抑郁的多基因遗传基础

抑郁具有复杂的、非孟德尔式的多基因遗传模式, 但是目前多数抑郁的遗传研究集中于考察单个候选基因, 不能全面揭示遗传因素的作用机制。近年来, 多基因遗传得分研究和基因−基因交互研究分别为抑郁的多基因累加效应和交互效应提供了新的证据。多基因不仅直接影响抑郁, 还通过与环境因素的交互作用影响抑郁的发生发展, 并且这一复杂交互作用存在性别差异。抑郁的内表型研究发现多基因可能通过认知因素、人格、压力荷尔蒙等间接影响个体的抑郁水平。未来研究应更加关注多基因与多种环境因素如何相互作用影响抑郁, 探索多基因遗传机制的性别差异, 考察多基因对抑郁影响随年龄的发展动态变化。     

数形联觉——数字空间表征研究“新”取向

数字空间表征是人类对数字进行表征的重要方式。数形联觉（number-form synesthesia）是一种数字可以有意识地引起空间知觉的独特现象,与此类似的是非联觉者中广泛存在的无意识的心理数字线（mental number line）现象。两者在行为和脑机制上存在着很多重叠,也存在着值得思考的差异。数形联觉的研究能够提供实质性的行为和脑机制数据,用以解决数字空间表征研究中出现的问题,加强对于数字空间表征的理解;也为更加全面深入地开展进一步研究提供了新的启示,成为数字空间表征研究中值得推崇的新取向。     

多动症的遗传学研究概述

多动症多始于儿童期,并能持续至成年期。传统的家庭、双生子和养子女研究表明,多动症是受遗传影响的。双生子研究现在被用来定义多动症表型,分析性别差异,测试基因对持续性和共病的影响,以及研究遗传与环境的互动。多动症的分子遗传学研究集中在功能候选基因的关联分析上。多动症与DRD4和DRD5的关系比较一致。最新的研究也显示COMT的影响。关联分析（linkage analysis）显示这些单个基因的影响都不大。这个领域还有待于大规模的“全基因关联”分析。至今为止的证据显示,研究基因-表型关联以及基因与环境互动对多动症的影响将日趋重要     

非药物成瘾的遗传学和神经生物学机制研究述评

非药物成瘾又称“非物质相关性成瘾”或“行为成瘾”。特征性表现包括对成瘾对象的渴望、受损的冲动控制、对成瘾对象的耐受、撤退反应和高复发率等。目前发现的非药物成瘾类型包括病理性赌博、网络成瘾、购物成瘾、游戏成瘾、性瘾以及贪食等。非药物成瘾与药物成瘾在症状学上表现出很高的相似性且具有较高的共病率, 提示二者之间可能存在着共同的发病机制。从遗传学和神经生物学的角度探讨非药物成瘾的机制具有重要的理论价值和临床应用价值。家庭研究和双生子研究发现, 男性的病理性赌博和贪食障碍具有中度以上的遗传度。分子遗传学研究发现, 单胺能神经递质相关基因, 如5-羟色胺转运体基因、多巴胺受体基因和单胺氧化酶A基因等, 与非药物成瘾有关。神经影像学研究发现, 非药物成瘾者脑内负责奖赏,线索加工和冲动控制的神经通路活动性异于正常对照。未来研究需要进一步从多个角度入手, 探讨非药物成瘾与药物成瘾的共性和特性。     

MAOA基因与抑郁的关系

抑郁的发生具有遗传基础。近年来, 随着分子遗传技术的发展, 对抑郁遗传机制的研究已经深入到分子水平。既有研究表明, MAOA基因在抑郁的发生发展中发挥着十分重要的作用。MAOA基因与抑郁间存在紧密的直接关联, 而且MAOA基因与环境及其他基因亦交互作用于抑郁, 然而, 既有相关研究结论尚存分歧。未来研究应更加关注MAOA基因与多种环境因素及其它基因间的复杂交互作用, 考察MAOA基因的年龄效应, 揭示MAOA基因作用于抑郁的脑机制。     

BDNF基因rs6265多态性与父母教育卷入对小学儿童基本数学能力的交互作用

数学能力发展的遗传机制日益成为研究者关注的前沿课题之一,但既有研究尚处于起步阶段。本研究以602名小学儿童及其父母作为被试,旨在考察BDNF基因rs6265多态性与父母教育卷入对儿童基本数学能力的潜在交互影响。结果显示,(1)rs6265多态性可显著预测儿童的逻辑思维与空间-视觉功能领域能力(AA基因型携带者的基本数学能力显著高于G等位基因携带者);(2)rs6265多态性与父母教育卷入交互作用于儿童的逻辑思维与空间-视觉功能领域能力,父母教育卷入能显著正向预测G等位基因儿童的逻辑思维与空间-视觉功能领域能力,但对AA基因型儿童的预测作用不显著,该交互作用可能更加符合强素质-压力模型假说(rs6265位点G等位基因可能是风险基因)。上述发现推进了数学能力遗传机制的研究,并为素质-压力假说提供了新的研究证据。     

配对联想学习能力和语音意识在汉语儿童早期阅读中的作用

本研究以93个学前儿童为研究对象,考察了配对联想学习能力和语音意识在汉字阅读和词汇发展中的作用及其相互关系,其中,配对联想学习分为假词、非词、符号三种形式。结果发现,语音意识是解释汉字阅读的最重要变量,配对联想学习能力对词汇发展具有独特贡献;不会阅读者在假词和非词学习中比初学阅读者差,而在非语言的符号学习中没有差异。     

反社会行为潜在遗传因素的全基因组关联分析

反社会行为是一种受基因和环境共同影响的复杂性行为, 但单个基因如单胺氧化酶基因(MAOA)、5-羟色胺转运体启动因子基因(5-HTT)、儿茶酚-o-甲基转移酶(COMT)基因的影响并不能全面解释其产生的分子遗传机制。来自分子遗传学研究取向的方法—— 全基因组关联分析(genome-wide association study, GWAS), 把人类基因组中数以百万计的单核苷酸(SNPs)和复制数变异(CNVs)作为遗传标记, 在全基因组层面上, 开展多中心、大样本的关联研究, 经过反复验证来发现与外在表型相关的基因位点, 为进一步了解反社会行为复杂分子遗传机制提供了重要的线索。未来的研究应该通过科学的实验设计将精确的基因分型技术与心理、环境因素相结合, 实现对复杂性行为或特质的基因-心理-环境模型的成因性分析。     

多巴胺、5-羟色胺通路相关基因及家庭环境对创造力的影响及其作用机制

创造力的遗传基础是近年来创造力研究领域的前沿和热点问题, 但仍尚处于起步阶段, 也未有研究系统探讨遗传与环境因素的交互作用对创造力的影响及其作用机制。本课题拟在中国汉族人群中考察多巴胺(DA)、5-羟色胺(5-HT)神经递质通路上的32个基因约700个多态性位点与创造力的关系, 并首次探讨家庭环境在遗传多态性与创造力关系中的调节作用。研究内容包括：(1)通过单基因、基于通路以及基因—基因交互作用的关联分析, 考察遗传多态性对创造力的影响, 揭示创造力的遗传基础; (2)通过基因—环境交互作用的关联分析, 考察家庭环境在遗传与创造力关系中的调节作用; (3)通过结构方程模型的比较分析, 揭示遗传与家庭环境在创造力两个方面(创造思维与创造人格)共享的与特异的作用机制。该项目成果能够从遗传与环境交互作用的角度阐明创造力个体差异的原因, 有助于构建基于创造力个体差异分析的理论模型, 对创造人才的鉴别和培养具有重要现实意义。     

条件反射性抗体反应增强的动态分析——以OVA为非条件刺激物

研究了条件反射性抗体反应增强模型的建立。被试为49只雄性成年Wistar大鼠,采用糖精水作为条件性刺激,一种蛋白抗原卵清蛋白作为非条件性刺激配对给予大鼠,两者结合后,在初次抗体应答下降阶段再次单独给予条件刺激,用酶联免疫吸附法分时段检测抗体水平的变化。发现条件组在条件刺激后15,20,25天左右抗体水平明显高于对照组。这一过程与初次抗体应答的规律类似。这些结果证实经一次条件训练,单独给予条件刺激能诱导出明显的条件反射性抗体反应增高。     

Consistency and strength of grapheme-color associations are separable aspects of synesthetic experience

Consistency of synesthetic associations over time is a widely used test of synesthesia. Since many studies suggest that consistency is not a completely reliable feature, we compared the consistency and strength of synesthetes’ grapheme-color associations. Consistency was measured by scores on the Synesthesia Battery and by the Euclidean distance in color space for the specific graphemes tested for each participant. Strength was measured by congruency magnitudes on the Implicit Association Test. The strength of associations was substantially greater for synesthetes than non-synesthetes, suggesting that this is a novel, objective marker of synesthesia. Although, intuitively, strong associations should also be consistent, consistency and strength were uncorrelated, indicating that they are likely independent, at least for grapheme-color synesthesia. These findings have implications for our understanding of synesthesia and for estimates of its prevalence since synesthetes who experience strong, but inconsistent, associations may not be identified by tests that focus solely on consistency.     

Inducing synesthesia in non-synesthetes: Short-term visual deprivation facilitates auditory-evoked visual percepts

Sounds can modulate activity in visual cortex, facilitating the detection of visual targets. However, these sound-driven modulations are not thought to evoke conscious visual percepts in the general population. In individuals with synesthesia, however, multisensory interactions do lead to qualitatively different experiences such as sounds evoking flashes of light. Why, if multisensory interactions are present in all individuals, do only synesthetes experience abnormal qualia? Competing models differ in the time required for synesthetic experiences to emerge. The cross-activation model suggests synesthesia arises over months or years from the development of abnormal neural connections. Here we demonstrate that after ∼5 min of visual deprivation, sounds can evoke synesthesia-like percepts (vivid colors and Klüver form-constants) in ∼50% of non-synesthetes. These results challenge aspects of the cross-activation model and suggest that synesthesia exists as a latent feature in all individuals, manifesting when the balance of activity across the senses has been altered.     

Temporal sequences,synesthetic mappings,and cultural biases: The geography of time

Time–space synesthetes report that they experience the months of the year as having a spatial layout. In Study 1, we characterize the phenomenology of calendar sequences produced by synesthetes and non-synesthetes, and show a conservative estimate of time–space synesthesia at 2.2% of the population. We demonstrate that synesthetes most commonly experience the months in a circular path, while non-synesthetes default to linear rows or rectangles. Study 2 compared synesthetes’ and non-synesthetes’ ability to memorize a novel spatial calendar, and revealed better performance in synesthetes. The capacity to learn mappings between arbitrary spatial forms and temporal sequences is present in all individuals, and time–space synesthetes’ enhanced visuo-spatial memory abilities may underlie their creation of idiosyncratic spatial calendar forms.     

Executive functions in synesthesia

In grapheme-color synesthesia, a number or letter can evoke two different and possibly conflicting (real and synesthetic) color sensations at the same time. In this study, we investigate the relationship between synesthesia and executive control functions. First, no general skill differences were obtained between synesthetes and non-synesthetes in classic executive control paradigms. Furthermore, classic executive control effects did not interact with synesthetic behavioral effects. Third, we found support for our hypothesis that inhibition of a synesthetic color takes effort and time. Finally, individual differences analyses showed no relationship between the two skills; performance on a ‘normal’ Stroop task does not predict performance on a synesthetic Stroop task. Across four studies, the current results consistently show no clear relationship between executive control functions and synesthetic behavioral effects. This raises the question of which mechanisms are at play in synesthetic ‘management’ during the presence of two conflicting (real and synesthetic) sensations.     

Association between synesthetic colors and sensitivity to physical colors changed by type of synesthetic experience in grapheme-color synesthesia

Grapheme-color synesthesia is a condition in which visual perception of letters induces simultaneous perception of a specific color. Previous studies indicate that grapheme-color synesthetes are more sensitive to physical colors than non-synesthetes. Synesthetic colors are found to be concentrated in multiple regions of the color space, forming “synesthetic color clusters”. The present study investigated whether color sensitivity corresponding to synesthetic color clusters (clustered colors) is higher than color sensitivity that does not correspond to synesthetic color clusters (non-clustered colors). However, we found no difference in the color sensitivity for clustered and non-clustered colors. We also investigated whether the color sensitivity is dependent on the synesthetic experience (associators and projectors). We found that the greater the tendency toward associator characteristics, the greater the sensitivity for clustered colors compared to that for non-clustered colors. Our findings suggest an association between synesthetic colors and physical color sensitivity that is modulated by synesthetic experience.     

Does color synesthesia pose a paradox for early-selection theories of attention?

Abstract— P.M. is a synesthete who experiences colors when viewing alphanumeric symbols. Her search for a target differing from distractors by a synesthetic color feature takes the form of a pop-out search. Thus, it would seem that synesthesia can occur preattentively. However, discrepancies between the regression functions of response times observed in target-present trials and target-absent trials, and the fact that fast response times occur only when the target is within a few degrees of visual angle from fixation, indicate that P.M.'s synesthesia does not occur preattentively, but rather is within the focus of attention. We conclude that synesthesia is a genuine perceptual phenomenon that can have substantial influence on visual processing.     

Enhanced mental rotation ability in time-space synesthesia

Time-space synesthesia is a variant of sequence–space synesthesia and involves the involuntary association of months of the year with 2D and 3D spatial forms, such as arcs, circles, and ellipses. Previous studies have revealed conflicting results regarding the association between time-space synesthesia and enhanced spatial processing ability. Here, we tested 15 time-space synesthetes, and 15 non-synesthetic controls matched for age, education, and gender on standard tests of mental rotation ability, spatial working memory, and verbal working memory. Synesthetes performed better than controls on our test of mental rotation, but similarly to controls on tests of spatial and verbal working memory. Results support a dissociation between visuo-spatial imagery and spatial working memory capacity, and suggest time-space synesthesia is associated only with enhanced visuo-spatial imagery. These data are consistent with the time-space connectivity thesis that time-space synesthesia results from enhanced connectivity in the parietal lobe between regions supporting the representation of temporal sequences and those underlying visuo-spatial imagery.     

Synesthesia and number cognition in children

Grapheme-color synesthesia, when achromatic digits evoke an experience of a specific color (photisms), has been shown to be consistent, involuntary, and linked with number concept in adults, yet there have been no comparable investigations with children. We present a systematic study of grapheme-color synesthesia in children aged between 7 and 15 years. Here we show that such children (but not children with phoneme-color synesthesia) experience involuntary difficulties in numerical tasks when digits are presented in colors incongruent with their photisms. Synesthesia in children may thus have important consequences for certain aspects of numerical cognition.     

Consistency of synesthetic association varies with grapheme familiarity: A longitudinal study of grapheme-color synesthesia

Grapheme-color synesthesia is a condition in which the visual perception of letters or numbers induces a specific color sensation. The consistency of grapheme-color association has been considered as a fundamental characteristic of synesthesia. However, recent studies have indicated that this association can change across the adult lifespan, and it has become necessary to investigate the factors behind the changes within each synesthete. We conducted a longitudinal study of Japanese adult synesthetes to investigate long-term (5–8 years) changes in color responses to 300 graphemes (alphanumeric and Japanese characters). Graphemes with lower long-term consistency of synesthetic association also tended to have lower short-term consistency, indicating that grapheme-color association's consistency is determined for each grapheme. Further, less familiar graphemes had less consistent associations with their synesthetic colors. These findings suggest that a stronger grapheme-color association is formed for more familiar graphemes, leading to the consolidation of synesthetic color for such graphemes.     

Modality and variability of synesthetic experience

In synesthesia, stimulation of one sensory or cognitive pathway leads to additional, involuntary experiences in a second sensory or cognitive pathway. We here review previous surveys on this neurologically based phenomenon and report the results of 63 synesthetes who completed our Internet and paper questionnaire on synesthesia. In addition to asking for personal data and information on the participant's synesthesia, the questionnaire focused on the components of the inducer that elicit or modulate synesthesia. Synesthesia was most often developmental (92%) and of the grapheme-color type (86%). Sixty-two percent of the participants perceived time-related words in a spatial configuration. Music-color synesthesia was common (41%), and synesthesia for natural and artificial sounds (33%) was higher than in previous estimates. Eighty-one percent of participants experienced more than one form of synesthesia. Multimodal synesthesia, in which inducer and concurrent belong to 2 different sensory modalities, occurred in 92% of the participants. Overall, auditory stimuli were most often reported as inducers, and visual concurrents were most common. Modulations of the synesthetic experiences such as changes of the concurrent color, expansion within the same or to a different sensory modality, or reduction of the number of inducers over time were reported by 17% of participants. This challenges the presumed consistency of synesthesia and the adequacy of the test-retest consistency score still most commonly used to assess the veracity of reported synesthesia. Implications of the high prevalence of cross-modal synesthesia and the variability of synesthesia are discussed.