Symposiums

  1. Special Lecture
  2. Clinical Research Educational Seminar
  3. Symposiums
  4. Lunceon Seminar
  5. Oral Abstracts
  6. Poster Abstracts

S4-4

Recent progress of disease-modifying approach to the treatment for Alzheimer's disease

Makoto Ogo
Biology/Pharmacology, Discovery Research, Tsukuba, Neuroscience Unit, Eisai Product Creation Systems, Eisai Co., Ltd. Ibaraki, Japan

Alzheimer's disease (AD) is the most common form of irreversible dementia. AD is clinically characterized by the progression from mild episodic memory problems to very severe dementia with behavioral and psychiatric symptoms e.g. depression, hallucinations, delusions, and agitation. The current standard of care for mild to moderate AD includes treatment with acetylcholinesterase inhibitors to improve cognitive function. Memantine, a glutamatergic partial antagonist, has also been shown to improve cognitive function in people with more severe dementia. These current medications primarily offer symptomatic relief and do not have a proven disease-modifying effect. However, many new clinical candidates aiming at inhibiting disease progression are currently in clinical trials. Among these, strategies targeting the amyloid-β peptide (Aβ), that is believed to be central to the cascade which leads to the development of AD, are the most advanced. Aβ-targeted therapeutic approaches include modulation of Aβ production, inhibition of Aβ aggregation and immunotherapy targeted at Aβ. In addition, approaches aimed at modulating tau aggregation and those targeting metabolic dysfunction are also being evaluated in the clinic. This presentation will review multiple approaches to inhibit disease progression beneficial in combination with the current symptomatic treatments.

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S9-4

Prospects for the understanding impairments of social emotions in neuropsychiatric disorders

Hidehiko Takahashi1,2,3

  1. Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  2. Molecular Imaging Center at the NIRS.
  3. Japan Science and Technology Agency Basic Research Programs Presto.

In the first part, I present our fMRI studies about moral emotions. Moral emotions (guilt, shame and embarrassment) are called self-conscious emotions. Self-conscious emotions are emotions founded in social relationship and arise from concerns about others' opinions of self or the behavior of self. Negative evaluation of self or the behavior of self is fundamental to guilt, shame, and embarrassment, and positive evaluation of self is important for pride. Our results support the notion that recognizing these emotions requiring the ability to understand mental states of others. In the second part, I provide our findings about the neural correlates of painful emotions, jealousy and envy. Although envy and jealousy are used interchangeably in daily usage, research shows that these two emotions are actually different. Jealousy typically involves three people and occurs when one fears losing someone to another person. We found gender differences in neural correlates of jealousy. Envy typically involves two people and occurs when one lacks something enjoyed by another. We often evaluate self and others from social comparisons. We feel envy when the target person has superior and self-relevant characteristics. Schadenfreude occurs when envied persons fall from grace. The fMRI results indicate that social comparison play substantial roles in these social pain and pleasure. The findings also suggest that the central process of social pain and pleasure overlap those of physical pain and pleasure.

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S11-1

Relation among cognitive dysfunction, quality of life and clinical symptoms in schizophrenia patients

Masahito Tomotake
Department of Mental Health, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan

Recently, cognitive dysfunction of schizophrenia patients has been paid much more attention because it may lead to poor social functioning. Cognitive dysfunction is thought to be a core feature of schizophrenia, and it has been reported that cognitive functions of schizophrenia patients are of the order of one to two standard deviations below the mean of healthy controls in several cognitive dimensions, particularly memory, attention, verbal fluency, and executive function (Kraus et al, 2007; Savilla et al, 2008). As for outcome variables, quality of life is thought to be one of the key outcome variables in the treatment of schizophrenia, and the importance of evaluating it has been increasing in patient care and clinical research. Previous studies have revealed that some clinical factors such as negative and positive symptoms, depressive symptom, and extrapyramidal adverse effect are associated with lowered quality of life (Tomotake et al, 2006; Aki et al, 2008). In addition, some research groups have studied the relation between quality of life and cognitive function in people with schizophrenia, and reported the significant correlations between quality of life and some domains of cognitive function such as verbal memory, vocabulary, fluency performance, attention, social knowledge, and executive function (Dickerson et al, 1998; Addington et al, 2000; Bozikas et al, 2006; Savilla et al, 2008). Although, considering the results of previous studies, it is clear that cognitive dysfunctions and some clinical symptoms are significantly associated with lowered quality of life in schizophrenia patients, it seems to remain unclear how much impact these factors have on patients' quality of life.In this symposium, we will introduce the recent findings of our studies about the relation between cognitive dysfunction, quality of life, and clinical symptoms, and discuss some issues related to cognitive dysfunction of schizophrenia.

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S11-2

Neurophysiological basis for cognitive defi cits of schizophrenia and effect of psychotropic drugs

Tomiki Sumiyoshi1,2

  1. Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
  2. CREST, JST

There is considerable evidence for associations between social functioning/community outcome and cognitive function, as evaluated by neuropsychological tests, such as the MATRICS Consensus Cognitive Battery in patients with schizophrenia.1 Therefore, neural substrates underlying impaired cognitive performance need to be elucidated.
While brain imaging methods based on blood flow, e.g. functional magnetic resonance imaging and positron emission tomography, are characterized by high spatial resolutions, their time resolutions are limited compared to neurophysiological paradigms, e.g.electroencephalography (EEG) and magnetoencephalography. Specifically, electrophysiological biomarkers, such as EEG and eventrelated potentials (ERPs), have been suggested to provide objective indices of cognitive dysfunction in schizophrenia, and be more sensitive to drug-induced changes compared with other functional imaging modalities.2
Recent development of imaging technique, such as low resolution electromagnetic tomography and its modified versions, has improved the spatial resolution of ERPs, e.g. P300 and mismatch negativity (MMN), by providing three-dimensional distribution pattern of these electrophysiological activities. The speaker will present findings from electrical neuroimaging studies of schizophrenia and treatment response,3-5 and discuss: 1) neural basis for psychopathology of schizophrenia as demonstrated by current source imaging of P300; and 2) P300 and MMN indices in discrete brain areas and response to psychotropic drugs in relation to cognition and QOL.
These research directions are likely to facilitate the development of novel therapeutic strategies to maximize long-term outcome in people with schizophrenia or related disorders.

[References]
1. Green MF, Kern RS et al. Schizophr Res 2004;72:41
2. Javitt DC, Spencer KM et al. Nat Rev Drug Discov 2008;7:68
3. Kawasaki Y, Sumiyoshi T et al. Schizophr Res 2007;94:164
4. Higuchi Y, Sumiyoshi T et al. Schizophr Res 2008;101:320
5. Sumiyoshi T, Higuchi Y et al. Psychiatry Res Neuroimag 2009;172:180

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S11-3

Social cognition in schizophrenia: Why is it important and how can we improve it?

Michael Green
Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California, Los Angels, USA

Social cognition (i.e., the mental operations that underlie social interactions, including perceiving, interpreting, and generating responses to the intentions and behaviors of others) has become a high-priority area of research in the study of schizophrenia. Social cognition is considered to be a valuable domain for schizophrenia research because it appears to be a determinant of functional outcome in schizophrenia, and it appears to be involved in the formation of certain psychotic symptoms. In addition, social cognition can be used to explore the pathophysiology of schizophrenia through applications of various neuroscience methods, including fMRI and EEG. The findings that social cognition correlates with functional outcome in schizophrenia have generated follow up questions, including whether social cognition explains unique variance in outcome, and whether social cognition mediates the association between neurocognition and outcome. Several studies indicate that social cognition explains variance beyond that explained by neurocognition, and that it acts as a mediator in models of functional outcome. The stability of social cognitive impairment across phase of illness was recently examined in prodromal, first episode, and chronic patients and their matched control groups. All clinical groups showed comparable level of impairment, indicating that impairment in social cognition in schizophrenia is relatively stable across phase of illness. Because social cognition is related to functional outcome, social cognitive deficits are promising treatment targets for new interventions to improve functional outcome in schizophrenia. This talk will present data from two studies that evaluated a new social cognitive skills training program designed to address four aspects of social cognition (affect perception, social perception, attributional style, Theory of Mind) in stable outpatients with psychosis. These validation trials show that training for social cognition can improve social cognitive abilities, but the results do not generalize well to other types of functions. These trials are leading to new versions of this treatment approach with the aim of achieving broader improvements in social cognition and eventual generalization of treatment gains.

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  1. Special Lecture
  2. Clinical Research Educational Seminar
  3. Symposiums
  4. Lunceon Seminar
  5. Oral Abstracts
  6. Poster Abstracts