Symposium-77 took place under the title ‘Novel actions of antidepressant and antipsychotic drugs’, chaired by Drs. Garcia-Sevilla and Odagaki. The four speakers made presentation of their own interesting data. 1) Dr. Yamada showed the behavioral pharmacological and biochemical data on riluzole, a promising antidepressant/anxiolytic agent with novel mechanisms of action. 2) Dr. Takebayashi demonstrated that antidepressants such as amitriptyline acted directly on glial cells to result in GDNF (glial cell line-derived neurotrophic factor) production, which was mediated through multiple molecular cascades related to fibroblast growth factor receptor (FGFR) signaling. 3) Dr. González-Maeso noticed that histone deacetylases (HDACs) played a pivotal role as an epigenetic regulator of metabotropic glutamate receptor 2 (mGlu2) in the treatment with atypical antipsychotics, and provided the view that HDAC2 might be a novel therapeutic target to improve the antipsychotic efficacy. 4) Dr. Garcia-Sevilla showed the implications of Fas-associated death domain (FADD) in pathogenesis of major depressive disorders and mechanisms of action of antidepressants. The psychotropic drugs available at present are at most modifications of prototypal ones that had been empirically found more than a half century ago. The author believes that this symposium must contribute to the new concepts for developing drugs with novel mechanisms of action.

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Attention - deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, which is the most common psychiatric illness in child psychiatry with an estimated range of 5% to 10%. Several recent studies have indicated possible interactions between genetic, metabolic, environmental, and behavioral factors may be associated with the pathogenesis of ADHD. However, validation of the diagnosis is not well established. The high overlap between symptoms in mania and ADHD as well as the high comorbidity rates suggest that there are not only similarities at the symptom level but also common underlying pathophysiological processes. 　Recent studies support the concept that the sensation seeking and hyperactivity in both mania and ADHD can be interpreted as an autoregulatory reaction to an unstable regulation of vigilance (in the sense of “brain arousal” ). In addition, evidence is increasing that vigilance stabilizing drugs such as psychostimulants might be a treatment option not only in ADHD but also in mania. In the symposium, relationships between mania within bipolar disorder and ADHD in order to identify biomarkers of ADHD was discussed at the epidemiological, clinical, genetic, pathophysiological and therapeutic level.

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It has been hypothesized that in neurodevelopmental psychiatric disorders such as schizophrenia and autism, biological processes in brain development may be affected by genetic and environmental causes, leading to alterations in brain wiring and/or synaptic formation and function, which manifest as characteristic phenotypes of these disorders. In fact, genetic studies have identified several genetic changes associated with schizophrenia and autism that would alter molecular pathways involved in brain development. It is also noted that the same genetic changes would lead to different clinical entities, such as autism and schizophrenia, emphasizing the importance of understanding basic neurobiology of brain wiring and synapse formation/function, in order to understand how functional alterations (and distinct phenotypes among psychiatric disorders) appear when those processes go away in these psychiatric disorders. To this end, we could take advantage of genetic findings in humans to develop mouse models with construct validity that have alterations in genes associated with these psychiatric disorders in humans and should gain insights into neurobiology underlying these psychiatric disorders by characterizing them.

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The scalp EEG consists of the summed electrical field potentials from cortical neurons. The EEG amplitude reflects the amount of synchronized activity in the underlying cortex, and the inter-electrode functional connectivity measures their interactions. The very fast oscillation reflects local process and narrow range interactions, and slow wave synchronization mediates long range interaction of largely separated cortical areas. In 1929, H. Berger first reported human EEG and deduced from the ceaseless electrical oscillations that “we have to assume that the central nervous system is always in a state of considerable activity” . In the mid-1990s, a series of PET and fMRI studies confirmed that the brain is far from idling when not engaged in a conscious activity, and the default-mode network (DMN) is active during resting/inattention state. The DMN is thought to be a neural basis of introspective processes such as self-referential processing. The scalp alpha wave is an electrophysiological candidate of the DMN function, and its sophisticated analysis might contribute to clarify common psychological features of various psychiatric disorders.

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Early intervention or shortening of duration of untreated psychosis, is important from the perspective of improving outcome of patients. This concept has prompted the search for biological markers to predict outcome and transition to psychosis, e. g. schizophrenia. In this symposium, researchers from North America, Europe and Asia discussed cutting-edge presented findings to address this issue.

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