Can specific deficits in executive functioning explain the negative symptoms of schizophrenia? A review

The relationship between clinical symptoms and neurocognitive impairment has been a growing interest in the field of schizophrenia research. We review the empirical evidence for whether some schizophrenia symptoms can be viewed as expressions of disordered executive functioning. A specific focus of our review is Frith's (1992) neurocognitive theory of negative symptoms, and whether this theory is supported by studies of executive functioning in schizophrenia. The current trend towards viewing executive functioning in terms of fractionable cognitive processes is discussed. Difficulties with traditional clinical measures (e.g. the Wisconsin Card Sorting Test; WCST) in separating these processes are highlighted. Neurocognitive studies of schizophrenia are then reviewed in terms of this fractionated view of executive processes. We conclude that a more specific approach to executive functioning deficits in schizophrenia using more selective measures is needed before stronger conclusions can be drawn about their relationship to clinical symptoms.     

A systematic review of multisensory cognitive–affective integration in schizophrenia

The etymology of schizophrenia implies poor functional integration of sensory, cognitive and affective processes. Multisensory integration (MSI) is a spontaneous perceptual–cognitive process by which relevant information from multiple sensory modalities is extracted to generate a holistic experience. Deficits in MSI may hinder prompt and appropriate behavioural responses in a complex and transient environment. Despite extensive investigation of sensory, cognitive and affective processing in patients with schizophrenia, little is known about how MSI is affected in the illness. We systemically searched the PubMed electronic database and reviewed twenty-nine behavioural and neuroimaging studies examining MSI in patients with schizophrenia. The available evidence indicates impaired MSI for non-emotional stimuli in schizophrenia, especially for linguistic information. There is also evidence for altered MSI for emotional stimuli, although findings are inconsistent and may be modality-specific. Brain functional alterations in the superior temporal cortex and inferior frontal cortex appear to underlie the deficits in both non-emotional and emotional MSI. The limitations of the experimental paradigms used and directions for future research are also discussed.     

Do the obsessive-compulsive symptoms have an effect in schizophrenia?

Objective

Schizophrenia presents with different symptom domains and functionality during its course. Obsessive-compulsive (OC) symptoms in schizophrenia have many themes to be clarified. Our aim was to compare schizophrenia patients with and without OC symptoms in terms of symptom domains, cognitive functions, and quality of life.

Method

Sixty-two patients who met schizophrenia diagnosis were assessed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition consecutively over a period of 12 months in the setting of an outpatient clinic at medical university hospital. Yale-Brown Obsessive-Compulsive Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, and neuropsychologic tests were used. Quality of life was assessed with Quality of Life Scale for Patients with Schizophrenia.

Results

Obsessive-compulsive symptoms along with schizophrenia were present in a considerable number in our sample (35.5%). Level of psychotic symptoms was more severe and quality of life was lower in schizophrenia patients with OC symptoms. A positive correlation was found between obsessions and delusions. Moreover, there was a positive correlation between compulsions and total Scale for the Assessment of Positive Symptoms score and bizarre behaviors subscore. There was no difference between the 2 groups regarding neurocognitive functions. The level of quality of life of schizophrenic patients with OC symptoms was lower. Besides, no correlation was found between OC symptoms and neurocognition and quality of life.

Conclusions

The findings of this study indicate that schizophrenia patients with OC symptoms had severe psychotic symptoms with a distinctive clinical picture including good neurocognition but poor functioning.     

A role for the BDNF gene Val66Met polymorphism in schizophrenia? A comprehensive review

Schizophrenia is believed to arise from complex gene–environment interactions. Brain-derived neurotrophic factor (BDNF) is involved in neuronal development, differentiation and plasticity. A functional single nucleotide polymorphism that results in a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met) results in the aberrant sorting and release of mature BDNF through the activity-dependent secretion pathway. The Val66Met polymorphism has been linked to impaired neurocognitive function in healthy adults, and identified as a locus of risk for a range of neuropsychiatric disorders including schizophrenia. Here we provide a comprehensive review of the relationship between the BDNF Val66Met polymorphism and schizophrenia, integrating evidence from the fields of genetic epidemiology, clinical psychiatry, behavioral neuroscience and neuroimaging. We argue that while the Val66Met polymorphism may not be a major risk-conferring agent for the development of schizophrenia per se, there is mounting evidence that the polymorphism modulates a range of clinical features of the illness, including age of onset, symptoms, therapeutic responsiveness, neurocognitive function and brain morphology.     

Sleep state misperception in schizophrenia: Are negative symptoms at work?

ObjectiveThis study investigates subjective and objective sleep quality to ascertain whether there is a sleep state misperception in schizophrenia patients, as well as analyze potential effect factors.MethodsA total of 148 inpatients with schizophrenia admitted to Beijing HuiLongGuan Hospital were enrolled in this study. The quality of objective sleep was assessed by polysomnography (PSG). On the second day after the successful completion of the PSG evaluation, an interview was arranged to collect patients' recorded subjective evaluation on sleep time, sleep latency, and wake times. Demographic information was collected from an interview, medical records were reviewed, and psychiatric symptoms were assessed using the Positive And Negative Symptom Scale (PANSS).ResultsThe main finding of this study was that schizophrenic patients exhibited sleep state misperception with a pattern of overestimation of total sleep time (TST) as well as sleep efficiency (SE), and an underestimation of sleep onset latency (SOL). Regarding the ± standard deviation of the differences between subjective and objective TST as a clinical acceptable range, the patients were divided into three groups: the overestimate group, the normal group, and the underestimate group. The differences of total PANSS score, especially the PANSS-N score in the overestimate group, the normal group and the underestimate group were significant, and there were significant differences between the overestimate group and the other groups.ConclusionA comprehensive evaluation of the subjective and objective sleep quality in patients with schizophrenia is needed, especially when negative symptoms are severe.     

Is alexithymia related to negative symptoms of schizophrenia? A preliminary longitudinal study

BACKGROUND: Alexithymic features are close to anhedonia, blunted affect, and alogia that are also characteristics of the negative symptoms of schizophrenia. This study aimed to evaluate whether alexithymia is associated with negative symptoms and is related to the change of schizophrenic symptoms over time. SAMPLING AND METHODS: A consecutive sample of 29 schizophrenic outpatients was evaluated at baseline and at 3, 6, and 12 months during appropriate treatment. They completed the Positive and Negative Syndrome Scale, the Montgomery and Asberg Depression Rating Scale, the Global Assessment of Functioning Scale, and the 20-item Toronto Alexithymia Scale at any time points. RESULTS: The psychiatric scale scores showed significant symptom improvement over time but were unrelated to the alexithymia score that was instead stable over time. Hierarchical regression showed that the 20-item Toronto Alexithymia Scale at baseline was the sole predictor of alexithymia at 12 months, after controlling for psychopathology and psychological functioning. CONCLUSIONS: Alexithymia was unrelated to negative symptoms, suggesting it is an independent and separate construct from schizophrenia. As expected, the negative symptoms were associated instead with illness-related aspects of depression and psychosocial functioning. Caution should be expressed in generalization mainly because this study is limited by the small sample size.     

The development of psychotic symptoms in later life: late-onset schizophrenia or frontotemporal dementia? A case study

The diagnosis of psychotic disorders that develop later in life is complicated, as can be seen from the case of a 65-year-old woman. Initially she was admitted to hospital for psychotic depression, but after some time doubts arose regarding the diagnosis. The most striking symptoms were bizarre delusions with acoustic, haptic and gustatory hallucinations. In addition, she showed behavioral and personality changes. It is difficult to establish whether a patient has late-onset schizophrenia or frontotemporal dementia. The similarities and differences between the symptoms of these two disorders are discussed and advice is given to assist with clinicians with diagnosis in the future.     

Obsessive–compulsive symptoms in schizophrenia: prevalence and associated factors in a Nigerian population

Objectives: The objectives of this study were to determine the prevalence of obsessive–compulsive symptoms (OCS) among subjects with schizophrenia and also to determine their associated factors.

Methods: A cross-sectional study involving 232 patients with schizophrenia were recruited from a teaching hospital in Nigeria. Socio-demographic questionnaire, Obsessive–Compulsive Inventory, Positive and Negative Syndrome Scale and Suicidality module of the MINI International Neuropsychiatric Inventory were administered.

Results: The prevalence of OCS was 54.3% among patients with schizophrenia, and washing symptom was the most common (51.7%). Patients with schizophrenia that had OCS had more severe psychopathologies and higher levels of suicidality. OCS among patients with schizophrenia were also associated with the use of second-generation antipsychotic medications.

Conclusions: OCS are common in schizophrenia. Hence, there is a need for routine screening of patients with schizophrenia for OCS and then, manage them appropriately.     

Cardiorespiratory fitness in individuals with intellectual disabilities—A review

Cardiorespiratory fitness is the ability of the circulatory, respiratory and muscular systems to supply oxygen during sustained physical activity. Low cardiorespiratory fitness levels have been found in individuals with intellectual disabilities (ID), which puts them at higher risk for cardiovascular diseases and all-cause mortality. The aims of this review were to update previous reviews about (a) the cardiorespiratory fitness levels and their determinants in individuals with ID, and (b) the validity and reliability of cardiorespiratory fitness testing in individuals with ID. We searched the databases of Pubmed and Embase for relevant studies, resulting in 31 included articles. These studies mainly included younger participants with mild to moderate ID. Results confirmed previous findings of low cardiorespiratory fitness levels in individuals with ID. Cardiorespiratory fitness levels of children and adolescents with ID are already low, with further decline with increasing age. Furthermore, females have lower cardiorespiratory fitness levels than males. Physical inactivity and chronotropic incompetence are most likely to contribute to low cardiorespiratory fitness levels. Peak cardiorespiratory fitness levels of individuals with ID can be assessed with maximal treadmill protocols, after allowing for familiarization sessions. Although, predicting maximal oxygen uptake from field tests is problematic, field tests have been found valid and reliable as indicators of cardiorespiratory fitness.     

Negative symptoms in depressed and schizophrenic patients: how do they differ?

BACKGROUND: The present study evaluated differences in negative symptoms between schizophrenic and depressive patients and investigated whether a consideration of the nature of negative symptoms (enduring vs. nonenduring) can help to improve their specificity for schizophrenia. METHOD: Patients enrolled in the study were consecutively hospitalized with an acute exacerbation of schizophrenia (N = 33) or major depressive disorder (N = 43) (DSM-IV). Negative and depressive symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Montgomery-Asberg Depression Rating Scale, respectively. Duration of negative symptoms was assessed through a semistructured interview with the patients and their closest relatives. On the basis of the assessed duration of symptoms, negative symptoms were categorized as enduring or nonenduring. RESULTS: Analyses revealed high SANS ratings for both diagnostic groups. Negative symptoms in depressive patients (p =.01), but not in schizophrenic patients, were significantly associated with the presence or the emergence of depressive symptoms. The prevalence of enduring negative symptoms was significantly higher in schizophrenic patients than in depressive patients (p <.01). A consideration of enduring negative symptoms significantly increased the discriminative power of negative symptoms for schizophrenia (p =.02). CONCLUSION: The present findings suggest that negative symptoms in most depressive patients are just an epiphenomenon of depressive symptoms and can be distinguished from schizophrenic negative symptoms.     

Amisulpride: is there a treatment for negative symptoms in schizophrenia patients?

In this article we report on a meta-analysis of the published studies of amisulpride conducted in order to demonstrate efficacy on primary negative symptoms in schizophrenia. Four placebo-controlled studies were conducted in patients with predominantly negative symptoms. In all studies a significant improvement was observed on the Scale for the Assessment of Negative Symptoms (SANS) in the amisulpride groups (50-300 mg daily) as compared to placebo. The improvement on the SANS was not accompanied by a simultaneous improvement on the Scale for the Assessment of Positive Symptoms (SAPS) or a decrease in extrapyramidal symptoms (EPS) in three of the four studies, indicating a genuine effect on primary negative symptoms. The overall analysis shows that the improvement on the SANS was accompanied by a small simultaneous improvement on the SAPS. Moreover, in the studies where depressive symptoms were measured, a significant improvement was also shown in favor of amisulpride. However, as the SAPS and the Montgomery Asberg Depression Rating Scale (MADRS) baseline scores were rather low, the improvement on both scales in favor of amisulpride is probably not responsible for the improvement on the SANS. A positive correlation was found between the severity on the mean SANS score at baseline and mean improvement at endpoint, and a surprisingly high success rate was observed in the placebo groups, indicating either that primary negative symptoms are not as persistent as had previously been thought, or that the concept of primary negative symptoms should be reconsidered. Probably amisulpride is efficacious on these nonenduring primary negative symptoms.     

Does sex influence the relation between symptoms and neurocognitive functions in schizophrenia?

OBJECTIVE: A secondary analysis of our data to investigate if sex influences the specificity of the relationship between each of the 3 clinical syndromes (i.e., reality distortion, disorganization and psychomotor poverty) in schizophrenia and the neurocognitive functions that are thought to represent regional brain functions. PATIENTS AND DESIGN: Fifty-seven male and 30 female patients with a DSM-III-R diagnosis of schizophrenia were rated on the Scale for Assessment of Negative Symptoms and the Scale for Assessment of Positive Symptoms to derive scores for psychomotor poverty, disorganization, and reality distortion syndromes. All subjects completed a battery of neuropsychological tests purported to assess functioning of left temporal, right temporal, left basal frontal, right basal frontal, and dorsolateral prefrontal cortex. RESULTS: Correlation coefficients between syndrome scores and neuropsychological measures showed only word fluency (left frontal functioning) to have a statistically significant association with psychomotor poverty in women (p < 0.01). This relation was specific to psychomotor poverty syndrome. No relations between neurocognitive measures and symptoms were seen in men. CONCLUSIONS: The lack of specific relations between symptom dimensions in schizophrenia may be influenced by the fact that the neuronal circuitry associated with particular symptom dimensions may differ in men and women.     

Are cavum septum pellucidum abnormalities more common in schizophrenia spectrum disorders? A systematic review and meta-analysis

Magnetic resonance imaging (MRI) studies have reported a variety of brain abnormalities in association with schizophrenia. These include a higher incidence of cavum septum pellucidum (CSP), which is consistent with a neurodevelopmental model for this disorder. In this meta-analytic review, we describe and discuss the main CSP MRI findings in schizophrenia spectrum disorders (SSDs) to date. We adopted as keywords cavum and schizophrenia or psychosis, and the inclusion criteria were articles in English, with samples of SSD patients compared to healthy subjects, which used MRI to assess CSP, without time limit. From 18 potential reports, fifteen were eligible to be part of the current review. These studies included 1054 patients with SSD and 866 healthy volunteers. Six out of 15 studies pointed to a higher prevalence of CSP of any size in SSD patients, while five out of 15 showed that subjects with SSD had a greater occurrence of a large CSP than healthy individuals. However, the meta-analysis demonstrated that only the incidence of a large CSP was significantly higher in SSD relative to healthy comparisons (odds ratio=1.59; 95%CI 1.07-2.38; p=0.02). Overall our results suggest that only a large CSP is associated with SSD while a small CSP may be considered a normal neuroanatomical variation. Our review revealed a large degree of variability in the methods employed across the MRI studies published to date, as well as evidence of publication bias. Studies in large, community-based samples with greater standardization of methods should clarify the true significance of CSP in SSD.     

A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time?

CONTEXT: Despite improvements in mental health services in recent decades, it is unclear whether the risk of mortality in schizophrenia has changed over time. OBJECTIVE: To explore the distribution of standardized mortality ratios (SMRs) for people with schizophrenia. DATA SOURCES: Broad search terms were used in MEDLINE, PsychINFO, Web of Science, and Google Scholar to identify all studies that investigated mortality in schizophrenia, published between January 1, 1980, and January 31, 2006. References were also identified from review articles, reference lists, and communication with authors. STUDY SELECTION: Population-based studies that reported primary data on deaths in people with schizophrenia. DATA EXTRACTION: Operationalized criteria were used to extract key study features and mortality data. DATA SYNTHESIS: We examined the distribution of SMRs and pooled selected estimates using random-effects meta-analysis. We identified 37 articles drawn from 25 different nations. The median SMR for all persons for all-cause mortality was 2.58 (10%-90% quantile, 1.18-5.76), with a corresponding random-effects pooled SMR of 2.50 (95% confidence interval, 2.18-2.43). No sex difference was detected. Suicide was associated with the highest SMR (12.86); however, most of the major causes-of-death categories were found to be elevated in people with schizophrenia. The SMRs for all-cause mortality have increased during recent decades (P = .03). CONCLUSIONS: With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention.