral faces (p=0.60). Reduced N170 amplitude in response to neutral faces was correlated with low extraversion scores in patients with schizophrenia (r(s)=-0.69, p=0.005). The abnormal N170 and its association with extraversion in schizophrenia were found at the right rather than the left posterior temporal electrode. An abnormal N170 in schizophrenia may reflect impairments in the structural encoding of emotional faces, and indiscrimination between emotional and neutral faces at this stage of information processing. The association between abnormal N170 amplitudes and extraversion suggests that abnormal neural activity in the early stages of emotional face processing may underlie low extraversion characteristic of schizophrenia.     

Neurocognitive dysfunction in strategic and non-strategic gamblers

Objective

It has been theorized that there may be subtypes of pathological gambling, particularly in relation to the main type of gambling activities undertaken. Whether or not putative pathological gambling subtypes differ in terms of their clinical and cognitive profiles has received little attention.

Method

Subjects meeting DSM-IV criteria for pathological gambling were grouped into two categories of preferred forms of gambling — strategic (e.g., cards, dice, sports betting, stock market) and non-strategic (e.g., slots, video poker, pull tabs). Groups were compared on clinical characteristics (gambling severity, and time and money spent gambling), psychiatric comorbidity, and neurocognitive tests assessing motor impulsivity and cognitive flexibility.

Results

Seventy-seven subjects were included in this sample (45.5% females; mean age: 42.7 ± 14.9) which consisted of the following groups: strategic (n = 22; 28.6%) and non-strategic (n = 55; 71.4%). Non-strategic gamblers were significantly more likely to be older, female, and divorced. Money spent gambling did not differ significantly between groups although one measure of gambling severity reflected more severe problems for strategic gamblers. Strategic and non-strategic gamblers did not differ in terms of cognitive function; both groups showed impairments in cognitive flexibility and inhibitory control relative to matched healthy volunteers.

Conclusion

These preliminary results suggest that preferred form of gambling may be associated with specific clinical characteristics but are not dissociable in terms of cognitive inflexibility and motor impulsivity.     

Investigation of serum BDNF levels in drug-naive patients with schizophrenia

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate the neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported. In the present study, we assessed serum BDNF levels in a group of 14 drug-naive first-episode patients with schizophrenia (FEP), compared to 15 healthy controls. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to normal controls (23.92+/-5.99 ng/ml vs. 30.0+/-8.43 ng/ml, F=5.01, df=1, p=.034). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Positive and Negative subscale scores. Our findings indicate that BDNF levels at the onset of schizophrenia may reflect associated pathophysiological processes as well as the severity of positive and negative psychotic symptoms.     

Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls

It is known that 60 to 80% of schizophrenic patients show deficits in cognition. There may be an increase in these deficits as a result of additional regular use of cannabis. The aim of the study was to evaluate the effect of chronic cannabis consumption on the cognitive functions of schizophrenic patients and healthy control subjects after a minimum abstinence time of 28 days. The study sample consisted of 39 schizophrenics (19 cannabis-abusers and 20 non-abusers) and 39 healthy controls (18 cannabis-abusers, 21 non-abusers). In a 2x2-factorial design (Diagnostic Groups [healthy controls, schizophrenic patients]xCannabis abuse [without, with]) with diagnostic group and cannabis consumption considered between-subject factors) we tested the hypothesis that dually diagnosed patients (i.e. suffering both from schizophrenia and cannabis abuse) perform worse in neuropsychological tests than schizophrenic patients without cannabis abuse. On the whole, schizophrenic patients performed worse than healthy control subjects. Surprisingly, rather than deteriorating neuropsychological performance, regular cannabis abuse prior to the first psychotic episode improved cognition in some tests. This was even more pronounced when regular consumption started before the age of 17. On the other hand, cannabis use deteriorated test performance in healthy controls, especially in cases when regular consumption started before the age of 17. To sum up, regular cannabis abuse has a different effect on cognitive function in schizophrenic patients and healthy controls.     

Impact of coexistent schizotypal personality traits on frontal lobe function in obsessive-compulsive disorder

OBJECTIVE: This study was a post-hoc analysis of the results from a neuropsychological battery which was conducted to investigate the frontal lobe difference between obsessive-compulsive disorder (OCD) patients with and without schizotypal personality trait (SPT), especially dorsolateral prefrontal and medial frontal functions. METHODS: Fifty-five OCD patients were divided into two groups according to their Personality Disorder Questionnaire-4+ scores. Patients with OCD with SPT (n=17) and OCD without SPT (n=38) were compared to 52 schizophrenia patients and 67 healthy subjects. Two neuropsychological tasks, the Wisconsin Card Sorting Test (WCST) and verbal fluency tests which are considered to reflect dorsolateral and medial frontal functions, were selected for an analysis. RESULTS: OCD with SPT patients and patients with schizophrenia performed significantly worse than controls in both the WCST and verbal fluency tasks, whereas OCD without SPT patients showed no deficits in the same tasks. Moreover, we found no statistically significant difference in either task between patients having OCD with SPT and patients with schizophrenia. CONCLUSION: This study indicate that OCD with SPT may have distinct patterns of neurocognitive deficit that differ from those of OCD without SPT, especially in terms of frontal lobe function.     

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Dimensional correlates of poor insight in obsessive-compulsive disorder

Background

Cross-sectional studies have associated poor insight in patients with obsessive-compulsive disorder (OCD) with increased OCD symptom severity, earlier age of onset, comorbid depression, and treatment response. The goal of this current study was to examine the relationship between dimensions of OCD symptomatology and insight in a large clinical cohort of Brazilian patients with OCD. We hypothesized that poor insight would be associated with total symptom severity as well as with hoarding symptoms severity, specifically.

Methods

824 outpatients underwent a detailed clinical assessment for OCD, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), the Brown Assessment of Beliefs Scale (BABS), a socio-demographic questionnaire, and the Structured Clinical Interview for axis I DSM-IV disorders (SCID-P). Tobit regression models were used to examine the association between level of insight and clinical variables of interest.

Results

Increased severity of current and worst-ever hoarding symptoms and higher rate of unemployment were associated with poor insight in OCD after controlling for current OCD severity, age and gender. Poor insight was also correlated with increased severity of current OCD symptoms.

Conclusion

Hoarding and overall OCD severity were significantly but weakly associated with level of insight in OCD patients. Further studies should examine insight as a moderator and mediator of treatment response in OCD in both behavioral therapy and pharmacological trials. Behavioral techniques aimed at enhancing insight may be potentially beneficial in OCD, especially among patients with hoarding.     

Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: inverse association with positive symptoms

Excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased superoxide dismutase (SOD) activities, a critical enzyme in the detoxification of superoxide radicals. This study compared plasma SOD activities in 78 never-medicated first-episode and 100 medicated chronic schizophrenia patients to 100 healthy control subjects and correlated these SOD activities with the Positive and Negative Syndrome Scale (PANSS) among the schizophrenic patients. We found that both first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first episode schizophrenic patients. Plasma SOD activities were also negatively correlated with positive symptoms of schizophrenia, but only in first-episode patients. Thus, oxidative stress appears to be greater in first episode schizophrenic patients with fewer positive symptoms and may become greater as schizophrenia becomes more chronic, although we cannot exclude the possibility that chronic antipsychotic treatment may increase SOD activities and presumed oxidative stress in schizophrenia.     

Facial emotion perception in Chinese patients with schizophrenia and non-psychotic first-degree relatives

Although there is a consensus that patients with schizophrenia have certain deficits in perceiving and expressing facial emotions, previous studies of facial emotion perception in schizophrenia do not present consistent results. The objective of this study was to explore facial emotion perception deficits in Chinese patients with schizophrenia and their non-psychotic first-degree relatives. Sixty-nine patients with schizophrenia, 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger healthy controls matched to the patients and siblings, and 25 older healthy controls matched to the parents) completed a set of facial emotion perception tasks, including facial emotion discrimination, identification, intensity, valence, and corresponding face identification tasks. The results demonstrated that patients with schizophrenia performed significantly worse than their siblings and younger healthy controls in accuracy in a variety of facial emotion perception tasks, whereas the siblings of the patients performed as well as the corresponding younger healthy controls in all of the facial emotion perception tasks. Patients with schizophrenia also showed significantly reduced speed than younger healthy controls, while siblings of patients did not demonstrate significant differences with both patients and younger healthy controls in speed. Meanwhile, we also found that parents of the schizophrenia patients performed significantly worse than the corresponding older healthy controls in accuracy in terms of facial emotion identification, valence, and the composite index of the facial discrimination, identification, intensity and valence tasks. Moreover, no significant differences were found between the parents of patients and older healthy controls in speed after controlling the years of education and IQ. Taken together, the results suggest that facial emotion perception deficits may serve as potential endophenotypes for schizophrenia.     

Neurocognitive,clinical and functional correlates of subjective quality of life in Asian outpatients with schizophrenia

Quality of life (QOL) impairment is evident in patients with schizophrenia and is increasingly recognised as an important evaluation criterion of treatment outcome. Hence, this study aimed to identify the neurocognitive, clinical and functional parameters associated with subjective QOL in patients with schizophrenia within an Asian context, and specifically in an outpatient setting. This study was conducted on 83 outpatients with DSM-IV diagnosis of schizophrenia, and 47 age- and gender-matched healthy controls. All participants were administered with the World Health Organisation Quality of Life Assessment-Brief Form (WHOQOL-BREF) and Brief Assessment of Cognition in Schizophrenia (BACS), to measure quality of life and cognitive function respectively. Patients were also assessed for severity of psychopathology, as well as level of psychosocial functioning, using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) rating scales respectively. Specific psychopathology (greater severity of PANSS negative symptoms, general psychopathology subscale scores), cognitive deficits (working and verbal memories), and lower GAF scores were correlated with poorer QOL in patients. Multivariate analyses revealed that younger age, being single and lower level of psychosocial functioning were associated with poorer QOL but level of psychosocial functioning did not appear to mediate the effects of symptoms and neurocognitive deficits on QOL. Overall, this study highlighted the need for clinicians to pay more attention to these clinical, neurocognitive and functional parameters and their integrative relationships with QOL in order to optimise the treatment outcomes of patients with schizophrenia.     

Obsessive compulsive disorder and symptoms may have different effects on schizophrenia

The aim of this study is to investigate the possible different effects of obsessive compulsive disorder (OCD) and obsessive compulsive symptoms (OCS) on schizophrenia illness in regard to clinical characteristics such as severity of symptomatology.We included 184 patients with schizophrenia on monotherapy with a stable dose of antipsychotics for at least three months. Severity of clinical symptoms was evaluated by Positive and Negative Syndrome Scale. OCS was examined by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Checklist. We also assessed OCD by using Y-BOCS.Seventeen percent of the patients were diagnosed with current OCD, while 17.4% of the patients were found to have OCS without OCD. Age of onset for OCD group was earlier than non-OCS group (p = 0.007).The rate of occupation was higher (p = 0.001), prevalence of other comorbid psychiatric disorders was lower (p = 0.05), number of hospitalization was lower (p = 0.03), GAF score was higher (p = 0.03) and duration of education was longer (p = 0.02) in the OCS group than in the non-OCS group. The rate of occupation was higher (p = 0.04) and that rate of comorbid psychiatric disorders was lower (p = 0.01) in the OCS group than in the OCD group. We found more OCS in patients using atypical antipsychotics (p = 0.03).Our findings suggest that OCD and OCS might have different effects on schizophrenia.     

Gastric dysmotility in healthy first-degree relatives of patients with schizophrenia

Gastric dysmotility has been reported in patients suffering from major depression or schizophrenia. An increased sympathetic activity modulating the gastric pacemaker located in the antrum of the stomach has been suggested as the underlying pathology. Similar to patients suffering from schizophrenia, their first-degree relatives showed alterations in cardiac autonomic modulation. Here we aimed to investigate gastric myoelectrical activity in healthy relatives of patients suffering from paranoid schizophrenia.     

Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive-compulsive disorder

Evidence has supported a role for serotonin system dysfunction in the pathogenesis of the obsessive-compulsive disorder (OCD). Many studies examined the association between OCD and a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) but yielded inconsistent results. Current study aimed to determine conclusively whether there is an association by using a meta-analytic method. Over 3000 subjects from 13 independent case-control association studies were included in the analysis. By using random effects model, data from these studies were pooled to compare the genotypes and allelic distribution of the 5-HTTLPR polymorphism between OCD patients and control subjects. In the analysis, OCD was found to be associated with the SS homozygous genotype (OR=1.21, p=0.04), but was inversely associated with the LS heterozygous genotype (OR=0.79, p=0.03). No association with the LL homozygous genotype or the allelic distribution was found. These results suggest that variations of the serotonin transporter gene influence the risk of OCD, but their functional roles in the pathogenesis of OCD need to be elucidated.     

Shared impairment in associative learning in schizophrenia and bipolar disorder

Background

Schizophrenia (SCZ) and bipolar disorder (BD) share some cognitive commonalities. However, the role of associative learning, which is a cornerstone of human cognition mainly relying on hippocampus, has been under-investigated. We assessed behavioral performance during associative learning in a group of SCZ, BD and healthy controls (HC).

Methods

Nineteen patients with SCZ (36 ± 8.1 years; 13 males, 6 females; all Caucasians), 14 patients with BD (41 ± 9.6 years; 5 males, 9 females; all Caucasians) and 45 HC (27.7 ± 6.9 years; 18 males, 27 females; all Caucasians) were studied. Learning was assessed using an established object-location paired-associative learning paradigm. Subjects learned associations between nine equi-familiar common objects and locations in a nine-location grid. Performance data were analyzed in a repeated measures analysis of variance with time (repeated) and group as factors.

Results

Learning curves (performance = 1−e^−k?time) fitted to average performance data in the three groups revealed lower learning rates in SCZ and BD (k = 0.17 and k = 0.34) than HC (k = 0.78). Significant effects of group (F = 11.05, p < 0.001) and time (F = 122.06, p < 0.001) on learning performance were observed.

Conclusions

Our study showed that associative learning is impaired in both SCZ and BD, being potentially not affected by medication. Future studies should investigate the neural substrates of learning deficits in SCZ and BD, particularly focusing on hippocampus function and glutamatergic transmission.     

Reduced cardio-respiratory coupling indicates suppression of vagal activity in healthy relatives of patients with schizophrenia

Previous studies have observed reduced vagal modulation in patients with acute schizophrenia and their first-degree relatives, thus suggesting a genetic predisposition.     

Diagnostic specificity of the insular cortex abnormalities in first-episode psychotic disorders

Volume reductions of the insular cortex have been described in schizophrenia, but it remains unclear whether other psychotic disorders such as affective psychosis also exhibit insular cortex abnormalities. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the anterior (short) and posterior (long) insular cortices in 162 first-episode patients with various psychotic disorders (46 schizophrenia, 57 schizophreniform disorder, 34 affective psychosis, and 25 other psychoses) and 62 age- and gender-matched healthy comparison subjects. Patients with schizophrenia showed bilateral volume reduction of the anterior and posterior insular cortices compared with controls, but the remaining first-episode psychosis subgroups had normal insular volumes. The volumes of these insular subregions were significantly smaller in schizophrenia patients than in patients with schizophreniform disorder or affective psychoses. There was no association between the insular cortex volume and daily dosage or type of antipsychotic medication in any patient group. These findings suggest that the widespread volume reduction of the insular cortex is specific to established schizophrenia, implicating its role in the neurobiology of clinical characteristics associated with schizophrenia.     

Auditory orienting and inhibition of return in schizophrenia: A functional magnetic resonance imaging study

Patients with schizophrenia (SP) exhibit deficits in both attentional reorienting and inhibition of return (IOR) during visual tasks. However, it is currently unknown whether these deficits are supramodal in nature and how these deficits relate to other domains of cognitive dysfunction. In addition, the neuronal correlates of this pathological orienting response have not been investigated in either the visual or auditory modality. Therefore, 30 SP and 30 healthy controls (HC) were evaluated with an extensive clinical protocol and functional magnetic resonance imaging (fMRI) during an auditory cuing paradigm. SP exhibited both increased costs and delayed IOR during auditory orienting, suggesting a prolonged interval for attentional disengagement from cued locations. Moreover, a delay in the development of IOR was associated with cognitive deficits on formal neuropsychological testing in the domains of attention/inhibition and working memory. Event-related fMRI showed the characteristic activation of a frontoparietal network (invalid trials > valid trials), but there were no differences in functional activation between patients and HC during either attentional reorienting or IOR. Current results suggest that orienting deficits are supramodal in nature in SP, and are related to higher-order cognitive deficits that directly interfere with day-to-day functioning.