遲發性靜坐不能和認知缺陷（第 103 頁）
Tardive Akathisia and Cognitive Deficits (p. 103)
Gualtieri (1993) 觀察到遲發性靜坐不能患者的焦慮和情緒緊張是該疾病的主要情緒和認知成分。 在回顧了功能性神經解剖學後，Gualtieri 總結道，
Gualtieri (1993) observed that the anxiety and emotional tension suffered by tardive akathisia patients are primary emotional and cognitive components of the disease. After reviewing the functional neuroanatomy, Gualtieri concluded,
因此，人們有權推測，情感不穩定和智力障礙可能是基底節水平神經病理學的結果。 . . . TDAK [遲發性靜坐不能] 是這種效應的一種表現。 可能還有其他人。
One is entitled to surmise, therefore, that affective instability and intellectual impairment may be the consequence of neuropathology at the level of the basal ganglia. . . . TDAK [tardive akathisia] is one manifestation of that effect. There are probably others.
換言之，遲發性靜坐不能綜合徵的存在表明，精神安定藥可以對個體的精神生活產生不可逆轉的損害。
In other words, the existence of the syndrome of tardive akathisia demonstrates that the neuroleptics can produce irreversible damage to the mental life of the individual.
人類和動物屍檢研究（第 103 頁）
HUMAN AND ANIMAL AUTOPSY STUDIES (p. 103)
動物屍檢數據提供了強有力的證據，表明精神安定藥經常導致腦損傷。 人體屍檢研究太少且相互矛盾，無法得出明確的結論。 對它們的興趣再次下降。
Animal autopsy data provide strong evidence that the neuroleptics frequently cause brain damage. Human autopsy studies are too few and contradictory to lead to a definite conclusion. Once again, interest in them has declined.
抗精神病藥引起的腦損傷的動物屍檢研究（第 103 頁）
Animal Autopsy Studies of Neuroleptic-Induced Brain Damage (p. 103)
在本章前面，我總結了 Dorph-Petersen 等人的發現。 （2005 年），臨床劑量的氟哌啶醇和奧氮平在猴子中導致腦組織顯著收縮，細胞死亡通過大腦，但在額葉和頂葉最為明顯。 多項早期對照動物研究表明，長期，有時是短期的精神抑制治療會導致腦損傷。 結構損傷的證據，包括基底神經節中的細胞退化和死亡，在長期服用安定藥後尤其一致（Coln，1975；Jeste 等，1992；Mackiewicz 等，1964；Nielsen 等，1978；Pakkenberg 等人，1973 年；波波娃，1967 年；羅馬森科等人，1969 年；審查於布雷金，1983b）。 負面的研究要少得多（Fog et al., 1976; Gerlach, 1975）。
Earlier in the chapter I summarized the findings of Dorph-Petersen et al. (2005) that clinical doses of haloperidol and olanzapine in monkeys produced marked shrinkage of the brain tissue with cell death through the brain, but most markedly in the frontal and parietal lobes. Multiple earlier controlled animal studies indicate that long-term, and sometimes short-term, neuroleptic treatment cause brain damage. Evidence of structural damage, including cell degeneration and death in the basal ganglia, is especially consistent after chronic administration of neuroleptics (Coln, 1975; Jeste et al., 1992; Mackiewicz et al., 1964; Nielsen et al., 1978; Pakkenberg et al., 1973; Popova, 1967; Romasenko et al., 1969; reviewed in Breggin, 1983b). Far fewer studies have been negative (Fog et al., 1976; Gerlach, 1975).
在服用 0.5-5 mg/kg 的“相對低”劑量的氯丙嗪後，Popova (1967) 發現大鼠大腦中的結構發生了變化，包括許多區域的“神經細胞體腫脹、色解和空泡化”（第 87 頁）， 包括感覺運動皮層、中腦、下丘腦、丘腦和網狀結構。 1992 年，Jeste 等人。 回顧了文獻並發表了將大鼠暴露於氟奮乃靜癸酸酯（5 mg/kg，肌肉注射）每 2 週持續 4、8 或 12 個月的結果。 在犧牲後通過計算機圖像分析系統測量紋狀體中大神經元的密度。 該團隊發現經過 8 個月的治療後密度降低。
After one “comparatively low” dose of chlorpromazine, 0.5–5 mg/kg, Popova (1967) found structural changes in rat brains, including “swelling, chromatolysis and vacuolization of the nerve cell bodies” (p. 87) in many regions, including the sensory-motor cortex, midbrain, hypothalamus, thalamus, and reticular formation. In 1992, Jeste et al. reviewed the literature and published the results of exposing rats to fluphenazine decanoate (5 mg/kg, intramuscular) every 2 weeks for 4, 8, or 12 months. The density of large neurons in the striatum was measured after sacrifice by a computerized image analysis system. This team found a reduced density by 8 months of treatment.
大多數動物研究報告在相對短暫地暴露於抗精神病藥後會出現不可逆的神經元損傷，包括細胞死亡。 非常重要的是，對神經安定劑暴露時間較長的動物研究——1 年（Pakkenberg 等人，1973 年）、8 個月（Jeste 等人，1992 年）和 36 週（尼爾森等人，1978 年）——表明 預期基底神經節的神經元退化。
Most animal studies report irreversible neuronal damage, including cell death, after relatively brief exposure to neuroleptics. Of great importance, animal studies with longer durations of exposure to neuroleptics—1 year (Pakkenberg et al., 1973), 8 months (Jeste et al., 1992), and 36 weeks (Nielsen et al., 1978)—show the expected neuronal deterioration in the basal ganglia.
動物研究提供了明確且顯然無可爭辯的證據，表明抗精神病藥通常會導致不可逆轉的腦損傷。 這與本章前面回顧的最近的研究一致，這些研究證明了較舊和較新的非典型神經安定劑如何對動物的活細胞產生劇毒。
Animal research provides definitive and apparently incontrovertible evidence that neuroleptics often cause irreversible brain damage. This is consistent with more recent studies reviewed earlier in the chapter that demonstrate how both older and newer atypical neuroleptics are highly toxic to living cells in animals.
抗精神病藥引起的腦損傷的人體屍檢證據（第 104 頁）
Human Autopsy Evidence for Neuroleptic-Induced Brain Damage (p. 104)
令人驚訝的是，很少有人體屍檢報告檢查慢性精神病治療的效果。 Bracha 和 Kleinman (1986)、Brown 等人回顧了較早的研究。 （1986 年），傑斯特等人。 （1986 年）和 Rupniak 等人。 （1983 年）。 雖然有些不確定，但屍檢證據確實表明神經安定劑會損害基底神經節，這是一個對 TD 和遲發性癡呆產生潛在關鍵的區域。 但總體而言，文獻很少、相互矛盾，而且沒有定論。 Arai 等人的研究。 （1987 年），布朗等人。 （1986 年），克里斯滕森等人。 （1970），福雷斯特等人。 (1963)、Gross 和 Kaltenback (1968)、Hunter 等人。 (1968)、Jellinger (1977)、Roizin 等人。 （1959 年）和 Wildi 等人。 Breggin (1990) 對 (1967) 進行了更詳細的回顧。
There are surprisingly few human autopsy reports examining the effects of chronic neuroleptic therapy. Older studies have been reviewed by Bracha and Kleinman (1986), Brown et al. (1986), Jeste et al. (1986), and Rupniak et al. (1983). Although somewhat inconclusive, autopsy evidence does suggest that the neuroleptics can damage the basal ganglia, an area potentially critical in the production of both TD and tardive dementia. But the literature, overall, is scant, contradictory, and not conclusive. The studies of Arai et al. (1987), Brown et al. (1986), Christensen et al. (1970), Forrest et al. (1963), Gross and Kaltenback (1968), Hunter et al. (1968), Jellinger (1977), Roizin et al. (1959), and Wildi et al. (1967) are reviewed in more detail in Breggin (1990).
嗜睡性腦炎的教訓 (^4) (p. 104)
LESSONS OF LETHARGIC ENCEPHALITIS(^4) (p. 104)
第 3 章提到了抗精神病藥物惡性綜合徵與病毒性疾病、昏睡性腦炎（encephalitis lethargica 或 von Economo 病）的急性發作之間的相似性。 類似的情況表明，精神安定藥在其主要影響中會產生受控的化學性腦炎，當其失控時，會變成精神抑制藥惡性綜合徵，與暴發性病毒性腦炎無法區分（Breggin，1993）。
Chapter 3 mentioned the similarity between neuroleptic malignant syndrome and an acute episode of the viral disorder, lethargic encephalitis (encephalitis lethargica, or von Economo’s disease). The parallel suggests that the neuroleptics, in their primary impact, produce a controlled chemical encephalitis, which, when out of control, becomes neuroleptic malignant syndrome, indistinguishable from a fulminating viral encephalitis (Breggin, 1993).
正如第一次世界大戰期間和之後的報導（Breggin，1993），還有許多其他方式可以使神經安定藥物的效果與昏睡性腦炎的效果非常相似。 精神安定藥和病毒性疾病都會產生精神冷漠和冷漠。 在 1970 年的回顧展中，丹尼克爾觀察到，
There are many other ways in which neuroleptic drug effects closely mimic those of lethargic encephalitis, as reported during and after World War I (Breggin, 1993). Both the neuroleptics and the viral disease produce mental apathy and indifference. In a 1970 retrospective, Deniker observed,
結果發現，精神安定藥可以通過實驗重現幾乎所有昏睡性腦炎的症狀。 事實上，新藥有可能引起真正的腦炎流行。
It was found that neuroleptics could experimentally reproduce almost all symptoms of lethargic encephalitis. In fact, it would be possible to cause true encephalitis epidemics with the new drugs.
昏睡性腦炎和安定藥毒性之間的相似性在幾個方面是顯著的。 兩組患者最初都表現出冷漠或不感興趣，隨後出現各種運動障礙。 延遲一段時間後，兩組的運動障礙有時會成為永久性的。 許多昏昏欲睡的腦炎患者似乎康復了，但幾年後又復發成破壞性的神經系統疾病。 雖然帕金森樣障礙是與昏睡性腦炎相關的最常見的遲發性或遲發性運動障礙，但其他與藥物誘發的 TD 更相似的運動障礙也已知會發生。
The parallel between lethargic encephalitis and neuroleptic toxicity is remarkable in several respects. Both groups of patients initially display apathy or disinterest, followed by the onset of various dyskinesias. After a delay, the dyskinesias sometimes become permanent in both groups. Many lethargic encephalitis patients seemed to recover, only to relapse into devastating neurological disorders years later. While a Parkinson-like disorder was the most common tardive, or delayed, motor disorder associated with lethargic encephalitis, other dyskinesias more similar to drug-induced TD were also known to develop.
在明顯康復後，許多腦炎患者後來發展為嚴重的精神病和癡呆症（Abrahamson，1935；Matheson Commission，1939）。 因此，完成嗜睡性腦炎和安定藥作用之間的平行關係等待發現，除了 TD，遲發性精神病和遲發性癡呆可能會隨著暴露於安定藥而發生。
After an apparent recovery, many of the encephalitis victims later went on to develop severe psychoses and dementia (Abrahamson, 1935; Matheson Commission, 1939). Thus the completion of the parallel between lethargic encephalitis and neuroleptic effects awaited the discovery that in addition to TD, tardive psychosis and tardive dementia could follow the exposure to neuroleptics.
藥物作用和病毒性腦病作用之間的相似性發出了一個警告，即類似的機制——因此也有類似的不良後果——是可能的。 抗精神病藥問世僅幾年後，Paulson (1959) 在他寫道：
The parallel between the medication effects and the viral encephalopathic effects sounded a warning that similar mechanisms—and hence similar adverse outcomes—were possible. Only a few years after the advent of the neuroleptics, Paulson (1959) raised this concern when he wrote,
腦炎的後遺症包括許多肌肉、精神和自主反應； 吩噻嗪類藥物引起的大部分神經系統並發症都在腦炎後帕金森症的範圍內。 （第 800 頁）
The sequelae of encephalitis include many muscular, psychic and autonomic responses; and most of the neurologic complications from the phenothiazines are within the range of post-encephalitic Parkinsonism. (p. 800)
其他研究人員還注意到安定藥毒性和昏睡性腦炎之間的比較（Brill，1959；Hunter 等，1964）。 Brill (1959) 記錄了昏睡性腦炎中受打擊最嚴重的區域是基底神經節和黑質的細胞，這些區域在產生 TD 時受精神抑製藥物影響最大（參見 Breggin，1993，進一步討論了 解剖路徑）。 基底神經節、網狀激活系統、邊緣系統和大腦皮層之間存在多種相互聯繫，涉及運動和心理功能（例如，Adams 等人，1989；Alheid 等人，1990；Brodal，1969）。 由於相互聯繫，神經安定藥引起的基底神經節損傷如果足夠嚴重，預計會產生持續的認知缺陷和癡呆。
Other investigators also noticed comparisons between neuroleptic toxicity and lethargic encephalitis (Brill, 1959; Hunter et al., 1964). Brill (1959) documented that the hardest hit areas in lethargic encephalitis are the cells of the basal ganglia and the substantia nigra, the areas most affected by the neuroleptic medications in the production of TD (see Breggin, 1993, for a further discussion of the anatomic pathways). There are multiple interconnections between the basal ganglia, reticular activating system, limbic system, and cerebral cortex, involving both motor and mental functions (e.g., Adams et al., 1989; Alheid et al., 1990; Brodal, 1969). As a result of the interconnections, neuroleptic-induced damage to the basal ganglia, if severe enough, would be expected to produce persistent cognitive deficits and dementia.
精神退化與基底神經節和黑質疾病的關聯導致了皮層下癡呆的概念（Huber 等，1985），即由於基底神經節和周圍結構受損而引起的癡呆。 皮層下癡呆患者往往更加抑鬱和冷漠，沒有太多證據表明對高級皮層功能有嚴重損害。 基底神經節的皮層下損傷是大腦功能障礙之一，它使接受抗精神病藥物治療的患者更加溫順，對他人的麻煩也更少。 由於較高的皮層功能受到的損害不那麼明顯，因此觀察者可以放心，患者並沒有受到嚴重傷害，而實際上他們的整體能量水平和生活質量因皮層下功能的損害而受到損害。
The association of mental deterioration with diseases of the basal ganglia and substantia nigra led to the concept of subcortical dementia (Huber et al., 1985), that is, dementia arising from damage to the basal ganglia and surrounding structures. Patients with subcortical dementia tend to be more depressed and apathetic, without as much evidence of gross impairment to higher cortical functions. Subcortical damage to the basal ganglia is one of the brain-disabling mechanisms that make neuroleptic-treated patients more docile and less troublesome to others. Because higher cortical functions are less obviously damaged, observers can reassure themselves that the patients are not being grossly harmed, when in fact their overall energy level and quality of life are impaired by damage to subcortical functions.
Marsden (1976) 觀察到，“如果長期的精神安定治療可以引起紋狀體多巴胺受體作用的明顯永久性變化，那麼我們必須假設同樣的情況也可能發生在中腦邊緣皮質多巴胺受體中”（p. 1079），即 ，大腦的最高中心。 Marsden 和 Obeso (1994) 指出了基底神經節和額葉之間複雜的相互聯繫，以及它們在高級心理功能中的可能作用。
Marsden (1976) observed, “If long-term neuroleptic therapy can cause an apparently permanent change in striatal dopamine-receptor action, then one must assume that the same can occur in the mesolimbic cortical dopamine receptors” (p. 1079), that is, the highest centers of the brain. Marsden and Obeso (1994) pointed out the complex interconnections between the basal ganglia and the frontal lobes and their possible role in higher mental functioning.
動物研究證實，多巴胺受體的超敏反應在中腦邊緣和大腦皮質區域發展，就像在紋狀體中一樣（Chiodo 等人，1983 年；White 等人，1983 年），並且在終止精神安定藥後它可能會變成慢性 治療（Jenner 等人，1983 年；Rupniak 等人，1983 年）。 雖然 TD 難以在動物中繁殖，但 Gunne 和 Haggstrom (1985) 能夠在猴子和大鼠中產生急性和不可逆轉的運動障礙。 對於持續性運動障礙，他們發現了基底神經節和相關區域（黑質、內側蒼白球和丘腦底核）發生不可逆生化變化的證據。
Animal research confirmed that supersensitivity of dopamine receptors develops in the mesolimbic and cerebral cortical areas, much as it does in the striatum (Chiodo et al., 1983; White et al., 1983), and that it can become chronic after termination of neuroleptic treatment (Jenner et al., 1983; Rupniak et al., 1983). While TD is diffi cult to reproduce in animals, Gunne and Haggstrom (1985) were able to create both acute and irreversible dyskinesias in monkeys and rats. With persistent dyskinesias, they found evidence of irreversible biochemical changes in the basal ganglia and related areas (substantia nigra, medial globus pallidus, and nucleus subthalamicus).
許多研究人員評論了神經安定劑誘導的中腦邊緣和皮質多巴胺系統抑制與臨床產生遲鈍或冷漠之間的關係（Lehman，1975；White 等，1983）。 這些生物系統的不可逆變化導致了許多永久性認知功能障礙的發現。
Many researchers remarked on the relationship between neuroleptic-induced inhibition in the mesolimbic and cortical dopamine system and the clinical production of blunting or apathy (Lehman, 1975; White et al., 1983). Irreversible changes to these biological systems account for many findings of permanent cognitive dysfunction.
Gualtieri 和 Barnhill (1988) 證實了這些觀察結果：
Gualtieri and Barnhill (1988) confirmed these observations:
持續的 TD 可能是不可逆轉的紋狀體損傷的結果。 但是紋狀體不僅僅負責運動控制。 它是一個複雜的器官，會影響廣泛的複雜人類行為。 已知沒有一種影響紋狀體組織的疾病只會產生運動後果； 帕金森病和亨廷頓病只是兩個例子。 （第 150 頁）
Persistent TD is probably the consequence of irreversible striatal damage. But the corpus striatum is responsible for more than motor control; it is a complex organ that influences a wide range of complex human behaviors. No disease that afflicts striatal tissue is known to have only motor consequences; Parkinson’s disease and Huntington’s disease are only two examples. (p. 150)
可悲的是，精神病學堅持將抗精神病藥或精神安定藥作為“精神病”、“精神分裂症”和“躁狂症”的特定治療方法，而實際上這些藥物會導致嚴重的腦損傷和功能障礙，有效地使大腦和精神失能，使個體更溫順，對自己的需要或痛苦相對漠不關心。 精神安定藥的使用在很大程度上是為了方便醫生和看護人員，但犧牲了患者的健康。
It is tragic that psychiatry persists in promoting the antipsychotic or neuroleptic drugs as specific treatments for “psychosis,” “schizophrenia,” and “mania,” when in fact the drugs cause severe brain damage and dysfunction, effectively disabling the brain and mind, rendering individuals more docile as well as relatively indifferent to their own needs or suffering. The use of the neuroleptics is, to a great extent, a convenience for physicians and caretakers at the expense of the patients’ well-being.