相關閱讀資料
認知和行為遺傳學
因舊版課程無指定課堂作業與考試，因此統整所有作業、講義、考試內容合併列出。
認知和行為遺傳學
因舊版課程無指定課堂作業與考試，因此統整所有作業、講義、考試內容合併列出。
Pinker, S. 〈空白的石版、高貴的野人，還有機器裡的幽靈〉，見G. B. Peterson編：《譚納人性價值授課獎，第21屆》，鹽湖城：猶他大學出版，2000。
Pinker, S. "The Blank Slate, the Noble Savage, and the Ghost in the Machine." In The Tanner Lectures on Human Values 21. Edited by G. B. Peterson. Salt Lake City: University of Utah Press, 2000.
譯註：原文 pdf 可於此下載
Ridley, M. 〈第二十一號染色體：優生學〉，見《基因體》，New York: Harper Collins, 1999.
Ridley, M. "Chromosome 21: Eugenics." In Genome. New York: Harper Collins, 1999.
Turkheimer, E. 〈行為遺傳學的三個法則，以及其所代表的意義〉，摘自《心理科學目前發展方向第9期》 ，2000，160-164。
Turkheimer, E. "Three Laws of Behavioral Genetics and What They Mean." In Current Directions in Psychological Science, 9. 2000, 160-164.
Hyman, S. E. 〈精神疾患之複雜遺傳學導論〉，摘自《生物精神醫學第45期》，1999，518-521。
Hyman, S. E. "Introduction to the Complex Genetics of Mental Disorders." In Biological Psychiatry, 45. 1999, 518-521.
Plomin, R. 〈後基因體世界中的心理學：它將是前所未有的重要〉，《美國心理學協會觀察者第13期》，2000。
Plomin, R. "Psychology in a Post-genomics World: It will be More Important than Ever." American Psychological Society Observer, 13. 2000.
Lykken, D. T. 、 A. McGue 、 A. Tellegen 、 T. J. Bouchard Jr. 〈浮現遺傳：可能不會在家族中普遍可見的遺傳特徵〉，《美國心理學》，1992。
Lykken, D. T., A. McGue, A. Tellegen, and T. J. Bouchard Jr. "Emergenesis: Genetic Traits that May Not Run in Families." American Psychology, 1992.
PubMed摘要:受到多型態基因的排列結構而非簡單加總所影響的特徵，並未被視為是遺傳的，除非人們對同卵雙生兒（他們彼此分享所有的基因，所有的基因結構）進行研究，因為如此「出現的遺傳」特徵，將傾向不在家族中流傳。嬰兒時期分開並個別撫養的同卵雙生兒，被發現在個人的特質上，具有驚奇的一致性，因而可能是遺傳特徵。更不確定的是，重要的個人特徵，如領導能力，在許多表現形式上的天份，成為極為出色的治療專家或父母；同時，某些精神病理學綜合症狀，也可能出現遺傳。這些想法再次強調，基因變異性在人類生活中所扮演的重要角色。
PubMed abstract: Traits that are influenced by a configuration--rather than by a simple sum--of polymorphic genes may not be seen to be genetic unless one studies monozygotic twins (who share all their genes and thus all gene configurations) because such "emergenic" traits will tend not to run in families. Personal idiosyncrasies that have been found to be surprisingly concordant among MZ twins separated in infancy and reared apart may be emergenic traits. More speculatively, important human traits like leadership, genius in its many manifestations, being an effective therapist or parent, as well as certain psychopathological syndromes may also be emergenic. These ideas reemphasize the importance of the role played in human affairs by genetic variation.
PubMed摘要:人類染色體22號q11帶的半合隱蔽缺失已經與一些精神病學和行為學的顯型，包括精神分裂症相伴出現。在此我們進行了脯氨酸脫氫酶(PRODH)的離析和特性描述，黑腹果蠅的一個人類同源基因惰型-A(slgA)，對脯胺酸脫氫酶進行編碼，乃是slgA突變體之行為學顯型的原因。脯氨酸脫氫酶被定位在染色體22號q11，這是某些精神病病患身上被刪除的區域。我們也離析了小鼠身上之同源基因slgA(Prodh)，指出在Pro/Re高脯胺酸血症的小鼠品種上這種基因的變異，並且發現這些小鼠有感知動作門控上的缺失，伴隨著大腦中局部性神經化學的改變。感知動作門控是一種神經的篩濾過程，使得注意力被集中在一個給定的刺激物，並且在神經精神病理方面失調的病患身上受到影響。而且，幾條證據的線索指出，脯氨酸作為一種哺乳動物大腦中突觸之傳導的調節器。根據我們同時參照脯氨酸脫氫酶染色體定位的觀察，顯示這種基因在22q11聯結於精神病學的和行為學的顯型之間，存在可能的牽連。
PubMed abstract: Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes.
PubMed摘要:人類的焦慮症源自遺傳的脆弱性和創傷經驗的結合。具有GABAA受體突變的小鼠將可為此類疾病提供一個模型。
PubMed abstract: Human anxiety disorders arise from a combination of genetic vulnerability and traumatic experience. Mice with a GABAA receptor mutation may provide a model for these disorders.
PubMed摘要: 恐慌症的病患表現出在海馬回、副海馬回和前額腦區底部中GABAA受體的缺失。在小鼠身上，GABAA受體中突觸的叢集，為gamma2次單元而異型接合的是減少的，主要在海馬回和大腦皮質上。針對自然的嫌惡刺激之強化的行為抑制，以及恐懼條件反射度，以及模糊提示之辨別學習上的回應性的提高，gamma2 +/-的小鼠表現出更強的行為抑制。內隱和空間的記憶以及海馬回上的長期增益現象則並未改變。所以，gamma2 +/-表現了一個焦慮模型，其特徵是損害迴避行為和對於威脅暗示的一種外顯記憶傾向，這導致負面聯想敏感性的提高。這個模型暗示了在病患身上GABAA受體的官能障礙，作為一種焦慮症的病因體質。
PubMed abstract: Patients with panic disorders show a deficit of GABAA receptors in the hippocampus, parahippocampus and orbitofrontal cortex. Synaptic clustering of GABAA receptors in mice heterozygous for the gamma2 subunit was reduced, mainly in hippocampus and cerebral cortex. The gamma2 +/- mice showed enhanced behavioral inhibition toward natural aversive stimuli and heightened responsiveness in trace fear conditioning and ambiguous cue discrimination learning. Implicit and spatial memory as well as long-term potentiation in hippocampus were unchanged. Thus gamma2 +/- mice represent a model of anxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associations. This model implicates GABAA-receptor dysfunction in patients as a causal predisposition to anxiety disorders.
PubMed摘要:大腦內的抑制性神經傳導主要由GABA(A)受體調節。GABA(A)受體活性的增強作用，透過一種異位調節的苯重氮基鹽(BZ)部位產生鎮靜的、舒緩焦慮的、肌肉鬆弛的、解除驚厥的，以及臨床上將BZs作為鎮靜安眠藥使用的認知－減弱效果。我們創造了轉基因小鼠(alpha1 H101R)，以一種鎮靜安眠藥－感覺遲鈍的alpha1非典型和一種經選擇的BZ部位配位體，L-838,417，去探究GABA(A)子類對特定的生理學效應的調節。這兩種令人讚賞的方法揭示了alpha1子類所調節的鎮靜功能，而非苯重氮基鹽之舒緩焦慮的效果。這個發現指明了改善舒緩焦慮的方法，並得以為在不同的神經元回路中，特定之GABA(A)受體子類的其他神經方面失調，開發新藥。
PubMed abstract: Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits.
PubMed摘要: 當疼痛的刺激正常地消失或減少時，傷害性刺激神經元回路在胚胎和產後時期形成，。今天，對於新生兒之健康風險的醫療程式可以包含組織傷害和疼痛，對此長期的影響仍然未知。去探究新生兒在傷害性刺激神經元回路上，組織傷害和疼痛的影響，我們使用了一個後爪周邊組織持續發炎的動物模型。我們發現，這些成年動物展現了脊椎的神經元回路，具有增多的輸入、傷害性原始傳入軸突和對於感覺刺激改變了的反應。
PubMed abstract: Nociceptive neuronal circuits are formed during embryonic and postnatal times when painful stimuli are normally absent or limited. Today, medical procedures for neonates with health risks can involve tissue injury and pain for which the long-term effects are unknown. To investigate the impact of neonatal tissue injury and pain on development of nociceptive neuronal circuitry, we used an animal model of persistent hind paw peripheral inflammation. We found that, as adults, these animals exhibited spinal neuronal circuits with increased input and segmental changes in nociceptive primary afferent axons and altered responses to sensory stimulation.
PubMed摘要:為了識別基因對於人類認知發展的重要性，我們研究了Williams併發症(WS)，一種生長的失調包括視覺空間建構認知的缺乏。在此，我們描述了兩個帶有局部WS顯型的家族；受影響的成員具有特殊WS認知的剖面圖，和血管的疾病，但缺少其他WS特徵。亞微觀的染色體7q11.23刪除與兩個家族的顯型同時分離。藉由最小的刪除(83.6 kb) 所影響區域的DNA序列分析，揭示了兩種基因，彈力蛋白(ELN)和激酶1(LIMK1)。後者以LIM範圍編碼了一個新奇的蛋白質激酶，並且在大腦中強烈地表達。因為ELN突變引起血管的疾病，但沒有認知的異常，這些資料暗示了激酶1半合性基因在視覺空間建構認知障礙中的作用。
PubMed abstract: To identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in imparied visuospatial constructive cognition.
PubMed摘要:這份研究挑戰了，使用成人神經心理學模型來解釋遺傳學起源的發展疾病。當不規則的認知剖面圖在孩童或成人身上被發現，它預設了這些顯型的結果描繪出嬰兒的起始狀態，以及它也聲稱模組將有利於這些能力在完整的或障礙的情況下發揮作用。兩個來自對帶有Williams綜合症的嬰兒所進行的實驗發現（一種被選出的顯型以支持先天模組的主張），指出症狀內雙重分離：有大量的鑒定，他們在嬰兒時期發展良好，但在成人時期則表現不佳；反而在語言方面，他們在嬰兒時期表現不佳，卻在成人時期發展良好。對於這些結果理論的和臨床上的含義，將使集中在遺傳疾病的研究上的關注產生變化。
PubMed abstract: This study challenges the use of adult neuropsychological models for explaining developmental disorders of genetic origin. When uneven cognitive profiles are found in childhood or adulthood, it is assumed that such phenotypic outcomes characterize infant starting states, and it has been claimed that modules subserving these abilities start out either intact or impaired. Findings from two experiments with infants with Williams syndrome (a phenotype selected to bolster innate modularity claims) indicate a within-syndrome double dissociation: For numerosity judgments, they do well in infancy but poorly in adulthood, whereas for language, they perform poorly in infancy but well in adulthood. The theoretical and clinical implications of these results could lead to a shift in focus for studies of genetic disorders.
PubMed摘要: 特定型語言障礙(SLI)是一種疾病，其中語言習得能力對一個正常發育的孩童而言是受損的。SLI影響了大約7%的孩童。SLI純粹的語法形式的存在已經成為極端受爭議的，因為它表明了一種大腦中假定的語法子系統的存在和與生俱有。某些研究專家質疑SLI的一種純粹的語法形式的存在。他們假定孩童的SLI是由於聽力方面和／或一般認知過程的缺陷，或社會因素所引起。也有某些人指出，人們帶有SLI的認知能力並未被充分地說明，以證實在一種純粹語法的形式中存在著SLI。結果︰我們呈現了關於一個男孩，以AZ為名，具有SLI的案例研究。為了調查原始語法障礙的主張，我們區分了語法能力、非語法的語言能力與非語詞的認知能力。我們探究了AZ在這每個領域中的能力。AZ正常地表現了在聽力和認知上的任務，然而卻顯示了嚴重的語法障礙。這是一項對生長期語法缺陷的證據，而不能被解釋為是一種妨礙或是聽力困難的副產品。結論：AZ的案例提供了證據，支援一種遺傳學決定、特定化的機制，這對於人類語言的正常發展乃是必須的。
PubMed abstract: Specific language impairment (SLI) is a disorder in which language acquisition is impaired in an otherwise normally developing child. SLI affects around 7% of children. The existence of a purely grammatical form of SLI has become extremely controversial because it points to the existence and innateness of a putative grammatical subsystem in the brain. Some researchers dispute the existence of a purely grammatical form of SLI. They hypothesise that SLI in children is caused by deficits in auditory and/or general cognitive processing, or social factors. There are also claims that the cognitive abilities of people with SLI have not yet been sufficiently characterised to substantiate the existence of SLI in a pure grammatical form. RESULTS: We present a case study of a boy, known as AZ, with SLI. To investigate the claim for a primary grammatical impairment, we distinguish between grammatical abilities, non-grammatical language abilities and non-verbal cognitive abilities. We investigated AZ's abilities in each of these areas. AZ performed normally on auditory and cognitive tasks, yet exhibited severe grammatical impairments. This is evidence for a developmental grammatical deficit that cannot be explained as a by-product of retardation or auditory difficulties. CONCLUSIONS: The case of AZ provides evidence supporting the existence of a genetically determined, specialised mechanism that is necessary for the normal development of human language.
PubMed摘要:在2-5%未受減損的的孩童中，他們學習語言的表達和／或接受上，卻具有顯著的困難，儘管他們擁有足夠的智力和學習機會。同時孿生兒研究表明了，在言說和語言發展疾病上的遺傳學因素中之重要角色，多數家族分離了這種疾病而顯示出遺傳中的複雜形態，因此並不能適用于慣常使用的連鎖分析。一個罕見的例外是KE家族，一個龐大的三個世代的譜系，其中將近半數的成員受到嚴重的言說和語言失調的影響，顯示受到以此種遺傳作為常染色體顯性單的基因起源特徵。這個家族已經被廣為宣傳成為，主要遭受到在後綴規則的語法使用上的缺陷所困擾，所以，根據推測也支援了，語法之特定基因的存在。然而，這種顯型在本質上是作用更廣的，透過實際上語法和／或語言的每個方面受到影響。另外，受到影響的成員具有嚴重的口面運用障礙，並且他們的言詞對於年幼的聽者而言大部分是難以理解的。我們著手了一個針對連結在KE家族的全基因組研究，並且識別了一個在染色體7中的區域，和共同分離了言說和語言的失調(最大lod 值 = 6.62在theta = 0.0)，確認了常染色體具有完全外顯率的顯性遺傳。來自區域內微隨體的進一步分析，使得我們厘清了對應於（標定SPCH1）在7q31區間5.6- cM所在點的地圖，所以提供了一個朝向其識別的重要步驟。SPCH1的隔離將提供對於發展過程中的分子遺傳學之初步洞見，並在言說和語言的研究上達到頂點。
PubMed abstract: Between 2 and 5% of children who are otherwise unimpaired have significant difficulties in acquiring expressive and/or receptive language, despite adequate intelligence and opportunity. While twin studies indicate a significant role for genetic factors in developmental disorders of speech and language, the majority of families segregating such disorders show complex patterns of inheritance, and are thus not amenable for conventional linkage analysis. A rare exception is the KE family, a large three-generation pedigree in which approximately half of the members are affected with a severe speech and language disorder which appears to be transmitted as an autosomal dominant monogenic trait. This family has been widely publicised as suffering primarily from a defect in the use of grammatical suffixation rules, thus supposedly supporting the existence of genes specific to grammar. The phenotype, however, is broader in nature, with virtually every aspect of grammar and of language affected. In addition, affected members have a severe orofacial dyspraxia, and their speech is largely incomprehensible to the naive listener. We initiated a genome-wide search for linkage in the KE family and have identified a region on chromosome 7 which co-segregates with the speech and language disorder (maximum lod score = 6.62 at theta = 0.0), confirming autosomal dominant inheritance with full penetrance. Further analysis of microsatellites from within the region enabled us to fine map the locus responsible (designated SPCH1) to a 5.6-cM interval in 7q31, thus providing an important step towards its identification. Isolation of SPCH1 may offer the first insight into the molecular genetics of the developmental process that culminates in speech and language.
PubMed摘要:精神分裂症是一種複雜的疾病，並且存在著堅實的證據支持一種遺傳的病源學。儘管如此，先前意圖去局部化敏感性所在位置，已經產生了顯著地具有提示性的發現。一種針對精神分裂症敏感性位所在位置的全基因組掃描，在22個具有精神分裂症高罹患率的大家族中進行，提供了連結於染色體1 (1q21-q22)之高度有效的證據，使用一種最大異質性的關聯性對數比率（lod）值6.50。這種關聯性將可提供了充足的力量，使得基礎的敏感性基因之位置選殖法得以進行。
PubMed abstract: Schizophrenia is a complex disorder, and there is substantial evidence supporting a genetic etiology. Despite this, prior attempts to localize susceptibility loci have produced predominantly suggestive findings. A genome-wide scan for schizophrenia susceptibility loci in 22 extended families with high rates of schizophrenia provided highly significant evidence of linkage to chromosome 1 (1q21-q22), with a maximum heterogeneity logarithm of the likelihood of linkage (lod) score of 6.50. This linkage result should provide sufficient power to allow the positional cloning of the underlying susceptibility gene.