吾妻 壮

米国では、必要なサポートを得るために何らかのコミュニティに属することが重要であることが多い。米国の大都市圏に存在する日系コミュニティは、米国の邦人に対してメンタルヘルスケアを提供する際に重要な役割を担っている。本稿では、ニューヨークの日系コミュニティにおけるメンタルヘルスを取り巻く状況について報告する。ニューヨークには比較的豊富なメンタルヘルス資源が存在するが、精神科入院治療はとりわけ困難を伴いやすい。その場合、日系コミュニティにおける公的支援と私的支援を活用することが大切である。本稿では、実際にあった複数の事例から再構成した「病的旅」のフィクション事例を通して、日本に精神科患者を搬送する際の諸問題について論じる。事例を通して、総領事館からの援助とニューヨーク邦人メンタルヘルスネットワークの支援との連携を図ることが、患者の搬送および文化的・言語的差異の克服にどのように役に立ったかを論じる。「病的旅」は敢行されると特異な困難を呈するため、そのリスクを抱える者も前もって認識しておくことは重要である。(著者抄録)

本稿では、精神分析における様々な時間性の理解について論じ、それらが大きく2つに分けられることを示す。1つは、GreenとKernbergが論じる、無意識による「時間の無知」のための無時間性、およびエス由来の反復強迫による「時間の殺害」の結果としての無時間性であり、これらは客観的な時間性の理解である。一方Heideggerは、過去-現在-未来という時間契機が自らの外へ向かう運動性を持ち、その脱自性が時間の本質であると考えた。Loewaldは、Heideggerの影響下で、精神分析における時間経験のあり方について論じた。彼は、過去-現在-未来という時間契機を、相互作用する「アクティヴなモード」として理解した。Stolorowは、間主観性が外傷的に壊されることによって時間性の障害がもたらされることを論じたが、これはLoewaldの論の拡張とも考えられる。HeideggerからLoewald-Stolorowに至る存在論的時間性の理解は、自己の多重性という現代精神分析における新しい概念化と関連していることも示唆される。このように、Heideggerによる存在論的な時間性の理解は、現代精神分析における時間概念の発展の可能性を提供している。(著者抄録)

本稿で我々は、臨床的応用のために、精神分析における様々な対象概念を明確化し、分類する。Freudは1880年代後半から1905年までは願望モデルを、1905年から1910年までは機械的な欲動論を、そして1911年以降は同一化に基づく関係性の導入を概念化した。願望モデルは、知覚的経験の重要性を強調している点において、現代の関係モデルに類似している。欲動論においては、この内在的源はリビドーとして特定され、対象はリビドー的力の機能であると定義される。同一化の考えによって、Freudは外的世界の内的世界への影響についての理論的説明を得た。上記の議論に基づいて、我々は、対象概念は、(1)外的対象、(2)内的対象、に分けられ、後者はさらに、(2)-1表象あるいはファンタジーとしての対象;(2)-2自我機能を一部担った内的対象;(2)-3外的対象に高度に同一化された内的対象、に分けることができることを提案する。さらに我々は、臨床ヴィニェットを提示し、上記のような分類が臨床的にどのように有用であるかを示す。(著者抄録)

精神療法において、患者が重要な関係性に関連する感情を治療者に向けたり、そのような関係性を治療者との間に反復再現する傾向は、転移として知られている。そして治療者に転移を向けることによって過去の関係性にまつわる葛藤が置き換えられ、無意識的意味の理解なしに一時的な表面上の改善を得ることは、転移性治癒として知られている。今回われわれは、自殺企図、衝動行為などの激しい症状を呈し入退院を繰り返していた患者が、短期間の支持的精神療法的介入によって顕著に回復し、その後幾年も精神科的治療なしに安定した状態を維持することができた症例を経験した。患者は高校卒業後ころより精神科治療を受けていたが、ある時入院中に担当となった主治医に対して速やかに陽性の転移を形成した。その後患者の慢性の希死念慮は著明に軽減し、治療終結となった。その後主治医が遠方へ異動したが、その後も何年もの間安定した状態を保っていた。後に、主治医が異動先から戻ったことを知り、患者が再会を求めて受診してきた。その後洞察志向的な精神療法を開始することになり、その間の患者の主観的経験について知ることになった。転移性治癒の概念は広く知られるところであるが、この症例を通し、その持続性および限界について経験することができたため、これを報告することにより転移性治癒の理解を深める。(著者抄録)

BACKGROUND: Environmental cues associated with cocaine evoke craving and seeking. This process, termed cue reactivity, is a critical element of cocaine addiction. Although glutamatergic neurotransmission has been implicated in this effect of cocaine, the precise subtype and localization in the brain of the glutamatergic receptor critical for cocaine cue reactivity is not well-understood. METHODS: We used a conditional N-methyl-D-aspartic acid receptor (NMDAR) knockout mouse whose NMDAR gene was deleted by Cre expression restricted to striatal neurons. To evaluate the role of NMDAR in cocaine cue reactivity, conditional knockout mice and control mice (n = 5-8/group) were conditioned for place preference with cocaine (5 and 10 mg/kg SC) for 3 days. Their subsequent place preference was examined in a drug-free state. RESULTS: Although control mice developed cocaine conditioned place preference, mice deficient for NMDAR on striatal neurons failed to develop conditioned place preference. CONCLUSIONS: The NMDAR on striatal neurons is essential for the development of cocaine cue reactivity in the place conditioning paradigm. Our finding identifies a brain region whose constitutive NMDAR level serves as a determinant for susceptibility to this aspect of cocaine addiction.

Duplication of human chromosome 22q11.2 is associated with elevated rates of mental retardation, autism and many other behavioral phenotypes. However, because duplications cover 1.5-6 Mb, the precise manner in which segments of 22q11.2 causally affect behavior is not known in humans. We have now determined the developmental impact of over-expression of an approximately 190 kb segment of human 22q11.2, which includes the genes TXNRD2, COMT and ARVCF, on behaviors in bacterial artificial chromosome (BAC) transgenic (TG) mice. BAC TG mice and wild-type (WT) mice were tested for their cognitive capacities, affect- and stress-related behaviors and motor activity at 1 and 2 months of age. An enzymatic assay determined the impact of BAC over-expression on the activity level of COMT. BAC TG mice approached a rewarded goal faster (i.e. incentive learning), but were impaired in delayed rewarded alternation during development. In contrast, BAC TG and WT mice were indistinguishable in rewarded alternation without delays, spontaneous alternation, prepulse inhibition, social interaction, anxiety-, stress- and fear-related behaviors and motor activity. Compared with WT mice, BAC TG mice had an approximately 2-fold higher level of COMT activity in the prefrontal cortex, striatum and hippocampus. These data suggest that over-expression of this 22q11.2 segment enhances incentive learning and impairs the prolonged maintenance of working memory, but has no apparent effect on working memory per se, affect- and stress-related behaviors or motor capacity. High copy numbers of this 22q11.2 segment might contribute to a highly selective set of phenotypes in learning and cognition during development.

Deletion or duplication of the human chromosome 22q11.2 is associated with many behavioral traits and neuropsychiatric disorders, including autism spectrum disorders and schizophrenia. However, why phenotypes vary widely among individuals with identical deletions or duplications of 22q11.2 and which specific 22q11.2 genes contribute to these phenotypes are still poorly understood. Previous studies have identified a approximately 200 kb 22q11.2 region that contributes to behavioral phenotypes in mice. We tested the role of Septin 5 (Sept5), a gene encoded in the approximately 200 kb region, in affective behaviors, cognitive capacities and motor activity. To evaluate the impact of genetic backgrounds on behavioral phenotypes of Sept5 deficiency, we used mice on two genetic backgrounds. Our data show that Sept5 deficiency decreased affiliative active social interaction, but this phenotypic expression was influenced by genetic backgrounds. In contrast, Sept5 deficiency decreased anxiety-related behavior, increased prepulse inhibition and delayed acquisition of rewarded goal approach, independent of genetic background. These data suggest that Sept5 deficiency exerts pleiotropic effects on a select set of affective behaviors and cognitive processes and that genetic backgrounds could provide an epistatic influence on phenotypic expression.

Multiple genes are thought to influence both susceptibility to nicotine dependence and its comorbid behavioral traits in humans. However, which specific genes contribute to this pleiotropic effect is poorly understood. Previous rodent studies have shown that many addictive substances and stressful stimuli increase the expression of the transcription factor FosB in limbic and associated regions and that the protein products of fosB contribute to certain behavioral effects of cocaine and morphine. However, the role of this gene in nicotine-regulated behaviors and dependence-related behavioral traits is unknown. We tested the hypothesis that a constitutive level of FosB affects nicotine-regulated behaviors and comorbid behavioral traits using constitutive fosB knockout (KO) mice. Following repeated or prolonged nicotine administration, but not a single acute administration, KO mice were impaired in conditioned place preference, oral nicotine intake and motor suppression. In wild-type mice, repeated nicotine injections, but not a single acute injection, increased the expression of FosB and its truncated variant DeltaFosB in the targets but not at the origins of the mesolimbic and nigrostriatal dopamine pathways; no detectable level of FosB/DeltaFosB was found in KO mice. In tasks designed to assess behavioral traits, KO mice exhibited more pronounced behavioral abnormalities when stress levels were high than when they were minimized. Our results suggest that the constitutive absence of fosB has a pleiotropic influence on the behavioral effects of repeated or prolonged nicotine administration and on stress-related behavioral traits in mice.

Nicotine is thought to act on brain monoamine systems that normally mediate diverse motivational behaviors. How monoamine-related genes contribute to behavioral traits (e.g. responses to novel stimuli) comorbid with the susceptibility to nicotine addiction is still poorly understood. We examined the impact of constitutive monoamine oxidase A (MAOA) deficiency in mice on nicotine reward and responses to novel stimuli. Age-matched, male Maoa-knockout (KO) mice and wild-type (WT) littermates were tested for nicotine-induced conditioned place preference (CPP); voluntary oral nicotine preference/intake; spontaneous locomotor activity in a novel, inescapable open field; and novelty place preference. Nicotine preference in WT mice was reduced in Maoa-KO mice in the CPP and oral preference/intake tests. Control experiments showed that these phenotypes were not due to abnormalities in nicotine metabolism, fluid intake or response to taste. In contrast, Maoa-KO mice were normal in their behavioral response to a novel, inescapable open field and in their preference for a novel place. The observed phenotypes suggest that a constitutive deficiency of MAOA reduces the rewarding effects of nicotine without altering behavioral responses to novel stimuli in mice. Constitutive MAOA activity levels are likely to contribute to the vulnerability or resiliency to nicotine addiction by altering the rewarding effects of nicotine.

Human chromosome 22q11.2 has been implicated in various behavioral abnormalities, including schizophrenia and other neuropsychiatric/behavioral disorders. However, the specific genes within 22q11.2 that contribute to these disorders are still poorly understood. Here, we show that an approximately 200-kb segment of human 22q11.2 causes specific behavioral abnormalities in mice. Mice that overexpress an approximately 200-kb region of human 22q11.2, containing CDCrel, GP1Bbeta, TBX1, and WDR14, exhibited spontaneous sensitization of hyperactivity and a lack of habituation. These effects were ameliorated by antipsychotic drugs. The transgenic mice were also impaired in nesting behavior. Although Tbx1 has been shown to be responsible for many physical defects associated with 22q11.2 haploinsufficiency, Tbx1 heterozygous mice did not display these behavioral abnormalities. Our results show that the approximately 200-kb region of 22q11.2 contains a gene(s) responsible for behavioral abnormalities and suggest that distinct genetic components within 22q11.2 mediate physical and behavioral abnormalities.

BACKGROUND: The addictive properties of nicotine are mediated via dopaminergic pathways and their post-synaptic neurons in the striatum. Because post-synaptic neurons within the striatum contain high levels of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), we hypothesized that DARPP-32 may functionally contribute to the behavioral effects of nicotine. METHODS: We examined the behavioral effects of nicotine and the phosphorylation state of DARPP-32 in wild-type (WT) and DARPP-32 knockout (KO) mice. In one experiment, we assessed voluntary nicotine intake (0-50 microg/ml) of WT and KO mice in a two-bottle choice paradigm. In a separate experiment, the motor-depressant effects of acute and repeated nicotine injections (0-.8 mg/kg, subcutaneously [SC]) were assessed. The phosphorylation of DARPP-32 at threonine34 and threonine75 were examined using Western blotting. RESULTS: A heightened responsiveness to nicotine was seen in KO mice when compared with WT mice in oral intake and motor depression. The enhanced responsiveness in KO mice was not due to alterations in taste sensations, fluid intake, or blood nicotine or cotinine levels. Systemic injections of nicotine resulted in increased striatal DARPP-32 phosphorylation at threonine34 and threonine75. CONCLUSIONS: DARPP-32 opposes the behavioral effects of nicotine possibly via concurrent phosphorylation at the two threonine sites.