Predictors of clinical insight in first-episode psychosis: Different patterns in men and women.

BACKGROUND: We aimed to explore gender-related differences in the associations of insight impairment with clinical symptoms, metacognition, and social cognition in psychosis. METHODS: Regression analysis of several clinical insight dimensions was conducted on the data from 116 men and 56 women with first-episode psychosis. Various clinical symptoms and measures of metacognition and social cognition were entered as predictors. RESULTS: In both men and women, delusions emerged as a strong predictor of all insight dimensions, and verbal hallucinations as a strong predictor of symptom relabelling. In men, certain negative symptoms as well as self-certainty, lack of self-reflectiveness, impaired theory of mind, attributional biases, and a jumping-to-conclusions bias were additional predictors of poor insight, while good insight was associated with depression, anxiety, avolition, blunted affect, and impaired emotional recognition. In women, poor insight was associated with a self-serving/externalising bias, impaired emotional recognition, and attention disorders. CONCLUSIONS: Poor insight in first-episode psychosis is strongly linked to deficits in metacognition and social cognition, with marked differences between men and women with respect to the specific skills involved in the impairment. Meanwhile, good insight is linked to a variety of affective manifestations in men. These findings suggest new avenues for more targeted cognitive interventions to improve clinical insight in psychosis.

Neurocognitive bases of self-monitoring of inner speech in hallucination prone individuals.

Verbal hallucinations in schizophrenia patients might be seen as internal verbal productions mistaken for perceptions as a result of over-salient inner speech and/or defective self-monitoring processes. Similar cognitive mechanisms might underpin verbal hallucination proneness in the general population. We investigated, in a non-clinical sample, the cerebral activity associated with verbal hallucinatory predisposition during false recognition of familiar words -assumed to stem from poor monitoring of inner speech-vs. uncommon words. Thirty-seven healthy participants underwent a verbal recognition task. High- and low-frequency words were presented outside the scanner. In the scanner, the participants were then required to recognize the target words among equivalent distractors. Results showed that verbal hallucination proneness was associated with higher rates of false recognition of high-frequency words. It was further associated with activation of language and decisional brain areas during false recognitions of low-, but not high-, frequency words, and with activation of a recollective brain area during correct recognitions of low-, but not high-, frequency words. The increased tendency to report familiar words as targets, along with a lack of activation of the language, recollective, and decisional brain areas necessary for their judgement, suggests failure in the self-monitoring of inner speech in verbal hallucination-prone individuals.

Clinical insight in first-episode psychosis: Clinical, neurocognitive and metacognitive predictors.

OBJECTIVE: Poor insight is a major problem in psychosis, being detrimental for treatment compliance and recovery. Previous studies have identified various correlates of insight impairment, mostly in chronic samples. The current study aimed to determine clinical, neurocognitive, metacognitive, and socio-cognitive predictors of insight in first-episode psychosis. METHODS: Regression analyses of different insight dimensions were conducted in 190 patients with first-episode psychosis. Measures of clinical symptoms, neurocognition, metacognition, social cognition, and 'jumping to conclusions' bias were entered as predictors. RESULTS: Delusions, disorganisation, and certain negative symptoms were associated with unawareness in various domains, while depression was associated with greater awareness of illness. Deficit in theory of mind and self-reflective processes, as well as a 'jumping to conclusions' bias, contributed to poor insight. Several neuropsychological scores also contributed to this but their contribution was no longer observed in regression analyses that included all the previously identified clinical and cognitive predictors. A measure of perseverative errors was still associated with unawareness and misattribution of symptoms. CONCLUSION: In models that account for 28 % to 50 % of the variance, poor insight in first-episode psychosis is mainly associated with delusions and certain negative symptoms. At the cognitive level it does not appear to result from neuropsychological impairment but rather from altered reasoning bias and dysfunction in metacognitive processes. Therapeutic strategies specifically directed at these mechanisms could help improve the evolution of insight in first episode psychosis.

Subclinical depression and anxiety impact verbal memory functioning differently in men and women -an fMRI study.

BACKGROUND: Depressive symptoms are known to affect memory efficiency in various populations. More specifically, several studies conducted in patients suffering from schizophrenia have indicated that memory efficiency is affected by depressed mood in female patients and by anxiety in male patients. We investigated, using neuroimaging techniques, whether similar gender-specific associations with subclinical depression and anxiety could be observed in a non-clinical sample. METHOD: Forty-five healthy Spanish-speaking individuals (23 females) were administered a verbal memory task. Lists of high- and low-frequency words were presented. Immediate free recall was requested after the learning of each list, and a yes/no recognition task was completed during the acquisition of the fMRI data. RESULTS: Regression analyses revealed that higher depression scores in women, and higher anxiety scores in men, were associated with poorer recall. In women, higher depression scores were further associated with decreased cerebral activity in the right temporoparietal junction, left inferior occipitotemporal gyrus, bilateral thalamus, and left anterior cingulate during correct recognition of target words. In men, anxiety scores were not associated with any cerebral activity. CONCLUSIONS: Subclinical depression in women appears to affect memory efficiency by impacting cerebral regions specifically recruited for the cognitive demands of the task, as well as cerebral regions more generally involved in arousal, decision-making, and emotional regulation. Anxiety in men might impact the encoding memory processes. The results, although preliminary, suggest that gender differences may need to be taken into account when developing strategies for the cognitive and pharmacological remediation of memory impairment.

Comparison of the touch-screen and traditional versions of the Corsi block-tapping test in patients with psychosis and healthy controls.

BACKGROUND: Working memory (WM) refers to the capacity system for temporary storage and processing of information, which is known to depend on the integrity of the prefrontal cortex. Impairment in working memory is a core cognitive deficit among individuals with psychotic disorders. The Corsi block-tapping test is a widely-used instrument to assess visuospatial working memory. The traditional version is composed of 9 square blocks positioned on a physical board. In recent years, the number of digital instruments has increased significantly; several advantages might derive from the use of a digital version of the Corsi test. METHODS: This study aimed to compare the digital and traditional versions of the Corsi test in 45 patients with psychotic disorders and 45 healthy controls. Both groups completed a neuropsychological assessment involving attention and working memory divided into the two conditions. RESULTS: Results were consistent between the traditional and digital versions of the Corsi test. The digital version, as well as the traditional version, can discriminate between patients with psychosis and healthy controls. Overall, patients performed worse with respect to the healthy comparison group. The traditional Corsi test was positively related to intelligence and verbal working memory, probably due to a more significant effort to execute the test. CONCLUSIONS: The digital Corsi might be used to enhance clinical practice diagnosis and treatment.The digital version can be administered in a natural environment in real-time. Further, it is easy to administer while ensuring a standard procedure.

Impaired memory for temporal context in schizophrenia patients with hallucinations and thought disorganisation.

INTRODUCTION: Context processing deficiencies have been established in patients with schizophrenia and it has been proposed that these deficiencies are involved in the formation of positive symptoms. METHOD: We administered a temporal context discrimination task to 60 schizophrenia patients and 60 healthy individuals. Pictures were presented in two sessions separated by half an hour and the participants were required to remember afterwards whether the pictures had been presented in the first or the second session. RESULTS: The number of temporal context errors was significantly increased in the patient group. More specifically, it was highly significantly increased in a subgroup of patients presenting hallucinations, while the patients without hallucinations were equivalent to the healthy individuals. Regression analyses revealed that, independently of memory of the pictures themselves, verbal and visual hallucinations, as well as thought disorganisation, were associated with more temporal context errors. In contrast, affective flattening and anhedonia were associated with fewer of these errors. CONCLUSION: Inability to process or remember the temporal context of production of events might be a mechanism underlying both hallucinations and thought disorganisation.

Fluctuating asymmetry in patients with schizophrenia is related to hallucinations and thought disorganisation.

Fluctuating asymmetry represents the degree to which the right and left side of the body are asymmetrical, and is a sign of developmental instability. Higher levels of fluctuating asymmetry have been observed in individuals within the schizophrenia spectrum. We aimed to explore the associations of fluctuating asymmetry with psychotic and affective symptoms in schizophrenia patients, as well as with propensity to these symptoms in non-clinical individuals. A measure of morphological fluctuating asymmetry was calculated for 39 patients with schizophrenia and 60 healthy individuals, and a range of clinical and subclinical psychiatric symptoms was assessed. Regression analyses of the fluctuating asymmetry measure were conducted within each group. In the patient cohort, fluctuating asymmetry was significantly associated with the hallucination and thought disorganisation scores. T-test comparisons revealed that the patients presenting either hallucinations or thought disorganisation were significantly more asymmetrical than were the healthy individuals, while the patients without these key symptoms were equivalent to the healthy individuals. A positive association with the anxiety score emerged in a subsample of 36 healthy participants who were rated on affective symptoms. These findings suggest that fluctuating asymmetry may be an indicator of clinical hallucinations and thought disorganisation rather than an indicator of schizophrenia disease.

Clinical and non-clinical hallucinations are similarly associated with source memory errors in a visual memory task.

Hallucinations have been found to be associated with various types of source memory failure in both schizophrenia patients and hallucination-prone healthy individuals. We investigated the associations of clinical and non-clinical hallucinations with source memory errors in a visual memory task that involved the remembering of picture presentation context. 59 schizophrenia patients and 61 healthy individuals took part in the study. Pictures were presented either at different locations or in association with different visual stimuli. The participants were required afterwards to recognize the target pictures among distractors, and then to remember their spatial location or the visual stimulus that was associated with them. Liberal response bias in picture recognition was associated with hallucination proneness and auditory-verbal hallucinations in subsamples of participants with significant non-clinical or clinical hallucinations. After controlling for overall memory performance, failure to remember the spatial location of the pictures was associated with visual hallucinations in male patients; failure to remember the associated visual stimulus was related to auditory-verbal hallucinations in female patients and to hallucination proneness in healthy women. The findings suggest that both clinical and non-clinical hallucinations are associated with loss of contextual information relative to the acquisition of events.

Depression, auditory-verbal hallucinations, and delusions in patients with schizophrenia: Different patterns of association with prefrontal gray and white matter volume.

Structural brain abnormalities, including decreased gray matter (GM) and white matter (WM) volume, have been observed in patients with schizophrenia. These decrements were found to be associated with positive and negative symptoms, but affective symptoms (depression and anxiety) were poorly explored. We hypothesized that abnormalities in GM and WM volume might also be related to affective symptoms. GM and WM volumes were calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, and the associations of positive, negative, and affective symptoms with the brain volumes that showed significant reduction in patients were investigated. Patients demonstrated GM volume reductions in the bilateral prefrontal cortex, and WM volume reductions in the right frontal and left corpus callosum. Prefrontal cortex volume was significantly and inversely associated with both auditory-verbal hallucinations and depression severity. WM volume alterations, in contrast, were related to alogia, anhedonia, and delusions. The combined impact of auditory-verbal hallucinations and depression on similar sub-regions of the prefrontal cortex suggests that depression is involved in hearing voices. Further, this adverse impact of depression on prefrontal GM volume may underlie the impairment demonstrated by these patients in cognitive tasks that rely on executive processes.

Measurement invariance of the Spanish Launay-Slade Hallucinations Scale-Extended version between putatively healthy controls and people diagnosed with a mental disorder.

OBJECTIVES: The current study aimed at evaluating the reliability, convergent and divergent validity, and factor structure of the Spanish Launay-Slade Hallucinations Scale-Extended version (LSHS-E) in people with mental disorders and healthy controls. METHODS: Four hundred and twenty-two individuals completed the Spanish LSHS-E and the Spanish Community Assessment of Psychic Experiences. The convergent and divergent validity of the LSHS-E was assessed with the three dimensions of the Community Assessment of Psychic Experiences (positive, negative, and depressive dimensions) in healthy controls and people with a mental disorder. Factor structure of the LSHS-E was assessed using confirmatory factor analysis and measurement invariance. RESULTS: The LSHS-E had a good reliability in healthy controls and people with a mental disorder (Cronbach's = 0.83 and 0.91, respectively). The LSHS-E was more strongly associated with positive psychotic-like experiences than with depressive and negative symptoms. Four factors were found: (a) "intrusive thoughts"; (b) "vivid daydreams"; (c) "multisensory hallucination-like experiences"; and (d) "auditory-visual hallucination-like experiences" that were invariant between the group of healthy controls and people with a mental disorder. CONCLUSION: The Spanish version of the LSHS-E possesses adequate psychometric properties, and the confirmatory factor analysis findings provide further support for the multidimensionality of proneness to hallucination in clinical and nonclinical samples.

Second-to-fourth digit length ratio is associated with negative and affective symptoms in schizophrenia patients.

BACKGROUND: Higher levels of circulating oestrogens in women and testosterone in men have been shown to have a protective effect against the clinical manifestations of schizophrenia, mostly with respect to negative symptomatology. Certain studies suggest that they also have a protective effect against the neuropsychological impairment observed in the disease. We investigated whether greater prenatal exposure to estrogens in women and to testosterone in men, reflected by the 2D:4D ratio, was similarly associated with decreased negative symptomatology and improved neuropsychological functioning in patients. METHOD: 51 schizophrenia patients and 50 healthy participants were administered a neuropsychological battery. The 2D:4D ratio was measured in all participants. Positive, negative, and affective symptoms were assessed in patients. Regression analyses were conducted separately in male and female subgroups. RESULTS: No associations with positive symptoms were revealed. In male patients, the 2D:4D ratio was positively associated with avolition and inversely associated with anxiety. In female patients, it was inversely associated with alogia, and tended to be positively associated with depression. No association between higher prenatal concentration of the relevant sex hormone and improved neuropsychological performance emerged in patients. CONCLUSIONS: Higher concentrations of prenatal testosterone in male patients, and prenatal oestrogens in female patients, are associated with a decrement in certain aspects of negative symptomatology. In addition, prenatal sex hormone concentration seems to be associated with predisposition to anxiety in male patients, and to depression in female patients.

Amendment of traditional assessment measures for the negative symptoms of schizophrenia.

Schizophrenia research based on traditional assessment measures for negative symptoms appears to be, to some extent, unreliable. The limitations of the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) have been extensively acknowledged and should be taken into account. The aim of this study is to show how the PANSS and the SANS conflate negative symptoms and cognition and to offer alternatives for the limitations found. METHODS: A sample of 117 participants with schizophrenia from two independent studies was retrospectively investigated. Linear regression models were computed to explore the effect of negative symptoms and illness duration as predictors of cognitive performance. RESULTS: For the PANSS, the item "abstract thinking" accounted for the association between negative symptoms and cognition. For the SANS, the "attention" subscale predicted the performance in verbal memory, but illness duration emerged as a stronger predictor than negative symptoms for outcomes of processing speed, verbal and working memory. CONCLUSION: Utilizing alternative models to the traditional PANSS and SANS formats, and accounting for illness duration, provide more precise evidence on the relationship between negative symptoms and cognition. Since these measures are still extensively utilized, we recommend adopting more rigorous approaches to avoid misleading results.

Verbal fluency in male and female schizophrenia patients: Different patterns of association with processing speed, working memory span, and clinical symptoms.

OBJECTIVE: Decreased processing speed in schizophrenia patients has been identified as a major impairment factor in various neuropsychological domains. Working memory span has been found to be involved in several deep or effortful cognitive processes. We investigated the impact that these 2 cognitive functions may have on phonological and semantic fluency in schizophrenia patients and healthy participants. METHOD: Fifty-five patients with schizophrenia and 60 healthy participants were administered a neuropsychological battery including phonological and semantic fluency, working memory, and cognitive and motor speed. RESULTS: Regression analyses revealed that motor speed was related to phonological fluency in female patients, whereas cognitive speed was related to semantic fluency in male patients. In addition, working memory span was related to verbal fluency in women from both the patient and the healthy control groups. Decreased processing speed, but not decreased working memory span, accounted for the verbal fluency deficit in patients. Verbal fluency was inversely related to attention deficit in female patients and to negative symptoms in male patients. CONCLUSIONS: Decreased processing speed may be the main factor in verbal fluency impairment of patients. Further, the cognitive and clinical predictors of verbal fluency efficiency are different in men and women. (PsycINFO Database Record

A large-scale study on the effects of sex on gray matter asymmetry.

Research on sex-related brain asymmetries has not yielded consistent results. Despite its importance to further understanding of normal brain development and mental disorders, the field remains relatively unexplored. Here we employ a recently developed asymmetry measure, based on the Dice coefficient, to detect sex-related gray matter asymmetries in a sample of 457 healthy participants (266 men and 191 women) obtained from 5 independent databases. Results show that women's brains are more globally symmetric than men's (p < 0.001). Although the new measure accounts for asymmetries distributed all over the brain, several specific structures were identified as systematically more symmetric in women, such as the thalamus and the cerebellum, among other structures, some of which are typically involved in language production. These sex-related asymmetry differences may be defined at the neurodevelopmental stage and could be associated with functional and cognitive sex differences, as well as with proneness to develop a mental disorder.

Remembering verbally-presented items as pictures: Brain activity underlying visual mental images in schizophrenia patients with visual hallucinations.

BACKGROUND: Previous research suggests that visual hallucinations in schizophrenia consist of mental images mistaken for percepts due to failure of the reality-monitoring processes. However, the neural substrates that underpin such dysfunction are currently unknown. We conducted a brain imaging study to investigate the role of visual mental imagery in visual hallucinations. METHOD: Twenty-three patients with schizophrenia and 26 healthy participants were administered a reality-monitoring task whilst undergoing an fMRI protocol. At the encoding phase, a mixture of pictures of common items and labels designating common items were presented. On the memory test, participants were requested to remember whether a picture of the item had been presented or merely its label. RESULTS: Visual hallucination scores were associated with a liberal response bias reflecting propensity to erroneously remember pictures of the items that had in fact been presented as words. At encoding, patients with visual hallucinations differentially activated the right fusiform gyrus when processing the words they later remembered as pictures, which suggests the formation of visual mental images. On the memory test, the whole patient group activated the anterior cingulate and medial superior frontal gyrus when falsely remembering pictures. However, no differential activation was observed in patients with visual hallucinations, whereas in the healthy sample, the production of visual mental images at encoding led to greater activation of a fronto-parietal decisional network on the memory test. CONCLUSIONS: Visual hallucinations are associated with enhanced visual imagery and possibly with a failure of the reality-monitoring processes that enable discrimination between imagined and perceived events.

Visual Imagery and False Memory for Pictures: A Functional Magnetic Resonance Imaging Study in Healthy Participants.

BACKGROUND: Visual mental imagery might be critical in the ability to discriminate imagined from perceived pictures. Our aim was to investigate the neural bases of this specific type of reality-monitoring process in individuals with high visual imagery abilities. METHODS: A reality-monitoring task was administered to twenty-six healthy participants using functional magnetic resonance imaging. During the encoding phase, 45 words designating common items, and 45 pictures of other common items, were presented in random order. During the recall phase, participants were required to remember whether a picture of the item had been presented, or only a word. Two subgroups of participants with a propensity for high vs. low visual imagery were contrasted. RESULTS: Activation of the amygdala, left inferior occipital gyrus, insula, and precuneus were observed when high visual imagers encoded words later remembered as pictures. At the recall phase, these same participants activated the middle frontal gyrus and inferior and superior parietal lobes when erroneously remembering pictures. CONCLUSIONS: The formation of visual mental images might activate visual brain areas as well as structures involved in emotional processing. High visual imagers demonstrate increased activation of a fronto-parietal source-monitoring network that enables distinction between imagined and perceived pictures.

Impaired Self-Monitoring of Inner Speech in Schizophrenia Patients with Verbal Hallucinations and in Non-clinical Individuals Prone to Hallucinations.

BACKGROUND: Previous research has shown that various memory errors reflecting failure in the self-monitoring of speech were associated with auditory/verbal hallucinations in schizophrenia patients and with proneness to hallucinations in non-clinical individuals. METHOD: We administered to 57 schizophrenia patients and 60 healthy participants a verbal memory task involving free recall and recognition of lists of words with different structures (high-frequency, low-frequency, and semantically organisable words). Extra-list intrusions in free recall were tallied, and the response bias reflecting tendency to make false recognitions of non-presented words was computed for each list. RESULTS: In the male patient subsample, extra-list intrusions were positively associated with verbal hallucinations and inversely associated with negative symptoms. In the healthy participants the extra-list intrusions were positively associated with proneness to hallucinations. A liberal response bias in the recognition of the high-frequency words was associated with verbal hallucinations in male patients and with proneness to hallucinations in healthy men. Meanwhile, a conservative response bias for these high-frequency words was associated with negative symptoms in male patients and with social anhedonia in healthy men. CONCLUSION: Misattribution of inner speech to an external source, reflected by false recollection of familiar material, seems to underlie both clinical and non-clinical hallucinations. Further, both clinical and non-clinical negative symptoms may exert on verbal memory errors an effect opposite to that of hallucinations.

Neural activity during object perception in schizophrenia patients is associated with illness duration and affective symptoms.

BACKGROUND: Abnormalities in visual processes have been observed in schizophrenia patients and have been associated with alteration of the lateral occipital complex and visual cortex. However, the relationship of these abnormalities with clinical symptomatology is largely unknown. METHODS: We investigated the brain activity associated with object perception in schizophrenia. Pictures of common objects were presented to 26 healthy participants (age=36.9; 11 females) and 20 schizophrenia patients (age=39.9; 8 females) in an fMRI study. RESULTS: In the healthy sample the presentation of pictures yielded significant activation (pFWE (cluster)<0.001) of the bilateral fusiform gyrus, bilateral lingual gyrus, and bilateral middle occipital gyrus. In patients, the bilateral fusiform gyrus and bilateral lingual gyrus were significantly activated (pFWE (cluster)<0.001), but not so the middle occipital gyrus. However, significant bilateral activation of the middle occipital gyrus (pFWE (cluster)<0.05) was revealed when illness duration was controlled for. Depression was significantly associated with increased activation, and anxiety with decreased activation, of the right middle occipital gyrus and several other brain areas in the patient group. No association with positive or negative symptoms was revealed. CONCLUSIONS: Illness duration accounts for the weak activation of the middle occipital gyrus in patients during picture presentation. Affective symptoms, but not positive or negative symptoms, influence the activation of the right middle occipital gyrus and other brain areas.

Effects of caffeine intake and smoking on neurocognition in schizophrenia.

Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.

Association of auditory-verbal and visual hallucinations with impaired and improved recognition of colored pictures.

OBJECTIVE: A number of cognitive underpinnings of auditory hallucinations have been established in schizophrenia patients, but few have, as yet, been uncovered for visual hallucinations. In previous research, we unexpectedly observed that auditory hallucinations were associated with poor recognition of color, but not black-and-white (b/w), pictures. In this study, we attempted to replicate and explain this finding. Potential associations with visual hallucinations were explored. METHOD: B/w and color pictures were presented to 50 schizophrenia patients and 45 healthy individuals under 2 conditions of visual context presentation corresponding to 2 levels of visual encoding complexity. Then, participants had to recognize the target pictures among distractors. RESULTS: Auditory-verbal hallucinations were inversely associated with the recognition of the color pictures presented under the most effortful encoding condition. This association was fully mediated by working-memory span. Visual hallucinations were associated with improved recognition of the color pictures presented under the less effortful condition. Patients suffering from visual hallucinations were not impaired, relative to the healthy participants, in the recognition of these pictures. CONCLUSION: Decreased working-memory span in patients with auditory-verbal hallucinations might impede the effortful encoding of stimuli. Visual hallucinations might be associated with facilitation in the visual encoding of natural scenes, or with enhanced color perception abilities.