Building a neurocognitive profile of suicidal risk in severe mental disorders.

BACKGROUND: Research on the influence of neurocognitive factors on suicide risk, regardless of the diagnosis, is inconsistent. Recently, suicide risk studies propose applying a trans-diagnostic framework in line with the launch of the Research Domain Criteria Cognitive Systems model. In the present study, we highlight the extent of cognitive impairment using a standardized battery in a psychiatric sample stratified for different degrees of suicidal risk. We also differentiate in our sample various neurocognitive profiles associated with different levels of risk. MATERIALS AND METHODS: We divided a sample of 106 subjects into three groups stratified by suicide risk level: Suicide Attempt (SA), Suicidal Ideation (SI), Patient Controls (PC) and Healthy Controls (HC). We conducted a multivariate Analysis of Variance (MANOVA) for each cognitive domain measured through the standardized battery MATRICS Consensus Cognitive Battery (MCCB). RESULTS: We found that the group of patients performed worse than the group of healthy controls on most domains; social cognition was impaired in the suicide risk groups compared both to HC and PC. Patients in the SA group performed worse than those in the SI group. CONCLUSION: Social cognition impairment may play a crucial role in suicidality among individuals diagnosed with serious mental illness as it is involved in both SI and SA; noteworthy, it is more compromised in the SA group fitting as a marker of risk severity.

Neurocognitive Assessment and Retinal Thickness Alterations in Alzheimer Disease: Is There a Correlation?

BACKGROUND: The relation of retinal thickness to neuropsychological indexes of cognitive impairment in patients with Alzheimer disease (AD) remains an area of investigation. The scope of this investigation was to compare volume and thickness changes of neuronal retinal layers in subjects with AD with those of age-matched healthy controls and to estimate the relation between cognitive functioning evaluated by neuropsychological assessment and thickness changes of the retina. METHODS: This was a prospective single-site study where we evaluated 25 subjects with probable AD matched for age, sex, and education to 17 healthy control subjects (HC). All participants underwent a full medical evaluation, neuropsychological assessment, and optical coherence tomography (OCT) to evaluate the peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell complex (GCC) thickness, and macular volume. RESULTS: The pRNFL thickness of AD patients showed a significant overall reduction compared with healthy controls (P = <0.0001). Furthermore, pRNFL was reduced in each retinal quadrant, particularly the inferior, nasal, and superior quadrants. GCC thickness and macular volume were reduced in AD patients in comparison with HC (P = 0.004; P = 0.001). Of particular interest was the correlation between OCT findings and neuropsychological assessment; we did not find a significant association of retinal thinning with worse MMSE score, but reduction of macular volume was associated with worse constructional praxis performance. Impairment of semantic-lexical and processing speed was associated with attenuation of macular GCC thickness. CONCLUSIONS: OCT can show early thickness changes in AD patients with subtle memory disturbances. These results suggest that correlations between retinal thinning and cognitive performance warrant further investigation.

Neurovascular Dysfunction in Alzheimer Disease: Assessment of Cerebral Vasoreactivity by Ultrasound Techniques and Evaluation of Circulating Progenitor Cells and Inflammatory Markers.

AIMS: The aims of this study were to assess vascular dysfunction in patients with Alzheimer disease (AD) by investigating cerebral vasomotor reactivity using transcranial Doppler ultrasound (TCD) and to evaluate any correlations between cerebral vasoreactivity and endothelium dysfunction. Moreover, the frequency of circulating progenitor cells (CPCs) and the blood concentration of vascular/inflammatory markers were evaluated. MATERIALS AND METHODS: We recruited 35 AD subjects and 17 age-matched, sex-matched, and education-matched healthy control subjects. Cerebral vasomotor reactivity was assessed by means of the TCD-based breath-holding index test (BHI). The level of CPCs was evaluated by means of flow cytometry from venous blood samples, while blood vascular/inflammatory markers were measured by means of enzyme-linked immunosorbent assay. RESULTS: Both cerebral assay blood flow velocity in the middle cerebral artery (MCAFV) and BHI values were significantly lower in AD subjects than in healthy controls (P<0.05). A positive trend was found between MCAFV and BHI values and Mini-Mental State Evaluation (MMSE) scores. Moreover, the hematopoietic progenitor cells' count was found to be lower in patients with AD than in controls (P<0.05). Finally, a significantly higher expression of the plasma chemokine CCL-2 was observed in AD patients than in healthy controls. CONCLUSIONS: Our results confirm that cerebral hemodynamic deterioration may be a critical marker of cognitive decline. Further studies are needed to investigate the role of circulating CPCs and chemokines as potential contributors to neurovascular dysfunction.

Cognitive profiles in degenerative dementia without evidence of small vessel pathology and small vessel vascular dementia.

Although a large number of studies have examined possible differences in cognitive performance between Alzheimer's disease (AD) and vascular dementia (VaD), the data in the literature are conflicting. The aims of this study were to analyze the neuropsychological pattern of subjects affected by degenerative dementia without evidence of small vessel pathology (DD) and small vessel VaD subjects in the early stages and to investigate differences in the progression of cognitive impairment. Seventy-five patients with probable VaD and 75 patients with probable DD were included. All the subjects underwent a standard neuropsychological evaluation, including the following test: Visual Search, Attentional matrices, Story Recall, Raven's Coloured Progressive Matrices, Phonological and Semantic Verbal Fluency, Token, and Copying Drawings. The severity of cognitive impairment was stratified according to the MMSE score. Fifteen subjects with probable DD and 10 subjects with probable VaD underwent a 12-month cognitive re-evaluation. No significant difference was found between DD and VaD subjects in any of the neuropsychological tests except Story Recall in the mild cognitive impairment (P < 0.001). The re-test value was significantly worse than the baseline value in the MMSE (P = 0.037), Corsi (P = 0.041), Story Recall (P = 0.032), Phonological Verbal Fluency (P = 0.02), and Copying Drawings (P = 0.043) in DD patients and in the Visual Search test (P = 0.036) in VaD subjects. These results suggest that a neuropsychological evaluation might help to differentiate degenerative dementia without evidence of small vessel pathology from small vessel VaD in the early stages of these diseases.

Anomalous self-experiences and their relationship with symptoms, neuro-cognition, and functioning in at-risk adolescents and young adults.

Empirical and theoretical studies support the notion that anomalous self-experience (ASE) may constitute a phenotypic aspect of vulnerability to schizophrenia, but there are no studies examining the relationship of ASE with other clinical risk factors in a sample of ultra-high risk (UHR) subjects. The aim of the present study was to explore the relationship between ASE, prodromal symptoms, neurocognition, and global functioning in a sample of 45 UHR adolescents and young adults (age range 15-25years) at first contact with Public Mental Health Services. Prodromal symptoms and global functioning were assessed through the SIPS interview. ASE was evaluated through the Examination of Anomalous Self-Experience (EASE); for neurocognition, we utilized a battery of tests examining seven cognitive domains as recommended by the Measurement And Treatment Research to Improve Cognition in Schizophrenia. In the UHR group, higher levels in two domains of the EASE (stream of consciousness and self-awareness) were found in comparison with help-seeking subjects. Correlational analysis corrected for possible confounding variables showed a strong association (p>0.001) between higher EASE scores and global functioning. A principal factor analysis with Varimax rotation yielded a two-factor solution, jointly accounting for 70.58% of the total variance in the UHR sample. The first factor was comprised of SOPS domains, while the second was comprised of EASE-total, EASE-10, and GAF variables. Our findings provide support for the notion that disorders of self-experience are present early in schizophrenia and are related to global functioning. As such, they may constitute a potential marker of risk supplementing the UHR approach.

Basic symptoms and psychotic symptoms: their relationships in the at risk mental states, first episode and multi-episode schizophrenia.

In the field of the early psychosis two main approaches attempt to develop rating tools, one investigating the basic symptoms domain, and the other the attenuated psychotic symptoms. To explore the relationship between basic symptoms (BSs) and other symptom domains in different phases of the psychotic illness 32 at ultra-high risk (UHR), 49 first episode schizophrenia (FES), 42 multiple episode schizophrenia (MES), and 28 generalized anxiety disorder (GAD) patients were enrolled. Participants were assessed using the SIPS/SOPS and the FCQ scales. Analyses of covariance taking into account socio-demographic and clinical variables significantly different between groups were applied to compare FCQ and SOPS scores. Finally FCQ and SOPS principal component analysis was carried out in the schizophrenia spectrum group. SOPS scores were higher in the UHR, FES and MES groups compared to the GAD control group. Concordantly, FES and MES groups had a higher number of basic symptoms in comparison with the GAD group, whereas UHR did not differ from the control group. The largest number of correlations between BSs and psychotic symptoms was found in the GAD group. According to the principal component analysis (PCA) five factors were extracted, with the BSs loading on a unique factor. Our findings imply that the boundary between psychotic and non-psychotic conditions cannot be outlined on the basis of the presence/absence of basic and psychotic symptoms.

Symptom correlates of facial emotion recognition impairment in schizophrenia.

BACKGROUND: The ability to facial emotion recognition (FER), a key component of socioemotional competence, is often impaired in schizophrenic disorders. The purpose of the present study was to examine the relationship between emotion recognition performance and symptoms in a group of patients with schizophrenia spectrum disorders. SAMPLING AND METHODS: Seventy-nine patients meeting DSM-IV-TR criteria for schizophrenia, schizophreniform disorder and schizoaffective disorder were assessed by the Positive and Negative Syndrome Scale and a FER task. In schizophrenia patients and healthy control subjects, FER performance was compared. In order to avoid a possible confounding role of cognitive impairment, we carried out partial correlations corrected for an index of global cognition. RESULTS: Patients performed worse than a healthy control group on all negative emotions. Partial correlations showed that cognitive/disorganized symptoms correlated with a worse performance in the FER task, whereas no correlations were found with positive, negative, excitement and depressive symptoms. CONCLUSIONS: Our findings support that in schizophrenia FER impairment is specific for negative emotions and that there is a relationship between this deficit and cognitive/disorganized symptoms, regardless of the general cognitive level.

A case of rapid conversion to psychosis of delusional misidentification associated with derealisation, verbal memory impairment and FDG-PET imaging abnormalities.

The delusional misidentification syndromes, occurring within the context of different nosological settings, such as schizophrenia, are psychopathological phenomena related to the experience of depersonalisation/derealisation. Extensive research indicates that individuals meeting specific "prodromal" criteria, such as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or functional decline and family history of schizophrenia have increased risk for impending psychosis. Despite depersonalisation and/or derealisation often precede psychotic onset, they are not included among the prodromal criteria of the Australian-American approach. A 17-year-old boy with acute agitation, violent behaviour and aggression, and dissociative amnesia had a mild verbal memory impairment and temporo-limbic hypometabolism on the positron-emission tomography. The patient was assessed with both the ultra-high risk (UHR) and the basic symptom approaches and was not found to be prodromal with imminent risk of transition to psychosis. He was hospitalised briefly and 2 weeks after discharge he developed delusional misidentification. This case shows that even the integration of both UHR and basic symptoms criteria may give false negatives in the prediction of psychosis, especially in those cases in which a long prodromal phase is absent.

Relationships between psychopathological variables and insight in psychosis risk syndrome and first-episode and multiepisode schizophrenia.

Insight may vary across psychosis risk syndrome (PRS), first-episode schizophrenia (FES), or multiepisode schizophrenia (MES). We aimed to compare insight domains (awareness, relabeling, and compliance) in PRS, FES, and MES groups and to correlate scores with psychopathological measures. Insight was assessed in 48 (14 PRS, 16 FES, and 18 MES) patients using the Schedule for the Assessment of Insight-Expanded Version. We conducted psychopathological assessment through the Brief Psychiatric Rating Scale (BPRS). In the whole group, the BPRS psychosis factor correlated with all insight domains. In the MES group, the more severe the anxiety/depression, the higher the insight score in the symptom relabeling domain. Insight did not differ significantly between the PRS, FES, and MES groups. Our results suggest that, across different phases of the illness, lack of insight behaves like a trait and is modulated by positive symptom severity. Anxiety and depression may be associated with increased insight in patients with chronic schizophrenia.

Neurocognition, psychopathology, and subjective disturbances in schizophrenia: a comparison between short-term and remitted patients.

Patients with schizophrenia present deficits in multiple domains of cognition. The study of the relationship between cognitive performance and symptoms of schizophrenia has yielded heterogeneous results. The purposes of this study were to examine the extent of the relationship between psychopathologic symptoms, cognitive function, and subjective disturbances in a group of patients affected by schizophrenia spectrum disorders and to compare short-term with remitted patients. Seventy-nine patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenia, schizophreniform disorder, and schizoaffective disorder were assessed through the Positive and Negative Syndrome Scale, the Frankfurt Complaint Questionnaire, and a neuropsychologic battery exploring the 7 Measurement and Treatment Research to improve Cognition in Schizophrenia cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) plus executive control. Neuropsychologic and psychopathologic variables were compared and correlated. Treatment groups did not differ in neuropsychologic and psychopathologic measures. The cognitive factor of the Positive and Negative Syndrome Scale correlated with worse performance on cognitive tasks and with higher scores on the Frankfurt Complaint Questionnaire 24 in the short-term, remitted, and combined groups. Subjective disturbances correlated with impaired executive control, reasoning and problem solving, and social cognition but not during the short-term phase. Both "objective" and subjective psychopathology are intertwined with cognitive function, suggesting some common underlying neural bases. The condition of being in a short-term or a remitted phase of the illness influences this interrelationship, regardless of the type of antipsychotic medication taken.

Subjective disturbance of perception is related to facial affect recognition in schizophrenia.

To examine the relationship between facial affect recognition (FAR) and subjective perceptual disturbances (SPDs), we assessed SPDs in 82 patients with DSM-IV schizophrenia (44 with first-episode psychosis [FEP] and 38 with multiple episodes [ME]) using two subscales of the Frankfurt Complaint Questionnaire (FCQ), WAS (simple perception) and WAK (complex perception). Emotional judgment ability was assessed using Ekman and Friesen's FAR task. Impaired recognition of emotion correlated with scores on the WAS but not on the WAK. The association was significant in the entire group and in the ME group. FAR was more impaired in the ME than in the FEP group. Our findings suggest that there is a relationship between SPDs and FAR impairment in schizophrenia, particularly in multiple-episode patients.

Extraversion and accuracy of aspects of memory for pain in the cold water pressor test.

The role of Erlebnistypus personality features were investigated in 40 healthy subjects, as defined by the Rorschach Comprehensive System by Exner, in determining accuracy in recollecting acute tonic experimental pain, induced by the Cold Water Pressor Test. Multiple-regression analysis revealed that the difference between the number of movement answers and the number of chromatic answers in the Rorschach test, an index of general Extroversion, predicted accuracy in recollecting the qualitative features of pain, defined as affective and evaluative pain scores on the McGill Pain Questionnaire. Also, Extratensive subjects were less accurate than Introversive and Ambitent participants at recollecting sensory scores. The data suggest that general extroversion may have a role in individual differences in the higher cognitive processing of pain comprising pain memory.

Relationship between aberrant salience and positive emotion misrecognition in acute relapse of schizophrenia.

INTRODUCTION: Aberrant salience is the incorrect assignment of salience or significance to innocuous stimuli, and been hypothesized to be a central mechanism in the development of psychosis. In addition to aberrant salience, social-cognitive models of psychosis suggest that the way people process information about the self is important in all stages of psychosis. The aim of the present study is to explore the relationship between aberrant salience and emotion processing in schizophrenia patients with psychotic relapse. METHODS: A sample of 42 patients with relapse was recruited. Aberrant salience was measured with the Aberrant Salience Inventory (ASI). Assessment of social cognition was carried out using the Facial Emotion Identification Test (FEIT). Partial correlations were controlled for possible confounding variables. RESULTS: The ASI factors "increase in meaning" and "heightened cognition" positively correlated with impaired recognition of positive emotions, and ASI total score inversely correlated to time to response to task. Most of incorrect answers corresponded to misclassification of positive emotions. CONCLUSION: Our findings show that there is evidence for a relationship between aberrant salience and emotion processing during a psychotic episode; we propose that aberrant salience and alterations in emotion processing trigger the loss of modulating feedback from the external world to produce a self-referential mental state.

Heritability of neurocognitive functioning in the elderly: evidence from an Italian twin study.

BACKGROUND: the genetic and environmental origins of individual differences in specific cognitive abilities in the elderly are poorly understood. One reason is the lack of studies performed in cohorts with normal cognitive functions. OBJECTIVE: to estimate the relative contributions of genetic and environmental factors in determining inter-individual variation in neurocognitive abilities in the Italian population. DESIGN: cross-sectional analysis of twin data. SETTING: a sample of older twins with normal cognition from the population-based Italian Twin Registry (ITR). SUBJECTS: twin pairs resident in Rome and born between 1926 and 1940, identified through the ITR in 2002. The final study population included 93 twin pairs. METHODS: subjects underwent neuropsychological tests providing information about different cognitive domains. The contributions of genetic and environmental effects were assessed using standard univariate twin modelling based on linear structural equations. RESULTS: the best-fitting model incorporated additive genetic (A) and unique environmental (E) sources of variance for the following tests: Mini-Mental State Examination (A = 55%), Raven (A = 56%), Attentional Matrices (A = 79%), Copying Drawings (A = 69%) and Story Recall (A = 54%). For Phonological and Semantic Verbal Fluency, the best model included non-additive (D) and unique environmental influences (D = 62 and 54%, respectively). Cigarette smoking was estimated to be negatively associated with the score of Phonological Verbal Fluency. For Token test, the inter-individual variance was entirely due to environmental factors not shared by the twins. CONCLUSION: our data showed that most of the specific cognitive abilities are moderately to highly heritable, and that the environmental factors of relevance for these abilities are those causing within-family differences.

Long-Acting Injectable Second-Generation Antipsychotics Improve Negative Symptoms and Suicidal Ideation in Recent Diagnosed Schizophrenia Patients: A 1-Year Follow-up Pilot Study.

Long-acting injectable second-generation antipsychotics (LAI-SGA) are typically used to maintain treatment adherence in patients with chronic schizophrenia. Recent research suggests that they may also provide an effective treatment strategy for patients with early-phase disease. The aim of this study is to evaluate clinical and psychosocial outcomes among recent and long-term diagnosed schizophrenia outpatients treated with LAI-SGA during a follow-up period of 12 months. Stable schizophrenia patients receiving LAI-SGA with 5 or less years of illness duration (n = 10) were compared to those with more than 5 years of illness duration (n = 15). Clinical data was assessed through the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF), the Columbia Suicide Severity Rating Scale (C-SSRS), the Recovery Style Questionnaire (RSQ), and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) Managing Emotion branch. Recently diagnosed patients showed greater improvement versus patients diagnosed for more than 5 years in adjusted mean GAF score, in PANSS factor score for negative and depressive symptoms, and in severity and intensity of suicidal ideation. Our preliminary findings support the hypothesis that LAI-SGA may influence the course of the illness if administered at the early phase of the illness. However, replicate studies are needed, possibly with larger samples.

Health-related quality of life in myotonic dystrophy type 1 and its relationship with cognitive and emotional functioning.

OBJECTIVE: To evaluate the health-related quality of life in myotonic dystrophy type 1 and its relationships with clinical, genetic, neuropsychological and emotional factors. DESIGN: Case-control study of a continuous series of patients with myotonic dystrophy type 1. PATIENTS AND METHODS: Twenty patients, and 20 age-, sex- and education-matched healthy controls underwent the MOS 36-Item Short-Form Health Survey (SF-36), an extensive neuropsychological battery and emotional functioning tests. RESULTS: Patients' SF-36 mean scores were lower than those of controls in all dimensions. The neuropsychological study showed a significant impairment in visuospatial and verbal abstract reasoning (p=0.001), visuospatial memory (p=0.002) and attentive functions (p=0.03) in patients with myotonic dystrophy type 1. The emotional assessment showed significantly high scores in anxiety (p=0.002) and depression (p=0.001), which occurred in approximately 50% of patients. Both physical and mental SF-36 areas were inversely correlated with age, duration and grade of disease, depression and anxiety and positively correlated with attentive control. SF-36 areas were not correlated with cytosine thymine guanidine expansion. CONCLUSION: Health-related quality of life is severely impaired in myotonic dystrophy type 1 and it is negatively influenced by severity and duration of disease as well as by specific cognitive deficits and changes in emotional functioning. Therapeutic intervention in this field could contribute to ameliorate health-related quality of life in myotonic dystrophy type 1.

Validity of the Italian telephone version of the mini-mental state examination in the elderly healthy population.

The biggest challenge regarding cognitive prospective evaluations in the elderly is the identification of subjects that go on to develop cognitive impairment. In this study, we compared the Italian telephone version of the MMSE (Itel-MMSE) with both the MMSE and a battery of neuropsychological tests in a group of 107 healthy elderly subjects. The aim of the study was to identify a subset of subjects who, despite having an overall score within the normal range, performed poorly in the cognitive neuropsychological evaluation. The Itel-MMSE score showed a good internal consistency as well as a significant correlation with the MMSE score, age and education. A score of < or = 21 on the Itel-MMSE was the score which reflected the highest degree of sensitivity in the neuropsychological tests. There was a statistically significant difference between subjects with an Itel-MMSE score of < or = 21 and those with a score of 22 in age, education, Attentional Matrices and Copying Drawings. Despite some potential limitations, our results strongly suggest that the Itel-MMSE may be used as a screening test to identify healthy elderly subjects whose cognitive performance is poor.

Correlation between metal ions and clinical findings in subjects affected by Alzheimer's disease.

There is a growing interest to evaluate metals in biological fluids in Alzheimer's disease (AD). There are numerous studies on this theme, but just few papers analyzed the relationship between haematic metal concentrations and the clinical features of the disease. In this study, possible associations between clinical features of AD and the variations in serum and blood concentration of some metals, as well as the serum oxidative status and the antioxidant capacity have been investigated. Sixty subjects with AD were enrolled. Some elements correlated with gender, depression and duration of the disease. However, the most significant result was the relationship between blood Ca and Fe levels and the severity of cognitive impairment. We hypothesize that Ca and Fe might play an important role in the pathogenetic mechanisms of AD.