三种非典型抗精神病药对儿童青少年精神分裂症患者血脂、肝功能和认知功能的影响

摘要 目的：探讨利培酮、阿立哌唑、奥氮平分别对儿童青少年精神分裂症患者肝功能、血脂和认知功能的影响。方法：选取2015年1月至2019年12月我院收治的84例儿童青少年精神分裂症患者,采用乱数表法随机分为阿立哌唑组（n=28,阿立哌唑治疗）、利培酮组（n=28,利培酮治疗）、奥氮平组（n=28,奥氮平治疗）,均治疗8周,对比三组患者症状评分、血脂、肝功能、认知功能以及不良反应。结果：三组治疗8周后阳性与阴性症状量表（PANSS）评分整体比较无差异（P>0.05）,三组治疗8周后PANSS评分均较治疗前降低（P<0.05）。奥氮平组、利培酮组治疗8周后三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)高于阿立哌唑组,且奥氮平组高于利培酮组（P<0.05）;奥氮平组、利培酮组治疗8周后高密度脂蛋白(HDL-C)低于阿立哌唑组,且奥氮平组低于利培酮组（P<0.05）。三组不良反应发生率整体比较无差异（P>0.05）。阿立哌唑组治疗8周后延迟回忆数、即刻回忆数、回忆总数、再认数评分均高于利培酮组、奥氮平组（P<0.05）。利培酮组治疗8周后ALT、AST、TBIL高于治疗前（P<0.05）,利培酮组治疗8周后ALT、AST、TBIL高于阿立哌唑组、奥氮平组（P<0.05）。结论：利培酮、阿立哌唑、奥氮平应用于儿童青少年精神分裂症中,可获得相当的治疗效果,其中利培酮对肝功能影响较大,奥氮平对人体血脂影响较大,阿立哌唑对血脂、肝功能影响轻,改善认知功能效果优于利培酮、奥氮平。     

3111T/C CLOCK GENE POLYMORPHISM IS NOT ASSOCIATED WITH SLEEP DISTURBANCES IN UNTREATED DEPRESSED PATIENTS

Sleep patterns, frequently altered in depression, have been hypothesized to be under genetic control. The circadian locomotor output cycles kaput (CLOCK) T3111C variant has been studied in association with sleep disturbances in depressed patients. The aim of this study was to investigate possible effects of T3111C CLOCK on insomnia, daytime sleepiness, sleep quality, and depression severity in a sample of 100 major depressive disorder patients. Inclusion criteria were: major depressive disorder, drug-free for any antidepressant and/or benzodiazepines for at least four weeks previously to the study, and a minimum score of >17 on the Hamilton Rating Scale for Depression. The Morningness–Eveningness Questionnaire, Epworth Sleepiness Scale, Athens Insomnia Scale, and Pittsburgh Sleep Quality Index were applied. No significant difference was found concerning genotype or allele groups and Hamilton Rating Scale for Depression items or clusters. No difference was found between genotypes and comorbidity, chronotype distribution, Epworth Sleepiness Scale, Athens Insomnia Scale, or Pittsburgh Sleep Quality Index total scores. Overall, the present findings did not support the hypothesis of an effect of the T3111C CLOCK variant on sleep disturbances in major depressive disorder. Further analysis of clock machinery will clarify the contribution of clock genes to the maintenance of mental health. (Author correspondence: alessandro.serretti@unibo.it)     

Evaluation of plasma antioxidant levels during different phases of illness in adult patients with bipolar disorder

The aim of the present study is to evaluate role of plasma antioxidants (albumin, bilirubin and uric acid) in patients suffering from type I Bipolar Disorder (BD-I) during different phases of illness: acute mania, euthymia and bipolar depression. Medical records of consecutive 110 BD-I patients (38 patients with acute mania, 35 in euthymic state, full remission, and 37 in depressive phase) were reviewed to evaluate plasma antioxidant levels. Laboratory data of 40 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. Serum uric acid levels were higher in acute mania than other patient subgroups and healthy controls. Serum uric acid levels directly correlated with BRMRS and YMRS scores. No differences were found between clinical groups during different phases and healthy controls concerning albumin and bilirubin. In conclusion, the results of the present study support the notion that serum uric acid levels may be higher in patients with BP-I (especially during manic phases) which may suggest a dysregulation of the purinergic system. However, limitations should be considered and further studies are needed.     

Influence of personality disorder on the treatment of panic disorder--comparison study

Most clinicians tend to believe that the occurrence of the anxiety disorder in comorbidity with a personality disorder often leads to longer treatment, worsens the prognosis, and thus increasing treatment costs. The study is designed to compare the short-term effectiveness of combination of cognitive behavioral therapy and pharmacotherapy in patient suffering with panic disorder with and without personality disorder. METHOD: We compare the efficacy of 6th week therapeutic program and 6th week follow up in patients suffering with panic disorder and/or agoraphobia and comorbid personality disorder (29 patients) and panic disorder and/or agoraphobia without comorbid personality disorder (31 patients). Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI and support with psychological methods: IPDE, MCMI-III and TCI. Patients were treated with CBT and psychopharmacs. They were regularly assessed in week 0, 2, 4, 6 and 12 by an independent reviewer on the CGI (Clinical Global Improvement) for severity and change, PDSS (Panic Disorder Severity Scale), HAMA (Hamilton Anxiety Rating Scale), SDS (Sheehan Disability Scale), HDRS (Hamilton Depression Rating Scale), and in self-assessments BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory). RESULTS: A combination of CBT and pharmacotherapy proved to be the effective treatment of patients suffering with panic disorder and/or agoraphobia with or without comorbid personality disorder. The 12th week treatment efficacy in the patients with panic disorder without personality disorder had been showed significantly better compared with the group with panic disorder comorbid with personality disorder in CGI and specific inventory for panic disorder--PDSS. Also the scores in depression inventories HDRS and BDI showed significantly higher decrease during the treatment comparing with group without personality disorder. But the treatment effect between groups did not differ in objective anxiety scale HAMA, and subjective anxiety scale BAI.     

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

We summarized and compared meta‐analyses of pharmacological and non‐pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta‐analyses were included, representing 128 meta‐analyzed trials and 47,231 study participants. While meta‐analyses were generally of adequate or high quality, meta‐analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=–0.98) and exercise interventions (SMD=–0.96), followed by psychoeducation (SMD=–0.77), aripiprazole augmentation (SMD=–0.73), topiramate (SMD=–0.72), d‐fenfluramine (SMD=–0.54) and metformin (SMD=–0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=–1.10) and topiramate (SMD=–0.69) demonstrated the best evidence, followed by dietary interventions (SMD=–0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=–0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=–0.71) and metformin (SMD=–0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon‐like peptide‐1 receptor agonists (SMD=–0.39), dietary interventions (SMD=–0.37) and aripiprazole augmentation (SMD=–0.34), whereas insulin resistance improved the most with metformin (SMD=–0.75) and rosiglitazone (SMD=–0.44). Topiramate had the greatest efficacy for triglycerides (SMD=–0.68) and low‐density lipoprotein (LDL)‐cholesterol (SMD=–0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=–0.51) and high‐density lipoprotein (HDL)‐cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL‐cholesterol (SMD=–0.35 to –0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non‐pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.     

Serum cholesterol concentration and structured individual psychoanalytic psychotherapy in suicidal and non-suicidal male patients suffering from borderline personality disorder

Findings from numerous studies suggest an association between low cholesterol levels and suicidal behavior in patients with different psychiatric diagnoses. The aims of this case-control study were to test whether cholesterol levels in male suicidal patients (N=20) with borderline personality disorder (BPD) are lower than in male non-suicidal patients (N=20) with BPD and male healthy control group (N=20), and to evaluate the influence of structured individual psychoanalytic psychotherapy on suicidal behavior. The groups were matched for age and body mass index (BMI). Results showed that serum cholesterol levels did not differ significantly between suicidal and non-suicidal BPD patients and healthy controls. The level of psychopathology (measured by Brief Psychiatric Rating Scale and Hamilton Depression Rating Scale) was significantly higher in the group of suicidal patients, which indicates the importance of evaluating particular clinical symptoms in BPD, in order to prevent suicidal behavior. Non-suicidal male patients suffering from BPD received more frequently structured individual psychoanalytic psychotherapy prior to the hospitalization than suicidal group. These results emphasized the role of this type of psychotherapy in preventing suicidal behavior in BPD patients.     

The mixed amphetamine salt extended release (Adderall XR, Max-XR) as an adjunctive to SSRIS or SNRIS in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety: an open-label study

To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the ADHD symptoms effectively in order to achieve better resolution of anxiety symptoms.     

Rapid clinical effectiveness of MIF-I in the treatment of major depressive illness

A double-blind 28 day study was conducted to compare the anti-depressant efficacy of MIF-I with that of imipramine. Twenty patients hospitalized with major depressive illness participated. Clinical responses were measured by using the Hamilton Depression Rating Scale, the Global Severity of Illness Scale, the Zung Self-Rating Depression Scale as well as the 100 mm line self-rating for depression. The results indicate that MIF-I was at least as effective as imipramine in this study, and that its anti-depressive effect was a rapid and often dramatic one.     

奥氮平联合氟西汀治疗对抑郁症患者血清NE水平以及抑郁情绪影响的临床研究

摘要 目的：研究奥氮平联合氟西汀治疗抑郁症患者的临床疗效,并探讨联合治疗对抑郁症患者血清去甲肾上腺素（Norepinephrine,NE）和抑郁情绪的影响。方法：纳入2018年6月到2020年5月在我院接受治疗的抑郁症患者56例,随机数表法将其分为对照组和研究组两组。对照组患者接受氟西汀治疗,而研究组患者接受奥氮平联合氟西汀治疗,两组患者均治疗8周。比较两组患者年龄、性别、身高、BMI以及病程等一般资料,并比较两组患者临床治疗疗效、治疗期间不良反应发生率、治疗前后血清NE水平。用汉密顿抑郁量表(Hamilton Rating Scale for Depression,HAMD)和抑郁自评量表（Self-Rating Depression Scale,SDS）评估两组患者抑郁情绪。结果：两组患者性别、年龄、身高、BMI、病程以及合并症等一般情况均显示无显著差异（P>0.05）。研究组治疗总有效率（92.86%）显著高于对照组（64.29%）总治疗有效率（P<0.05）,但研究组患者治疗期间不良发生率（32.14%）与对照组（28.57%）比较无显著差异（P>0.05）。治疗后,两组患者血清NE水平均较治疗前显著升高（P<0.05）,并且研究组患者治疗后血清NE水平均显著高于对照组患者（P<0.05）;两组患者血清HAMD和SDS评分均较治疗前显著降低（P<0.05）,并且研究组患者治疗后HAMD和SDS评分均显著低于对照组患者（P<0.05）。结论：奥氮平联合氟西汀治疗抑郁症患者安全有效,不良反应发生率较低,可有效升高抑郁症患者血清NE水平,而改善患者抑郁情绪。     

Major depressive disorder, anhedonia and agomelatine: an open-label study

Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p<.05), HAM-A(p<.01), SHAPS (p<.05), LSEQ (p<.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.     

Preventing Olanzapine-Induced Weight Gain Using Betahistine: A Study in a Rat Model with Chronic Olanzapine Treatment

Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H₁ receptors (H₁R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H₁R agonist and H₃R antagonist) and olanzapine (O+B) reduced (−45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (−51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H₁R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP₁ and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H₁R, pAMPKα, BAT UCP₁ and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.     

Effects of Olanzapine–Fluoxetine Combination Treatment of Major Depressive Disorders on the Quality of Life During Acute Treatment Period

The objective of the study was to explore the effects of olanzapine–fluoxetine combination (OFC) treatment of major depressive disorders on the quality of life in the acute treatment period. Methods were prospective and observational design. One hundred and three patients of major depressive disorders were observed. One group of 53 patients received OFC treatment (OFC group); the other group of 50 patients received the treatment of duloxetine (duloxetine group). Two groups were needed to be observed 8 weeks. Observed indicators were Hamilton Depression Rating Scale for Depression (HAMD-24) and four factor scores: the slow, sleep disorders, anxiety/somatization, and hopelessness, Clinical Global Impression-Severity of Illness (CGI-S), WHO quality of life scale (WHOQOL-BREF), and sub-rate measurements. HAMD-24 and four factor scores observation time were assessed before and after treatment; 1, 2, 4, 8 weeks, WHOQOL-BREF score, and sub-time measurements were assessed before treatment and 8 weeks after treatment. HAMD-24 scores of OFC patients in the first week were significantly lower than those of the duloxetine group. The sleep factor scores of OFC patients were significantly lower than those of the duloxetine group in 4 and 8 weeks. By the end of 8 weeks, OFC group was rated significantly lower than the duloxetine group in the physical area. In the acute treatment period, OFC treatment effected faster than the single duloxetine in patients with major depressive disorders. OFC effected within 1 week and was better than the single duloxetine in improving the sleep and physical conditions.     

Eat Me If You Can: Cognitive Mechanisms Underlying the Distance Effect

Proximal objects provide affordances that activate the motor information involved in interacting with the objects. This effect has previously been shown for artifacts but not for natural objects, such as food. This study examined whether the sight of proximal food, compared to distant food activates eating-related information. In two experiments reaction times to verbal labels following the sight of proximal and distant objects (food and toys) were measured. Verbal labels included function words that were compatible with one object category (eating and playing) and observation words compatible with both object categories. The sight of food was expected to activate eating-related information when presented at proximity but not at distance, as reflected by faster reaction times to proximal than distant compatible eating words and no difference between reaction times to proximal and distant food for observation words (Experiment 1). Experiment 2 additionally compared the reaction times to wrapped and unwrapped food. The distance effect was expected to occur only for unwrapped food because only unwrapped food is readily edible. As expected, Experiment 1 and 2 revealed faster responses to compatible eating words at proximity than at distance. In Experiment 2 this distance effect occurred only for readily edible, unwrapped food but not for wrapped food. For observation words no difference in response times between the distances was found. These findings suggest that the sight of proximal food activates eating-related information, which could explain people’s differential behavioral responses to reachable versus distant food. The activation of eating-related information upon sight of accessible food could provide a cognition-based explanation for mindless eating.     

A comparison of olanzapine and risperidone on the risk of psychiatric hospitalization in the naturalistic treatment of patients with schizophrenia

BACKGROUND: Decreasing hospital admissions is important for improving outcomes for people with schizophrenia and for reducing cost of hospitalization, the largest expenditure in treating this persistent and severe mental illness. This prospective observational study compared olanzapine and risperidone on one-year psychiatric hospitalization rate, duration, and time to hospitalization in the treatment of patients with schizophrenia in usual care. METHODS: We examined data of patients newly initiated on olanzapine (N = 159) or risperidone (N = 112) who continued on the index antipsychotic for at least one year following initiation. Patients were participants in a 3-year prospective, observational study of schizophrenia patients in the US. Outcome measures were percent of hospitalized patients, total days hospitalized per patient, and time to first hospitalization during the one-year post initiation. Analyses employed a generalized linear model with adjustments for demographic and clinical variables. A two-part model was used to confirm the findings. Time to hospitalization was measured by the Kaplan-Meier survival formula. RESULTS: Compared to risperidone, olanzapine-treated patients had significantly lower hospitalization rates, (24.1% vs. 14.4%, respectively, p = 0.040) and significantly fewer hospitalization days (14.5 days vs. 9.9 days, respectively, p = 0.035). The mean difference of 4.6 days translated to $2,502 in annual psychiatric hospitalization cost savings per olanzapine-treated patient, on average. CONCLUSIONS: Consistent with prior clinical trial research, treatment-adherent schizophrenia patients who were treated in usual care with olanzapine had a lower risk of psychiatric hospitalization than risperidone-treated patients. Lower hospitalization costs appear to more than offset the higher medication acquisition cost of olanzapine.     

Real-time self-regulation of emotion networks in patients with depression

Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression.     

Body dysmorphic disorder, inhibiteurs de la recapture de la sérotonine et délire

Body dysmorphic disorder (BDD) has only been recognized as a specific mental disorder since 1987, after having been long considered an obsessive compulsive or delusional disorder or a symptom of schizophrenia. Regardless, the condition does not respond to antipsychotic treatment. During the 1990s, controlled studies have demonstrated the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the treatment of BDD. Moreover, SSRIs are equally effective on the delusional and non-delusional forms of BDD. The surprising efficacy of SSRIs in treating delusional disorders suggests the possibility of a special category of psychosis responsive to SSRIs rather than to traditional antipsychotic drugs.     

Metformin ameliorates olanzapine-induced disturbances in POMC neuron number,axonal projection,and hypothalamic leptin resistance

Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.     

Clinical correlates of chronotypes in young persons with mental disorders

While important changes in circadian rhythms take place during adolescence and young adulthood, it is unclear how circadian profiles during this period relate to emerging mental disorders. This study aimed to: (i) characterise morningness–eveningness preference in young people with primary anxiety, depression, bipolar or psychotic disorders as compared to healthy controls, and (ii) to investigate associations between morningness–eveningness preference and the severity of psychiatric symptoms. Four hundred and ninety-six males and females aged between 12 and 30 years were divided into five groups according to primary diagnosis. The Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale were administered by a research psychologist and participants completed the Kessler Psychological Distress Scale and the Horne–Östberg Morningness–Eveningness Questionnaire (ME). ME scores were significantly lower (i.e. higher levels of “eveningness”) in all patient diagnosis subgroups compared to the control group. The psychosis group had higher ME scores than the depression and anxiety groups. Compared to the control group, the anxiety, depression and bipolar subgroups had a significantly higher proportion of “moderate evening” types, with a similar trend for the psychosis group. The proportion of “extreme evening” types was significantly higher in the anxiety and depression subgroups than in the control group. Lower ME scores correlated with worse psychological distress in males from the bipolar group. Lower ME scores correlated with higher depression severity in females with depression and in males with bipolar disorder. These results suggest that young persons with various mental disorders, especially those with affective disorders, present with a stronger “eveningness” preference and higher rates of evening chronotypes than healthy controls from the same age group. Later chronotypes were generally associated with worse psychological distress and symptoms severity. These associations were modulated by sex and primary diagnosis.     

Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa

Circulating ghrelin and growth hormone (GH) are up-regulated in anorexia nervosa (AN) as a consequence of prolonged starvation. The current study examines the effect of nutritional rehabilitation with improvement of eating behavior on ghrelin and GH levels in AN patients during the course of inpatient treatment. The subjects included 34 female AN patients and 9 age-matched female controls. Fasting blood samples were collected before, during and after treatment. For data analysis, AN subjects were divided into three subtypes. The first group included seven patients with emergent hospitalization (E-AN), who were accompanied by severe emaciation due to their inability for food intake for more than a month. The other two groups included 14 AN with restricting (AN-R) and 13 AN with binge-eating/purging (AN-BP) patients. There were significant correlations between ghrelin, GH and body mass index (BMI) before treatment in all subjects. However, ghrelin levels were not significantly correlated with BMI and GH although there was a relationship between GH and BMI after treatment. Before treatment, E-AN patients had the highest levels of ghrelin and GH with the lowest glucose levels and liver dysfunction. The AN-BP group had a higher level of ghrelin than the AN-R group. During treatment, comparing with the controls group only the AN-R group showed higher level of ghrelin. Contrarily, the ghrelin levels in the E-AN group, who showed improved glucose levels, and the AN-BP group, who stopped vomiting behavior due to our treatment, decreased ghrelin levels. After treatment, only the AN-BP group showed a higher ghrelin level as compared to the controls. Although GH levels of the three AN groups decreased gradually according to our treatment progress, it still showed the higher value than the control group at the end of the treatment because every AN patients could not reach to more than 80% of their ideal body weight at discharge. These findings suggest that (1) severe emaciation with abnormal fasting hypoglycemia in AN patients may cause very high levels of GH and ghrelin, (2) that GH levels in AN patients may relate to nutritional status and (3) that ghrelin may be influenced by not only nutritional status but also the eating behavior of the patients.     

Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized,Open-Label,Comparative Clinical Trial

Objective

The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia.

Methods

One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8.

Results

One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups.

Conclusions

Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia.

Trial Registration

chictr.org ChiCTR-IOR-15006278