Persistent Negative Symptoms Research Articles

Neurobiological background of negative symptoms.

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 Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included.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.

Management of Primary Negative Symptoms in Schizophrenia: an One-year Study in “real World” in According to the Recommendations of Consensus Development Conference Attendees

Introduction Negative symptoms constitute an important diagnostic and therapeutic challenge (Galderisi & Maj 2008). Negative symptoms are thought to be part of schizophrenia, at least in some patients (Kirkpatrick 2014). Despite that there are few treatment trials focused on primary negative symptoms (Chue P, Lalon de JK 2014). Objectives Open-observational study to evaluate the efficacy of SGA on negative symptoms, in according to the recommendations of Consensus Development Conference Attendes(CDCA) . Aims To consider the impact of SGAs in the treatment of primary negative symptoms. Methods We evaluated in 12-month-study efficacy of SGA in 42 inpatients with schizophrenia(DSM-5). Inclusion criteria: persistent negative symptoms with adequate antipsychotic treatment, clinically stable, minimal psychotic symptoms, depression/anxiety, EPS. Patients were treated with SGAs (clozapine; risperidone; quetiapine, olanzapine) and evaluated at baseline and after 1, 3, 6, 12 mouths with: PANSS; BPRS; Brief Negative Symptoms Scale (BNSS); CDSS. Data were collected and evaluated by EZanalize /Excel. Results Data obtained with BNSS and PANSS scales show no significant differences in olanzapine and risperidone groups. Clozapine-treated patients had a significant reduction in BNSS score (p Conclusion There are not studies that show a superiority of a drug over another in negative symptoms therapy. However, emergine results show that some antipsychotics act preferentially on some specific items of group of symptoms.

Conceptualization and treatment of negative symptoms in schizophrenia.

Negative symptoms of schizophrenia including social withdrawal, diminished affective response, lack of interest, poor social drive, and decreased sense of purpose or goal directed activity predict poor functional outcomes for patients with schizophrenia. They may develop and be maintained as a result of structural and functional brain abnormalities, particularly associated with dopamine reward pathways and by environmental and psychosocial factors such as self-defeating cognitions and the relief from overstimulation that accompanies withdrawal from social and role functioning. Negative symptoms are more difficult to treat than the positive symptoms of schizophrenia and represent an unmet therapeutic need for large numbers of patients with schizophrenia. While antipsychotic medications to treat the symptoms of schizophrenia have been around for decades, they have done little to address the significant functional impairments in the disorder that are associated with negative symptoms. Negative symptoms and the resulting loss in productivity are responsible for much of the world-wide personal and economic burden of schizophrenia. Pharmacologic treatments may be somewhat successful in treating secondary causes of negative symptoms, such as antipsychotic side effects and depression. However, in the United States there are no currently approved treatments for severe and persistent negative symptoms (PNS) that are not responsive to treatments for secondary causes. Pharmacotherapy and psychosocial treatments are currently being developed and tested with severe and PNS as their primary targets. Academia, clinicians, the pharmaceutical industry, research funders, payers and regulators will need to work together to pursue novel treatments to address this major public health issue.

Rasagiline in the Treatment of the Persistent Negative Symptoms of Schizophrenia.

The current study examined the efficacy and safety of rasagiline, a selective MAO-B inhibitor, for the treatment of persistent negative symptoms. Sixty people with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder, who met a priori criteria for persistent negative symptoms, were randomized to receive rasagiline, 1mg/d (n = 31) or placebo (n = 29) in a 12-week, double-blind, placebo-controlled clinical trial. The Scale for the Assessment of Negative Symptoms (SANS) total score was used to assess change in negative symptoms. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), N-Back test, a probabilistic learning task, and a delayed discounting task were used to assess cognition. In a mixed model analysis of covariance (MM-ANCOVA), with time as a continuous variable, there was a significant treatment × time effect for SANS total score (F = 5.61(df = 1,40.3), P = .023). The treatment × time interaction effect was also significant for the SANS avolition subscale score (F(1,40.2) = 10.41, P = .002). In a post hoc MM-ANCOVA analyses, with time as a categorical variable, group differences were significant at week 12 for SANS total score (t(37.3) = 2.15; P = .04; d = -0.41) and SANS avolition subscale score (t(49.0) = 3.06; P = .004; d = -0.46). There was a significant difference in number of participants with a ≥20% reduction in SANS avolition score (χ(2)(1) = 10.94; P = .0009), but not in SANS total score (χ(2)(1) = 1.11; P = .29). There were no significant group differences on the RBANS, N-Back, probabilistic learning, or delayed discounting tasks. Study results support future studies of the utility of rasagiline for the treatment of negative symptoms, including avolition (clinicaltrials.gov trial number: NCT00492336).

Non-glutamatergic clozapine augmentation strategies: a review and meta-analysis.

Persistent negative symptoms and cognitive impairment are major clinical problems in the treatment of schizophrenia. There is no convincing evidence regarding the efficacy of augmentation of clozapine with a second antipsychotic, ethyl eicosapentaenoic acid (E-EPA), an antidepressant, a mood stabilizer or extract of Ginkgo biloba in clozapine-resistant schizophrenia. We present an overview of studies in which the potential clinical utility of the addition of non-glutamatergic agents to clozapine is assessed. We performed a meta-analysis on the efficacy of both risperidone and aripiprazole compared to placebo. We compared the effects of the addition of a second antipsychotic or an antidepressant to clozapine on positive, negative, overall and affective symptoms of schizophrenia in double-blind placebo-controlled trials.

Persistent negative symptoms after first episode schizophrenia: A 2-year follow-up study

BackgroundThe aim of this study is to determine the rate of persistent negative symptoms according to different criteria during two years of follow-up after first-episode schizophrenia. MethodsThe study sample consisted of 105 patients with first-episode schizophrenia who completed at least 12months of follow-up period. We used 6 different definitions of persistent negative symptoms (PNS) based on the Scale for the Assessment of Negative Symptoms subscale scores at seven time points throughout the follow-up. In some definitions of PNS, patients with suprathreshold depressive symptoms were excluded. Premorbid adjustment and baseline cognitive performances of the patients were assessed. ResultsThe PNS rates were between 14.2 and 27.9% in the first year and 11.1 and 25.8% in the second year. Seventy-eight percent of the patients who met the strictest PNS criteria during the first 12months met the same criteria also during the second 12-month-period. Those with PNS had earlier onset, lower premorbid functioning, worse executive functioning and attention at baseline, and lower rates of working/studying during the 2-year follow-up. Duration of education and untreated psychosis are the independent variables that contribute to the PNS status at the first year of follow-up in logistic regression analysis. ConclusionOur findings suggest that PNS has specific predictors and effect on the course of illness after first-episode schizophrenia.

Cortical thinning in temporo-parietal junction (TPJ) in non-affective first-episode of psychosis patients with persistent negative symptoms.

BackgroundNegative symptoms represent an unmet therapeutic need in many patients with schizophrenia. In an extension to our previous voxel-based morphometry findings, we employed a more specific, vertex-based approach to explore cortical thinning in relation to persistent negative symptoms (PNS) in non-affective first-episode of psychosis (FEP) patients to advance our understanding of the pathophysiology of primary negative symptoms.MethodsThis study included 62 non-affective FEP patients and 60 non-clinical controls; 16 patients were identified with PNS (i.e., at least 1 primary negative symptom at moderate or greater severity sustained for at least 6 consecutive months). Using cortical thickness analyses, we explored for differences between PNS and non-PNS patients as well as between each patient group and healthy controls; cut-off threshold was set at p<0.01, corrected for multiple comparisons.ResultsA thinner cortex prominently in the right superior temporal gyrus extending into the temporo-parietal junction (TPJ), right parahippocampal gyrus, and left orbital frontal gyrus was identified in PNS patients vs. non-PNS patients. Compared with healthy controls, PNS patients showed a thinner cortex prominently in the right superior temporal gyrus, right parahippocampal gyrus, and right cingulate; non-PNS patients showed a thinner cortex prominently in the parahippocampal gyrus bi-laterally.ConclusionCortical thinning in the early stages of non-affective psychosis is present in the frontal and temporo-parietal regions in patients with PNS. With these brain regions strongly related to social cognitive functioning, our finding suggests a potential link between primary negative symptoms and social cognitive deficits through common brain etiologies.

Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options.

The negative symptoms of schizophrenia represent an impairment of normal emotional responses, thought processes and behaviors, and include blunting or flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and asociality. Negative symptoms contribute to a reduced quality of life, increased functional disability, increased burden of illness, and poorer long-term outcomes, to a greater degree than positive symptoms. Primary negative symptoms are prominent and persistent in up to 26% of patients with schizophrenia, and they are estimated to occur in up to 58% of outpatients at any given time. Negative symptoms respond less well to medications than positive symptoms, and to date treatment options for negative symptoms have been limited, with no accepted standard treatment. Modest benefits have been reported with a variety of different agents, including second-generation antipsychotics and add-on therapy with antidepressants and other pharmacological classes. Recent clinical research focusing on negative symptoms target novel biological systems, such as glutamatergic neurotransmission. Different approaches include: enhancing N-methyl-D-aspartate receptor function with agents that bind directly to the glycine ligand site or with glycine reuptake inhibitors; influencing the metabotropic glutamate receptor (mGluR2/3) with positive allosteric modulators; and stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly efficacious pharmacological treatments for the management of negative symptoms represents a significant unmet need, especially considering the importance of these symptoms on patient outcomes. Hence, further research to identify and characterize novel pharmacological treatments for negative symptoms is greatly needed.

The Selective Glycine Uptake Inhibitor Org 25935 as an Adjunctive Treatment to Atypical Antipsychotics in Predominant Persistent Negative Symptoms of Schizophrenia

Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic (SGA) was hypothesized to ameliorate negative and/or cognitive symptoms in subjects with schizophrenia. Subjects with predominant persistent negative symptoms (previously stabilized ≥3 months on an SGA) were enrolled in a randomized, placebo-controlled trial to investigate adjunctive treatment with Org 25935, a selective inhibitor of type 1 glycine transporter, over 12 weeks in a flexible dose design. Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo. Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score. Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores, depressive symptoms (Calgary Depression Scale for Schizophrenia), global functioning (Global Assessment of Functioning scale), and cognitive measures using a computerized battery (Central Nervous System Vital Signs). Responder rates were assessed post hoc. A total of 215 subjects were randomized, of which 187 (87%) completed the trial. Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms, Positive and Negative Syndrome Scale (total or subscale scores), Global Assessment of Functioning, or the majority of tested cognitive domains. Org 25935 was generally well tolerated within the tested dose range, with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects. Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA. In our study population, Org 25935 appeared to be well tolerated in the tested dose ranges.

Current and emergent treatments for symptoms and neurocognitive impairment in schizophrenia.

Current treatments for schizophrenia function by blocking neurotransmission at dopamine D2 receptors. These compounds have proven highly effective for treatment of schizophrenia and especially for management of positive symptoms. A range of compounds and formulations are presently available, which permits tailoring of side effects to optimize treatment for individual subjects. Nevertheless, many patients suffer from persistent negative symptoms and neurocognitive deficits that contribute to persistent psychosocial impairments and long-term disability. At present, there are no approved pharmacological treatments for either negative symptoms or neurocognitive dysfunction. Instead, various behavioral approaches such as diet, exercise and cognitive remediation may be needed to help optimize cognitive function and mitigate symptoms. Furthermore, neuromodulation approaches, such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) are beginning to be employed both to minimize symptoms and to augment cognitive retraining approaches. At present, encouraging effects of tDCS on persistent auditory hallucinations have been reported, and if confirmed, may open the way for more widespread use of non-pharmacological treatments. At present, phase III studies remain ongoing for α7 nicotinic agonists in treatment of cognitive impairments and glycine reuptake inhibitors for suboptimal treatment response. Furthermore, preclinical studies suggest that glutamate-based treatment approaches may be effective if applied early in the illness. Future studies are needed to determine whether this will lead to effective approaches to halt illness progression for individuals at high clinical risk for schizophrenia.

Med Check

Back to table of contents Previous article Next article Med CheckFull AccessMed CheckVabren WattsVabren WattsSearch for more papers by this authorPublished Online:7 Mar 2014https://doi.org/10.1176/appi.pn.2014.3a3CVS Caremark to Rid Shelves Of Tobacco ProductsRob Wilson/ShutterstockOn February 5, CVS Caremark announced that it will stop selling cigarettes and other tobacco products at its more than 7,600 pharmacy locations nationwide by October 1.“Ending the sale of cigarettes and tobacco products at CVS/pharmacy is the right thing for us to do for our customers and our company to help people on their path to better health,” said Larry Merlo, president and CEO of CVS Caremark, in statement. “Put simply, the sale of tobacco products is inconsistent with our purpose.”The company plans to launch a national smoking-cessation program this spring that will include information and treatment options for those who want to free themselves of tobacco addiction. According to CVS Caremark, approximately 70 percent of smokers say they want to quit smoking, and 50 percent attempt to quit each year.CVS Caremark estimates that it will lose approximately $2 billion in revenues on an annual basis from tobacco shoppers.Roche Schizophrenia Drug Not Looking PromisingBitopertin, the first in a new class of medicines known as glycine reuptake inhibitors, is being developed by Roche to remedy negative symptoms of schizophrenia, such as social withdrawal and lack of motivation. However, data from phase 3 clinical trials are showing that the anticipated “blockbuster” therapy keeps missing the mark.Roche conducted two clinical trials evaluating the effects of bitopertin as an add-on treatment to other antipsychotics to reduce negative symptoms associated with schizophrenia in adults with psychosis. Results showed that bitopertin failed to meet the primary endpoint of a significant improvement on the Positive and Negative Syndrome Scale in both trials.Current antipsychotics have been successful at remedying positive symptoms of schizophrenia, such as hallucinations and delusions, but no pharmaceutical company has reported success in developing drugs to reduce negative symptoms. “These results are disappointing for people with negative symptoms because more effective treatments are needed for these debilitating effects of schizophrenia,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development at Roche. “We will await data from the remaining bitopertin studies in schizophrenia before deciding on next steps.”A third phase 3 trial investigating patients with persistent negative symptoms is ongoing, with three more trials evaluating the role of drugs in patients who continue to have positive symptoms of schizophrenia despite antipsychotic therapy.Rivals Join Forces With NIH on Drug DevelopmentOn February 4, National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D., announced that 10 rival pharmaceutical companies have formed a pact to assist government-backed efforts in the accelerated discovery of new drugs indicated for undertreated illnesses such as Alzheimer’s disease, lupus, and rheumatoid arthritis. The collaboration, called the Accelerating Medicines Partnership, will cost approximately $230 million and will consist of the sharing of scientists, tissue and blood samples, and data among NIH and participating drugmakers. The pact prohibits all involved companies from using any discovery for their own drug development until it is agreed by involved parties to make the data on that specific discovery public.Some big-name companies involved include GlaxoSmithKline, Bristol-MyersSquibb, Sanofi, Takeda, and Johnson & Johnson.Shire’s ADHD Medication Fails Depression TrialsShire announced in February that it is no longer pursuing its top-selling attention-deficit/hyperactivity disorder medication, Vyvanse, as an adjunctive therapy indicated for adults with major depressive disorder (MDD) after the pharmacotherapy performed poorly against placebo in two phase 3 clinical trials.Each clinical trial consisted of approximately 400 patients aged 18 to 65 who met DSM-IV-TR criteria for a diagnosis of MDD. After eight weeks of treatment, subjects taking Vyvanse averaged a mean reduction of 6.7 points on the Montgomery-Asberg Depression Rating Scale, compared with a 6.6 mean reduction among those taking placebo.Shire is now exploring new indications for Vyvanse, such as binge-eating disorder.Schizophrenia Drug Completes Phase 2 TrialOmeros Corporation announced on January 29 positive results from a phase 2 clinical trial of OMS824—the company’s newly developed inhibitor of phosphodiesterase 10, an enzyme expressed in the brain that is suggested to contribute to cognitive impairment in those with schizophrenia and Huntington’s disease. The phase 2 trial included 33 psychiatrically stable patients with schizophrenia who were administered OMS824 or placebo for two weeks. The drug was well tolerated by participants, and pharmacokinetics of OMS824 were not affected by concomitant antipsychotic medications, suggesting that the drug may be developed as both a monotherapy and as an adjunctive therapy to currently approved antipsychotics, according to Omeros. Efficacy conclusions cannot be drawn until sample sizes are increased in future phase 2 and 3 clinical trialsThis quarter, Omeros expects to begin enrollment for phase 2 clinical trials evaluating tolerability of OMS824 in patients with Huntington’s disease. ■ ISSUES NewArchived

Persistent negative visual aura in migraine without headache: a case report

IntroductionPersistent migraine aura without headache is an extremely rare condition. The International Headache Society defines various subtypes of migraines, including “persistent migraine aura without infarction” and “typical aura without headache.”Case presentationWe describe the case of a 21-year-old Asian woman with a history of migraine without aura who had (as her first aura episode) persistent negative visual symptoms without headache for 6 months. We detected no lesions that could cause her persistent visual symptoms. Based on the patient’s history of migraine without aura and responsiveness to furosemide and lamotrigine, we concluded that the visual symptoms in this case were related to migraine visual auras.ConclusionsPersistent visual aura without headache overlapped the criteria for the two migraine subtypes mentioned above and thus did not fit an exact diagnosis. Therefore, we assert that new criteria are needed to encompass uncertain visual symptoms of migraine aura.

The journey from RDC/DSM diagnoses toward RDoC dimensions

The journey from RDC/DSM diagnoses toward RDoC dimensions

Two grams of sarcosine in schizophrenia &amp;ndash; is it too much? A potential role of glutamate- serotonin interaction

Glutamate is the main excitatory neurotransmitter in the central nervous system. Dysfunction of the glutamatergic system plays an important role in the pathogenesis of schizophrenia. Therefore, glutamatergic agents such as N-methyl-D-aspartate receptor co-agonists (ie, glycine, D-cycloserine) and glycine transporter type 1 inhibitors (eg, sarcosine) are studied for their efficacy in ameliorating negative and cognitive symptomatology in patients with schizophrenia. We report the case of a 23-year-old schizophrenic patient treated with quetiapine and citalopram, who was offered concomitant sarcosine treatment. After obtaining an informed consent, we started administration of 2 g of sarcosine per day to treat persistent negative and cognitive symptoms. The patient’s activity and mood improved within 2 weeks, but in the following 2 weeks the patient reported increased drive, activity, libido, unpleasant inner tension, and irritability. We ruled out hypomania and decided to decrease the daily dose of sarcosine to 1 g, which resulted in reduction of drive and irritability. Activity and mood improved compared with his state before adding sarcosine. We suggest a sarcosine dose between 1 g and 2 g per day with an initial dose of 2 g, but if side effects occur, the dose should be decreased to 1 g per day. We would like to emphasize the clinically important glutamate-serotonin interaction during concomitant use of sarcosine, citalopram, and quetiapine in our patient, which may lead to serious discomfort.

Integrated Psychosocial Treatment for Negative Symptoms

Negative symptoms, including restricted affect, diminished emotional range, poverty of speech, decreased motivation and interests, diminished sense of purpose, and diminished social drive, contribute substantially to lost productivity, poor quality of life, social deficits, poor occupational and educational attainment, and generally poor outcomes observed for many individuals with schizophrenia. Although these symptoms may develop from neurobiological factors or as reactions to overstimulation in the acute psychotic phase, they are thought to be maintained by a confluence of biological, cognitive, behavioral, and environmental factors that are not adequately addressed by available treatments. We have developed a multicomponent set of intervention strategies to address persistent negative symptoms called the motivation and engagement (MOVE) program. MOVE builds on research on emotional processing as well as techniques from a variety of behavioral and skill-building approaches to specifically target a broad range of negative symptoms and their functional consequences in an integrated program delivered in the individual's home environment. In this manuscript, we describe an integrated theory for the development and maintenance of negative symptoms, available treatments that target aspects of the syndrome, and evidence supporting the components of MOVE for those with persistent negative symptoms.

EPA-0937 - Association in patients with treatment-resistant schizophrenia between withdrawal psychosis and antipsychotics

Patients with schizophrenia experiences varying clinical courses in the symptoms and up to 30-60% of patients with schizophrenia do not respond sufficiently to antipsychotics. Treatment-resistant Schizophrenia (TRS) can have several reasons, including early onset, nonadherence to oral medication regimens, and persistent negative symptoms known as deficit syndrome. Patients with TRS experience frequent exacerbations, leading to the need for higher doses of antipsychotics to achieve a clinical result. Recently, dopamine supersensitivity psychosis (DSP) and tardive dyskinesia (TD), both of which could be caused by inappropriate pharmacotherapy, as typified by excessive dosages of antipsychotics, have also been presumed relevant to TRS. Several lines of evidence suggest that both DSP and withdrawal psychosis are closely linked to the supersensitivity of dopamine D2 receptors; this could be caused by a potent blockade of the receptors by antipsychotics. Indeed our study recently has found that patients with DSP are overlapped with the concept of treatment-resistance, and these patients can be recovered by long-acting injectable form, via amelioration of Dopamine supersensitivity state. However, it was also observed that one group did not improve at the clinical symptomatic level, despite the presence of DSP. Here, we try to verify relation in patients with treatment-resistant schizophrenia between several classes of antipsychotics or clinical symptoms and treatment process with oral antipsychotics after the initiation of RLAI. This study is a naturalistic, one-arm design with a 12-month observation period of a moderate sample size ( N =115).

EPA-1455 - Reward anticipation in schizophrenia: A functional magnetic resonance imaging study

Introduction Previous studies have reported that patient with schizophrenia have preserved hedonic capacity, but impaired ability to anticipate future reward (anticipatory anhedonia) that, according to some authors, may underlie other aspects of negative symptoms, such as avolition. Objectives/Aims The aim of our study was to demonstrate an impairment of reward anticipation in patients with deficit schizophrenia (DS), characterized by primary and persistent negative symptoms, but not in those with non-deficit schizophrenia (NDS) with respect to healthy controls (HC), by means of functional magnetic resonance imaging (fMRI). Methods fMRI was recorded during the execution of the ’Monetary Incentive Delay’ task in 11 patients with DS, 23 patients with NDS and 23 HC, during the anticipation of five different outcomes, small (SR) or large (LR) reward, small (SP) or large (LP) punishment or no-outcome (NO). Results The ventral striatum response to reward anticipation was preserved in subjects with schizophrenia. Only patients with DS, compared with HC, showed a significant reduction in the left caudate during the anticipation of reward. The reduced activity of the caudate correlated with the scores for avolition but not for anhedonia. Conclusion Our preliminary data suggest an involvement of the caudate in the abnormal processing of reward stimuli in patients with DS and show that avolition and anhedonia are subtended by different functional abnormalities.

Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: A pooled analysis

BackgroundA Phase 2 efficacy study suggested that asenapine (ASE) was superior to risperidone in decreasing negative symptoms in schizophrenia at 6 weeks, prompting design of two negative symptom studies. Two 26-week core studies with 26-week extensions compared asenapine (ASE: 5–10mg twice-daily] and olanzapine (OLA: 5–20mg once-daily) as monotherapies in reducing persistent negative symptoms (PNS). While neither study met the primary endpoint of superiority of ASE over OLA, ASE was statistically superior to OLA in one extension study. This prompted a pooled analysis of the treatment effects of both drugs. MethodsData were pooled from two 26-week core studies and extensions. Efficacy endpoints: change in Negative Symptom Assessment scale-16 (NSA-16) total score at Week 26 (prespecified primary endpoint) and Week 52. Additional measures: change in Positive and Negative Syndrome Scale (PANSS)-total, Marder factors, negative subscale scores, Clinical Global Impression Severity of Illness score (CGI-S) assessments, NSA-16 factor domains, NSA global score, and individual items. ResultsPooled data from the extension studies (n=502) showed no differences between ASE and OLA at Week 26. At Week 52, ASE showed superiority over OLA in NSA-16 total score, NSA global, PANSS Marder negative and PANSS negative subscales, some NSA-16 items, and four of five factor domains. In addition, pooled data for patients who entered the core trials (n=949) were analyzed over 52weeks (whether or not patients entered the extension). No significant differences between groups were observed in change in NSA-16 total score at 26-weeks. At Week 52, ASE was significantly superior over OLA in this measure, NSA global score and PANSS Marder negative factor. There were more early dropouts due to AEs, including worsening of the disease, in the ASE group. ConclusionIn this pooled analysis, ASE and OLA did not differ significantly over 26 weeks, but indicated a signal of superiority for ASE with continued treatment up to 52 weeks.

Persistent negative symptoms in schizophrenia: survey of Canadian psychiatrists

A sample of 206 Canadian psychiatrists who routinely treat patients with psychotic disorders were randomly surveyed regarding their knowledge and practice in relation to persistent negative symptoms of schizophrenia. Large majorities reported observing a high prevalence of persistent negative symptoms that do not respond to available treatments (83%), have a profound impact on functional outcomes (96.5%) and contribute to family burden. Almost half the sample (43%) recognised the importance of formally assessing persistent symptoms and nearly a third (30%) indicated that this was a part of their usual practice. These survey results correspond with recent consensus and highlight the importance and challenge of treating persistent negative symptoms in schizophrenia.

Impairment in verbal memory observed in first episode psychosis patients with persistent negative symptoms

Negative symptoms are present early on during the first episode of psychosis (FEP). The severity of these symptoms has been linked to cognitive deficits, including memory; however, its relationship with persistent negative symptoms (PNS) remains unclear. Thus, the goals of the current paper were to explore memory profiles in FEP patients identified as having PNS and to delineate this relationship in PNS over a 1-year period. Patients diagnosed as having a first episode of psychosis were segregated into groups of patients who met the criteria for PNS (N=39) and patients who did not, or non-PNS (N=97). At an initial assessment, all subjects were administered neurocognitive tests for three memory domains including verbal, visual and working memory. In addition, in FEP patients, clinical symptoms including negative, positive and depressive symptoms were also measured at the initial assessment as well as months 1, 2, 3, 6, 9, and 12. A significant interaction of memory×group was observed (F=4.997, d.f.=1,181, P=0.002), with post hoc comparisons indicating that the PNS group performed more poorly than non-PNS only in the verbal memory domain. All three-memory domains remained stable over time. Hence, in comparison to non-PNS patients, FEP patients with PNS appear to have greater (selective) verbal memory impairments throughout the first year of treatment.