Improvement In Positive Symptoms Research Articles

Effect of parental age on treatment response in adolescents with schizophrenia

BackgroundAdvanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. MethodsAssociation of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT00518323). ResultsThe mean (SD) paternal age was 29.2 (6.2) years, range (16–50) and maternal age was 26.8 (5.7) years, range (17–42) at childbirth for the 201 adolescents (ages 12–17years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal ages showed significant effects on treatment response (p<0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents' ages. ConclusionsAPA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder.

Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy

A growing number of studies have investigated the efficacy of novel, adjunctive pharmacotherapies for treatment of cognitive deficits in schizophrenia with conflicting results. To investigate the comparative efficacy of these agents on cognition and symptoms in schizophrenia, and to identify promising cognitive domains and candidate medications that can be incorporated in treatment trials combined with cognitive remediation to maximise treatment effects. A total of 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic or serotonergic receptor classes and with participants with schizophrenia or schizoaffective disorder were identified. Medications targeted at the cholinergic receptor class produced marginal improvements in verbal learning and memory (d = 0.23, P = 0.06), and donepezil, a specific type of cholinergic agonist, produced a moderate effect (d = 0.58) on spatial learning and memory. Cholinergic and glutamatergic agents produced moderate effect-size improvements on negative symptoms (d = 0.54 and d = 0.62 respectively), and small effect-size improvements on general symptoms (d = 0.46 and d = 0.41 respectively). Serotonergic agents produced small effect-size improvements in positive symptoms (d = 0.33). Cholinergic medications produced marginal improvement in verbal learning and memory and moderate improvements on spatial learning and memory, although there was no evidence to support the use of glutamatergic or serotonergic medications as a stand-alone treatment for improving cognitive function. Cholinergic and glutamatergic agents improved negative and general symptoms, whereas serotenergic medications improved positive symptoms.

A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular levomepromazine in agitated elderly patients with schizophrenia.

BackgroundThere have not been any reports in Japan clarifying the efficacy and safety of intramuscular (IM) olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia. This study was a comparative investigation of the clinical efficacy and safety of IM olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia at 2 hours post-dose.MethodsThe subjects were 52 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Their clinical symptoms were assessed using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS, and Agitation Calmness Evaluation Scale (ACES), and their safety was assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), and glucose test.ResultsThe PANSS-EC total score, the ACES score, and the glucose level significantly decreased from baseline in both the IM olanzapine group and the levomepromazine injection group; however, no between-group differences were observed. Mean change from baseline in the PANSS total score, positive score, the BARS score, and the DIEPSS total score was significantly greater in the IM olanzapine injection group compared with the levomepromazine injection group.ConclusionThe results of this study suggest that agitated elderly patients rapidly respond to IM olanzapine and IM levomepromazine treatment. Furthermore, these results suggest that IM olanzapine is safer than IM levomepromazine and causes greater improvement in positive symptoms.

Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic-naive patients with first-episode schizophrenia and 24 healthy controls initially matched on age, sex, and parental socioeconomic status were examined with functional magnetic resonance imaging while playing a variant of the monetary incentive delay task. INTERVENTIONS Patients were treated for 6 weeks with the antipsychotic compound amisulpride. Controls were followed up without treatment. MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as measured by functional magnetic resonance imaging before and after antipsychotic treatment. RESULTS At baseline, patients, as compared with controls, demonstrated an attenuation of brain activation during reward anticipation in the ventral striatum, bilaterally. After 6 weeks of treatment, patients showed an increase in the anticipation-related functional magnetic resonance imaging signal and were no longer statistically distinguishable from healthy controls. Among the patients, there was a correlation between the improvement of positive symptoms and normalization of reward-related activation. Those who showed the greatest clinical improvement in positive symptoms also showed the greatest increase in reward-related activation after treatment. CONCLUSIONS To our knowledge, this is the first controlled, longitudinal study of reward disturbances in schizophrenic patients before and after their first antipsychotic treatment. Our results demonstrate that alterations in reward processing are fundamental to the illness and are seen prior to any treatment. Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829.

Mood and physical symptoms improve in women with severe cyclical changes by taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl estradiol

BackgroundThe purpose of this study was to investigate how women without and with different severity of premenstrual symptoms react to treatment with a combined oral contraceptive containing 250-mcg norgestimate/35-mcg ethinyl estradiol (EE). Focus was placed on mood and physical symptoms. Study DesignThis open, prospective study evaluated 24 women using norgestimate/EE for three cycles in a 21/7 regimen. Symptoms and bleeding pattern were captured by daily ratings on the Cyclicity Diagnoser scale. ResultsWomen with severe premenstrual mood symptoms improved in summarized negative mood (p<.001) and summarized positive mood (p<.05), as well as in swelling (p<.05) and effect on daily life (p<.05). Women with no or mild or moderate symptoms did not show any significant improvement or deterioration in any symptom after 3 months of treatment. ConclusionsNorgestimate 250 mcg/EE 35 mcg significantly improved premenstrual summarized negative mood symptoms during 3 treatment months compared to pretreatment in women with severe premenstrual symptoms, together with improvement in positive symptoms, swelling and effect on daily life.

Genetic Variation in KCNH2 Associated With Expression in the Brain of a Unique hERG Isoform Modulates Treatment Response in Patients With Schizophrenia

Antidopaminergic drugs bind to hERG1 potassium channels encoded by the gene KCNH2, which accounts for the side effect of QT interval prolongation. KCNH2 has also been associated with schizophrenia risk, and risk alleles predict increased expression of a brain-selective isoform, KCNH2 3.1, that has unique physiological properties. The authors assessed whether genetic variation associated with KCNH2 3.1 expression influences the therapeutic effects of antipsychotic drugs. The authors performed a pharmacogenetic analysis of antipsychotic treatment response in patients with schizophrenia using data from two independent studies: a National Institute of Mental Health (NIMH) double-blind, placebo-controlled inpatient crossover trial (N=54) and the multicenter outpatient Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study (N=364). The KCNH2 genotype that was previously associated with increased expression of KCNH2 3.1 in the brain was treated as a predictor variable. Treatment-associated changes in symptoms were evaluated in both groups with the Positive and Negative Syndrome Scale. The authors also analyzed time to discontinuation in the olanzapine arm of the CATIE study. In the NIMH study, individuals who were homozygous for the KCNH2 3.1 increased expression-associated T allele of rs1036145 showed significant improvement in positive symptoms, general psychopathology, and thought disturbance, while patients with other genotypes showed little change. In the CATIE study, analogous significant genotypic effects were observed. Moreover, individuals who were homozygous for the T allele at rs1036145 were one-fifth as likely to discontinue olanzapine. These consistent findings in two markedly different treatment studies support the hypothesis that hERG1-mediated effects of antipsychotics may not be limited to their potential cardiovascular side effects but may also involve therapeutic actions related to the brainspecific 3.1 isoform of KCNH2.

Psychopathology: genetics and the stress-vulnerability hypothesis

Since the findings of dopamine blockade by antipsychotics, a dysfunction of the dopamine system has been proposed to underly psychopathological symptoms in schizophrenia. In SPECT and PET imaging studies, radioligand binding to the dopamine receptor or transporter reflects the occupancy by dopamine itself or antipsychotics. Using dual-isotope imaging for the evaluation of pre- and postsynaptic site, Schmitt et al. [1] examined striatal dopamine transporter and dopamine D2 receptor availability in first-episode schizophrenia patients and patients with haloperidol treatment compared to healthy controls. In drug-naive patients with positive symptoms, dopamine transporter availability correlated negatively with psychopathology as did D2 receptor binding with disorganization and hallucinatory behavior, thus strengthening the dopamine hypothesis for positive symptoms. D2 receptor and dopamine transporter availability was lower in the haloperidol group which confirms previous dopamine blockade studies. However, response to antipsychotics is individual, and genetic factors may contribute to a different outcome. Mossner et al. [2] reported that patients homozygous for the risk allele ZNF804A show poorer improvement of positive symptoms compared to patients with a protective allele. Thus, identification of risk genes may help identifying patients with a different course of the disorder. A pharmacogenetic study of Crisafulli et al. [3] investigated 10 SNPs of genes related to pathophysiological pathways in Korean patients. They found a SNP within 5HTR1A associated with clinical improvement in both positive and negative symptoms. In schizophrenia patients, improvement of quality of life as treatment outcome among others is dependent on support in case of problems and assistance in coping with daily life demands. Landolt et al. [4] revealed that unmet needs changing to fulfilled ones enhanced quality of life. In this context, psychosocial functioning and psychotic symptoms may be influenced by alterations of theory of mind and empathy as underlying social-cognitive deficits and possibly are heritable. In first-degree relatives of schizophrenia patients, Montag et al. [5] showed impairment in cognitive skills, suggesting that social-cognitive abilities may serve as an intermediate phenotype for schizophrenia. In a re-analysis of AMDP data by nonmetric multidimensional scaling, Lage et al. [6] replicated clusters of psychopathological symptoms in two independent samples dating from 1980 and 2003. In individual’s health, the psychological well-being dimension and depressive symptoms are important variables and Morelatto de Souza and Paz Loayza Hidalgo [7] validated the WHO well-being index in a Brazilian population and showed this scale to be a useful tool for screening of depressive symptoms. Hagihara and Abe [8] highlight the influence of media reports on suicide and counteracting effects of stopping the sale of suicide-related products in Japan. Beside genetics, stressful experience and trauma are risk factors for the development of psychiatric diseases. Linden et al. [9] analyzed 100 case files of German servicemen during World War I and classified them in agreement with modern diagnoses. Most ancient diagnoses were “psychopathic constitution” or “hysteria.” Using contemporary diagnostics, some of these soldiers had symptoms of post-traumatic stress disorder. There was a high incidence of pseudoseizures that highlights different human responses to traumatic experience and stress in a historical context. Stressful experiences are known to increase vulnerability to schizophrenia. Rossi et al. [10] evaluated the Community Assessment of Psychic Experiences (CAPE) in students who survived an earthquake 2009 in Italy. Unexpectedly, earth quake survivors showed lower CAPE scores than nonexposed subjects. This is in line with the hypothesis that stressful events preceding psychosis are not derived from external traumatic experiences. In a previous study, Puustinen et al. [11] reported C-reactive protein, marker of cardiovascular disease, to be associated with psychological distress. However, in a cross-sectional and 3-year follow-up study in Japanese male workers, Kawada [12] failed to show this relationship, which is probably due to ethnicity. Life experience, stressful events and other environmental factors are known to influence the risk of developing mental diseases. The missing link between environment and neurobiology may be explained by epigenetic mechanisms, such as DNA methylation and acetylation in disease-related brain regions. Wiers [13] refers to an fMRI study of the COMT gene with the Val allele being associated with DNA methylation [14]. She proposes the use of genetic imaging in combination with investigations of epigenetic markers in blood cells to unravel gene-environmental interactions in severe psychiatric disorders.

Efficiency of cognitive rehabilitation with REHACOP in chronic treatment resistant Hispanic patients

Cognitive rehabilitation in schizophrenia has been proved to benefit cognition depending on the severity of the illness and the cognitive deficits. Nevertheless studies of efficiency with chronic patients, refractory to additional treatment interventions, have not yet been published. Ninety three patients with schizophrenia were recruited from the Treatment Resistant Schizophrenia Unit in Alava (Spain). All subjects underwent a baseline and a 3 months assessment including cognition, clinical symptoms and functional capacity. Patients were randomly assigned to receive either neuropsychological rehabilitation or occupational therapy for 3 months in addition to treatment as usual (TAU). Patients at the Rehacop group showed significantly greater improvements at 3 months in most areas of cognition evaluated including speed of processing, language, memory and executive functioning, compared to the occupational therapy group (group x time interactions p< 0.001). The Rehacop group also showed significant improvement in positive symptoms, functional and insight measures. Although data was not statistically significant, the Rehacop group showed a tendency to also improve negative symptoms compared to controls. Despite to their limited respond to TAU, our data suggest that chronic refractory patients can improve their cognitive performance after neuropsychological rehabilitation with the Rehacop. These findings support the feasibility of integrating neuropsychological rehabilitation into TAU programs for patients with lower responses to other treatment plans.

Attachment style predicts 6‐month improvement in psychoticism in persons with at‐risk mental states for psychosis

Insecure attachment may influence vulnerability to and outcome of psychotic symptomatology. The present study examined whether attachment style predicted symptoms and functioning of at-risk mental state (ARMS) patients after 6 months of psychosocial intervention, over and above the effects of initial clinical severity and premorbid social adjustment (PSA). Symptoms and functioning were assessed at baseline and 6 months later in 31 ARMS patients (mean age = 15.7). No patient received antipsychotic medication, but all engaged in intense psychosocial needs-adapted treatment. Clinicians (unaware of the aims of the study) rated attachment, PSA, symptoms, and functioning. Attachment was not related to baseline clinical severity. However, improvement in psychoticism was predicted by attachment (in particular by secure, preoccupied and dismissing) beyond the effects of baseline clinical severity and PSA. Secure attachment also predicted improvements in disorganization and functioning. Poor PSA predicted less improvement in disorganization and negative symptoms but did not impact psychoticism. The three attachment prototypes that predicted improvement in psychoticism (secure, preoccupied and dismissing) share the existence of at least one positive psychological model (either about self or about others). It may be that the psychosocial intervention helped ARMS patients to disconfirm negative models and/or reinforce positive ones. Patients' attachment styles were not related to baseline clinical severity but impacted improvement of positive symptoms. These findings appear consistent with evidence that impaired self-esteem and dysfunctional self and others schemas constitute risk factors for reality distortion.

Reasons for continuing or discontinuing olanzapine in the treatment of schizophrenia from the perspectives of patients and clinicians

BackgroundThe aim of this study was to assess the reasons for discontinuing or continuing olanzapine in patients with schizophrenia, from the perspectives of the patients and their clinicians.MethodsThe Reasons for Antipsychotic Discontinuation/Continuation (RAD) is a pair of questionnaires assessing these reasons from the perspectives of patients and their clinicians. Outpatients with schizophrenia (n = 199) who were not acutely ill participated in a 22-week open-label study of olanzapine from November 2006 to September 2008. Reasons for continuing or discontinuing olanzapine (on a five-point scale), along with the single most important reason and the top primary reasons, were identified. Concordance between reasons given by patients and clinicians was assessed.ResultsThe top primary reasons for continuing olanzapine were patients’ perceptions of improvement, improvement of positive symptoms, and improved functioning. The study discontinuation rate was low (30.2%), and only a subset of patients who discontinued reported reasons for medication discontinuation. The top primary reasons for discontinuing olanzapine were insufficient improvement or worsening of positive symptoms, adverse events, and insufficient improvement or worsening of negative symptoms. Ratings given by patients and clinicians were highly concordant.ConclusionThe main reason for continuing or discontinuing olanzapine appears to be medication efficacy, especially for positive symptoms. Reasons for medication discontinuation differ somewhat from reasons for continuation, with a high level of concordance between patient and clinician responses.

Comparing the Influence of Dopamine D2 Polymorphisms and Plasma Drug Concentrations on the Clinical Response to Risperidone

Although several studies have reported that dopamine D₂ receptor (DRD2) polymorphisms affect the therapeutic efficacy of antipsychotics, other studies have suggested that the plasma drug concentration is related to the clinical response. Currently, there are no definitive data regarding which factor has greater clinical significance. Sixty patients with acute exacerbations of schizophrenia received 6 mg/d of risperidone for 4 weeks. Clinical evaluations using the Brief Psychiatric Rating Scale and the Udvalg for Klinicke Undersøgelser Side Effect Rating Scale were performed before and after administration of risperidone. TaqI A and -141C Ins/Del polymorphisms were determined, and the plasma concentrations of risperidone and 9-hydroxyrisperidone were measured. The TaqI A polymorphism had no effect on therapeutic efficacy, but the -141C Ins/Del polymorphism was associated with an improvement in positive symptoms. In addition, the plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) correlated with the improvement in the total Brief Psychiatric Rating Scale score as well as with positive symptoms. Although there were no associations between DRD2 polymorphisms and psychic adverse effects, the plasma drug concentration was associated with psychic adverse effects. These findings suggest that DRD2 polymorphisms are associated with the therapeutic effects of risperidone as they relate to positive symptoms and that plasma drug concentrations are associated with overall symptoms as well as excitement and cognitive symptoms. Both the genotyping of DRD2 and the monitoring of plasma drug concentrations may be useful for improving clinically dominant symptoms. Further work involving replication in a larger sample is required to support our findings.

The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms

Genetic factors determining the response to antipsychotic treatment in schizophrenia are poorly understood. A new schizophrenia susceptibility gene, the zinc-finger gene ZNF804A, has recently been identified. To assess the pharmacogenetic importance of this gene, we treated 144 schizophrenia patients and assessed the response of positive and negative symptoms by PANSS. Patients homozygous for the ZNF804A risk allele for schizophrenia (rs1344706 AA) showed poorer improvement of positive symptoms (7.35 ± 0.46) compared to patients with a protective allele (9.41 ± 0.71, P = 0.022). This provides further evidence that ZNF804A is of functional relevance to schizophrenia and indicates that ZNF804A may be a novel target for pharmacological interventions.

Factors associated with adherence to treatment with olanzapine and other atypical antipsychotic medications in patients with schizophrenia

ObjectivesPoor treatment response is an important factor contributing to lack of treatment adherence. The goals of this research were to determine whether improvements in Positive and Negative Syndrome Scale (PANSS) symptom domains predict the likelihood of staying on treatment and whether differential responses to treatment with various atypical antipsychotics in specific symptom domains account for differences in discontinuation rates or treatment adherence. MethodsWe conducted a post-hoc analysis of pooled data from 5 randomized, double-blind, 24- to 28-week clinical trials in 1103 olanzapine-treated and 1090 risperidone-, quetiapine-, ziprasidone-, or aripiprazole-treated adult patients with schizophrenia. The 5 PANSS factors were tested as potential predictors of treatment adherence for all treatment groups combined. Treatment differences in the 5 PANSS factors and individual items were assessed between olanzapine and the other atypical antipsychotics combined. Secondary analyses repeated for the 21 Heinrichs Quality of Life Scale (QLS) items. ResultsImprovement in PANSS positive factor was the strongest predictor of treatment adherence, irrespective of medication (based on standardized scores, hazard ratio [HR], 1.58; 95% confidence interval [CI], +1.40 to +1.79; P < .001). Improvement in PANSS hostility (HR, 1.23; 95% CI, +1.11 to +1.37; P < .001) and depressive (HR, 1.15; 95% CI, +1.05 to +1.27; P = .002) factors was also a significant predictor; negative and disorganized thoughts factors were not. All QLS items had significant predictive effects. Olanzapine-treated patients showed significantly greater improvements than all other groups at week 24 on all 5 PANSS factors (P = .028 for negative; P < .001 for all others) and on 3 QLS items. ConclusionSignificant improvement in positive symptoms, regardless of treatment, followed by significant improvement in hostility and depressive symptoms, may best predict treatment adherence. Olanzapine-treated patients experienced significantly greater improvements in these specific symptoms than patients treated with the other atypical antipsychotics examined. These findings may further explain why olanzapine-treated patients continue treatment more often.

Journal Digest

Journal Digest

Membrane fatty acid levels as a predictor of treatment response in chronic schizophrenia

Abnormal fatty acid composition in neural membranes, that is, the balance between essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has been suggested to be related to the psychotic symptoms and cognitive impairment of schizophrenia. This study was conducted to test the hypothesis that the ability of atypical antipsychotic drugs to ameliorate positive symptoms and cognitive function relevant to daily living would be predicted by baseline EPUFAs concentrations in the erythrocyte membrane in subjects with schizophrenia. A total of 24 actively psychotic patients with schizophrenia participated in the study. After blood drawing, they were treated with olanzapine or perospirone. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative symptoms (SANS), as well as the script tasks, a measure of event schema recognition, were administered at baseline and 3 months after the start of treatment. Erythrocyte membrane fatty acid levels were analysed using a gas chromatography system. Scores of SAPS and SANS, as well as script task performance, were improved during treatment with either antipsychotic drug. Regression analysis indicates baseline EPUFAs concentrations were positively and negatively related with percent improvement of positive symptoms and script task performance, respectively. The results of this study suggest composition of phospholipids in the erythrocyte membrane provide a feasible marker to predict treatment response in patients with schizophrenia.

More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial

Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies. Recently, we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics (FGAs) in a 6 week randomized controlled trial (RCT). The short duration of that trial was its limitation. This study aimed to explore whether longer treatment is worthwhile. Completers of the RCT (n = 39) received open-label add-on mirtazapine for additional 6 weeks. The Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) and several other clinical parameters were measured prospectively. During the open-label phase, significant improvement was achieved in all parameters, with an effect size of 0.94 (CI 95% = 0.45-1.43) on the primary outcome and an impressive additive antipsychotic effect. Patients who received mirtazapine during both phases demonstrated greater improvement in positive symptoms (29.6% versus 21.2%, p = 0.027) than those who received mirtazapine during open-label extension phase only. These findings support our previous data on the additive antipsychotic effect of mirtazapine in FGAs-treated schizophrenia. Mirtazapine may be effective in other symptom domains, too. Longer duration of mirtazapine treatment may yield additional benefits. If these results will be confirmed in larger studies, add-on mirtazapine may become a feasible option in difficult-to-treat schizophrenia.

Neuropharmacology of schizophrenia: is there a role for leptin?

A significant relationship between beneficial therapeutic effects and antipsychotic-induced weight gain has been demonstrated in various studies for various medications including clozapine, olanzapine and risperido new summarized in (1)x.Of interest, leptin has been postulated as a potential mediator underlying this intriguing link between weight gain and better clinical outcome (1). In this letter, we describe for the first time a significant positive correlation between base line serum leptin concentrations and improvements in positive symptoms in patients with schizophrenia following antipsychotic treatment.

N-acetyl aspartate concentration in the anterior cingulate cortex in patients with schizophrenia: A study of clinical and neuropsychological correlates and preliminary exploration of cognitive behaviour therapy effects

This study investigated the clinical and neuropsychological correlates of N-acetyl aspartate (NAA) concentration in the anterior cingulate cortex (ACC) in schizophrenia, and explored whether ACC NAA concentration is sensitive to symptom change following cognitive behaviour therapy for psychosis (CBTp). Participants comprised 30 patients and 15 healthy controls who underwent magnetic resonance spectroscopy of the ACC and were assessed on frontal lobe based neuropsychological tasks. Twenty-four (of 30) patients were followed-up; 11 subsequently received 8–9months of CBTp in addition to standard care (CBTp+SC) and 13 received SC only. At baseline (i) NAA and Cr concentrations were lower in patients compared to controls, (ii) in patients, NAA concentration correlated inversely with positive symptoms and general psychopathology (positive symptoms explained 21% of the variance; total variance explained=25%) and Cho concentration correlated inversely with positive symptoms, and (iii) in controls, NAA concentration correlated positively with working and short-term memory and Cr concentration inversely with executive function. NAA concentration tended to increase in CBTp+SC patients at follow-up (n=7 with usable data) concomitant with improvement in positive symptoms. NAA concentration may be more closely associated with symptoms and symptom change than frontal lobe based neuropsychological function in schizophrenia, perhaps because the latter is relatively stable during the long-term illness course.

Model-based parametric study of frontostriatal abnormalities in schizophrenia patients

BackgroundSeveral studies have suggested that the activity of the prefrontal cortex (PFC) and the dopamine (DA) release in the striatum has an inverse relationship. One would attribute this relationship primarily to the circuitry comprised of the glutamatergic projection from the PFC to the striatum and the GABAergic projection from the striatum to the midbrain DA nucleus. However, this circuitry has not characterized satisfactorily yet, so that no quantitative analysis has ever been made on the activities of the PFC and the striatum and also the DA release in the striatum.MethodsIn this study, a system dynamics model of the corticostriatal system with dopaminergic innervations is constructed to describe the relationships between the activities of the PFC and the striatum and the DA release in the striatum. By taking published receptor imaging data from schizophrenia patients and healthy subjects into this model, this article analyzes the effects of striatal D2 receptor activation on the balance of the activity and neurotransmission in the frontostriatal system of schizophrenic patients in comparison with healthy controls.ResultsThe model predicts that the suppressive effect by D2 receptors at the terminals of the glutamatergic afferents to the striatum from the PFC enhances the hypofrontality-induced elevation of striatal DA release by at most 83%. The occupancy-based estimation of the 'optimum' D2 receptor occupancy by antipsychotic drugs is 52%. This study further predicts that patients with lower PFC activity tend to have greater improvement of positive symptoms following antipsychotic medication.ConclusionThis model-based parametric study would be useful for system-level analysis of the brains with psychiatric diseases. It will be able to make reliable prediction of clinical outcome when sufficient data will be available.

Bases Clínicas para un Nuevo Modelo de Atención a las Psicosis

The purpose of this paper is to summarize our current knowledge about pharmacological, psychosocial, and other emerging treatments for psychoses. Although antipsychotic medications are the mainstay of treatment for psychoses, and particularly for schizophrenia, the degree of improvement in positive symptoms is moderate, and has no demonstrable efficacy against positive enduring or deficit negative symptoms. Indeed, many patients continue to suffer from persistent positive symptoms and relapses, particularly when they fail to adhere to prescribed medications. This underlines the need for additional treatment methods to help patients understand and manage their disorders, alleviate symptoms, improve adherence, social functioning and quality of life, and solve problems that do not fully respond to medication. Nowadays, comprehensive treatment entails a multi-modal approach, including medication, psychotherapy and social treatments (psychoeducation and coping-oriented interventions, cognitive behaviour therapy, cognitive remediation, social skills training and assertive community treatment), as well as assistance with housing and financial sustenance. In the foreseeable future, phase-specific interventions ought to be applied to different stages of psychosis.