Neurobiological Background Research Articles

In utero Δ9-tetrahydrocannabinol exposure confers vulnerability towards cognitive impairments and alcohol drinking in the adolescent offspring: Is there a role for neuropeptide Y?

Cannabinoid consumption during pregnancy has been increasing on the wave of the broad-based legalisation of cannabis in Western countries, raising concern about the putative detrimental outcomes on foetal neurodevelopment. Indeed, since the endocannabinoid system regulates synaptic plasticity, emotional and cognitive processes from early stages of life interfering with it and other excitability endogenous modulators, such as neuropeptide Y (NPY), might contribute to the occurrence of a vulnerable phenotype later in life. This research investigated whether in utero exposure to Δ9-tetrahydrocannabinol (THC) may induce deficits in emotional/cognitive processes and alcohol vulnerability in adolescent offspring. NPY and excitatory postsynaptic density (PSD) machinery were measured as markers of neurobiological vulnerability. Following in utero THC exposure (2 mg/kg delivered subcutaneously), preadolescent male rat offspring were assessed for: behavioural reactivity in the open field test, neutral declarative memory and aversive limbic memory in the Novel Object and Emotional Object Recognition tests, immunofluorescence for NPY neurons and the PSD proteins Homer-1, 1b/c and 2 in the prefrontal cortex, amygdala and nucleus accumbens at adolescence (cohort 1); and instrumental learning, alcohol taking, relapse and conflict behaviour in the operant chamber throughout adolescence until early adulthood (cohort 2). In utero THC-exposed adolescent rats showed: (a) increased locomotor activity; (b) no alteration in neutral declarative memory; (c) impaired aversive limbic memory; (d) decreased NPY-positive neurons in limbic regions; (e) region-specific variations in Homer-1, 1b/c and 2 immunoreactivity; (f) decreased instrumental learning and increased alcohol drinking, relapse and conflict behaviour in the operant chamber. Gestational THC impaired the formation of memory traces when integration between environmental encoding and emotional/motivational processing was required and promoted the development of alcohol-addictive behaviours. The abnormalities in NPY signalling and PSD make-up may represent the common neurobiological background, suggesting new targets for future research.

Individual susceptibility or resistance to posttraumatic stress disorder-like behaviours

The aim of this study was to explore the neurobiological background of individual susceptibility and resistance to the development of posttraumatic stress disorder (PTSD)-like behaviours. Rats were divided into susceptible, PTSD(+), and resistant, PTSD(-), groups based on freezing duration during exposure to aversive context and the time spent in the central area in open field test one week after threefold stress experience (modified single prolonged stress). PTSD(-) rats showed increased concentrations of corticosterone in plasma and changes in GAD67 expression: decreased in the infralimbic cortex (IL) and increased in the lateral amygdala (LA), dentate gyrus (DG), and CA1 area of the hippocampus. Moreover, in this group, we found an increase in the number of CRF-positive nuclei in the parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN). The PTSD(+) group, compared to PTSD(-) rats, had decreased concentrations of corticosterone in plasma and reduced CRF expression in the pPVN, higher CRF expression in the CA1, increased expression of CRF-positive nuclei and GR receptors in the CA3 area of the hippocampus, and increased expression of GR receptors in the DG and the central amygdala (CeA). Biochemical analysis showed higher concentrations of noradrenaline, glutamic acid in the dorsal hippocampus and amygdala and lower levels of dopamine and its metabolites in the amygdala of the PTSD(+) group than in the PTSD(-) group. The study revealed different behavioural and biochemical profiles of PTSD(+) and PTSD(-) rats and suggested that individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity may determine hippocampal- and amygdala-dependent memory and fear processing.

Emotion recognition and social cognition in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy. Disease onset is typically in puberty and poor social adjustment and behavioral disturbances, which resemble frontal lobe dysfunction, are often observed. In recent advanced brain imaging studies on JME patients, emotional and behavioral problems have been associated to subtle structural and functional alterations mainly in frontal cortex and thalamus. There is emerging evidence that patients with abnormal emotion processing and regulation, such as those with bipolar disorder, show disrupted connectivity between limbic structures and frontal cortices. There are no neuroimaging or neuropsychological studies related to emotion processing in patients with JME with a focus on limbic structures. We aimed to address the problem of emotional disturbances and social adjustment in JME patients from multiple aspects through thorough functional and structural assessment, which would potentially enable elaboration of a unifying concept explaining neurobiological background of disturbances in emotional processing and social adjustment in JME patients. Results of this study may potentially enable the development of psychological and pharmacological interventional strategies for managing behavioral disturbances in patients with JME.

S197. OBSTETRIC COMPLICATIONS, NEUROCOGNITION, AND SCHIZOPHRENIA

BackgroundSchizophrenia is a disorder with a heterogeneous genetic and neurobiological background that influences early brain development. The symptoms is the behavioural outcome of deviations in early neurodevelopment, including prenatal insults such as obstetric complications (OC). OC have been linked to an increased risk for schizophrenia in offspring, especially in early-onset schizophrenia (EOS). Extensive cognitive deficits occur in EOS, whereof executive function is one of the best documented. Cognitive dysfunction reflects underlying abnormalities in the brain neurodevelopment, and is considered to be an intermediate variable between OC and schizophrenia. Our research group (Teigset et al, 2016) is the only study that has investigated the relationship between OC and cognition in EOS. This study aimed to examine the frequency of OC in EOS compared to controls, and also investigate the relationship between OC and neurocognitive dysfunction. In the present presentation we will focus upon executive function and report the findings when comparing the same sample of patients and controls as in the Teigset et al study.MethodsNineteen EOS patients and 53 healthy controls were tested with the MATRICS Consensus Cognitive Battery(MCCB), and two tests for assessment of executive functioning. The selected subtests for measuring executive function were the D-KEFS Color Word Interference Test (Stroop) and the Wisconsin Card Sorting Test. WCST assesses perseverative responses and failure to maintain set, and the Stroop assesses time in seconds for completing the Inhibition and Switching conditions. The cognitive measures were combined with data from the Norwegian Birth Registry (NMBR). Information on OC was collected from the NMBR containing information about all births in Norway, including information about maternal health before and during pregnancy, and any complications arising during pregnancy or birth. The registry includes information about medication during pregnancy, labor interventions, birth complications, maternal complications after birth, whether this was a live birth, any diagnoses in the child or evidence of congenital abnormalities.ResultsGroup differences in OC were studied with Student’s t-tests and Chi-square tests. The association between OC and cognitive function were studied using linear regression analyses. The results indicated no group differences in OC in EOS and healthy controls. However, a shorter gestational length in the EOS group led to significant decreases in the overall neurocognitive composite score (MCCB), in processing speed and in the two executive function tasks.DiscussionOur findings indicate that a shorter gestational length did not increase the risk for developing EOS, but was significantly associated with the cognitive difficulties in this group. In particular, executive functioning were affected, a finding in line with those of Brown et al (2009), showing that prenatal infections were associated with impaired executive function. Interestingly, reductions in neurocognitive performance among those exposed to OC was less extensive in the healthy control group with the same labor-conditions, which may indicate a greater effect of OC on neuropsychological development in schizophrenia. In conclusion, gestational length does not increase the risk for developing EOS, but significantly affects the cognitive difficulties - particularly executive function - seen among cases.

Nicotine-induced CREB and DeltaFosB activity is modified by caffeine in the brain reward system of the rat

Coffee and nicotine consumption are frequently combined, indicating possible intensifying effect of caffeine on smoking behavior, although neurobiological background of this phenomenon remains unknown.We aimed at determining the effect of caffeine and nicotine, applied separately or simultaneously, on activation of six structures of the brain reward system: nucleus accumbens (NAc), ventral tegmental area (VTA), amygdala (Amg), hippocampus (Hip), medial prefrontal cortex (mPfr) and dorsal striatum (CdP) in the adult male Wistar rats. Activation of two transcription factors, the phosphorylated form of cyclic AMP-response element binding protein (pCREB) and DeltaFosB (ΔFosB) was assessed by immunohistochemistry after multiple-dose five-days psychostimulants administration followed by 20min and 24h survival, respectively.Nicotine evoked the highest increase of pCREB-immunoreactivity (-ir) in NAc, while caffeine exerted the weakest effect in mPfr and CdP. Nicotine/caffeine co-administration resulted in decrease of pCREB-ir in NAc and increase in Amg, compared with the effect of each psychostimulant used separately.Nicotine was the strongest psychostimulant activating ΔFosB-ir in Amg, whereas caffeine – in Hip. Nicotine/caffeine-exerted effect upon ΔFosB-ir in Amg was weaker, whereas in mPfr stronger, than nicotine-evoked effect in these structures.In summary, pCREB and ΔFosB activation is dependent on the type of stimulus, brain structure and functional context. Activation of both transcription factors is responsible for caffeine’s modifying effect upon nicotine-related behaviors and must be taken into account while quitting cigarette smoking.

Improving individual predictions: Machine learning approaches for detecting and attacking heterogeneity in schizophrenia (and other psychiatric diseases)

Psychiatric diseases are very heterogeneous both in clinical manifestation and etiology. With the recent rise of using machine learning techniques to attempt to diagnose and prognose these disorders, the issue of heterogeneity becomes increasingly important. With the growing interest in personalized medicine, it becomes even more important to not only classify someone as a patient with a certain disorder, its treatment needs a more precise definition of the underlying neurobiology, since different biological origins of the same disease may require (very) different treatments.We review the possible contributions that machine learning techniques could make to explore the heterogeneous nature of psychiatric disorders with a focus on schizophrenia. First we will review how heterogeneity shows up and how machine learning, or multivariate pattern recognition methods in general, can be used to discover it. Secondly, we will discuss the possible uses of these techniques to attack heterogeneity, leading to improved predictions and understanding of the neurobiological background of the disorder.

Abnormal Resting-State Connectivity in a Substantia Nigra-Related Striato-Thalamo-Cortical Network in a Large Sample of First-Episode Drug-Naïve Patients With Schizophrenia.

The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.

Neuroimage studies: The effect of methylphenidate in cocaine users with ADHD

BackgroundAttention deficit/hyperactivity disorder (ADHD) is an important contributing factor in the pathophysiology of substance use disorders (SUD), and ADHD occurs more often in populations with SUD compared to the general population. This high prevalence rate and comorbidity may relate to a shared neurobiological vulnerability, including a deregulation of the brain's dopamine system. This comorbidity directly impacts the treatment of ADHD: treatment with methylphenidate is less effective in patients with ADHD and SUD compared to ADHD patients without SUD.MethodsWe investigate the underlying neurobiological background of reduced treatment effectiveness for adult ADHD patients with comorbid SUD.ResultsWe observed lower available dopamine transporters, as well as a reduced binding of methylphenidate to these transporters, and more neurocognitive dysfunction in adults ADHD patients with SUD compared to ADHD patients without SUD.ConclusionComorbid ADHD and SUD has a high prevalence rate and reduces ADHD treatment effectiveness, which makes it necessary to screen for the presence of ADHD in patients seeking SUD treatment. Neurobiological and neurocognitive differences are present between ADHD patients with and without SUD, which together may partially explain the reduced effectiveness of methylphenidate in adult ADHD patients with SUD.Disclosure of interestThe author has not supplied his declaration of competing interest.

Staging in bipolar disorder: Clinical, biochemical, and functional correlates

In the field of bipolar disorder, some proposals of a staging model have been suggested considering the progressive features of the disorder. The staging model regards special features of the patients and further draws a route to define the prognosis and treatment as well as the neurobiological background of the disorder. The aim of this model is to identify rational therapeutic targets and provide the most effective and less toxic intervention in a time-sensitive manner. Advocating for a model of staging in bipolar disorder that can group the patients according to quantitative cut-offs of common practice clinical variables as well as defining a biochemical correlation seems to be a further step towards an operative and valid model of staging in bipolar disorder.Disclosure of interestDr. I. Grande has received a Juan Rodés Contract (JR15/00012), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Barcelona, Spain and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag.

Theranostic Biomarkers for Schizophrenia.

Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most frequently used biomarkers in schizophrenia are those associated with the neuroimmune and neuroendocrine system, metabolism, different neurotransmitter systems and neurotrophic factors. However, there are still no validated and reliable biomarkers in clinical use for schizophrenia. This review will address potential biomarkers in schizophrenia. It will discuss biomarkers in schizophrenia and propose the use of specific blood-based panels that will include a set of markers associated with immune processes, metabolic disorders, and neuroendocrine/neurotrophin/neurotransmitter alterations. The combination of different markers, or complex multi-marker panels, might help in the discrimination of patients with different underlying pathologies and in the better classification of the more homogenous groups. Therefore, the development of the diagnostic, prognostic and theranostic biomarkers is an urgent and an unmet need in psychiatry, with the aim of improving diagnosis, therapy monitoring, prediction of treatment outcome and focus on the personal medicine approach in order to improve the quality of life in patients with schizophrenia and decrease health costs worldwide.

Nazwy własne jako przedmiot badań neuronauk

This descriptive review presents proper names from the perspective of brain science. It contains the characteristics of individual groups of proper nouns (and common nouns for comparison) and takes account of their neurobiological background. This makes it possible to confirm many opinions on the status of proper names reported by linguists. The baker and baker paradox and the so-called double dissociation in the search of proper names and common names are discussed in order to confirm (at least in part) the thesis that proper names and common nouns are searched for in the mental lexicon independently of each other. The author also presents the characteristics of proper names to make a thesis about the uniqueness of this class of lexemes. It becomes clear that they are more difficult to learn, especially in patients with neurological deficits, and it takes healthy individuals longer to recall them than to search for common names. Moreover, the recollection of names is associated with more phonological mistakes and is often accompanied by the tip-of-the-tongue syndrome (TOT syndrome), which becomes most evident in elderly patients. The article also presents individual adaptive compensation techniques in impaired naming of objects and faces (e.g. aphasia), which facilitate the recreation of categories within the mental proper name lexicon.

Maternal and paternal personality profiles of adolescent suicide attempters

Personality features have been correlated with suicidal behaviors in recent decades. Given its neurobiological background, Cloninger's model of personality, the Temperament and Character Inventory (TCI), may help to identify the maternal and paternal personality dimensions associated with adolescent suicide attempts. The present study is the first that specifically compares the temperament and character profiles of both mothers and fathers of the adolescent suicide attempters with a control group, by considering the influence of demographic and clinical factors. The study group comprised 117 parents of 71 adolescent suicide attempters and 119 parents of 71 age- and gender-matched adolescents without a suicide attempt included as a control group. The TCI and Brief Symptom Inventory (BSI) were applied to the parents in both groups. Logistic regression analysis, which was performed to adjust confounding factors, demonstrated significantly higher scores for harm avoidance among the mothers and lower scores of self-directedness among the fathers of the adolescent suicide attempters. New psychotherapeutic modalities considering the high-risk parental personality traits would be beneficial to support parent-adolescent relationships and may have a preventative effect on adolescent suicide.

Lower cortisol level in response to a psychosocial stressor in young females with self-harm

BackgroundSelf-harm is highly prevalent in adolescence, often serving an emotion regulation function. Social stressors such as bullying are associated with self-harm. The neurobiological background of the relationship between social stressors and self-harm needs to be further understood to inform prevention and therapy. MethodsParticipants were members of an epidemiological cohort study. 130 female participants underwent the Trier Social Stress Test (TSST) at age 19. Of them, 21 reported a history of self-harm as assessed by the Youth Self Report. Psychiatric diagnoses were recorded. ResultsParticipants with a history of self-harm showed significantly lower blood cortisol levels throughout the TSST. Early psychosocial adversity did not significantly differ between groups with and without self-harm, with self-harming participants reporting more childhood adversities. ConclusionThese results add to the limited field of studies showing an altered HPA axis activity in females with self-harm. Future studies need to address the causal mechanisms behind this association.

Emotional intelligence and coping as predictors of acculturation styles

Self-harm is highly prevalent in adolescence, often serving an emotion regulation function. Social stressors such as bullying are associated with self-harm. The neurobiological background of the relationship between social stressors and self-harm needs to be further understood to inform prevention and therapy.Participants were members of an epidemiological cohort study. 130 female participants underwent the Trier Social Stress Test (TSST) at age 19. Of them, 21 reported a history of self-harm as assessed by the Youth Self Report. Psychiatric diagnoses were recorded.Participants with a history of self-harm showed significantly lower blood cortisol levels throughout the TSST. Early psychosocial adversity did not significantly differ between groups with and without self-harm, with self-harming participants reporting more childhood adversities.These results add to the limited field of studies showing an altered HPA axis activity in females with self-harm. Future studies need to address the causal mechanisms behind this association.

Copy number variation analysis in adults with catatonia confirms haploinsufficiency of SHANK3 as a predisposing factor

BackgroundCatatonia is a motor dysregulation syndrome co-occurring with a variety of psychiatric and medical disorders. Response to treatment with benzodiazepines and electroconvulsive therapy suggests a neurobiological background. The genetic etiology however remains largely unexplored. Copy Number Variants (CNV), known to predispose to neurodevelopmental disorders, may play a role in the etiology of catatonia. MethodsThis study is exploring the genetic field of catatonia through CNV analysis in a cohort of psychiatric patients featuring intellectual disability and catatonia. Fifteen adults admitted to a psychiatric inpatient unit and diagnosed with catatonia were selected for array Comparative Genomic Hybridization analysis at 200 kb resolution. We introduced a CNV interpretation algorithm to define detected CNVs as benign, unclassified, likely pathogenic or causal with regard to catatonia. ResultsCo-morbid psychiatric diagnoses in these patients were autism, psychotic or mood disorders. Eight patients were found to carry rare CNVs, which could not be classified as benign, comprising 6 duplications and 2 deletions. Microdeletions on 22q13.3, considered causal for catatonia, were detected in 2 patients. Duplications on 16p11.2 and 22q11.2 were previously implicated in psychiatric disorders, but not in catatonia, and were therefore considered likely pathogenic. Driven by the identification of a rare 14q11.2 duplication in one catatonic patient, additional patients with overlapping duplications were gathered to delineate a novel susceptibility locus for intellectual disability and psychiatric disorders on 14q11.2, harboring the gene SUPT16H. Three remaining variants respectively on 2q36.1, 16p13.13 and 17p13.3 were considered variants of unknown significance. ConclusionThe identification of catatonia-related copy number changes in this study, underscores the importance of genetic research in patients with catatonia. We confirmed that 22q13.3 deletions, affecting the gene SHANK3, predispose to catatonia, and we uncover 14q11.2 duplications as a novel susceptibility factor for intellectual and psychiatric disorders.

Psychoses in epilepsy: A comparison of postictal and interictal psychoses.

We retrospectively analyzed data of patients with epilepsy (n=1434) evaluated with prolonged EEG monitoring in order to estimate the prevalence of postictal psychosis (PP) and interictal psychosis (IP), to investigate a potential association of psychosis subtype with epilepsy type, and to assess differences between PP and IP. The overall prevalence of psychosis was 5.9% (N=85); prevalence of PP (N=53) and IP (N=32) was 3.7% and 2.2%, respectively. Of patients with psychosis, 97.6% had localization-related epilepsy (LRE). Prevalence of psychosis was highest (9.3%) in patients with temporal lobe epilepsy (TLE). When comparing PP with IP groups on demographic, clinical, and psychopathological variables, patients with IP were younger at occurrence of first psychosis (P=0.048), had a shorter interval between epilepsy onset and first psychosis (P=0.002), and more frequently exhibited schizophreniform traits (conceptual disorganization: P=0.008; negative symptoms: P=0.017) than those with PP. Postictal psychosis was significantly associated with a temporal seizure onset on ictal EEG (P=0.000) and a higher incidence of violent behavior during psychosis (P=0.047). To conclude, our results support the presumption of a preponderance of LRE in patients with psychosis and that of a specific association of TLE with psychosis, in particular with PP. Given the significant differences between groups, PP and IP may represent distinct clinical entities potentially with a different neurobiological background.

The Role of Psychotropic Medications in the Management of Anorexia Nervosa: Rationale, Evidence and Future Prospects.

Anorexia nervosa (AN) is a severe psychiatric disorder without approved medication intervention. Every class of psychoactive medication has been tried to improve treatment outcome; however, randomized controlled trials have been ambiguous at best and across studies have not shown robust improvements in weight gain and recovery. Here we review the available literature on pharmacological interventions since AN came to greater public recognition in the 1960s, including a critical review of why those trials may not have been successful. We further provide a neurobiological background for the disorder and discuss how cognition, learning, and emotion-regulating circuits could become treatment targets in the future. Making every effort to develop effective pharmacological treatment options for AN is imperative as it continues to be a complex psychiatric disorder with high disease burden and mortality.

Neurobiological background of borderline personality disorder, PTSD and ADHD

Neurobiological background of borderline personality disorder, PTSD and ADHD

Neural Signaling of Food Healthiness Associated with Emotion Processing.

The ability to differentiate healthy from unhealthy foods is important in order to promote good health. Food, however, may have an emotional connotation, which could be inversely related to healthiness. The neurobiological background of differentiating healthy and unhealthy food and its relations to emotion processing are not yet well understood. We addressed the neural activations, particularly considering the single subject level, when one evaluates a food item to be of a higher, compared to a lower grade of healthiness with a particular view on emotion processing brain regions. Thirty-seven healthy subjects underwent functional magnetic resonance imaging while evaluating the healthiness of food presented as photographs with a subsequent rating on a visual analog scale. We compared individual evaluations of high and low healthiness of food items and also considered gender differences. We found increased activation when food was evaluated to be healthy in the left dorsolateral prefrontal cortex and precuneus in whole brain analyses. In ROI analyses, perceived and rated higher healthiness was associated with lower amygdala activity and higher ventral striatal and orbitofrontal cortex activity. Females exerted a higher activation in midbrain areas when rating food items as being healthy. Our results underline the close relationship between food and emotion processing, which makes sense considering evolutionary aspects. Actively evaluating and deciding whether food is healthy is accompanied by neural signaling associated with reward and self-relevance, which could promote salutary nutrition behavior. The involved brain regions may be amenable to mechanisms of emotion regulation in the context of psychotherapeutic regulation of food intake.

Schizophrenia.

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell-cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive-behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial.