Gross G, Huber G
Universitäts-Nervenklinik, Bonn, Germany.
Fortschr Neurol Psychiatr. 2008 May;76 Suppl 1:S49-56. doi: 10.1055/s-2008-1038152.
While in the midth the 19th century Griesinger and 80 years later Mayer-Gross regarded schizophrenia as a brain disease, a far-reaching change in the view of schizophrenia found expression in the review of Manfred Bleuler in 1951: All classical assumptions of the schizophrenia doctrine and especially, that schizophrenia could be classified a somatically conditioned illness and not psychogenic, would be, as he wrote, shaken severely. On the 1st International Meeting of Neuropathology in Rome (1952) the opinion became generally accepted that pathological changes of the brain could not be expected in schizophrenias. The neuropathological research into psychoses, considered as unfruitful, has been practically stopped. The World Congress of Zürich "The group of schizophrenias" has summarized through Walter Schulte that schizophrenia must be understood as a "riddle of the human being", unapproachable for the methods of scientific medicine. In contrary to the main trends of psychiatry of that time, we were convinced that schizophrenias have a pathological-somatic basis and considered the search for empirical indications of the somatosis hypothesis an aim of research having priority. Thus, we tried to associate findings gained with the available somatic methods (neurohistopathology, neuroradiology, neurophysiology, neuropsychology, neurochemistry) with clinical syndromes and course of the disorder. These investigations, directed to psychopathological-somatic correlations went already since the monograph of 1957 hand in hand with the gradual development of the basic symptom concept (BSC) and of the Bonn Scale for the Assessment of Basic symptoms (BSABS) and with our long-term course- and early recognition research. I originated with three observations, made at the Heidelberg Clinic of Kurt Schneider, (1.) the cenesthetic schizophrenia; (2.) the asthenic pure defect and (3.) lethal catatonias, patients who were diagnosed clinically as idiopathic schizophrenias, but could be separated from idiopathic schizophrenias as symptomatic by neurohistopathological findings of post mortem examinations and e.g. diagnosed as sporadic, atypical encephalitis. The cenesthetic type had a pilot function for the development of the BSC, because in its course the basic symptomatology determined as well the prodromes before the first psychotic episode, as after that the reversible postpsychotic basic stages respectively the irreversible pure defect syndromes, into which two thirds of cenesthetic schizophrenias terminate; then, because with this type the first time has been observed, that from initially quite uncharacteristic basic symptoms (BS) (level 1 BS), qualitatively peculiar basic symptoms (level 2 BS) and then distinct psychotic symptoms, i.e. bodily hallucinations arise; and because in patients with persisting pure deficiency syndromes neuromorphological changes in the sense of a basal ganglia syndrome could be proved. The clinical neuroradiological correlation study in 195 schizophrenic patients with slight residues or full remissions and 212 chronic schizophrenias as well as in 535 patients with organic psychosyndromes of different diagnostic groups reveal that brain imaging and biological-psychiatric research are only promising in close connection with clinical psychopathology and observation of the course, if they aim to assign certain structural or functional cerebral disturbances with certain clinical symptoms and syndromes. In this respect schizophrenic, schizoaffective and affective idiopathic psychosyndromes do not differ from somatically based psychoses in definable brain diseases. With functional-dynamic parameters the differentiation in process active and inactive stages has to be made guided by the actual clinical psychopathological syndrome at the moment of the collecting of the electroencephalographic, neurochemical, fMRI or PET findings. The reasons of inconsistencies of the EEG, PEG, CT, MRI, PET findings are analysed and it is shown that they are frequently conditioned by insufficient definition of the random sample and, with functional-dynamic parameters by the missing consideration of the process activity. The Bonn Schizophrenia Long-term Study and the Bonn-Cologne early recognition study established that the dichotomic models of course of schizophrenia cannot be maintained: Negative respectively minus symptoms in the sense of basic symptoms precede the positive ones many years, negative schizophrenias pass over into positive ones and vice versa. In the search for morphological brain findings an irreversible psychopathological alteration with the component of a pure dynamic-cognitive deficiency syndrome is relevant as clinical criterion, while other persisting psychosyndromes as structural deformities and "pure psychosis" usually show no morphological brain changes. "Schizophrenia" is not always associated with neuromorphological changes. There exists a group of neuroradiologically negative schizophrenias with small dysplastic ventricles and other constitutional anomalies that is characterized by a premorbid psychopathic personality and a typically schizophrenic personality deformation. Brain alterations, regarding the 3rd and the lateral ventricles in the neighbourhood of the basal ganglia, can be found in the subgroup with irreversible dynamic-cognitive pure defect, but not in courses with full psychopathological remission. According to Dewan for the first time a correlation between psychopathological and brain morphological findings in schizophrenics with the component of pure residual syndrome has been found by our studies, as well as a parallel progression of the cerebral atrophy and the psychopathological changes. Quantitative-morphometric and MRI changes of regions of the limbic system and neurophysiological findings are hints that disorders in limbic key structures are able to explain the basic symptoms and the first rank symptoms, developing out of distinct transition relevant basic symptoms. Finally, the process activity concept and its criteria and its meaning for the studies with functional brain imaging methods are described.
19世纪中叶,格里辛格(Griesinger)以及80年后的迈耶 - 格罗斯(Mayer - Gross)都将精神分裂症视为一种脑部疾病。然而,1951年曼弗雷德·布鲁勒(Manfred Bleuler)的综述中,对精神分裂症的看法发生了深远变化:他写道,精神分裂症学说的所有经典假设,尤其是认为精神分裂症可归类为躯体性疾病而非心因性疾病的观点,将受到严重动摇。在罗马召开的第一届国际神经病理学会议(1952年)上,人们普遍接受这样的观点,即精神分裂症患者脑部不应出现病理性改变。对精神病的神经病理学研究被认为毫无成果,实际上已基本停止。苏黎世世界大会“精神分裂症群组”通过沃尔特·舒尔特(Walter Schulte)总结认为,精神分裂症必须被理解为“人类之谜”,科学医学方法难以触及。与当时精神病学的主流趋势相反,我们坚信精神分裂症有病理 - 躯体基础,并将寻找躯体病变假说的实证依据视为研究的首要目标。因此,我们尝试将通过现有躯体方法(神经组织病理学、神经放射学、神经生理学、神经心理学、神经化学)获得的发现与临床综合征及疾病进程联系起来。这些针对精神病理 - 躯体相关性的研究,自1957年的专著以来,就与基本症状概念(BSC)以及波恩基本症状评估量表(BSABS)的逐步发展,以及我们的长期病程和早期识别研究携手并进。我最初源于在海德堡库尔特·施奈德诊所进行的三项观察:(1)体感型精神分裂症;(2)虚弱性单纯缺陷型;(3)致死性紧张症,这些患者临床上被诊断为特发性精神分裂症,但通过尸检的神经组织病理学发现可与特发性精神分裂症相区分,例如被诊断为散发性、非典型脑炎。体感型对BSC的发展具有先导作用,因为在其病程中,基本症状学既决定了首次精神病发作前的前驱症状,也决定了首次发作后的可逆性精神病后基本阶段以及不可逆性单纯缺陷综合征,三分之二的体感型精神分裂症会发展为这种综合征;其次,因为首次观察到,从最初相当不典型的基本症状(1级BS)开始,出现了质上特殊的基本症状(2级BS),然后是明显的精神病性症状,即躯体幻觉;还因为在持续存在单纯缺陷综合征的患者中,可以证明存在基底神经节综合征意义上的神经形态学改变。对195例有轻微残留或完全缓解的精神分裂症患者、212例慢性精神分裂症患者以及535例不同诊断组的器质性精神综合征患者进行的临床神经放射学相关性研究表明,脑成像和生物精神病学研究只有在与临床精神病理学及病程观察紧密结合时才有前景,前提是它们旨在将某些脑结构或功能障碍与特定的临床症状和综合征联系起来。在这方面,精神分裂症、分裂情感性和情感性特发性精神综合征与可定义的脑部疾病中的躯体性精神病并无不同。对于功能性 - 动态参数,在收集脑电图、神经化学、功能磁共振成像或正电子发射断层扫描结果时,必须根据实际临床精神病理综合征来区分过程的活跃和不活跃阶段。分析了脑电图、正电子发射断层扫描、计算机断层扫描、磁共振成像、正电子发射断层扫描结果不一致的原因,结果表明它们常常是由于随机样本定义不充分所致,对于功能性 - 动态参数而言,则是由于未考虑过程的活动状态。波恩精神分裂症长期研究和波恩 - 科隆早期识别研究表明,精神分裂症病程的二分法模型无法成立:基本症状意义上的阴性或减症状在多年前就先于阳性症状出现,阴性精神分裂症会转变为阳性精神分裂症,反之亦然。在寻找脑部形态学发现时,具有纯动态 - 认知缺陷综合征成分的不可逆精神病理改变作为临床标准具有相关性,而其他持续存在的精神综合征,如结构畸形和“纯精神病”,通常未显示脑部形态学改变。“精神分裂症”并不总是与神经形态学改变相关。存在一组神经放射学阴性的精神分裂症患者,其脑室发育不良且有其他体质异常,其特征是病前有精神病态人格和典型的精神分裂症人格变形。在具有不可逆动态 - 认知单纯缺陷的亚组中,可以发现基底神经节附近第三脑室和侧脑室的脑部改变,但在精神病理完全缓解的病程中则未发现。根据德万(Dewan)的研究,我们首次发现了精神分裂症患者精神病理与脑部形态学发现之间的相关性,其成分包括纯残留综合征,以及脑萎缩与精神病理改变的平行进展。边缘系统区域的定量形态测量和磁共振成像变化以及神经生理学发现表明,边缘关键结构的紊乱能够解释从明显的过渡相关基本症状发展而来的基本症状和一级症状。最后,描述了过程活动概念及其标准以及它在功能性脑成像方法研究中的意义。