Developing treatments for impaired cognition in schizophrenia

Schizophrenia is one of the most debilitating of all common brain disorders, exacting a heavy toll on the afflicted and having a tremendous public health impact. Clinical outcome is more strongly predicted by cognitive deficits than psychotic symptoms, with no established treatment for these deficits. In this review, we discuss the status of treatment development for impaired cognition in schizophrenia. These treatments include a range of pharmacological targets within diverse neurotransmitter systems. New technologies, including transcranial magnetic stimulation and transcranial direct current stimulation, and psychological therapies, such as computer-based cognitive training, may also benefit cognition in schizophrenia. Each of these approaches shows promise and their integration may optimize benefits for patients in the future.     

精神分裂症患者的语音感知

精神分裂症是一种常见的精神疾病, 表现为多方面的症状, 其中, 语言异常是精神分裂症患者认知损伤的核心症状之一。本文关注精神分裂症患者的语音感知, 从音段和超音段两方面简述国内外对精神分裂症患者语音感知开展的行为和神经科学实验, 指出中国应加大对中国精神分裂症患者的汉语语音感知探索。     

Subjective and objective measures of quality of life have different predictors for people with schizophrenia

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.     

Schizophrenia or Possession?

Schizophrenia is typically a life-long condition characterized by acute symptom exacerbations and widely varying degrees of functional disability. Some of its symptoms, such as delusions and hallucinations, produce great subjective psychological pain. The most common delusion types are as follows: “My feelings and movements are controlled by others in a certain way” and “They put thoughts in my head that are not mine.” Hallucinatory experiences are generally voices talking to the patient or among themselves. Hallucinations are a cardinal positive symptom of schizophrenia which deserves careful study in the hope it will give information about the pathophysiology of the disorder. We thought that many so-called hallucinations in schizophrenia are really illusions related to a real environmental stimulus. One approach to this hallucination problem is to consider the possibility of a demonic world. Demons are unseen creatures that are believed to exist in all major religions and have the power to possess humans and control their body. Demonic possession can manifest with a range of bizarre behaviors which could be interpreted as a number of different psychotic disorders with delusions and hallucinations. The hallucination in schizophrenia may therefore be an illusion—a false interpretation of a real sensory image formed by demons. A local faith healer in our region helps the patients with schizophrenia. His method of treatment seems to be successful because his patients become symptom free after 3 months. Therefore, it would be useful for medical professions to work together with faith healers to define better treatment pathways for schizophrenia.     

Historical origins of schizophrenia: two early madmen and their illness

Schizophrenia is a serious mental illness with a remarkably short recorded history. Unlike depression and mania, which are recognizable in ancient texts, schizophrenia-like disorder appeared rather suddenly in the psychiatric literature of the early nineteenth century. This could mean that the illness is a recent disease that was largely unknown in earlier times. But perhaps schizophrenia existed, embedded and disguised within more general concepts of madness and within the arcane languages and cultures of remote times. Both possibilities present major challenges to historical and psychiatric scholarship. These challenges are explored in this paper by presenting two "new" cases of schizophrenia, one from the eighteenth and one from the fourteenth century. The cases suggest that the illness may have existed as early as the medieval period. However, establishing the population prevalence of schizophrenia in earlier times--and therefore resolving the permanence-recency debate--may not be a feasible enterprise.     

Is there evidence that cognitive behaviour therapy is an effective treatment for schizophrenia? A cautious or cautionary tale?

Schizophrenia is a severe and disabling disorder with considerable psychological, social and economic costs. Over the last 15 years there has been a significant development in the use of cognitive behaviour therapy for psychosis (CBTp) in the treatment of schizophrenia, with 20 randomised controlled trials having been published. The majority of this work has been with alleviating medication resistant symptoms in chronic patients, but preliminary work has also been carried out with speeding recovery in acute schizophrenia and in relapse prevention and early intervention. A review of these studies indicates modest effect sizes, with the strongest evidence available for chronic patients. There is evidence that the effect size of the trials is significantly and negatively correlated to their methodological quality. We conclude cautiously that overall there is good evidence for the efficacy and effectiveness of CBTp in the treatment of schizophrenia.     

How semantic content of stimuli works on episodic memory processes in negative schizophrenia: Evidence from picture recognition

IntroductionEven though episodic memory is impaired in schizophrenia, semantic processing strategies can improve patients’ performance. However, it is less clear if negative schizophrenia patients can benefit from semantic strategies, and if both familiarity and recollection processes can be enhanced in patients with schizophrenia.ObjectiveThe aim of this study was to investigate the possibility for negative schizophrenia patients to enhance their familiarity and/or recollection processes in the presence of concrete images.MethodA recognition memory task using concrete versus abstract images as stimuli was designed to assess the performance of schizophrenia patients for single item recognition and the recollection of spatial context, allowing us to calculate the estimates of familiarity and recollection processes. Thirty-six patients with schizophrenia and 18 healthy individuals participated to the study. Schizophrenia patients were divided into two groups according to their scores on the negative scale of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS).ResultsResults showed that, while healthy participants enhanced their recollection estimates in the presence of concrete images, both schizophrenia groups could enhance their familiarity estimates.ConclusionSemantic strategies are helpful to promote successful familiarity process in schizophrenia patients, independently from clinical dimension of negativity. However, recollection process seems not to respond to such strategies.     

Risk Factors for Suicidality Among Clients With Schizophrenia

Among clients with schizophrenia, suicidality is associated with extreme personal distress, an increased number of inpatient hospitalizations, increased health care expenditures, and early mortality. This study attempted to identify risk factors for current suicidality in clients diagnosed with schizophrenia (N = 223). Results indicated that severity of depressive symptoms most strongly correlated with degree of suicidality. Younger age and recent traumatic stress each significantly predicted suicidality independent of depressive symptoms. Stepwise regression procedures showed that the combination of depression, younger age, and traumatic stress might provide a general prediction model for suicidality among clients diagnosed with schizophrenia. Counseling implications of these findings are outlined.     

Cognitive-Behavioral Therapy for Individuals Recovering from a First Episode of Psychosis

Schizophrenia is one of the most devastating psychiatric illnesses. There has been a tremendous worldwide research and clinical effort into early intervention for psychosis. However, despite significant improvement in symptoms after a first episode, there is no corresponding quality improvement in function for many individuals. Thus, increased attention has been given to psychological intervention in particular cognitive behavioral therapy (CBT) with the hope of enhancing functional recovery. Outcome trials of CBT for schizophrenia are promising and other work in CBT suggests this may be a viable psychological intervention for this population. This paper will review the need for a CBT approach after a first episode of psychosis and describe a modular CBT approach for this population. This approach addresses adaptation as well as both functional and symptomatic outcome, an approach which parallels the theoretical shift in CBT that occurred in the last decade.     

Parvalbumin阳性中间神经元缺陷在精神分裂症病理机制中的作用

精神分裂症是一种多发于青壮年的重性精神病, 其原因尚不明确。经典的多巴胺缺陷理论假说在某些方面欠缺解释力; 与此同时, 关于Parvalbumin阳性的中间神经元(后简称PV+神经元)缺陷在精神分裂症病理机制中的作用逐渐明晰, 并引起了越来越多的关注。PV+神经元在绝大部分脑区中是一种快速放电的抑制性神经元, 参与了突触可塑性的调节, 兴奋/抑制平衡的维持和神经发生等。而在精神分裂症中, PV+神经元的异常在患者和动物研究中都被普遍证实, 并发现与 NMDA受体缺陷、gamma波异常和氧化应激存在某些关联。     

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early‐onset schizophrenia patients

Cognitive deficits in several domains have been demonstrated in early‐onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early‐onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual‐construction, aspects of visual and verbal memory, and executive functions in chronic, early‐onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early‐onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual‐construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early‐onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms     

Narrative identity in schizophrenia

This study examined narrative identity in a group of 81 patients with schizophrenia and 50 healthy controls through the recall of self-defining memories. The results indicated that patients’ narratives were less coherent and elaborate than those of controls. Schizophrenia patients were severely impaired in the ability to make connections with the self and extract meaning from their memories, which significantly correlated with illness duration. In agreement with earlier research, patients exhibited an early reminiscence bump. Moreover, the period of the reminiscence bump, which is highly relevant for identity development, was characterized by fewer achievements and more life-threatening event experiences, compared with controls. A negative correlation was found between negative symptoms, number of self-event connections and specificity of narratives. Our results suggest that schizophrenia patients have difficulties to organize and extract meaning from their past experiences in order to create coherent personal narratives.     

Loving, discernment, and distance: pastoral care in schizophrenia

Schizophrenia is very common in our society, yet many people, both clergy and lay, are afraid of it and do not know what to do when confronted with someone who suffers from the disorder. Strange ideas and behavior can be frightening for those who don't understand and often result in further marginalization, even within the church community. This article seeks to outline the main features of schizophrenia and considers how to deal with particular situations which may arise in pastoral care. It suggests ways of dealing with people who express religious delusions and also argues that the "staples" of pastoral care--relationship building, empathy and inclusion--may not always be appropriate in the care of people with schizophrenia, who often need a "safe distance" between themselves and others. Some practical advice for families is also offered.     

Schizotypy: An Organizing Framework for Schizophrenia Research

ABSTRACT— Schizophrenia is the most devastating form of psychopathology known to humankind, and it has been slow to yield clues to its origins. Meehl's (1962, 1990) model detailed the nature of the latent liability for schizophrenia known as schizotypy and provided a major organizing function for research on schizophrenia. The schizotypy model integrates genetic and environmental contributions to liability as well as accounting for a range of clinical outcomes, all deriving from a genuine liability for the illness. Schizotypy, as a latent personality organization that harbors the liability for schizophrenia, provides a framework for detecting fundamental features of liability to schizophrenia prior to the onset of clinical illness. The schizotypy model is reviewed, the strategic benefits of it are discussed, and methods for detecting schizotypy are presented. A focus on perceptual aberrations—a schizotypic feature—in individuals unaffected by schizophrenia has yielded valuable clues to preclinical disturbances in neurocognitive processes, risk for schizophrenia among biological relatives, and genomic substrates, all of which are of interest to schizophrenia researchers.     

Left ear (right temporal hemisphere) advantage and left temporal hemispheric dysfunction in schizophrenia.

In this study, to investigate the right or left ear advantages in psychiatric patients. the durations of hearing for right and left ears were assessed in 61 psychiatric patients, 26 with schizophrenia, 17 with depressive disorder, 13 with bipolar affective disorder, and 5 with brief psychotic disorder, plus 24 controls. Diagnoses were made on the basis of information provided from clinical interviews and the Structured Clinical Interview for DSM-IV (SCID). Schizophrenia was associated with a left ear advantage, and both depressive disorder and brief psychotic disorder were associated with right ear advantage as well as controls. These results suggest that their schizophrenia may be associated with a left temporal lobe dysfunction.     

Distinct conflict resolution deficits related to different facets of Schizophrenia

An important issue in understanding the nature of conflict processing is whether it is a unitary or multidimensional construct. One way to examine this is to study whether people with impaired conflict processing exhibit a general pattern of deficits or whether they exhibit impairments in distinct aspects of conflict processing. One group who might exhibit conflict deficits are people with schizophrenia. Schizophrenia is a heterogeneous disorder, with one way to break down the heterogeneity of schizophrenia is to examine specific symptoms. Previous research has found that specific symptoms of schizophrenia are associated with specific deficits in conflict processing. In particular, disorganization is associated with increased response conflict, alogia is associated with increased retrieval conflict, and anhedonia is associated with increased emotional conflict. Moreover, there is evidence that different types of conflict processing are unassociated with each other. This evidence suggests that conflict processing is a multidimensional construct and that different aspects of schizophrenia are associated with impairments in processing different types of conflict.     

The primacy of cognition in schizophrenia

Cognitive tasks and concepts are used increasingly in schizophrenia science and treatment. Recent meta-analyses show that across a spectrum of research domains only cognitive measures distinguish a majority of schizophrenia patients from healthy people. Average effect sizes derived from common clinical tests of attention, memory, language, and reasoning are twice as large as those obtained in structural magnetic resonance imaging and positron emission tomography studies. Chronic stress, genes, brain disturbances, task structure, gender, and sociocultural background may all enhance the sensitivity of cognitive performance to schizophrenia. At the same time, disease heterogeneity and the presence of endophenotypes and subtypes within the patient population may place upper limits on the strength of any specific cognitive finding. Schizophrenia is a complex biobehavioral disorder that manifests itself primarily in cognition.     

Development of social functioning in preschizophrenia children and adolescents: a systematic review

Schizophrenia is associated with severe deficits in social functioning. Similar deficits may be present prior to psychosis onset, in childhood and adolescence. If so, then prepsychosis social deficits could provide clues to the development of pathological processes in preschizophrenia children and could potentially improve early identification of the disorder and suggest targets for intervention. Evidence is reviewed from birth cohort, case- control, and familial high-risk studies within distinct periods of development to clarify the nature, timing, and specificity of social deficits in preschizophrenia children and adolescents. The results indicate that poor social functioning does differentiate preschizophrenia children and adolescents from their peers and can be a sensitive and potentially specific predictor of schizophrenia, not just psychopathology in general. Furthermore, age (but not sex) appears to be an important moderator of the strength and specificity of the association between particular social deficits (e.g., externalizing, internalizing) and later schizophrenia. Results are discussed in the context of current developmental theories of timing and pathophysiology of schizophrenia involving hypothalamic- pituitary-adrenal dysregulation. Implications for the early identification and treatment of preschizophrenia individuals are also considered.     

Learning and forgetting in schizophrenia

Recent studies of patients with schizophrenia have consistently demonstrated marked deficits on measures of initial learning. However, contradictory results have been reported concerning retention and forgetting. The present study examined the level of initial and delayed recall of stories and visual figures in a group of 76 patients with schizophrenia and 51 normal controls. Schizophrenia patients demonstrated marked impairments in initial and delayed recall as well as significantly worse percentage retention scores. However, schizophrenia patients and healthy controls individually matched on level of initial recall had nearly identical delayed recall performance. The results suggest a primary deficit in the initial acquisition of information rather than an accelerated rate of forgetting in schizophrenia.     

Preventing clinical deterioration in the course of schizophrenia: the potential for neuroprotection

Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia.