Cognitive and prepulse inhibition deficits in psychometrically high schizotypal subjects in the general population: relevance to schizophrenia research

Schizophrenia and schizotypal personality disorder share common clinical profiles, neurobiological and genetic substrates along with Prepulse Inhibition and cognitive deficits; among those, executive, attention, and memory dysfunctions are more consistent. Schizotypy is considered to be a non-specific "psychosis-proneness," and understanding the relationship between schizotypal traits and cognitive function in the general population is a promising approach for endophenotypic research in schizophrenia spectrum disorders. In this review, findings for executive function, attention, memory, and Prepulse Inhibition impairments in psychometrically defined schizotypal subjects have been summarized and compared to schizophrenia patients and their unaffected first-degree relatives. Cognitive flexibility, sustained attention, working memory, and Prepulse Inhibition impairments were consistently reported in high schizotypal subjects in accordance to schizophrenia patients. Genetic studies assessing the effects of various candidate gene polymorphisms in schizotypal traits and cognitive function are promising, further supporting a polygenic mode of inheritance. The implications of the findings, methodological issues, and suggestions for future research are discussed. (JINS, 2012, 18, 1-14).     

Declarative memory and WCST-64 performance in subjects with schizophrenia and healthy controls

The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive functioning in schizophrenia. Declarative memory deficits have also been associated with schizophrenia and may affect WCST performance because continued correct responding depends on remembering the outcome of previous responses. This study examined whether performance in visual and verbal declarative memory tasks were associated with WCST performance. Subjects comprised 30 patients with schizophrenia or schizoaffective disorder (SCZ) and 30 demographically matched healthy controls (CON) who were tested on the WCST, the Benton Visual Retention Test (BVRT), the California Verbal Learning Test (CVLT), and the Continuous Performance Test (CPT). SCZ subjects showed significant correlations between visual and verbal declarative memory and performance on the WCST-64 that were in the hypothesized direction such that worse memory performance was associated with worse performance on the WCST. CON subjects did not show a significant relationship between visual or verbal memory and WCST-64 performance. Fisher's r to z transformations indicated that the associations between declarative memory and WCST-64 performance in the SCZ subjects differed significantly from those of CON subjects. The findings suggest that interpretations of WCST-64 scores for subjects with schizophrenia should be considered in light of their declarative memory functioning.     

Childhood-onset schizotypal disorder: a follow-up study and comparison with childhood-onset schizophrenia

OBJECTIVE: This paper presents results from the UCLA Follow-Up Study of Childhood-Onset Schizophrenia (SZ) Spectrum Disorders. METHOD: We assessed 12 children with schizotypal personality disorder (SPD) and 18 children with schizophrenia 1-7 years following initial project intake. RESULTS: There was significant continuity between SZ spectrum disorders in childhood and adolescence. Although not all children who presented initially with SZ spectrum disorders continued to meet criteria for SZ spectrum disorder as they progressed through the follow-up period, rates of SZ spectrum disorders ranged from 75% to 92% across the 3 follow-up years for children initially presenting with SPD, and from 78% to 89% for children initially presenting with SZ. CONCLUSION: The most common clinical outcome for children with SPD was continuing SPD, supporting the hypothesis of continuity between childhood and later SPD. However, 25% of the SPD sample developed more severe SZ spectrum disorders (schizophrenia or schizoaffective disorder), also supporting the hypothesis that SPD represents a risk or precursor state for more severe SZ spectrum disorders.     

Cannabis‐related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects

Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis‐related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group‐matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON‐CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ‐CUD). Large‐deformation, high‐dimensional brain mapping with MRI produced surface‐based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON‐CUD and SCZ‐CUD were characterized by distinct cannabis‐related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON‐CUD were associated with poorer EM performance, while shape differences observed in SCZ‐CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis‐related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis. © 2015 Wiley Periodicals, Inc.     

Cognitive deficits in early-onset schizophrenia spectrum patients and their non-psychotic siblings: a comparison with ADHD

BACKGROUND: Previous research has shown cognitive deficits in patients with schizophrenia spectrum disorders in the areas of executive function, verbal memory and attention. Subtle deficits have been shown in healthy first-degree relatives of patients, suggesting that they may be trait markers. The specificity of these markers for schizophrenia compared with another neurodevelopmental disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably established. METHODS: The Rey Auditory Verbal Learning Test (RAVLT), Hayling Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS) and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC; n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27). RESULTS: The SZ group were impaired on all measures. The SZ-SIB group were impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response initiation (HSCT); error rates for the FAS and HSCT. There were no significant differences between the SZ-SIB and ADHD groups on individual measures of cognitive function. Principal Components Analysis revealed four factors on which further analyses were conducted. The SZ-SIB and ADHD groups showed different profiles of impairment on components related to response initiation and sustained attention/vigilance when each was compared with the HC group. CONCLUSIONS: Deficits in intellectual function, verbal memory and response initiation/inhibition were found in the SZ-SIB group indicating that these are markers of risk for schizophrenia. Subtle differences in profiles of impairment in the SZ-SIB and ADHD groups on composite measures of attention and response initiation require further investigation.     

Verbal memory and verbal fluency in adolescents with schizophrenia spectrum disorders

Aim: Although impaired verbal memory and verbal fluency are frequently found in adults with schizophrenia, there has been a paucity of studies investigating adolescents with schizophrenia. Thus, the aim of the present study was to investigate the main subcomponents of verbal memory and verbal fluency in adolescents with schizophrenia spectrum disorders. Methods: Verbal learning and memory and verbal fluency was assessed in 21 adolescents with schizophrenia spectrum disorders (mean age, 15.4 years) compared with 28 healthy adolescents (mean age, 15.1 years). Results: The patient group performed significantly below healthy controls on measures of learning, delayed recall and on a frequency estimation task. No differences between the groups were found for measures of recognition, retention, implicit memory, or susceptibility to interference. Although they had impaired delayed recall the patients remembered most of what they actually learned. The patient group was impaired on phonological and semantic fluency, but there were no differences between the groups with respect to clustering or switching on the fluency tasks, when controlling for total output. There was no disproportionate impairment in semantic, as compared to phonological fluency, in the patient group. Conclusions: Adolescents with schizophrenia spectrum disorders exhibit impairments in verbal learning and verbal fluency, which might have an impact on the individual's everyday functioning.     

Disordered connectivity associated with memory deficits in children with autism spectrum disorders

The present study examined the memory performance and cortical connectivity of children with ASD, and investigated whether the memory deficits exhibited by these children were associated with the cortical connectivity. Twenty-one children with ASD and 21 children with normal development (NC), aged 5–14 years, participated in the study. Each child was administered a neuropsychological battery that included the Test of Non-verbal Intelligence (TONI-III), Digit Span test (DS), Rey-Osterrieth Complex Figure Test (Rey-O), and Hong Kong List Learning Test (HKLLT); and an EEG recording session when performing the visual encoding Object Recognition (OR) task. Six neuropsychological measures from the test battery and six EEG coherence measures in the theta band were compared between the children with ASD and normal children. Results indicated that children with ASD performed at comparable levels with normal children in the DS and Rey-O, but were significantly poorer in HKLLT and OR. They also exhibited significantly elevated long-range coherences in the fronto-posterior connections involving the left hemisphere (left anterior–left posterior; left anterior–right posterior). Pearson correlation showed significant negative associations between the anterior–posterior EEG coherences and memory performance.     

Elevated levels of schizotypal features in parents of patients with a family history of schizophrenia spectrum disorders

There is some evidence that schizotypal traits are related to a genetic or familial liability to develop schizophrenia. However, it is unclear whether the number of schizotypal traits is elevated in parents of schizophrenia patients compared with controls. This study used the Schizotypal Personality Questionnaire to investigate the difference in number of schizotypal traits between both parents of 36 patients with schizophrenia (n = 72 persons) and 26 healthy married control couples (n = 52 persons). Parents of patients had a lower score on the positive dimension of schizotypy than healthy controls. There was no difference on the negative or disorganization dimension between groups. The difference on the positive dimension might have been caused by a difference in response style between parents of patients and controls due to the fact that parents are more familiar with schizophrenia than controls. Of interest, parents with a family history of schizophrenia spectrum disorders had more positive and negative schizotypal traits than parents without a family history of schizophrenia spectrum disorders. Because these two groups of parents differ in only genetic risk, not familiarity with schizophrenia, results suggest that the negative and positive dimension of schizotypy are related to a familial or genetic vulnerability to schizophrenia.     

The Emotional Stroop task: A comparison between schizophrenic subjects and controls

The colour-word Emotional Stroop task (ES task) has been proposed to assess the interferences between emotion and attention. Using this task, first, we examined how attention (using reaction times) can be modified by emotionally relevant words in schizophrenics as compared with controls as a function of the emotional significance of the word; second, we tested the assumption that schizophrenics with the most negative symptoms will show higher impairment in relationship to negative emotional words. In general, schizophrenics were slower to react. In both groups, mean reaction times were slower for emotional as compared with neutral words. No significant differences were observed between negative and positive words either in schizophrenics (n = 21) or in controls (n = 20). Even in the most negative schizophrenic patients, there were no differences between negative and positive words. There were no significant interactions between type of stimulus and any clinical variables (PANSS negative or non negative categorization, etc.). Also, there were no statistically significant correlations between reaction times and neuroleptic dosage or anhedonia scores. In conclusion, schizophrenia patients showed the same degree of interference from emotional words as compared with controls. Moreover, patients with a higher level of negative symptoms did not differently experience positive and negative words.     

Prefrontal hyperactivation during a working memory task in early-onset schizophrenia spectrum disorders: An fMRI study

Working memory (WM) dysfunction is increasingly recognized as a core feature of schizophrenia, but few studies have investigated prefrontal activation during WM tasks in early-onset schizophrenia spectrum disorder (EOS). Our aim was to explore prefrontal activation during a WM-task in EOS patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Fifteen patients with EOS and 15 matched healthy controls performed a 0-back and a 2-back task while fMRI data were acquired. Results indicated that even though performance between patients and controls was comparable on both tasks, there was a hyperactivation in patients' ventrolateral prefrontal cortex (VLPFC) during the 2-back task compared to healthy controls. This pattern of activation suggests that, in patients with EOS, the VLPFC compensated in order to match performance of the controls. The activations in the EOS group may reflect the use of a compensatory, cognitive strategy while solving WM-tasks.     

Immediate effects of risperidone on cerebral activity in healthy subjects: a comparison with subjects with first-episode schizophrenia

OBJECTIVE: To test the hypothesis that administration of risperidone to healthy subjects produces reductions in metabolism in the frontal cortex similar to those produced by administration of risperidone to patients experiencing a first episode of schizophrenia. METHODS: Positron emission tomography was used to measure the changes in regional metabolism produced by a single 2-mg dose of risperidone and by placebo, administered under randomized, double-blind conditions, in 9 healthy subjects. Conjunction analysis was used to identify those cerebral sites where changes in metabolism in the healthy subjects coincided with similar changes in metabolism observed in patients with schizophrenia. RESULTS: Compared with placebo, risperidone produced reductions in metabolism in the left lateral frontal cortex and right medial frontal cortex in healthy subjects. Conjunction analysis revealed that these changes occurred at locations similar to the loci of change produced by risperidone in patients with schizophrenia. CONCLUSION: Because the reduction in metabolism in the medial frontal cortex produced by risperidone is associated with alleviation of positive symptoms in patients with schizophrenia, the observation of a reduction in metabolism at a similar site in healthy subjects supports the hypothesis that the antipsychotic effect of risperidone arises, at least in part, from a physiologic effect that occurs in both patients with schizophrenia and healthy subjects.     

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.     

Elevated levels of cognitive-perceptual deficits in individuals with a family history of schizophrenia spectrum disorders

This study finds that the relatives of schizophrenics have elevated scores on the cognitive-perceptual factor of the schizotypal personality questionnaire (SPQ), particularly for the 'unusual perceptual experiences' and 'ideas of reference' subscales. These results support recent findings by Kremen et al. (1998) and suggest that previous failures to demonstrate elevated scores on 'positive' symptoms of schizotypy may be a function of instrumentation.     

Identification and management of cardiometabolic risk in subjects with schizophrenia spectrum disorders: A Delphi expert consensus study

BackgroundPatients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method.MethodsThe steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists.ResultsConsensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners.ConclusionsThis study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.     

Associations of anhedonia and cognition in persons with schizophrenia spectrum disorders, their siblings, and controls

The aim of the current study was to investigate the levels of social and physical anhedonia, as measured with the Chapman Scales for social and physical anhedonia in groups of patients with schizophrenia spectrum psychosis (n = 91), their unaffected siblings (n = 105), and control subjects drawn from a general population (n = 67). The second aim was to explore the effect of physical and social anhedonia on neuropsychological variables. Subjects with schizophrenia spectrum disorder had significantly more anhedonia than population controls, but the unaffected siblings did not differ from controls. Subjects with schizophrenia spectrum disorders had generalized cognitive deficits. Unaffected sibling status predicted impairments in executive and performance speed measures. Elevated physical anhedonia associated with deficits in verbal functions, but this was not related to genetic liability to schizophrenia. In conclusion, social and physical anhedonia did not seem to mediate neuropsychological deficits of schizophrenia family members.     

Serotonin function in schizophrenia: effects of meta-chlorophenylpiperazine in schizophrenic patients and healthy subjects.

This study examined serotonin (5-hydroxytryptamine; 5HT) receptor responsivity in 22 chronic schizophrenic patients and 17 healthy control subjects. The 5HT agonist meta-chlorophenylpiperazine (MCPP) was used as a probe of serotonergic function. MCPP (0.35 mg/kg) or placebo was administered orally after a 3-week drug-free period in a randomized double-blind design. Hormonal (adrenocorticotropic hormone and prolactin), temperature, and behavioral responses and MCPP blood levels were assessed for 210 minutes after administration of the capsules. The schizophrenic patients had blunted temperature responses compared with those of the healthy control subjects: MCPP raised body temperature in the control subjects, but not in the patients. Behavioral responses also differed in the two groups: MCPP increased the total Brief Psychiatric Rating Scale (BPRS) score in the control subjects and tended to decrease it in the patients. In patients, MCPP decreased the BPRS psychosis subscore. Hormonal responses did not differ significantly in the two groups. These findings suggest that further exploration of 5HT function in schizophrenia is warranted.