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Introduction Although not included in current diagnostic systems, deficit versus non-deficit and resistant versus non-resistant schizophrenia subtypes look more promising than traditional schizophrenia subtypes in terms of stability across time, clinical utility and interest for research. Aims To critically analyze evidence supporting the validity of two schizophrenia subtypes: Deficit Schizophrenia (DS) and Treatment Resistant Schizophrenia (TRS). Methods Empirical data supporting the validity of DS and TRS subtypes will be critically reviewed. Results DS, in comparison with non-deficit schizophrenia, is characterized by poorer premorbid functioning, more insidious onset, lower prevalence of dysphoria, hostility, suicidal ideation, depressive symptoms and substance abuse, different neurobiological abnormalities, and poorer response to treatment. The diagnosis of DS shows high reliability and stability across time. However, research based on this approach has proven difficult, especially in first-episode schizophrenia, and findings have not been as homogeneous as expected. TRS patients, as compared to non-TRS ones, show persisting psychotic symptoms, greater severity of negative symptoms, more severe cognitive dysfunctions, poorer premorbid functioning, longer duration of untreated psychosis, more frequent co-morbidity with personality disorders, earlier illness onset and poorer social functioning. Conclusions Future research should consider a) refining diagnostic criteria for DS and identifying valid DS endophenotypes; b) dissecting TRS based on psychopathological characteristics (e.g. presence of primary and persistent negative symptoms or persistently severe positive symptoms), and underlying neurobiological mechanisms (e.g. dopamine synthesis capacity and glutamatergic transmission).

Purpose of review To provide a review on studies published in the last year relevant to the categorization and assessment of negative symptoms. Recent findings Recent research supported the validity of thedeficit/non-deficit schizophrenia categorization. Few studies confirmed the validity of the category persistent negative symptoms, whereas no recent study explored the validity of the category predominant negative symptoms. The two-factor structure of the negative dimension is supported by studies reporting different correlates for the two subdomains: diminished expression and avolition/apathy. The need to further split avolition/apathy in two distinct components, that is anhedonia and amotivation, is confirmed in recent papers. Additional approaches to the assessment of negative symptoms have been proposed, including the self-assessment of negative symptoms, and the evaluation of negative symptoms in daily life and their assessment by means of computerized analyses. Summary Negative symptoms represent an unmet need in the care of schizophrenia, as they are associated to poor response to available treatments and to poor functional outcome. Their accurate categorization and assessment represent a major challenge for research on neurobiological substrates and new treatment strategies.

IntroductionNegative symptoms represent a separate dimension of schizophrenia psychopathology, distinct from positive symptoms, disorganization and cognitive impairment. It is increasingly acknowledged that negative symptoms are associated with poor functional outcome and represent an unmet need in schizophrenia treatment. Improvement in definition of their phenomenology, assessment instruments and experimental models are needed in order to improve schizophrenia prognosis.AimsThe presentation will review key aspects of the evolution of negative symptom constructs. In particular, findings concerning phenomenology, clinical assessment, association with functional outcome and brain imaging correlates will be presented.MethodsWe searched PubMed for English full-text publications with the keywordsSchizophrenia AND “negative symptoms”/“primary negative symptoms”/“deficit schizophrenia”/“persistent negative symptoms”/“affective flattening”/alogia/“expressive deficit”/apathy/asociality/“social withdrawal”/anhedonia/“anticipatory anhedonia”/avolition/neuroimaging.ResultsThe distinction between secondary negative symptoms (i.e., those due to identifiable factors, such as drug effects, psychotic symptoms or depression), and primary or persistent negative symptoms (i.e., those etiologically related to the core pathophysiology of schizophrenia) is grounded on solid research evidence and might have major implications for both treatment development and clinical care. The evidence that negative symptoms cluster in motivation- and expressive-related domains is founded on large consensus and empirical evidence and will foster pathophysiological modeling. The motivation-related domain is a stronger predictor of functional outcome than the expressive one.ConclusionsAn improved definition and assessment of negative symptoms needs to translate in large-scale studies to advance knowledge. In the short-term, the improved identification of treatable causes of secondary negative symptoms can translate into better care for people with schizophrenia.Disclosure of interestAM received honoraria or advisory board/consulting fees from the following companies: Janssen Pharmaceuticals, Otsuka, Pfizer and Pierre Fabre.SG received honoraria or advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter.

IntroductionThe abnormal bodily phenomena questionnaire (ABPq) originates from the analysis of clinical files of more than 350 patients with schizophrenia. It consists in a semi-structured interview created to evaluate the subjective anomalies in feelings, sensations, perceptions and cognition in the domain of the lived body.ObjectivesThe present study is aimed at providing preliminary data for the validation of the Italian version of the ABPq.MethodsThe ABPq was translated and adapted into Italian. ABPq scores were correlated to those obtained by the schizophrenia proneness instrument, Adult version–body perception disturbances (SPI-A E, body) that evaluates the same kind of phenomena, in order to examine its convergent validity. Moreover, ABPq was correlated to psychopathological domains assessed by the Positive and Negative Syndrome Scale (PANSS) and by the Brief Negative Symptom Scale (BNSS).ResultsThe experimental sample included 40 clinically stable patients. Our findings showed a strong correlation between ABPq and SPI-A E, body. An association of ABPq total score with the positive and disorganized dimensions was also observed.ConclusionsOur preliminary data suggest that the Italian version of ABPq has a good convergent validity. The presence of abnormal bodily phenomena resulted to be associated to a greater severity of the disease and therefore it could be hypothesized that they represent an indicator of clinical severity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionThe delay between psychosis onset and initiation of treatment (duration of untreated psychosis, DUP) is associated with a poorer treatment response and overall functional outcome. In Europe several early detection and intervention programs have been developed to reduce the DUP and promote Phase-specific Treatments (PsTs).AimsTo review the evidence of a) the effectiveness of European Early Interventions (EEIs) in reducing DUP; b) an impact of PsTs on clinical and social outcomes; and c) EEIs cost-effectiveness.MethodsA literature search in PubMed, PsychInfo, Cochrane and individual journals through cross-referencing was performed. All European Randomized Controlled Trials (RCTs) designed to reduce DUP and/or to implement PsTs for people with first-episode psychosis were included in the review.ResultsStudies examining early detection programs compared with Standard Care (SC) reported discrepant findings as to their impact on the DUP. PsTs generally reduce hospitalizations and improve service engagement when compared with SC; their impact on other clinical variables, e.g. symptomatology and social functioning, is unclear. Studies assessing EEIs cost-effectiveness in comparison with SC consistently report an advantage for EEIs in the long run.ConclusionsEEIs, as compared to SC, show several advantages that seem to result in an overall reduction in the cost of care. Therefore, the development of EEI is recommended.On the other hand, some inconsistencies in the reported results suggest that EEIs should include psychosocial interventions targeting unmet needs of schizophrenia patients, such as cognitive dysfunction and negative symptoms.Disclosure of interestSG received honoraria or Advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter. All other authors have declared.

IntroductionCognitive deficits are considered central and persistent features of schizophrenia and have a significant impact on outcome and quality of life. The computerized interactive remediation of cognition (CIRCuiTS) is a new computerized cognitive remediation program aimed at improving different cognitive domains in patients with schizophrenia. In particular, the program was designed to mainly rehabilitate executive functions, attention and memory by training each cognitive function through several exercises and by improving metacognition.ObjectivesIn the present study, CIRCuiTS was translated and adapted into Italian. The applicability and feasibility of the Italian version was evaluated. Moreover, preliminary data on the effectiveness of the program were investigated.MethodsFour patients with a diagnosis of schizophrenia were recruited for the study. We investigated the changes in neurocognition, psychopathology, self-esteem and functional outcome at the end of the remediation program. The level of satisfaction of operators and participants was evaluated by means of the client satisfaction questionnaire (CSQ).For each patient, the entire program took place through 2 weekly sessions of 50 minutes for a total duration of 40 sessions.ResultsCIRCuiTS produced an improvement in all domains of neurocognition, disorganization, self-esteem and real-life functioning in the areas “self-care” and “interpersonal relationships”. Moreover, high levels of satisfaction were shown by CSQ for both, operators and participants.ConclusionThe Italian version of CIRCuiTS demonstrates high levels of acceptability and feasibility for both, patients and clinicians. Additionally, preliminary data suggest that the use of CIRCuiTS provides an improvement on several aspects of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Primary and persistent negative symptoms (PPNS) represent an unmet need in the care of people with schizophrenia. They have an unfavourable impact on real-life functioning and do not respond to available treatments. Underlying etiopathogenetic mechanisms of PPNS are still unknown. The presence of primary and enduring negative symptoms characterizes deficit schizophrenia (DS), proposed as a separate disease entity with respect to non-deficit schizophrenia (NDS). More recently, to reduce the heterogeneity of negative symptoms by using criteria easily applicable in the context of clinical trials, the concept of persistent negative symptoms (PNS) was developed. Both PNS and DS constructs include enduring negative symptoms (at least 6months for PNS and 12months for DS) that do not respond to available treatments. PNS exclude secondary negative symptoms based on a cross-sectional evaluation of severity thresholds on commonly used rating scales for positive symptoms, depression and extrapyramidal side effects; the DS diagnosis, instead, excludes all potential sources of secondary negative symptoms based on a clinical longitudinal assessment. In this paper we review the evolution of concepts and assessment modalities relevant to PPNS, data on prevalence of DS and PNS, as well as studies on clinical, neuropsychological, brain imaging electrophysiological and psychosocial functioning aspects of DS and PNS.

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

The present investigation explores the relationship between facial emotion recognition (FER) and symptom domains in three groups of schizophrenia spectrum patients (43 ultra-high-risk, 50 first episode and 44 multi-episode patients) in which the existence of FER impairment has already been demonstrated. Regression analysis showed that symptoms and FER impairment are related in multi-episode patients, regardless of the illness duration. We suggest that the link between symptoms and FER impairment is involved in the progression of the disease.

Background The response to antipsychotic treatment in patients with psychosis is difficult to predict on the basis of the patient’s clinical features. As a result, patients are generally treated in a similar way, even though their response can vary dramatically. Recent neuroimaging studies suggest that the pattern of brain abnormalities in patients with psychosis may vary in relation to treatment response. However, in many of these studies, patients had already been treated, and it was unclear if this had contributed to the findings. Methods In Optimise we obtained a structural Magnetic Resonance Imaging data from n=203 minimally treated patients at their first presentation for a psychotic episode. All patients then started treatment with standard doses of amisulpride. After 4 weeks, 56% were in symptomatic remission. Results We identified brain neoplasms in 3 patients, but the most common radiological findings were non-specific white matter T2-weighted hyperintensities (n=48); cavum septi pelludici (n=34); and arachnoid cysts (n=9). Cortical thickness, surface area, and gyrification were measured using Freesurfer (). Preliminary analyses applying machine learning to these measures at baseline indicated that symptomatic remission at 4 weeks could be predicted with an accuracy of 64%. Discussion These findings suggest that radiological assessment can identify abnormalties that require an alternative to conventional treatment in a minority of patients. In most patients with psychosis, neuroimaging abnormalities may be better detected using statistical approaches, and these have greater potential for the stratification of patients according to future antipsychotic response.

Background Cognitive deficits are common in people with schizophrenia and have a negative impact on functioning. Cognitive Remediation (CR) is an effective approach to reduce the burden of cognitive difficulties however there are individual differences in therapy response. Previous research suggests that participants age may be a significant moderator of therapy efficacy but results are inconclusive. This study attempts to fill this gap by exploring how age may influence CR outcomes. Methods Data from ten trials from the NIMH Database of Cognitive Training and Remediation Studies (DoCTRS) were used. We considered the following therapy outcomes: Executive function as assessed by the Trail making test part B (TMTB), the Wisconsin Card Sorting Test (WCST) and Verbal fluency (FAS) scores. Working memory was assessed with the Letter-Number Span (LNS) and the Digit span. Symptoms were evaluated with the Positive, Negative and General scores from the Positive and Negative Syndrome Scale (PANSS). Functioning was assessed using the Heinrichs-Carpenter quality of life (HCQOL) scale. To evaluate the effect of age on outcomes we classified participants into under 40 and over 40 years old. We compared outcomes across age groups using mixed linear models. Results We considered data from 711 people with schizophrenia (407 received CR and 304 the control condition). For the under 40 group the average age was 29.26 (SD 6.83) while the average yeas spent in education was 12.11 (2.61). The over 40 group had a mean age of 40.09 (SD 6.09) and 12.11 (2.54) years of education. We found a significant interaction between age and working memory and functioning improvement for the over 40 group. The younger group showed a larger effect of CR in term of general symptoms reduction. We did not find an effect of age on executive function, positive and negative symptom. Discussion The results indicate that CR may benefit people with schizophrenia in different way depending on their age. Age may represent a large number of complex factors and more work is needed in this area to better understand how individual characteristics and illness history may influence CR response. Work in this sense will help to reduce CR response heterogeneity and improve therapy personalisation.

Schizophrenia (SZ) is a complex psychiatric disorder with a large genetic burden and an estimated hereditability of 80%. A large number of neuroanatomical and psychopharmacological studies suggest a central role of the endocannabinoid (eCB) system in the susceptibility of the disease. To further investigate this hypothesis, we performed an association study with genes codifying for key elements of the eCB system in a sample of 170 schizophrenic patients and 350 healthy controls of Italian ancestry. A total of 57 Tag SNPs (tSNPs) were selected using HapMap CEU population SNP database spanning the following genes: cannabinoid receptor 1 (CNR1), peroxisome proliferator activator receptor-α (PPARA), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Seven out of the 32 tSNPs within PPARA (rs4253765, rs4263776, rs6007662, rs1800206, rs4253763, rs6008197 and rs4253655) and 3 out of 12 tSNPs within CNR1 (rs1049353, rs7766029 and rs806366) were nominally associated with SZ (uncorrected p0.05). The same pattern of association was observed in the genotype analysis, with rs4253765 showing the highest level of significance (uncorrected p=2×10(-3)). None of these associations survived after permutation test. Our findings suggest a potential role for PPARA in the susceptibility to SZ, but further studies on larger independent samples are warranted in order to clarify the involvement of this gene in the pathophysiology of SZ.

Objectives: Bulimia nervosa (BN) is associated with a deficit of self-regulatory control and impulsivity. The present study aimed to clarify whether an impaired inhibitory control due to hyperarousal underlies impulsivity in BN subjects. Methods: Event-related potentials (ERPs) were recorded in 17 female patients with BN and 17 healthy controls during a three-tone oddball task. ERP components related to inhibition of irrelevant distractor stimuli, as well as effortful processing, were analyzed. Standardized low-resolution electromagnetic tomography (sLORETA) was used to assess ERP source activity. Results: Compared to healthy controls, BN patients showed reduced amplitude and shorter latency of the N200 (N2), increased amplitude and shorter latency of the target slow wave (SW), and higher amplitude of the P300 for distractor stimuli (P3a) and for targets (P3b). sLORETA showed the following: (1) higher activity of the P3a generators in the left parietal cortex, bilateral precuneus and right frontal and anterior cingulate for distractor stimuli and (2) lower activity of the SW generators in the left medial frontal gyrus, bilateral superior frontal, anterior cingulate and cuneus for target stimuli. The reduction of the N2 latency was associated with the Barratt scores for impulsiveness. Conclusions: The observed electrophysiological abnormalities suggest a condition of hyperarousal, with impaired suppression of irrelevant stimuli due to abnormal cortical activation and reduced signal-to-noise ratio. Our findings point to functional abnormalities within a neural system that subserves attention and self-regulatory control, which may contribute to impulsive behaviors in BN.

A method for postprocessing of segmented routine brain MRI studies providing automated definition of major structures (frontal, parietal, occipital, and temporal lobes; cerebellar hemispheres; and lateral ventricles) according to the Talairach atlas is presented. The method was applied to MRI studies from 25 normal subjects (NV), 14 patients with deficit schizophrenia (DS), and 14 with nondeficit schizophrenia (NDS), to evaluate their gray matter and CSF regional volumes. The two patient groups did not differ in mean age at illness onset, duration of illness, severity of psychotic symptoms, or disorganization; DS had more severe avolition and worse social functioning than NDS. For validation purposes, brain structures were manually outlined on original MR images in 10 studies, thus obtaining reference measures. Manual and automated measures were repeated 1 month apart to measure reproducibilities of both methods. The automated method required less than 1 min/operator per study vs more than 30 min for manual assessment. Mean absolute difference per structure between the two techniques was 4.8 ml. Overall reproducibility did not significantly differ between the two methods. In subjects with schizophrenia, a significant decrease in GM and increase in CSF were found. GM loss was confined to frontal and temporal lobes. Lateral ventricles were significantly larger bilaterally in NDS compared to NV and only on the right in NDS compared to DS. The finding of greater structural brain abnormalities in NDS adds to the evidence that deficit schizophrenia does not represent just the more severe end of the schizophrenia continuum.

Summary Background: Negative symptoms represent core features of schizophrenia and have an unfavorable impact on the disease outcome. Unfortunately, their aetiopathology has not been elucidated yet and the effectiveness of available treatments is not satisfactory. Aims: This review aims to provide a critical overview of research findings concerning negative symptom aetiopathology, highlighting limitations and future perspectives. Results: Enduring and transient negative symptoms, as well as motivation-related and expression-related domains of negative symptoms, have different risk factors and clinical correlates, and are associated to distinct brain abnormalities. Enduring negative symptoms seem to be related to subtle, pervasive deviations in neurodevelopmental trajectories. Expression deficit, as compared with avolition, shows a stronger association with neurological soft signs, cognitive impairment and diffuse disconnectivity. Avolition/apathy is a multifaceted construct probably related to deficits of reward and action valuation and instrumental learning, subtended by cortico-striatal dysfunctions. Conclusions: Research findings support the heterogeneity of negative symptoms and are likely to pave the way for the discovery of more effective treatments.

Objective Investigate impairment of reward anticipation in subjects with schizophrenia (SCZ) and its association with negative symptom dimensions and hedonic experience. Methods Event-related potentials (ERPs) were recorded, in thirty SCZ and twenty-three matched healthy controls (HC), during a "Monetary Incentive Delay" task in which reward and loss cues (incentive cues of positive and negative value) of different magnitude, as well as neutral cues were presented. Assessments: anticipatory and consummatory pleasure, trait anhedonia and motivation in all subjects; avolition and expressive deficit in SCZ. Results SCZ had lower motivation but comparable hedonic experience with respect to HC. In HC, during reward anticipation, the early P3 was larger for large magnitude incentives, irrespective of their valence, while the late P3 was larger for large reward. In SCZ, early P3 did not discriminate the incentive magnitude and the late P3 was larger for large loss. Early P3 amplitude for large magnitude incentives was inversely related to trait social anhedonia but not to negative symptoms dimensions. Conclusions SCZ are unable to integrate the incentive magnitude and reward value of future events in the context of their ongoing task. P3 abnormalities are associated with trait anhedonia, but not with negative symptoms dimensions. Significance In line with recent studies, our findings indicate that anhedonia and avolition are partially independent constructs.

The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia.

Schizofrenia is a complex psychiatric disorder associated with disruption in cognition, emotion, psychosocial and occupational functioning. the course of the illness can be chronic or recurrent and often characterized by residual symptoms and incomplete social recovery. To improve schizophrenia outcome, integrated and personalized treatment programs are increasingly regarded as the most promising approach to the treatment of persons with schizophrenia. evidence from studies evaluating the effcacy of frst- and second-generation antipsychotic drugs indicates that an early pharmacological intervention yields a more favorable treatment response and greater improvement of patients global functioning. adherence remains an important issue and studies using second generation long-acting injections are needed to clarify possible advantages of this treatment strategy. Pharmacological treatments so far proved to be ineffective for primary and persistent negative symptoms and cognitive impairment. To address these important unmet needs, several psychosocial interventions have been developed. To date, increasing evidence shows that psychosocial interventions for people with schizophrenia can improve cognition, treatment adherence and social functioning and reduce psychotic symptoms and relapse. Howewer, several aspects of these programs, such as methods to individualize treatment and guarantee duration and generalization of eventual improvements, remain controversial.

Robin Emsley and colleagues question the use of placebos when established treatment is effective and lack of harm has not been proved

All drugs used in psychiatry might induce CNS toxicity, particularly when polypharmacy is required for management of patients. Toxic effects can occur at therapeutic doses when concomitant medical conditions or treatments interfere with drug metabolism and/or cause a potentiation of CNS toxicity, for example in old subjects treated with lithium a delirium due to encephalopathy can be precipitated by renal failure, deydration following diuretics or adjunctive neuroleptic therapy. A standard EEG (sEEG) investigation may be useful to diagnose an encephalopathic process, which will be documented by diffuse slowing or the presence of triphasic waves, or an epileptic condition, indexed by spike and spike-and-wave potentials. Data indicating the usefulness of sEEG for the diagnosis of drug-induced CNS side effects or toxicity are summarized and discussed for antipsychotics, antidepressants, anxiolytics, lithium, other mood stabilizers and recreational drugs. A case vignette of SEEG usefulness in diagnosing drug-induced toxic encephalopathy is provided.

A review of the main sEEG findings in psychotic, affective and catatonic syndromes is provided. The sEEG findings are discussed with particular reference to their prognostic implications and to the differential diagnosis with general medical conditions (GMCs) which might present with psychiatric symptomatology. It is argued that recent onset patients with psychosis should be screened for CNS pathology and that sEEG should be among the routine examinations. A clinical vignette concerning the differential diagnosis between schizophrenia and fronto-temporal dementia is included. sEEG findings relevant to the exclusion of epilepsy (including non-convulsive status epilepticus), and focal or general encephalopathies are reviewed. As to catatonic syndromes, several case series are summarized to illustrate the possible etiologies of catatonia and the work-up of patients which is needed to exclude GMCs.

A 16-year-old female who manifested psychotic symptoms underwent CT and MRI for the evaluation of an incidentally discovered asymptomatic palpable mass of the right occipital region of the skull. The correlation between clinical and radiological data and biopsy data led to the diagnosis of eosinophilic granuloma. The radiological finding is discussed and reviewed in relation to clinical aspects and literature data.

BackgroundStudies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN.MethodAttention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17β-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory – Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery–Asberg Depression Rating Scale (MADRS) were administered.ResultsNo impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and ‘Self-directedness’ were associated with better performance on conditional learning whereas 17β-estradiol had a negative influence on this domain; ‘Reward dependence’ was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively.ConclusionsNo cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings.

Background A disorganization factor was found by several factor-analytic studies of schizophrenia symptoms. This factor does not appear to be affected by age, severity of other symptoms and chronicity of illness. A greater severity of disorganization is associated with poor functioning. Despite the general similarity of different factorial model, there is no consensus about which symptoms have to be included in the disorganization factor. Using the Positive and Negative Syndrome Scale (PANSS), Conceptual disorganization’ (P2), ‘Difficulty in abstract thinking’ (N5) and ‘Poor attention’ (G11) were core features of the disorganization factor. The overlap of these items with neurocognitive functions is still debated. However, the heterogeneity of this factor and its neurobiological basis should be further investigated. In the context of the multicenter study of the Italian Network for Research on Psychoses, the main aims of our study were to investigate electrophysiological and neurocognitive correlates of the disorganization factor, and to assess if each PANSS item, loading on the disorganization factor, could be underpinned by similar electrophysiological or cognitive alterations. Methods Resting state EEGs were recorded for 5 minutes in 145 stabilized subjects with schizophrenia (SCZ) and 69 matched healthy controls (HC). The disorganization factor was evaluated using three PANSS items: P2, N5, and G11 (4). Neurocognitive functions were assessed using the MATRICS Consensus Cognitive Battery (MCCB). Spectral amplitude was quantified in nine frequency bands. All statistical analyses of the scalp multichannel spectral amplitude (SAmp) data were performed using RAGU software. Statistical comparisons between the SAmp maps of SCZ and HC were assessed by topographic analyses of variance (TANOVA). In SCZ, topographic analyses of covariance (TANCOVA) evaluated correlations between SAmp and disorganization, its constituent items and MCCB domains. Furthermore, Pearson’s correlations were performed between disorganization and its constituent items and MCCB neurocognitive domains. Results TANOVA, comparing the group SAmp maps revealed increased Delta, Theta, and Beta1 and decreased Alpha2 SAmp in SCZ. In the SCZ group, disorganization was significantly correlated to the Alpha1 SAmp. This relation was negative and most pronounced at occipital sites. At the items level, only N5 showed the same negative correlation at occipital sites. MCCB neurocognitive composite score was associated with disorganization factor, and its constituent items P2 and N5. No significant correlation between Alpha1 SAmp and MCCB cognitive domains was observed. Discussion Our findings illustrate the heterogeneity of disorganization dimension and a partial overlap with neurocognitive domains. ‘Difficulty in abstract thinking’ showed a unique association with Alpha1 activity, which is thought to be involved in the construction of conceptual maps. Furthermore, the observed association of Alpha1 with ‘Difficulty in abstract thinking’ suggests that some aspects of disorganization could be underpinned by the impairment of basic neurobiological functions that are only partially evaluated using MCCB.

Background Negative symptoms represent a core feature of schizophrenia. They have been associated to poor functional outcome, worse quality of life and poor response to pharmacological treatment. Several factor analytic studies have reported that negative symptoms can be divided into two domains referred to as Avolition-apathy which includes Avolition, Anhedonia and Asociality and the Expressive deficit domain, which includes Alogia and Blunted affect. Avolition-apathy has been associated to a dysfunction of brain circuits involved in motivation, in particular to those related to the ability to anticipate pleasure and learn from rewards. It is highly controversial whether Avolition-apathy and all subcomponent symptoms share the same neurobiological underpinnings. Our study, using brain electrical microstates (MS) which reflect global, subsecond patterns of functional connectivity, had two primary aims: 1) to identify differences between healthy controls (HC) and clinically stable people with schizophrenia (SCZ) in brain electrical microstate parameters and 2) to investigate the associations of the microstate parameters with the Avolition-apathy domain and its subcomponent symptoms. Methods We analyzed multichannel resting EEGs in 142 SCZ and in 64 HC, recruited within the add-on EEG study of the Italian Network for Research on Psychoses. The microstate analysis was performed using an in-house plugin for Brain Vision Analyzer. Based on the microstate map templates from a large normative study, each moment of the ongoing EEGs was assigned to one of four microstates (MS) classes (MS-A, MS-B, MS-C, MS-D). Microstates were then quantified in terms of relative time contribution, duration and occurrence. Negative symptoms were assessed using the Brief Negative Symptoms Scale (BNSS): Avolition-apathy was obteined by summing the scores on the subscales Anhedonia (consummatory and anticipatory anhedonia), Avolition and Asociality; Expressive deficit was computed by summing the scores on the subscales Blunted Affect and Alogia. Analysis of variance (ANOVA) was used to test group differences on MS parameters. Pearson’s r coefficients were computed to investigate the correlations of MS parameters with the negative symptom domains and subcomponent symptoms. Results There was no significant group difference in sex (p=0.073) and age (p=0.547) between SCZ and HC. SCZ, in comparison to HC, showed increased contribution (p=0.009) and duration (p=0.016) of MS-C. As regard to negative symptoms, the total score of the BNSS was positively correlated with the contribution of MS-A (r= 0.19, p

The concept of deficit schizophrenia is regarded as one of the most promising attempts to reduce heterogeneity within schizophrenia. This paper summarizes the clinical, neurocognitive, brain imaging and electrophysiological correlates of this subtype of schizophrenia. Attempts to identify genetic and non-genetic risk factors are reviewed. Methodological limitations of studies supporting the efficacy of atypical antipsychotics in the treatment of the syndrome are highlighted. Two decades of research on deficit schizophrenia have failed to prove that it represents the extreme end of a severity continuum in schizophrenia, while some findings support the claim that it may be a separate disease entity.

Background: Profile and correlates of cognitive deficits in first episode (FE) schizophrenia patients are still debated. The present study is aimed to clarify in a large sample of FIE patients the extent of impairment in key cognitive domains and its relationships with demographic and clinical variables. Method: The European First Episode Schizophrenia Trial collected demographic, clinical and neurocognitive baseline data in 498 FE patients with minimal or no prior exposure to antipsychotics. Two-hundred-twenty healthy subjects (HS) were also evaluated. Neurocognitive assessment included the Rey Auditory Verbal Learning Test: Trail Making A and B, Purdue Pegboard and Digit-Symbol Coding. Results: Patients performed worse than HS on all tests (effect sizes from - 0.88 to - 1,73). Correlations with psychopathological dimensions were weak and involved reality distortion and disorganization. The duration of untreated psychosis (DUP) was not associated with cognitive impairment. Subjects living alone had a better neurocognitive performance, while the occupation status did not reveal any association with cognition. Conclusions: A moderate/severe impairment of processing speed, motor dexterity, verbal memory and cognitive flexibility was found in the largest sample of FE patients analyzed so far. The impairment was largely independent from psychopathology and not associated with DUP. (C) 2009 Elsevier B.V. All rights reserved.

Pini S, Abelli M, Shear KM, Cardini A, Lari L, Gesi C, Muti M, Calugi S, Galderisi S, Troisi A, Bertolino A, Cassano GB. Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disorders. Objective: To evaluate the frequency and clinical correlates of adult separation anxiety disorder in a large cohort of patients with mood and anxiety disorders. Method: Overall, 508 outpatients with anxiety and mood disorders were assessed by the structured clinical interview for diagnostic and statistical manual (IV edition) axis I disorders for principal diagnosis and comorbidity and by other appropriate instruments for separation anxiety into adulthood or childhood. Results: Overall, 105 subjects (20.7%) were assessed as having adult separation anxiety disorder without a history of childhood separation anxiety and 110 (21.7%) had adult separation anxiety disorder with a history of childhood separation anxiety. Adult separation anxiety was associated with severe role impairment in work and social relationships after controlling for potential confounding effect of anxiety comorbidity. Conclusion: Adult separation anxiety disorder is likely to be much more common in adults than previously recognized. Research is needed to better understand the relationships of this condition with other co-occurring affective disorders.

Background: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. Methods: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. Findings: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0·37, [95% CI 0·24-0·57]), olanzapine (HR 0·28 [0·18-0·43]), quetiapine (HR 0·52 [0·35-0·76]), and ziprasidone (HR 0·51 [0·32-0·81]). However, symptom reductions were virtually the same in all the groups, at around 60%. Interpretation: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement. Funding: AstraZeneca, Pfizer, Sanofi-Aventis. © 2008 Elsevier Ltd. All rights reserved.

Background: In patients with panic disorder (PD), the difficulty to identify and manage emotional experience might contribute to the enduring vulnerability to panic attacks. Such a difficulty might reflect a dysfunction of fronto-temporo-limbic circuits. The present study was designed to test the hypothesis that drug-free patients with PD, as compared with healthy subjects (HS), show a higher prevalence of alexithymia, greater difficulty in emotional stimuli processing and poorer performance on neuropsychological tests exploring the activity of fronto-temporo-limbic circuits. Methods: Alexithymia, general cognitive abilities, focused and sustained attention, working memory, secondary memory, incidental learning, susceptibility to interference from both cognitive and emotional stimuli, and ability to recognize facial emotional expressions were assessed in 32 drug-free patients with PD and 32 HS. Results: Alexithymia was more frequent in patients with PD than in HS. Patients with PD, as compared to HS, had lower verbal cognitive abilities and more difficulty to inhibit interference from nonverbal stimuli and from panic-related words; they performed better than HS on the test assessing spatial incidental learning. Anxiety, panic symptomatology and verbal cognitive abilities (VIQ) were associated with alexithymia. Conclusions: Findings are compatible with a dysfunction of frontolimbic circuits, in particular orbitofrontal and cingulate cortices. A reduction in verbal cognitive abilities was also observed, which might suggest reduced abstraction and symbolization in these patients.

The P3 is probably the most well known component of the brain event-related potentials (ERPs). Using a three-tone oddball paradigm two different components can be identified: the P3b elicited by rare target stimuli and the P3a elicited by the presentation of rare non-target stimuli. Although the two components may partially overlap in time and space, they have a different scalp topography suggesting different neural generators. The present study is aimed at defining the scalp topography of the two P3 components by means of reference-independent methods and identifying their electrical cortical generators by using the low-resolution electromagnetic tomography (LORETA). ERPs were recorded during a three-tone oddball task in 32 healthy, right-handed university students. The scalp topography of the P3 components was assessed by means of the brain electrical microstates technique and their cortical sources were evaluated by LORETA. P3a and P3b showed different scalp topography and cortical sources. The P3a electrical field had a more anterior distribution as compared to the P3b and its generators were localized in cingulate, frontal and right parietal areas. P3b sources included bilateral frontal, parietal, limbic, cingulate and temporo-occipital regions. Differences in scalp topography and cortical sources suggest that the two components reflect different neural processes. Our findings on cortical generators are in line with the hypothesis that P3a reflects the automatic allocation of attention, while P3b is related to the effortful processing of task-relevant events. (c) 2007 Elsevier Inc. All rights reserved.

Objective: Cognitive impairment, more often involving memory and/or executive functions, has been reported in obsessive–compulsive (OC) patients. The present study aimed at: i) replicating, in an independent sample, previous findings by our group showing neurocognitive slowness limited to executive tasks; ii) assessing the influence of deficit in general cognitive abilities on executive dysfunction. Method: A comprehensive neuropsychological battery was administered to 30 drug-free OC patients and 30 healthy controls. Results: Obsessive–compulsive patients performed worse on visuospatial tests, were slower on executive tasks, and performed worse on the Wisconsin Card Sorting Test. After covarying for Wechsler Adult Intelligence Scale-Revised performance Intellectual Quotient, a lesser degree of executive dysfunction was observed. Conclusion: Obsessive–compulsive patients exhibit an impairment of executive functions, especially when tasks also require visuospatial abilities. The impairment might reflect a hyperactivity of the executive control.

Evidence has been provided that high frequency oscillations within the gamma band reflect mechanisms of cortical integration. In the light of recently proposed pathophysiological models of schizophrenia, suggesting a disturbance of the functional connectivity within distributed neural networks, it has been hypothesized that abnormalities in the gamma band underlie perceptual and cognitive dysfunctions in patients with schizophrenia. In the present study we investigated evoked and induced 40-Hz gamma power as well as frontoparietal and frontotem-poral event-related coherence in patients with deficit and nondeficit schizophrenia and in matched healthy controls. In patients, correlations between gamma oscillations and psychopathological dimensions were also investigated. A reduction of both induced gamma power and event-related coherence was observed in patients with nondeficit schizophrenia, but not in those with deficit schizophrenia. Our findings support the hypothesis that deficit and nondeficit schizophrenia represent separate disease entities, suggesting the presence of a poor integration of the neuronal activity within distributed neural network only in the subgroup of schizophrenic patients without primary and persistent negative symptoms. Associations between an excess of gamma oscillations and psychopathological dimensions were observed, suggesting that abnormal thoughts, behaviors and perceptions might be related to the formation of inappropriate neural connections.

BackgroundThe neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia.MethodWe used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation.ResultsThe whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group.ConclusionsThese findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation.

Objectives. To evaluate the safety, efficacy, and feasibility of inhibitory transcranial direct current stimulation (tDCS) for the treatment of behavioural abnormalities of autistic patients. Methods. Twelve young adult patients with autistic disorder were enrolled. All subjects presented intellectual disability and most of them had speech impairment. The Aberrant Behavior Checklist (ABC) was administered as the primary outcome measure before and after a 2-week tDCS course. All subjects received 10 daily applications of 20 min/1.5 mA/cathodal (inhibitory) tDCS over the left dorso-lateral pre-frontal cortex. Results. Eight out of 10 study completers improved in their abnormal behaviours, reaching an average reduction of 26.7% of the total ABC score. The remaining two patients showed no changes. In the whole group of completers, among the five subscales contributing to the significant reduction of the total score, the most remarkable and statistically significant change was seen in the subscale assessing hyperactivity and non-compliance (-35.9%, P = 0.002). No adverse effects were reported. Conclusions. Inhibitory tDCS improved the ABC rating scores for autistic behaviours. Owing to its ease of use, cost-effectiveness and the limited availability of specific treatment strategies, tDCS might be a valid therapeutic option to be tested in autistic patients.

Magnetic Resonance Imaging (MRI) measures are promising outcome markers for schizophrenia, since regional frontal and temporal grey matter volumes reductions, and enlargement of the ventricles, have been associated with outcome in this disorder. However, a number of methodological issues have limited the potential clinical utility of these findings. This article reviewed studies that examined brain structure at illness onset as a predictor of outcome, discusses the limitations of the findings, and highlights the challenges that would need to be addressed if structural data are to inform the management of an individual patient. Methods: Using a set of a priori criteria, we systematically searched Medline and EMBASE databases for articles evaluating brain structure at the time of the first psychotic episode and assessed response to treatment, symptomatic outcome, or functional outcome at any point in the first 12 months of illness. Results: The 11 studies identified suggest that alterations in medial temporal and prefrontal cortical areas, and in the networks that connect them with subcortical structures, are promising neuroanatomical markers of poor symptomatic and functional outcomes. Conclusion: Neuroimaging data, possibly in combination with other biomarkers of disease, could help stratifying patients with psychoses to generate patient clusters clinically meaningful, and useful to detect true therapeutic effects in clinical trials. Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), a large multicenter study funded by the FP7 European Commission, could generate these much-needed findings.

Impaired premorbid adjustment has been reported in patients with schizophrenia, generally in association with unfavorable aspects of the illness (e.g., poor outcome and severe negative symptoms). Several studies attempted to define the domains of premorbid dysfunction associated with negative symptoms and poor outcome; however, most of them assessed broadly defined negative symptoms. The present study was aimed to characterize premorbid functioning in a group of patients with deficit schizophrenia (DS), characterized by the presence of at least two primary and persistent negative symptoms (PPNS), and one of patients with a diagnosis of schizophrenia who did not meet criteria for DS (NDS). The presence of emotional/behavioral problems during childhood was investigated using the Childhood Behavior Checklist (CBCL) in both patient groups and in their respective healthy siblings. The Premorbid Adjustment Scale (PAS) was also used to assess premorbid functioning during childhood in the two patient groups. PPNS were also treated as a continuous variable and correlated with the indices of premorbid functioning regardless the DS/NDS categorization. DS patients, as compared to NDS, showed higher scores on the CBCL subscale "Withdrawn". Both DS and NDS patients showed, as compared to their healthy siblings, a greater impairment on almost all CBCL subscales. PAS findings revealed that DS patients had poorer premorbid adjustment than NDS. No significant correlation between premorbid functioning and PPNS was observed. These findings support the hypothesis that DS has a different developmental trajectory with respect to NDS, and that premorbid adjustment is one of the essential aspects of its characterization.

Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.

According to the World Health Organization (WHO), mental health is “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community” (1). This definition, while representing a substantial progress with respect to moving away from the conceptualization of mental health as a state of absence of mental illness, raises several concerns and lends itself to potential misunderstandings when it identifies positive feelings and positive functioning as key factors for mental health. In fact, regarding well-being as a key aspect of mental health is difficult to reconcile with the many challenging life situations in which well-being may even be unhealthy: most people would consider as mentally unhealthy an individual experiencing a state of well-being while killing several persons during a war action, and would regard as healthy a person feeling desperate after being fired from his/her job in a situation in which occupational opportunities are scarce. People in good mental health are often sad, unwell, angry or unhappy, and this is part of a fully lived life for a human being. In spite of this, mental health has been often conceptualized as a purely positive affect, marked by feelings of happiness and sense of mastery over the environment (2–4). Concepts used in several papers on mental health include both key aspects of the WHO definition, i.e. positive emotions and positive functioning. Keyes (5,6) identifies three components of mental health: emotional well-being, psychological well-being and social well-being. Emotional well-being includes happiness, interest in life, and satisfaction; psychological well-being includes liking most parts of one's own personality, being good at managing the responsibilities of daily life, having good relationships with others, and being satisfied with one's own life; social well-being refers to positive functioning and involves having something to contribute to society (social contribution), feeling part of a community (social integration), believing that society is becoming a better place for all people (social actualization), and that the way society works makes sense to them (social coherence). However, such a perspective of mental health, influenced by hedonic and eudaimonic traditions, which champion positive emotions and excellence in functioning, respectively (7), risks excluding most adolescents, many of whom are somewhat shy, those who fight against perceived injustice and inequalities or are discouraged from doing so after years of useless efforts, as well as migrants and minorities experiencing rejection and discrimination. The concept of positive functioning is also translated by several definitions and theories about mental health into the ability to work productively (1,8), and may lead to the wrong conclusion that an individual at an age or in a physical condition preventing her/him from working productively is not by definition in good mental health. Working productively and fruitfully is often not possible for contextual reasons (e.g., for migrants or for discriminated people), which may prevent people from contributing to their community. Jahoda (9) subdivided mental health into three domains: self-realization, in that individuals are able to fully exploit their potential; sense of mastery over the environment; and sense of autonomy, i.e. ability to identify, confront, and solve problems. Murphy (10) argued that these ideas were laden with cultural values considered important by North Americans. However, even for a North American person, it is hard to imagine, for example, that a mentally healthy human being in the hands of terrorists, under the threat of beheading, can experience a sense of happiness and mastery over the environment. The definition of mental health is clearly influenced by the culture that defines it. However, as also advocated by Vaillant (11), common sense should prevail and certain elements that have a universal importance for mental health might be identified. For example, in spite of cultural differences in eating habits, the acknowledgement of the importance of vitamins and the four basic food groups is universal.

Psychosocial therapies play an important role in the treatment of schizophrenia. These therapies are aimed at improving the functioning of the patient in the community, which in turn can lead to clinical improvement, such as reduction in the number of relapses or hospitalizations. Substantial evidence supports the use of many psychosocial therapies in schizophrenia, including cognitive behavioral therapy, assertive community treatment, cognitive remediation and functional skills training. The customization of pharmacological therapy in schizophrenia, besides the experience of the clinician and individual preferences of the patient, should be based on three sets of objective data: 1) clinical predictors of response to therapy; 2) predictable side effects of therapy; 3) pharmacogenetic and pharmacogenomic data. It has been made a considerable effort to improve adherence to antipsychotic treatment through the development of drugs with better tolerability, in formulations that enable long-term administration of the drug, including injectable long-acting (depot) antipsychotics. In recent years the development of these formulations of atypical antipsychotics and the promising results obtained in clinical trials are changing the attitude toward these drugs, traditionally reserved for patients with repeated non-adherence to treatment.

In spite of its origins deeply rooted in the discipline, pharmaco-EEG applications in psychiatry remain limited to its achievements in the field of psychotropic drugs classification and, in few instances, discovery. In the present paper two attempts to transfer pharmaco-EEG methods to psychiatric clinical routine will be described: 1) monitoring of psychotropic drug toxicity at the central nervous system level, and 2) prediction of clinical response to treatment with psychotropic drugs. Both applications have been the object of several investigations providing promising and sometimes consistent findings which, however, had no impact on clinical practice. For the first topic, the review is limited to antipsychotics, lithium and recreational drugs, as for other psychotropic drugs mostly case studies are available, while for the response prediction it will include antipsychotics, antidepressants, anxiolytics, psychostimulants and nootropics. In spite of several methodological limitations, pharmaco-EEG studies dealing with monitoring of antipsychotic- and lithium-induced EEG abnormalities went close to, but never became, a clinical routine. EEG studies of recreational drugs are flawed by several limitations, and failed, so far, to identify reliable indices of CNS toxicity to be used in clinical settings. Several QEEG studies on early predictors of treatment response to first generation antipsychotics have produced consistent findings, but had no clinical impact. For other psychotropic drug classes few and inconsistent reports have appeared. Pharmaco-EEG had the potential for important clinical applications, but so far none of them entered clinical routine. The ability to upgrade theories and methods and promote large scale studies represent the future challenge.

Previous studies on motion perception revealed motion-processing brain areas sensitive to changes in luminance and texture (low-level) and changes in salience (high-level). The present functional magnetic resonance imaging (fMRI) study focused on motion standstill. This phenomenon, occurring at fast presentation frequencies of visual moving objects that are perceived as static, has not been previously explored by neuroimaging techniques. Thirteen subjects were investigated while perceiving apparent motion at 4 Hz, at 30 Hz (motion standstill), isoluminant static and flickering stimuli, fixation cross, and blank screen, presented randomly and balanced for rapid event-related fMRI design. Blood oxygenation level-dependent (BOLD) signal in the occipito-temporal brain region MT/V5 increased during apparent motion perception. Here we could demonstrate that brain areas like the posterior part of the right inferior parietal lobule (LPL) demonstrated higher BOLD-signal during motion standstill. These findings suggest that the activation of higher-order motion areas is elicited by apparent motion at high presentation rates (motion standstill). We interpret this observation as a manifestation of an orienting reaction in IPL towards stimulus motion that might be detected but not resolved by other motion-processing areas. Previous studies on motion perception revealed motion-processing brain areas sensitive to changes in luminance and texture (low-level) and changes in salience (high-level). The present functional magnetic resonance imaging (fMRI) study focused on motion standstill. This phenomenon, occurring at fast presentation frequencies of visual moving objects that are perceived as static, has not been previously explored by neuroimaging techniques. Thirteen subjects were investigated while perceiving apparent motion at 4 Hz, at 30 Hz (motion standstill), isoluminant static and flickering stimuli, fixation cross, and blank screen, presented randomly and balanced for rapid event-related fMRI design. Blood oxygenation level-dependent (BOLD) signal in the occipito-temporal brain region MT/V5 increased during apparent motion perception. Here we could demonstrate that brain areas like the posterior part of the right inferior parietal lobule (IPL) demonstrated higher BOLD-signal during motion standstill. These findings suggest that the activation of higher-order motion areas is elicited by apparent motion at high presentation rates (motion standstill). We interpret this observation as a manifestation of an orienting reaction in IPL towards stimulus motion that might be detected but not resolved by other motion-processing areas (i.e., MT/V5). © 2005 Wiley-Liss, Inc.