Social anxiety and premorbid personality disorders in paranoid schizophrenic patients treated with clozapine

The concept of anxiety as a distinct comorbid disorder in schizophrenia has recently been rediscovered after having been neglected for a long period of time due to both theoretical and clinical approaches adopted from the appearance of the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1950. This rediscovery was accentuated by the fact that the concept of comorbidity in various psychiatric disorders has recently won widespread favor within the scientific community, and that the use of atypical neuroleptic medication to treat patients with schizophrenia has been reported to lead to the emergence of anxiety symptoms. Of the atypical neuroleptic medications used to treat schizophrenia, clozapine has most frequently been reported to induce anxiety symptoms. In this paper, 12 cases of patients with paranoid schizophrenia who developed social phobia during clozapine treatment are reported, and their response to fluoxetine augmentation is assessed. Premorbid personality disorders were also investigated; patients were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). In addition, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Liebowitz Social Anxiety Scale (LSAS), the Frankfurt Beschwerde Fragebogen (Frankfurt Questionnaire of Complaints), and the Brief Psychiatric Rating Scale were used to rate clinical symptomatology. All patients were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine. In 8 (66.6%) of the 12 cases, symptoms responded (>/=35% LSAS score reduction) to an adjunctive regimen of fluoxetine. Furthermore, in 7 (58.3%) of the 12 cases, an anxious personality disorder (avoidant=33.3%; dependent=25%) was identified, but no significant differences in the prevalence of comorbid personality disorders emerged in comparison with a group of 16 patients with paranoid schizophrenia treated with clozapine who did not show symptoms of social phobia. The clinical relevance of the assessment and treatment of anxiety disorders is discussed in light of a clinical therapeutic approach that overcomes the implicit hierarchy of classification. Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with schizophrenia (or, at least for those treated with clozapine) should be adopted.     

On "risk" and reward: investigating state anhedonia in psychometrically defined schizotypy and schizophrenia

Anhedonia, defined as dysfunction in the experience of pleasant emotions, is a hallmark symptom of the schizophrenia spectrum. Of interest, it is well documented that patients with schizophrenia, at least as a group, do not show reductions in their state experience of pleasant stimuli. However, there is emerging evidence to suggest that individuals with schizotypy--defined as the personality organization reflecting the latent vulnerability for schizophrenia--do show these state deficits. This is paradoxical in that schizophrenia reflects a more pathological state in virtually every conceivable domain as compared with schizotypy. The present study examined self-reported affective reactions to neutral-, bad-, and good-valenced stimuli in individuals with psychometrically defined schizotypy and schizophrenia. Two separate control groups were also included, comprising psychometrically defined controls and stable outpatients with affective disorders. With no exceptions, the schizotypy group reported significantly less pleasant affect for each of the three conditions than each of the other groups. Conversely, the schizophrenia group did not statistically differ from the control groups for any of the conditions. Within both the schizotypy and schizophrenia groups, severity of negative symptoms/traits was associated with less pleasant report. We found that individuals with prominent negative symptoms and traits from the schizophrenia and schizotypy groups resembled each other in terms of state anhedonia. The present findings did not appear to reflect comorbid depression or anxiety. Our discussion centers on this apparent paradox in the schizophrenia spectrum--that individuals with schizotypy exhibit state anhedonia, whereas patients with schizophrenia do not.     

Clozapintherapie bei therapieresistenter Schizophrenie

Antipsychotics are used to treat the psychiatric disorder schizophrenia. However, antipsychotics only improve some of the symptoms but not in all patients. In treatment-resistant schizophrenia, clozapine is considered the gold standard worldwide. Due to safety concerns (agranulocytosis, clozapine myocarditis) and poor tolerance (e.g., epileptic seizures, salivation, weight gain, sedation) it is rarely and almost always prescribed only many years after the first manifestation of schizophrenia. Patients with treatment-resistant schizophrenia are too seldom prescribed clozapine. For fear of threatening side effects by the treating physician, clozapine therapy is also frequently switched back.     

Indications for the Use of Atypical Antipsychotics in the Elderly

There has been an expanding role for the new generation atypical antipsychotic agents (clozapine, risperidone, olanzapine, and quetiapine) in elderly patients. Their efficacy in the treatment of psychoses associated with schizophrenia is now well established. But psychoses occur in other conditions. This paper will review the current research examining the use of the atypical agents in the treatment of psychoses in the elderly in three somewhat overlapping conditions: schizophrenia, dementia, and Parkinson's disease, as well as in the amelioration of a variety of movement disorders. In the elderly, any of the atypicals can be used to treat schizophrenia, although clozapine may be a second line agent because of its side effect profile. Risperidone may be the drug of choice for the treatment of psychoses and behavioral disturbances in dementia. Clozapine is a primary choice and quetiapine an alternative for the treatment of psychoses in Parkinson's disease; while clozapine and possibly risperidone may be preferred for the initial treatment of some movement disorders. The differential effectiveness of these agents across treatment indications may, in part, be related to their differing affinities at several neurotransmitter receptors. Examination of these relationships in large scale longitudinal studies may help in the development of effective tailored treatments for the elderly.     

Therapeutic Factors Contributing to Change in Cognitive-Behavioral Group Therapy for Older Persons with Schizophrenia

The contributions of homework, therapy participation, cognitive insight, and skills acquisition to treatment outcomes in group CBT for schizophrenia were examined. Increased cognitive insight was associated with reduced positive, negative and total symptoms, but not improved psychosocial functioning. Greater participation was associated with increased cognitive insight, reduction in total and negative symptoms, and a trend was found for positive symptoms. Greater homework adherence was associated with greater skill acquisition, but skill acquisition was not significantly associated with change in any outcome. The therapeutic factors contributing to change in CBT for schizophrenia appear different for symptom and psychosocial functioning outcomes.     

Systematic Review of the Clinical Presentation of Schizophrenia in Intellectual Disability

Schizophrenia and intellectual disability (ID) co-occur three times more than would be expected by chance. This has led to speculation that a particular form of schizophrenia may give rise to both the symptoms of schizophrenia and the intellectual impairment. If this was the case, one may expect the presentation of schizophrenia in an ID population to differ from that in a population with average/high IQ. A systematic review and meta-analysis was undertaken of studies comparing the clinical presentation of schizophrenia in people with mild/borderline ID to that in people with average/high IQ. Five studies were eligible for inclusion. Four reported more negative symptoms in the ID population, while two reported more positive symptoms. Meta-analysis demonstrated that the ID population experienced more negative symptoms. The available evidence supports the proposal that the clinical presentation of schizophrenia in an ID population differs from that in a population with normal IQ.     

Generalized anxiety disorder: acute and chronic treatment

Clinical and epidemiological data suggest that generalized anxiety disorder (GAD) is a chronic illness causing patients to suffer for many years leading to significant distress in daily life functioning. The literature suggests the several conclusions. GAD is a disorder in need of appropriate treatment and often has a chronic course with comorbid conditions, such as major depression and other anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely, when prescribed for >4 weeks cause rebound anxiety and following prolonged therapy may lead to withdrawal symptoms. Antidepressants cause significant anxiety relief compared with placebo and for psychosocial treatment cognitive-behavioral therapy is an efficacious psychosocial treatment. Many GAD patients are in need of long-term medication management. Furthermore, there is limited data for patients diagnosed with GAD the treatment outcome with the combination of medication and psychotherapy both acutely and long-term; how to best sequence these treatments; for those patients who do not meet remission criteria what is the ideal approach for augmentation; and for patients with treatment-refractory GAD the empirical evidence is lacking on medication switching and augmentation strategies. Research is needed in the area of developing treatment strategies for patients suffering from treatment-refractory GAD. There is still an urgent need to explore treatment combinations and duration strategies in the management of patients suffering with GAD.     

Optimizing treatment of schizophrenia. Enhancing affective/cognitive and depressive functioning

Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.     

Neuroleptic-resistant schizophrenics

According to Crow's postulated positive-negative distinction, negative symptoms of schizophrenia are less responsive to neuroleptic drugs. Not all research evidence supports that expectation, however, so that neuroleptics need not be withheld from any schizophrenic patients. Other aspects of Crow's hypothesized distinction have indicated possible promising results, but more research is required.     

Suicide schema in schizophrenia: the effect of emotional reactivity, negative symptoms and schema elaboration

Suicide risk is thought to increase with a greater potential for activation of suicide-related schemas. Suicide schemas are less likely to be activated with reductions of emotional range associated with certain negative symptoms of schizophrenia. The study tested whether suicide risk would increase in patients with recent onset schizophrenia with increased potential for suicide schema activation as indicated by lower levels of specific negative symptoms that reflected emotional reactivity, namely emotional withdrawal and blunted affect. A logistic regression analysis of baseline data of 278 recent onset schizophrenic patients with a measure of suicide behaviour as the dependent variable and negative symptoms, delusions, hallucinations, depression, gender, episode, ethnicity, education, age, duration of untreated psychosis and substance use as independent variables was carried out. Emotional withdrawal, but not blunted affect was significant and negatively associated, and depression positively associated with suicide behaviour. There was evidence to indicate that restricted emotions are associated with reduced suicide risk as predicted.     

Verbal Fluency,Semantics, Context and Symptom Complexes in Schizophrenia

Lexical-semantic access and retrieval was examined in 15 adults diagnosed with schizophrenia and matched controls. This study extends the literature through the inclusion of multiple examinations of lexical-semantic production within the same patient group and through correlating performance on these tasks with various positive and negative clinical symptoms. On tasks of verbal fluency, meaning generation, sentence production using contextual information and confrontation naming, participants with schizophrenia made significantly more semantic errors on naming tasks; produced fewer meanings for homophones; produced fewer items on semantic, phonological, cued and switching fluency tasks; and produced more errors on sentence production tasks when compared to healthy controls. Significant correlations were also observed between ratings of psychomotor poverty and measures of semantic production and mental inflexibility. This study has provided additional evidence for deficits in lexical-semantic retrieval which are not due to underlying semantic store degradation, do not involve phonological based retrieval, and at the level of sentence generation appear to vary as a function of the contextual constraints provided.     

Behavioral disorganization in schizophrenia during a daily activity: the kitchen behavioral scoring scale

Executive dysfunction has been extensively described in schizophrenia and has been found to correlate with the negative symptoms of the disease. However, executive dysfunction is usually assessed by cognitive tests, and these are not necessarily good predictors of an individual's daily functioning. This study aimed to discover whether executive dysfunction in schizophrenia can be measured by analyzing a daily routine such as cooking a meal. Behavior was scored on the basis of the optimal sequence of macrostructures (order of dishes) and microsteps (order of actions) that must be performed to prepare the meal in a minimum of time and with the smallest delay between the completion of the first and last dishes. The results showed that patients with schizophrenia make macrostructure but not micro-step sequencing errors. The number of repetitions and omissions and the delay between the completion of the first and last dish were all greater in patients than in control subjects. In patients with schizophrenia, but not in normal controls, these behavioral malfunctions were significantly correlated with both negative symptoms and performance on the executive tasks. Poor performance on the memory tests was not correlated with the behavioral malfunction. Therefore, daily functioning in schizophrenia may be specifically influenced by executive dysfunction in schizophrenia, and this can be quantitatively assessed with a behavioral scale of action sequences.     

Update: new uses for lithium and anticonvulsants

Anticonvulsants are being used clinically as monotherapy and adjuncts in mental illnesses other than affective disorders. This review focuses on the literature for anticonvulsants and lithium in substance use disorders, anxiety disorders, and schizophrenia. Given the abuse potential and other difficulties with prescribing benzodiazepines for alcohol and benzodiazepine withdrawal, anticonvulsants have been considered as an alternative. Promising therapeutic effects have been demonstrated in many of the anxiety disorders, with the greatest number of trials and positive results in posttraumatic stress disorder. Although anticonvulsant and lithium augmentation for schizophrenia is common in practice and has been studied in double-blind, randomized, controlled trials, the sum of the evidence has been inconclusive.     

Enhancing exposure-based therapy from a translational research perspective

Combining an effective psychological treatment with conventional anxiolytic medication is typically not more effective than unimodal therapy for treating anxiety disorders. However, recent advances in the neuroscience of fear reduction have led to novel approaches for combining psychological therapy and pharmacological agents. Exposure-based treatments in humans partly rely on extinction to reduce the fear response in anxiety disorders. Animal studies have shown that D-cycloserine (DCS), a partial agonist at the glycine recognition site of the glutamatergic N-methyl-D-aspartate receptor facilitates extinction learning. Similarly, recent human trials have shown that DCS enhances fear reduction during exposure therapy of some anxiety disorders. This article discusses the biological and psychological mechanisms of extinction learning and the therapeutic value of DCS as an augmentation strategy for exposure therapy. Areas of future research will be identified.     

Poly I:C母体免疫刺激诱导的子代精神分裂症神经发育动物模型研究

精神分裂症是一组病因未明的重性精神障碍,其病理生理学机制极其复杂,建立能够确切模拟精神分裂症的动物模型对于其发病机制的研究及抗精神分裂症药物的研发具有十分重要的意义。本文意在介绍产前母体免疫刺激（聚肌胞苷酸聚肌苷酸-聚胞苷酸,poly-I:C）诱导子代出现精神分裂症样的神经发育动物模型,以及该模型对精神分裂症的病因研究、生物学机制及其治疗和药物研发的重要意义。     

自然自明性的失落——Blankenburg精神分裂理论述评

传统的精神分裂研究,关注的主要是精神分裂的妄想症候群。因为精神分裂中相对特殊的症状,在妄想形式中可以得到最轻易的把握。Blankenburg则认为:精神分裂的本质结构变异是先于妄想的。因此,他致力于在精神分裂的症状贫乏型(主要是青春型和单纯型)中,寻找精神分裂的本质变异。他发现:精神分裂异常中的核心缺损是自然自明性的失落。根据胡塞尔的超越现象学,自然自明性失落有四个原因:与世界关系的改变、时间建构的改变、自我建构的改变、交互主体性的改变。Blankenburg的精神分裂理论,作为二十世纪有关精神分裂的最重要工作之一,对于今天的精神分裂研究仍然有极其重要的意义。     

Manualized Group Cognitive-Behavioral Therapy for Social Anxiety in At-Risk Mental State and First Episode Psychosis: A Pilot Study of Feasibility and Outcomes

Social anxiety has received scant attention in studies of schizophrenia and related psychoses. However, some data suggest it may be an obstacle to vocational and functional outcome. This pilot study investigated the feasibility of a group-based cognitive behavioral therapy (CBGT) to reduce social anxiety in those at risk for developing psychosis or in the early phase. Twenty-nine patients with first-episode psychosis (FEP) or at ultra high risk for developing psychosis or often referred to as at-risk mental state (ARMS) with comorbid social anxiety attended a CBGT intervention weekly for 14 weeks in 90-minute sessions. Baseline, post-treatment, and follow-up ratings of social anxiety were measured using the Social Interaction Anxiety Scale, the Social Phobia Inventory, and the Brief Social Phobia Scale. Psychotic symptoms and general psychopathology were also measured before and after the intervention. Results suggest that the proposed CBGT is feasible and beneficial for socially anxious patients at risk, or with experience of, psychosis. Participants significantly improved on three outcome measures of social anxiety after completing this intervention (all p’s < .002). Participants who completed treatment also showed a significant reduction on measures of depression and negative symptoms. Future research should examine the relative efficacy of this brief manualized CBGT intervention for the treatment of social anxiety and psychotic symptoms in a larger randomized controlled trial.     

基于努力决策任务在精神分裂症患者动机缺失评估中的应用

国外运用基于努力决策任务,与阴性症状量表和访谈相结合,对精神分裂症患者的阴性症状特别是动机缺失进行研究。本文从基于努力决策任务出发,重点介绍该任务范式及其在精神分裂症患者动机缺失评估中的最新研究,并从心理学、神经生物学和脑神经科学三个维度,阐述动机缺失的认知神经机制,论文结尾讨论了该任务范式在评估精神分裂症患者或其他患者动机缺失中可能遇到的挑战,以及未来的发展趋势。     

The relationship between cognitive inhibition and psychotic symptoms

Cognitive models of schizophrenia have highlighted deficits of inhibitory attentional processes as central to the disorder. This has been investigated using "negative priming" (S. P. Tipper, 1985), with schizophrenia patients showing a reduction of negative priming in a number of studies. This study attempted to replicate these findings, but studied psychotic symptoms rather than the broad diagnostic category of schizophrenia. Psychotic individuals exhibiting positive symptoms were compared with asymptomatic psychiatric patients and with a normal control group. As predicted, the symptomatic group failed to show the usual negative priming effect, which was present in the asymptomatic and normal groups. A modest but significant correlation was found between negative priming and delusions. Neither diagnosis, nor affective or negative symptoms, nor chronicity, nor medication, was related to negative priming. These data replicate previous findings that positive symptoms are related to a reduction in cognitive inhibition, although considerable variability was observed among the psychotic patients.     

Assessing Social Affiliative Behavior: A Comparison of in Vivo and Video Tasks

Social affiliation, or engagement in positive social interactions, is often profoundly impaired in individuals with schizophrenia. Valid measures of social affiliation are needed to understand these impairments and their symptom and functional correlates; however, such measures are limited and have not been validated. This pilot study evaluated one such measure—the video-based Social Affiliation Interaction Task (SAIT)—and a novel in vivo behavioral measure, the Affiliative Conversation Task (ACT). Twenty participants with schizophrenia or schizoaffective disorder (SZ) and 35 nonpsychiatric controls (CT) completed both tasks and measures of negative symptoms and functioning. We explored group differences in social affiliation skills; convergent validity between social affiliation skill ratings from the two tasks; and concurrent validity with social affiliation skill ratings, negative symptoms, and functioning. SZ evidenced lower affiliation skill ratings than CT on the video SAIT, but not on the ACT, and the tasks displayed moderate convergent validity for affiliation skill ratings. Less affiliation skill in the SAIT was correlated with more negative symptoms and less functioning in the SZ group with medium effects, though the results were not significant. Findings suggest that the SAIT may be more sensitive to individual differences in skill level. Future research should continue to examine the SAIT for use in measuring affiliation skills.