Manic-depressive psychosis for the Kraepelinians in the early 1960s

Thomas A. Ban

Emil Kraepelin’s (1899) “manic-depressive (melancholic) psychosis” was derived by separating patients on the basis of the ”course”  and the ”outcome” of their clinical manifestations. It included all episodic psychoses with full remission between episodes, regardless whether the episodes included both “manic” and “depressive (melancholic)” syndromes, or were exclusively “manic”, “melancholic” or “mixed”.

The clinical features of both, the manic syndrome and the melancholic syndrome were based originally on the information Kraepelin (1899, 1913) collected on his “counting cards” (Zählenkarten), a symptom check list that included only ten items: nervousness, restlessness, irritability, depression, psychomotor retardation, aggression, grandiosity, negativistic behavior, hallucinations and paranoid ideas (Bech 2012; Kraepelin 1908-15; Weber and Engstrom1997). Yet, as time passed the symptoms of the core syndromes were crystallized and by the 1960s, those operating within the frame of reference of Kraepelin’s (1899) “nosology”, defined the “manic syndrome” as “hyperthymia” (elevated mood)  with “acceleration of mental (including psychomotor) activity” and  “sleep disturbance”, and the “melancholic syndrome” as  “dysthymia” (depressed mood) with “deceleration (slowing) of mental  (including psychomotor) activity”, and “sleep disturbance”. Furthermore, in recognition of the variations of clinical (psychopathological) manifestations in both syndromes, several “manic syndromes” and several “melancholic syndromes” were identified. The manic syndromes included “anxious mania”, “delirious mania”, “dysphoric mania”, “furious mania”, “hypochondriacal mania”, “querulous  mania”, “simple mania”, “stuporous mania”, “transitory mania” and “unproductive mania; and the melancholic syndromes included “anxious melancholia”, “agitated melancholia”, “hypochondriacal melancholia”, “simple melancholia” and “stuporous melancholia” (Nyiro 1962).



Bech P. Clinical Psychometrics. Copenhagen: Willey-Blackwell; 2012

Kraepelin E. Psychiatrie. Ein Lehrbuch fuer Studierende und Aerzte. 8 Aufl. Leipzig: Barth; 1908-1915.

Kraepelin E. Psychiatrie. Ein Lehrbuch fuer Studierende und Aerzte. 8 Aufl. Leipzig: Barth; 1913.

Nyiro Gy. Psychiatria. Budapset:medicina; 1962.

Weber MM, Engstrom EJ. Kraepelin;s diagnostic cards; the confluence of clinical research and preconceived categories. History of Psychiatry 1997; 8: 375-85.


Thomas A. Ban
November 12, 2015

Thomas A. Ban: Neuropsychopharmacology in Historical Perspective. Dementia Differential Diagnosis 


Diagnosing of Dementing Illness


       In recent years, numerous test batteries and clinical procedures have been implemented for the early detection and differential diagnosis of dementing illness. Although it is increasingly recognized that cognitive changes are not the earliest signs of dementing illness, some believe that testing of memory, language, perception, praxis, problem solving, attention and functional status might still be useful for "planning treatment and management programs for the patient, as well as in determining the rate of deterioration in patients followed over a period of time and the effect of any treatment" (Guterman and Elsdorfer 1989).


Routine Test Batteries 

       In recent years, there has been a steadily increasing number of "memory disorders clinics" established for the early detection of dementing illness (Knopman, Deinard, Kitto et al. 1985; Larson, Reifler, Featherstone and English 1984; Van der Cammen, Simpson, Fraser et al. 1987; Zemcov, Barclay, Brush and Blass 1984). The establishment of these clinics was triggered by the recognition that patients with a dementia syndrome may have a secondary or reversible dementia which should be detectable by employing a series of biochemical-laboratory tests, neuroradiologic screening and electrophysiologic examinations. However, by now it has been acknowledged that memory clinics employing these procedures have provided a low diagnostic yield (Brodaty 1990). In keeping with this are the  findings of Larson, Reifler, Sumi et al. (1986), in a study of the diagnostic evaluation of 200 patients older than 60 years with suspected dementia, found that in only 11 cases were laboratory tests required for the diagnosis.

       Considering all available information, first  Barry   and Moskowitz (1988), and later on Gordon and Freedman (1990), concluded that "the large battery of tests frequently ordered has proved to be inefficient and expensive for routine screening to identify total reversible dementia." Although Gordon and Freedman (1990) acknowledged that (in the majorly of cases) in the absence of "reversible dementia," there is still a possibility that a considerable proportion of patients has "modifiable" dementia, (i.e., a multifactorial disorder in which certain aspects can be ameliorated), they also recognized that only 3-11 percent of cases, at best, can be improved. Because of this, they asserted that "the most important diagnostic procedure involves careful history taking and physical examination, including assessment of the mental status, and not “an extensive laboratory and neurologic investigation.


Special Procedures: EEG and Brain Imaging 

       There are only a few special procedures which may contribute to diagnostic decisions in dementing illness. In spite of this, surface electroencephalography (EEG) and computerized tomography (CT) are routinely employed in the diagnostic evaluation of demented patients.

       Nevertheless, while EEG results have little to offer beyond the detection of the slowing of alpha rhythm and/or focal abnormalities, there are some indications that studying event related evoked potentials (ERP) may allow for discrimination between cortical and subcortical dementias (Canter, Hallett and Growdon 1982).

       Furthermore, some believe that topographic brain imaging by EEG may, in the future, become one of the most valuable tools for the clinical evaluation of dementia, both for initial diagnosis and longitudinal monitoring (Lehmann 1989).

       The same holds true tor brain imaging, where routine CT scans have little to offer beyond revealing subdural hematomas and other space occupying lesions, such as cerebral tumor, as well as ventricular enlargement and cortical atrophy. On the other band, there are some indications that regional cerebral blood flow (CBF) measurements, single photon emission computerized tomography (SPECT) and especially high-resolution proton emission tomography (PET) can separate even mildly demented patients from normal subjects by their more severe metabolic abnormalities in the association areas of the neocortex than in the sensorimotor and calcarine regions (Kumar, Schapiri and Grady 1991).

       Furthermore, some believe that by employing magnetic resonance imaging (MRI), periventricular white matter lesions, i.e., leukoaraiosis, may be detected at time when no other indicator of dementing illness is present (Hachinski 1990).

       However, in spite of the tremendous progress made in recent years in diagnostic techniques, Lehmann (1989) maintains that at the present time "none of the new sophisticated procedures can give specific and confident diagnostic information on dementias. There are many demented patients whose EEG and CT scans are not abnormal, particularly in the early states of the illness. There are even more patients with abnormal EEG and CT scan findings who are not demented."


Biologic Markers 

       Neurochemical investigations of the brains of demented patients have shown that there are generally present disturbances of choline, such as reduces concentrations of acetyltransferase activity and reduced concentrations of hydroxytryptamine and 5-hydroxyindolacetic acid in cortical and subcortical areas (Gottfries 1989). However, in studies by Parnetti, Gottfries, Karlsson et al. (1987), the only consistent finding in the CSF was the significantly reduced homovanillic acid concentration in AD as compared to SD and normal controls; and in the study by Navaratnam, Priddle, McDonald et al. (1991), an additional band of acetylcholine-esterase (AcHE-AD) in the CSF of patients with AD. It has also been noted that there is an increase in red cell choline in AD as compared to normal controls (Friedman, Sherman, Ferris et al. 1981). Nevertheless, because this increase of choline in the red cells is neither unique to AD red cells, nor in variance with it, Blass and Barclay (1986) maintain that its usefulness in AD diagnosis remains dubious.

       Based on an entirely different line of investigations, Wolozin and Davies (1987), identified a monoclonal antibody, referred to as ALZ 50, which reacts against brain tissue homogenates of patients with AD (Wolozin and Davies 1987). Recognition that ALZ 50 binds to a protein marker, referred to as A-88, which is highly selective of AD -- and can detect an early cytologic change that precedes the formation of neurofibrillary tangles and senile plaques -- led to the development of an enzyme immunoassay for the detection of AD associated proteins in postmortem human brain tissue (Ghanbari, Miller, Haigler et al. 1990) Pursuing the same line of research, another group of investigators - based on the recognition that the paired helical filaments (PHF), one of the hallmarks of AD, belong to the tau species of proteins - is in the process of developing a diagnostic kit which, by ELISA testing, should be able to determine the presence of the PHF antigen in the cerebrospinal fluid and thereby indicate the presence of AD (Iqbal, Grundke-Iqbal and Wisniewski 1987; Lehmann 1989;).

       Simultaneously with the development of this CSF-based diagnostic test, there is also a blood test in development for AD. It is based on the presence in the blood of a beta-amyloid protein (related to the specific amyloid found in senile plaques) which is similar to Glenner and Wong's (1984) beta-amyloid protein, present in the cerebral vessels of patients with AD and Down's syndrome.


Concluding Remarks 

       In variance with the commonly held belief that dementia begins with cognitive changes, there is increasing evidence that neurologic signs, transient consciousness disturbances, personality changes and psychopathologic symptoms are the earliest detectable manifestations of a dementing process. Because of this and other considerations a Canadian Task Force on the Periodic Health Examination (1989) concluded that in spite of the high incidence of dementing illness "there is insufficient evidence to include routine screening for cognitive impairment in or exclude it from the periodic examinations of people over 85 years." On the other hand, with consideration of their high prevalence rate and/or reversibility, in case of the slightest indications for their presence, checking for SDAT, MID, normal pressure hydrocephalus, drug toxicity, alcohol abuse, depression and certain metabolic disorders, is of primary importance.


September 2, 2021