¹Graduate School of Medicine, The University of Tokyo, Neuropsychiatry, Tokyo, Japan, ²The Institute of Medical Science, The University of Tokyo, Psychiatry, Tokyo, Japan

Background: In humans, the D-neuron system in nucleus accumbens (D16), projection field of mesolimbic dopamine (DA) system, is far developed than in other animal species. "D-cell hypothesis of schizophrenia" (Ikemoto K., Lancet, 2025) has shown the lack of D-neurons in the D16 of post-mortem brains of schizophrenia, being the cause of mesolimbic dopamine (DA) hyperactivity and psychostic states, such as paranoid-hallucinatory state, excitement or suicide. An immunohistochemical difficulty in visualization of human D-neurons (TAAR1 ligand neurons, = aromatic L-amino acid decarboxylase (AADC)-only-immunoreactive neurons) has unexpectedly delayed D-neuron reserach. The majority of pathological autopsy brain samples of schizophrenia used for the previous studies, was limited in chronic or residual state of schizophrenia, died in hospitals. Whereas, legal autopsy brain samples have only few clinical informations. Dysfunction of subventricular and/or hippocampal NSC would cause D-neuron dysfunction. Biochemical studies have shown increased level of serum β-phenylethylamine (β-PEA) in severest stage of manic state or paranoid-hallucinatory state of schizophrenia, and decreased level of β-PEA in chronic phase of both diseases. In former stage, inflammation is supposed to affect on D-neurons. Causative triggers of an acute psychotic state contained stress, abuse, excessive alcohol intake, psychostimulant (methamphetamine) use, trauma, infection, malnutrition, degeneration, and so on, which may cause inflammation and cell death. I had been only one woman psychiatrist in the nearest heart hospital from the 1st Nuclear Power Plant of Fukushima, Iwaki Kyoritsu General Hospital (= Iwaki City Medical Center, Japan) for about 12 years, following the Great East Japan Earthquake and nuclear disaster, and examined more than 500 suicidal attempt inpatients and patients with paranoid-hallucinatory state, introduced from the Emergency Center.

Aims & Objectives: The aim of the present study is to reveal trigger situations leading to the onset of psychotic states, such as paranoid-hallucinatory state and suicidal attempt, in which D-neuron dysfunction might be involved, and is also to explore how to protect the D16 D-neuron, projection field of mesolimbic DA system.

Method: I examined medical chart following the Great East Japan Earthquake, of Department of Psychiatry, Iwaki City Medical Center, Japan, retrospectively, focusing on causative triggers of paranoid-hallucinatory state, excitement and suicidal attempt, and referring recent publications available.

Results: Causative events seemingly trigger paranoid-hallucinatory state and suicidal attempt contained abuse, problems in work places or interpersonal relationships, substance abuse, physical problems etc.. Initial sexual intercourse (without any consent, and/or in extramarital state) or virgin killing was noted to precede depressive state, insomnia, suicidal idea, self-mutilation, and suicide. Clinical history of anxiety disorder, substance abuse, mood disorders (bipolar disorder, depression), post-traumatic stress disorder, or personality disorder was frequently seen among patients with suicidal attempt.

Discussion & Conclusions: In sound development of the D16 D-neuron, nutrition, exercise, BDNF, immune protection, activaion of subventricular and/or hippocampal NSC, are possibly involved. Drug intoxication, and female sexual abuse of virgin killing may injure D16 D-neurons, and cause sleep disorders. It has been known that incidence of hypnotic use among virgins in population more than 60 years old is less than half. Moral education might serve D16 D-neuron protection, leading to suicide prevention.