[Cognitive Behavioral Therapy and the Treatment of ADHD in Adults]. / La thérapie cognitive-comportementale dans le traitement du TDAH chez l'adulte.

Background The international prevalence of adult attention deficit hyperactivity disorder (ADHD) is estimated at 2.5%. ADHD is associated with serious impairment in academic, occupational, social and emotional functioning. Despite the debilitating nature of this disorder, few individuals with ADHD receive appropriate help. Further, although psychopharmacology is considered the first-line treatment of adults with ADHD, it is now recognized that medication alone may be insufficient. Thus, cognitive behavioral therapy (CBT) is a promising approach.Objectives This study aimed to review literature and investigate the efficacy of CBT, in reducing ADHD symptoms and comorbid conditions such anxiety and depression for adults with ADHD, by several studies through a meta-analysis.Methods We searched the literature from 1946 through 2015 using especially MEDLINE, EMBASE and PsycINFO. We used a random-effects model, Odds Ratios (OR) and Hedge's g.Results Data from 12 randomized controlled studies were included, totaling 575 subjects. The results showed a significant reduction in ADHD symptoms (Hedge's g = 0.95) and comorbid anxiety (Hedge's g = 0.39) and depression (Hedge's g = 0.30) for the CBT group in comparison with controls. Following the end of treatment, ADHD symptoms continue to improve, but not the comorbid conditions.Conclusion In summary, in adults with ADHD, CBT appears to be a promising treatment.

Neural correlates of clinical improvement after deep transcranial magnetic stimulation (DTMS) for treatment-resistant depression: a case report using functional magnetic resonance imaging.

We report the effects of a 4-week trial of deep transcranial magnetic stimulation (DTMS) on depressive and anxious symptoms and brain activity in a patient (Mrs A) with treatment-resistant depression (TRD). The protocol involved a pre- and a post-functional magnetic resonance imaging (fMRI) scan during which Mrs A had to perform a working memory task (i.e., n-back). Her baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D21) was 24, indicating severe depressive symptoms. Immediately after 4 weeks of daily DTMS treatment applied over the left dorsolateral prefrontal cortex (DLPFC), her HAM-D21 score decreased to 13 (a 46% reduction), and 1 month later, it was 12 (a 50% reduction). Moreover, Mrs A's accuracy scores on the n-back task (i.e., 2-back condition) improved from 79% (baseline) to 96% (after DTMS treatment). At the neural level, Mrs A showed significantly increased brain activity in the working memory network (e.g., DLPFC, parietal cortex) during the execution of the 2-back condition after DTMS treatment compared to baseline.

Neural correlates of recognition memory of social information in people with schizophrenia.

BACKGROUND: Social dysfunction is a hallmark characteristic of schizophrenia. Part of it may stem from an inability to efficiently encode social information into memory and retrieve it later. This study focused on whether patients with schizophrenia show a memory boost for socially relevant information and engage the same neural network as controls when processing social stimuli that were previously encoded into memory. METHODS: Patients with schizophrenia and healthy controls performed a social and nonsocial picture recognition memory task while being scanned. We calculated memory performance using d'. Our main analysis focused on brain activity associated with recognition memory of social and nonsocial pictures. RESULTS: Our study included 28 patients with schizophrenia and 26 controls. Healthy controls demonstrated a memory boost for socially relevant information. In contrast, patients with schizophrenia failed to show enhanced recognition sensitivity for social pictures. At the neural level, patients did not engage the dorsomedial prefrontal cortex (DMPFC) as much as controls while recognizing social pictures. LIMITATIONS: Our study did not include direct measures of self-referential processing. All but 3 patients were taking antipsychotic medications, which may have altered both the behavioural performance during the picture recognition memory task and brain activity. CONCLUSION: Impaired social memory in patients with schizophrenia may be associated with altered DMPFC activity. A reduction of DMPFC activity may reflect less involvement of self-referential processes during memory retrieval. Our functional MRI results contribute to a better mapping of the neural disturbances associated with social memory impairment in patients with schizophrenia and may facilitate the development of innovative treatments, such as transcranial magnetic stimulation.

Brain responses to body image stimuli but not food are altered in women with bulimia nervosa.

BACKGROUND: Research into the neural correlates of bulimia nervosa (BN) psychopathology remains limited. METHODS: In this functional magnetic resonance imaging study, 21 BN patients and 23 healthy controls (HCs) completed two paradigms: (1) processing of visual food stimuli and (2) comparing their own appearance with that of slim women. Participants also rated food craving and anxiety levels. RESULTS: Brain activation patterns in response to food cues did not differ between women with and without BN. However, when evaluating themselves against images of slim women, BN patients engaged the insula more and the fusiform gyrus less, compared to HCs, suggesting increased self-focus among women with BN whilst comparing themselves to a 'slim ideal'. In these BN patients, exposure to food and body image stimuli increased self-reported levels of anxiety, but not craving. CONCLUSIONS: Our findings suggest that women with BN differ from HCs in the way they process body image, but not in the way they process food stimuli.

Altered dynamic coupling of lateral occipital complex during visual perception in schizophrenia.

INTRODUCTION: There is mounting evidence that visual perception abnormalities in schizophrenia are partly explained by a dysfunction of the lateral occipital complex (LO). We previously demonstrated that schizophrenia patients had broader topography and reduced magnitude of activity of LO. However, the functional connectivity of LO with other brain regions during visual perception has not been directly investigated in schizophrenia. MATERIALS AND METHODS: Eighteen patients with schizophrenia and eighteen matched controls performed a backward masking task during functional magnetic resonance imaging (fMRI). Stimulus onset asynchronies were manipulated to change the level of target visibility. To examine connectivity with LO function we conducted psychophysiological interactions (PPI) analyses using: 1) a region of interest (ROI) approach and 2) a whole brain analysis. ROIs were defined based on a contrast of trials on which a target was presented versus null trials in which no stimuli were presented. RESULTS: Eleven ROIs were identified. Both groups showed similar strength of coupling between LO and the 11 ROIs when visibility was not taken into account. Healthy controls showed clear changes in coupling between LO and prefrontal and parietal regions as a function of target visibility (higher coupling with more visible targets). In comparison, patients showed reduced dynamic coupling with LO in the right superior frontal gyrus (significant after correcting for multiple comparisons) and a trend for reduced coupling in the left precuneus and left inferior frontal regions. Whole brain analysis identified additional regions that showed dynamic coupling with LO in healthy controls, but not in patients. DISCUSSION: The increased coupling between LO and higher-level parietal and prefrontal regions during visual awareness in healthy controls likely reflects visual reentrant processing. The lack of modulation of coupling between LO and key prefrontal and parietal regions found in schizophrenia may partly reflect abnormalities in LO tuning. The altered LO coupling may contribute to visual perception abnormalities in schizophrenia.

Medial prefrontal cortex activity during memory encoding of pictures and its relation to symptomatic improvement after citalopram treatment in patients with major depression.

BACKGROUND: Brain imaging studies of major depressive disorder have shown alterations in the brain regions typically involved in episodic memory, including the prefrontal cortex and medial temporal areas. Some studies of major depressive disorder have linked episodic memory performance to treatment response. In this study, we sought to identify brain regions whose activity, measured during the encoding of pictures, predicted symptomatic improvement after 8 weeks of citalopram treatment. METHODS: We included 20 unmedicated depressed patients. These patients performed an episodic recognition memory task during functional magnetic resonance imaging. During the encoding phase, 150 pictures depicting emotionally positive, negative or neutral content were presented, and the participants were required to classify each picture according to its emotional valence. The same 150 pictures were presented, along with 150 new ones, for a recognition task. We asked participants to distinguish the old pictures from the new ones. We assessed symptom severity by use of the 21-item Hamilton Rating Scale for Depression (HAM-D) at baseline and after 8 weeks of citalopram treatment. We performed subsequent memory effect analyses using SPM2 software. We explored the relation between brain activation during successful encoding of pictures and symptomatic improvement. RESULTS: Patients showed a mean symptomatic improvement of 54.5% on the HAM-D after 8 weeks. Symptomatic improvement was significantly and positively correlated with picture recognition memory accuracy. We also found that the activity of the ventromedial prefrontal cortex and anterior cingulate cortex during successful encoding was significantly correlated with symptomatic improvement. Finally, we found greater activation in the ventromedial prefrontal cortex during the successful encoding of positive pictures in comparison with neutral pictures. LIMITATIONS: During the recognition memory task, 5 participants (among the best responders to treatment) were not included in the valence-specific analyses because they had very few errors. A more challenging task would have allowed the inclusion of most patients. CONCLUSION: Different types of functional imaging paradigms have been used to explore whether the activity of specific brain regions measured at baseline is predictive of a better response to treatment in major depressive disorder. Among these regions, the medial prefrontal cortex and anterior cingulate cortex usually show the strongest predictive value. According to our results, the medial prefrontal cortex and anterior cingulate cortex could have an effect on treatment response in major depressive disorder by contributing to the successful encoding of positively valenced information.

Relation between emotional face memory and social anhedonia in schizophrenia.

BACKGROUND: There is an interest in investigating the relation between emotional memory impairments in schizophrenia and specific symptom dimensions. We explored potential links between emotional memory and social anhedonia severity in patients with schizophrenia and in healthy individuals. METHODS: Twenty-nine patients with schizophrenia and 27 matched healthy individuals completed the Chapman Revised Social Anhedonia Scale and then performed an emotional face recognition memory task involving happy, sad and neutral face expressions. We calculated emotional memory performance using 2 independent measures: the discrimination accuracy index Pr and the response bias Br. We also measured valence ratings of the face stimuli. We performed correlation analyses using the inter-individual variability in social anhedonia severity and the individual score obtained for each memory performance variable and for each face valence rating condition. RESULTS: Patients with schizophrenia reported higher levels of social anhedonia compared with healthy individuals. They also showed lower recognition accuracy for faces compared with healthy participants. We found no significant correlation between social anhedonia severity and any of the memory performance variables for both patients with schizophrenia and healthy individuals. Regarding potential links between social anhedonia severity and face valence ratings, we found that individuals with elevated social anhedonia had a tendency to rate the face stimuli as more negative. LIMITATIONS: Our negative finding may be partly explained by a lack of statistical power owing to our small patient sample. In addition, our patient sample had unusually high estimated IQ scores, which highlights potential issues regarding the generalization of our findings. Finally, we used a yes-no recognition memory task with a very short retention interval delay. CONCLUSION: Our results suggest that social anhedonia is not directly linked to emotional memory deficits and biases and does not interfere with the modulatory effect of positively valenced emotion on memory.

Functional neural correlates of social approval in schizophrenia.

Social approval is a reward that uses abstract social reinforcers to guide interpersonal interactions. Few studies have specifically explored social reward processing and its related neural substrates in schizophrenia. Fifteen patients with schizophrenia and fifteen healthy controls participated in a two-part study to explore the functional neural correlates of social approval. In the first session, participants were led to believe their personality would be assessed based on their results from various questionnaires and an interview. Participants were then presented with the results of their supposed evaluation in the scanner, while engaging in a relevant fMRI social approval task. Subjects provided subjective reports of pleasure associated with receiving self-directed positive or negative feedback. Higher activation of the right parietal lobe was found in controls compared with individuals with schizophrenia. Both groups rated traits from the high social reward condition as more pleasurable than the low social reward condition, while intergroup differences emerged in the low social reward condition. Positive correlations were found in patients only between subjective ratings of positive feedback and right insula activation, and a relevant behavioural measure. Evidence suggests potential neural substrates underlying the cognitive representation of social reputation in schizophrenia.

Does the Beck Cognitive Insight Scale Predict Response to Cognitive Remediation in Schizophrenia?

Cognitive remediation therapy (CRT) has emerged as a viable treatment option for people diagnosed with schizophrenia presenting disabling cognitive deficits. However, it is important to determine which variables can influence response to CRT in order to provide cost-effective treatment. This study's aim was to explore cognitive insight as a potential predictor of cognitive improvement after CRT. Twenty patients with schizophrenia completed a 24-session CRT program involving 18 hours of computer exercises and 6 hours of group discussion to encourage generalization of cognitive training to everyday activities. Pre- and posttest assessments included the CogState Research Battery and the Beck Cognitive Insight Scale (BCIS). Lower self-certainty on the BCIS at baseline was associated with greater improvement in speed of processing (r s = -0.48; p < 0.05) and visual memory (r s = -0.46; p < 0.05). The results of this study point out potential associations between self-certainty and cognitive improvement after CRT, a variable that can easily be measured in clinical settings to help evaluate which patients may benefit most from the intervention. They also underline the need to keep investigating the predictors of good CRT outcomes, which can vary widely between patients.

Verbal memory performance of patients with a first depressive episode and patients with unipolar and bipolar recurrent depression.

Depression is usually associated with episodic memory impairment. The main clinical features of depression associated with that memory impairment are not clearly defined. The main goal of that study was to assess the role of the diagnostic subtypes and the number of depressive episodes on the memory performance of acute unipolar (UP) and bipolar (BP) depressed patients.Twenty-three patients with a first major depressive episode (FE), 28 patients meeting DSM-IV criteria for UP recurrent depression (UR) and 18 BP patients with recurrent depression were compared with 88 healthy subjects on a verbal episodic memory task. Patients suffering from a first depressive episode did not show verbal memory impairment as compared to normal controls. Unlike FE patients, UR and BP patients exhibited verbal memory deficits with impaired free recall and normal cued recall and recognition. The memory deficits of the UR and BP patients was present in the first free recall trial. Depressed patients improved their memory performance across the three trials of the task at the same rate than normal controls. Our results suggest that the number of depressive episodes has a negative influence on verbal memory performance of acute depressed patients. The effects of the repetition of the depressive episodes are not modulated by the subtypes of depression and may reflect sensitization to the cognitive impact of depression associated with increasing prefrontal dysfunction.

TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis.

BACKGROUND: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known. AIMS: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP). METHODS: 173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates. RESULTS: Carriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F1,172=4.4, p=.038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F1,172=4.3, p=.039). CONCLUSIONS: rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result.

Neural substrates of empathic accuracy in people with schizophrenia.

INTRODUCTION: Empathic deficits in schizophrenia may lead to social dysfunction, but previous studies of schizophrenia have not modeled empathy through paradigms that (1) present participants with naturalistic social stimuli and (2) link brain activity to "accuracy" about inferring other's emotional states. This study addressed this gap by investigating the neural correlates of empathic accuracy (EA) in schizophrenia. METHODS: Fifteen schizophrenia patients and 15 controls were scanned while continuously rating the affective state of another person shown in a series of videos (ie, targets). These ratings were compared with targets' own self-rated affect, and EA was defined as the correlation between participants' ratings and targets' self-ratings. Targets' self-reported emotional expressivity also was measured. We searched for brain regions whose activity tracked parametrically with (1) perceivers' EA and (2) targets' expressivity. RESULTS: Patients showed reduced EA compared with controls. The left precuneus, left middle frontal gyrus, and bilateral thalamus were significantly more correlated with EA in controls compared with patients. High expressivity in targets was associated with better EA in controls but not in patients. High expressivity was associated with increased brain activity in a large set of regions in controls (eg, fusiform gyrus, medial prefrontal cortex) but not in patients. DISCUSSION: These results use a naturalistic performance measure to confirm that schizophrenic patients demonstrate impaired ability to understand others' internal states. They provide novel evidence about a potential mechanism for this impairment: schizophrenic patients failed to capitalize on targets' emotional expressivity and also demonstrate reduced neural sensitivity to targets' affective cues.

An intact social cognitive process in schizophrenia: situational context effects on perception of facial affect.

BACKGROUND: Impaired facial affect recognition is the most consistent social cognitive finding in schizophrenia. Although social situations provide powerful constraints on our perception, little is known about how situational context modulates facial affect recognition in schizophrenia. METHODS: Study 1 was a single-site study with 34 schizophrenia patients and 22 healthy controls. Study 2 was a 2-site study with 68 schizophrenia patients and 28 controls. Both studies administered a Situational Context Facial Affect Recognition Task with 2 conditions: a situational context condition and a no-context condition. For the situational context condition, a briefly shown face was preceded by a sentence describing either a fear- or surprise-inducing event. In the no-context condition, a face was presented without a sentence. For both conditions, subjects rated how fearful or surprised the face appeared on a 9-point Likert scale. RESULTS: For the situational context condition of study 1, both patients and controls rated faces as more afraid when they were paired with fear-inducing sentences and as more surprised when they were paired with surprise-inducing sentences. The degree of modulation was comparable across groups. For the no-context condition, patients rated faces comparably to controls. The findings of study 2 replicated those from study 1. CONCLUSIONS: Despite previous abnormalities in other types of context paradigms, this study found intact situational context processing in schizophrenia, suggesting that patients benefit from situational context when interpreting ambiguous facial expression. This area of relative social cognitive strength in schizophrenia has implications for social cognitive training programs.

Cannabis use and anticipatory pleasure as reported by subjects with early psychosis and community controls.

BACKGROUND: There is evidence of decreased pleasure and deficits in the anticipation of reward in both psychotic illness and drug addiction. Individuals with low anticipatory pleasure may preferentially engage in behaviours associated with immediate reward such as cannabis use. METHOD: Ninety-one psychosis patients and 91 controls without history of psychosis were administered the Temporal Experience of Pleasure Scale (TEPS), a self report which measures anticipatory and consummatory pleasure. Cannabis use diagnosis was assessed using the Structured Clinical Interview for DSM IV (SCID). Subjects reported the frequency of cannabis consumption and time since last use. RESULTS: Patients did not show a significant deficit in anticipatory or consummatory pleasure compared to controls; however, patients with an active cannabis-use disorder tended to have lower consummatory pleasure than controls with active cannabis disorder (p<.05). Patients who continued to use cannabis during treatment of their first episode of psychosis reported significantly lower anticipatory pleasure compared to those who had a lifetime cannabis diagnosis but were able to maintain abstinence (F(1,60)=5.6, p=.021). Frequency of cannabis use was negatively correlated to anticipatory and consummatory pleasure (Pearson R=-.46, -.48 respectively) in 37 patients currently using cannabis but not in 46 cannabis-using controls (partial R=-.04, -.07 respectively). CONCLUSION: Anticipatory pleasure may not be decreased in early psychosis patients. Lower hedonic response may be associated with persistent, heavy cannabis use in patients in the early phase of psychotic disorders.

Do patients with schizophrenia benefit from a self-referential memory bias?

BACKGROUND: Self-referential processing (i.e. linking internal and external stimuli to one's own self) has received scant attention thus far in schizophrenia. This type of processing is a key component of social cognition and thought to be important for adaptive social functioning. Memory studies in healthy subjects have shown that stimuli processed with reference to the self are better remembered than stimuli processed in other semantic forms. It is not known whether schizophrenia patients benefit from such a memory boost for self-referenced information. METHODS: Twenty-five schizophrenia patients and 22 controls were assessed with a self-referential recognition memory paradigm. During an encoding phase, participants rated personality adjectives in each of three conditions: (1) structural features (uppercase or lowercase letters?); (2) social desirability (is adjective socially desirable or not?); or (3) self-referential (does adjective describe me or not?). Recognition memory for these personality adjectives was then tested during an unexpected yes-no recognition test. RESULTS: Patients and controls were comparable in memory performance for the structural (p=0.12) and social desirability (p=0.30) conditions. In contrast, patients showed significantly reduced recognition sensitivity compared to controls for the self-referential condition (p=0.03). DISCUSSION: Compared to healthy controls, patients with schizophrenia did not benefit from a memory boost for self-referenced information. Such impaired self-referential memory may be associated with abnormal function of the medial prefrontal cortex. The inability to enhance memory for personally relevant information may partly explain poor social functioning in schizophrenia patients.

The parahippocampal gyrus as a neural marker of early remission in first-episode psychosis: a voxel-based morphometry study.

INTRODUCTION: Outcome from psychotic disorders is heterogeneous with poor long-term clinical outcome associated with such markers as decreased internal capsule volume and increased ventricular volumes. No previous study has examined neuroimaging markers in relation to early remission. METHODS: This neuroimaging study included 68 previously untreated first episode of psychosis (FEP) patients, of whom 28 achieved remission and 40 did not after six months of treatment, and 42 healthy controls. Using voxel-based morphometry (VBM), we set out to determine if specific neural correlates could be identified in FEP patients not achieving remission in a specialized early-intervention service. RESULTS: Nonremitted patients had significant lower grey matter concentration (GMC) in the parahippocampal gyrus bilaterally compared to remitted patients. A classification model utilizing parahippocampal GMC correctly classified remission status 79% of the time and accounted for 56% of the variance. Moreover, GMC on the left (r=-0.35, p=0.004) and right (r=-0.47, p<0.0001) side correlated with social withdrawal while only the left side correlated with verbal memory (r=0.21, p=0.03). CONCLUSIONS: Neural markers of early remission are present in first-episode patients. A better understanding of the neural etiology of psychosis and its relationship to outcome may encourage the search for new medications to help improve outcome in relation to the identified brain regions like the parahippocampal gyrus.

Functional neural substrates of self-reported physical anhedonia in non-clinical individuals and in patients with schizophrenia.

BACKGROUND: Anhedonia is a negative symptom of schizophrenia that has a detrimental impact on functioning and quality of life. Anhedonia also represents a vulnerability marker for schizophrenia when measured in non-clinical individuals. The investigation of the neural correlates of anhedonia in schizophrenia and non-clinical individuals could provide key insights on the pathophysiology of negative symptoms, as well as on the characterization of neural markers of vulnerability. METHODS: Thirty patients with schizophrenia and twenty-six non-clinical individuals were recruited. We used an event-related functional Magnetic Resonance Imaging paradigm involving an emotional picture viewing task. For each group, separately, we correlated the regional BOLD signal changes during hedonic processing with the Chapman Physical Anhedonia Scale scores. An interaction analysis identified the neural correlates of anhedonia specific to schizophrenia. RESULTS: We found that anhedonia severity in both groups was inversely correlated with the activity of a limited number of emotion-related regions, including the medial prefrontal cortex. The orbitofrontal cortex and putamen/ventral striatum activity was negatively correlated with anhedonia severity in people with schizophrenia only. CONCLUSIONS: The data first suggest that anhedonia severity is linked to a poor modulation of emotional/attentional brain regions during the processing of hedonic information. The link between anhedonia and the activity of the ventral striatum and orbitofrontal cortex found in schizophrenia could reflect the specific impairment of indirect factors, such as reward anticipation deficits, that influence the measurement of anhedonia severity through self-report questionnaires.

Structural neural correlates of impairments in social cognition in first episode psychosis.

Several studies have demonstrated that patients with schizophrenia show impairments in social cognition and current evidence indicate that this deficit is associated with abnormal activity in specific brain regions. In addition to functional imaging studies, we believe that the identification of structural correlates of social cognitive processes may help to better understand the neural underpinnings of these specific skills. The main objective of this study was to investigate the relationship between gray matter density and social cognitive deficits in first episode of schizophrenia spectrum psychosis, using a comprehensive assessment that we previously demonstrated to be a highly sensitive measure of social cognitive deficits in this population. Thirty-eight patients with a first episode of psychosis participated in this study, and the Four Factor Test of Social Intelligence was used as a measure of social cognition. Social cognitive impairments in first episode psychosis were significantly correlated with reduced gray-matter density in the left middle frontal gyrus other regions within the mirror neuron system network (MSN), namely the right supplementary motor cortex, the left superior temporal gyrus and the left inferior parietal lobule. We concluded that structural abnormalities within the MSN may account for the social cognitive deficits present in some psychiatric disorders, such as schizophrenia.

Benefits of enriched intervention compared with standard care for patients with recent-onset psychosis: a metaanalytic approach.

OBJECTIVE: To assess the effectiveness of enriched intervention (EI) on symptomatic and functional outcomes, compared with standard care (SC). METHOD: Studies were retrieved from search engines and, using a metaanalytic approach, we compared El trials with SC trials. Eleven EI sample trials (1053 patients) and 6 SC sample trials (500 patients), totalling data from 1553 patients (69% male), were examined. We calculated the effect sizes (ESs) of both symptomatic and functional improvement over a follow-up period of about 1 year. RESULTS: Significant differences between El and SC were observed at follow-up for the improvement of both positive and negative symptoms, respectively: positive, EI = -1.54 (95%CI, -1.63 to -1.45 ) and SC = -1.07 (95%CI, -1.19 to -0.94) (Qbetween = 40.3, df 1, P < 0.001); negative, EI= -0.44 (95%CI, -0.53 to -0.35) and SC = -0.18 (95%Cl, -0.31 to -0.05) (Qbetween = 10.6, df 1, P < 0.01). We also observed a significant difference between the El and the SC groups for functional improvement over the follow-up period with mean EI = 1.11 (95%CI, 0.99 to 1.23) and SC = 0.63 (95%CI, 0.49 to 0.77) (Qbetween = 24.5, df 1, P < 0.001). CONCLUSIONS: There is now quantitative evidence across multiple studies and sites to indicate that Els for patients with recent-onset psychosis are significantly more effective than SC for symptomatic and functional improvement over a period of about 1 year.