Paranoia (delusional disorder): a valid psychiatric entity?

TINS - January 1984

14 26 L@mo. Ilondon) 27 bmo. Spring 28

T. and Rosenthal. 221.493-513 T. and Westgaard, Harbor Synp.

26%274 Lundborg.

G..

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F. M.

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1. f/~ysio/.

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(1982) Brain Res. 232. 29 Maehlen. J. and NjS. (London) 322. ISI-166 30

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S. (1979)

37

Slack.

Hopkins.

J. R..

J. W.

Phyiol G. and

40 Thompson. Neuroscience

Pockett.

S.

Kenneth S. Kendler Since the days of Kraepelin, the diagnostic status of paranoia (here termed delusional dtiorier or bD) has beer; controversial. Three main views have emerged that consider DD to be (I) a subtype of schizophrenia. (2) a subtype of affective illness. and (3) a distinct diagnostic entity. After a brief historical review. we review here some of the literature relevant to the diagnostic status of DD. From the perspective of demographic factors familial distribution of psychopathology, and diagnostic stability, the bulk of the evidence supports the viewpoint that DD represents, along with schizophrenia and affective illness,a third major ‘functioml’ psychosis. Rksearch into the etiology and treatment of DD has been neglected and is much needed.

TABLE A. B.

C. D.

I. Proposed

diagnostic

criteria

for delusional

S. (1982)

Brain

S. H. (1983)

W. and Jansen. 2. 523-535

J. K.

Res. Science

S. (1977)

(London)

Paranoia (delusional disorder): a valid psychiatric entity?

The major contribution of Emil Kraepelin to psychiatric diagnosis is widely considered to be his division of the ‘functional’ psychoses into two major groups: dementia praecox (or schizophrenia) , and manic-depressive insanity (or affective illness)“. Although it is less widely recognized, this founder of modem psychiatric nosology always felt that a third ‘functional’ psychotic illness existed, which he termed paranoia. While the last several decades have seen major research efforts in the genetics, epidemiology, natural history and treatment of schizophrenia and affective illness, little attention has been paid to paranoia. In fact, opinion is still divided as to whether paranoia is best regarded as a separate psychiatric entity, or as a subtype of schizophrenia or of affective illness’. This review has several related goals: to review the clinical syndrome of paranoia, to outline briefly the controversial

Muscle Nerv. (in press) 38 Slack, J. R. and Pockett, 247. 138-140 39 Smith, R. G. and Appel. 219. 1079-1081

history of the disorder, to review proposed diagnostic criteria for the disorder, and to examine demographic family studies and follow-up studies of paranoia that are relevant to the question of whether paranoia is a valid psychiatric entity. The clinical syndrome of paranoia (delusionaldisorder)

As in many aspects of psychiatry, there is much confusion over the terminology regarding paranoia. Kraepelin originally applied the term paranoia to a group of patients with chronic, usually life-long delusions”. Since Kraepelin, many terms have been applied to this disorder including paranoid state, paranoid condition, paranoid reaction, paranoid psychosis, reactive paranoid psychosis, paranoid disorder and, most recently, delusional disorder’.“. This last term has a semantic appeal because it is both concise and summarizes the disorder

Persistent, non-bizarre delusions lasting at least I month. Absence of prominent affective symptoms sufficient to qualify for the diagnosis of affective disorder: or if such symptoms are present it is clear that they developed after the appearance of the delusions. Absence of symptoms characteristic of schizophrenia including prominent thought disorder, bizarre delusions, marked affective deterioration, and prominent hallucinations. The delusional symptoms do not occur only during drug intoxication or withdrawal, or other organic brain disorders.

M. C. Brown ic ar rhe Phyriology. Park Road,

Universify Oxford

Laborutocl OXI 3PT.

0.f UK.

essential clinical features of the disorder. Simx the term ‘paranoid’ has come to have so many meanings in psychiatry (especially to describe a mood of suspiciousness). excluding that term from the description of this diagnostic entity can only result in greater conceptual clarity. Therefore, in this review, we will use the term delusional disorder or DD to describe this diagnostic entity. The major symptom of DD is delusions. These are beliefs that are clearly deviant from cultural norms, are usually held with conviction, and result in a substantial effect on the individual’s life. Delusions differ in theme (i.e. persecutory, somatic, erotic, etc.) and in content. A characteristic of the delusions held in DD is their coherence and non-bizarreness. Patient with DD may present with the delusion that the Mafia is trying to kill them, or that a certain famous celebrity is in love with them. While such beliefs are ‘crazy’ they are, none the less, much closer to consensual reality than delusions commonly held in schizophrenia. An example of a bizarre delusion typicaIly seen in schizophrenia is that of a 44-year-old man who believed that a ‘scientist’ in the United Nations building turned on a ‘mind-control Xray machine’ every day from 2 p.m. to 3 p.m. which made the patient experience homosexual urges. Patients with DD differ from schizophrenics in other important ways. While hallucinations, usually auditory, are very common in schizophrenia, such phenomena are rarely seen in DD. Schizophrenics often demonstrate incoherent speech and substantial psychosocial deterioration, both of which are absent in DD. While many schizophrenic patients are unable to live independently or work, most patients with DD function at least adequately in these spheres. Unlike schizophrenics, who often act and talk in a ‘c&y fashion unless discussing their particular delusion, patients with DD usually do not demonstrate overt signs of mental ihess. Delusions can also occur in affective illness (depression and mania). In making

15 a diagnosis of DD it is important to exclude cases where delusions have arisen in the setting of an episode of depression or mania. This is only rarely a difficult problem. However, after the onset of delusions, patients with paranoia may develop some depressive symptoms. A well-documented history can usually distinguish such cases from true cases of psychotic depression where the delusions only occur after the depression has become intense. The last major issue in the diagnosis of paranoia is to exclude cases where delusions emerge from drug intoxication or withdrawal, or from an organic brain disease. Delusions can occur in chronic alcoholism and are common symptoms in the early stages of dementia. A careful history and mental status examination can usually exclude such cases. The history of delusional disorder

Kraepelin initially conceived of paranoia or DD as a disorder distinct from both schizophrenia and affective illness’ ‘. This viewpoint was challenged from both directions. Kolle and other German psychiatrists including Schneider and Freud maintained that DD was a mild form of schizophrenia4*‘. Specht suggested that cases of paranoia were in reality cases of affective illness where the affective symptoms were overshadowed by the prominent delusions. Kretschmer and later the Scandinavian school including Stromgren continued to support the existence of a separate diagnostic entity for DD distinct from both schizophrenia and affective ilhressg. This latter position has been the one favored by psychiatric nosologists so that both the ICD-9 of the World Health Organization and the DSM-III of the American Psychiatric Association maintain at least one category for DD ‘.

TABLE

II.

affective

Demographic

illness

Demographic

characterics

of delusional

disorder

variable

DD

compared

with

compared

with

schizophrenia

(S) and

compared

with

AI

Similar

much

older

Sex

Patients

more

likely

to bc

Marital

status

female Patients more married

likely

to have

Social

background

at first

DD

S

Patients

Age

(DD)

(AI)”

admission

Place

of birth

Condition

after

treatment Length of hospitalization

been

more

More

Patients more immigrants

disadvantaged Patients more immigrants

likely

to be

Somewhat

on information

ousy’.

The justification

rcviewcd

in Ref.

to have likely

been to bc

less likely

9.

of this position

paranoia as a chronic disorder”.

How-

ever, in the 8th edition of his famous textbook on psychiatry he came to recognize ‘remitting’ forms of the disorder”. Scandinavian psychiatrists have also emphasized that ‘paranoid psychosis’ can often be a transitory clinical phenomenon. Although chronic and remitting forms of the disorder may be etiologically information,

re-

stricting DD to only chronic forms appears unjustified. However, it is important to differentiate DD from the very brief psychotic reactions (hours or days) that can occur under severe emotional stress or in certain unstable personality disorders. Table I presents the author’s proposed diagnostic criteria for DD. of

to be male

Longer

shorter

is uncertain, and at least one empirical review of relevant evidence does not support the position taken by the DSMIII’. Therefore, current criteria for DD do not restrict the delusional theme that may occur in the disorder. Kraepelin also originally regarded

given current

likely

Rccovcry

Similar

likely

Similar

Similar

“Based

distinct,

Patients

’

Proposed diagnostic criteria for delusional disorder

Demographic characteristics delusional disorder

In addition to the differential diagnostic problems outlined above, two further issues are important in formulating diagnostic criteria for DD: delusional themes and the duration of the disorder. When Kraepelin originally articulated the diagnostic entity of paranoia, he did not restrict the possible delusional themes that might occur in this disorder and specifically described cases with persecutory, grandiose, jealous and perhaps somatic delusions. Unlike all previous nosological systems, the DSM-III of the American Psychiatric Association restricts the delusional themes in ‘paranoid disorder’ to persecution and jeal-

In trying to summarize our knowledge of DD it is probably best to start with demographic characteristic?. These are useful both in providing important basic information about the disorder and in beginning to examine ways in which the disorder may or may not resemble schizophrenia and affective illness. DD is neither a very rare nor a very common psychiatric condition. Between 1% and 4% of first admissions, to in-patient psychiatric facilities have DD. Schizophrenia and affective ilhress are at least 10 times as common in this setting as DD. The best estimate of the population incidence of DD is between 1 and 3 new cases per

year per 100 000 general population. DD is primarily an illness of middle to late adult life, with a peak frequency of first admission between the ages of 35 and 55. In contrast, schizophrenia usually occurs between the ages of 18 and 35. There is a modest female preponderance of hospitalized cases of DD. Between 60% and 75% of patients with DD have been married by the time they fall ill. Patients with DD are frequently from socially disadvantaged backgrounds and are often immigrants. Table II summarizes the demographic characteristics of DD compared to schizophrenia and affective illness.

The demographic characteristics of DD do not closely resemble those found for either schizophrenia or affective illness. Like affective illness, but unlike schizophrenia, DD usually occurs in middle-aged patients who have been married. Like schizophrenia, but unlike affective illness, DD occurs more commonly in socially disadvantaged individuals and produces a poor chance for full recovery. Patients with DD are more likely to be immigrants than either patients with schizophrenia or patients with affective illness. Family studies of delusional disorder

In addition to demographic factors, family studies provide another important method for examining the relationship between DD and schizophrenia and affective illness. Many studies have shown that both schizophrenia and affective illness tend to run in families. If DD is a subtype of schizophrenia, then the risk of schizophrenia in the famihes of a patient with DD should resemble that found in the families of a schizophrenic (i.e. around 610%). If there is no relationship between DD and schizophrenia, then the morbid risk of sctio-

TlNS - Jmuary

16 TABLE delusional

III.

Prevalence disorder

Study

Kolle Retterstol Debray Winokur Watt Kendler

of schizophrenia

Numhcr patients 66 206 II 29 2-l I2

of

and

affective

Number rclalives

illness

in the first-degree

of

513 I 341 IL? I68 I27 5x

Nt = not tested.

phrenia in the relatives of DD patients should resemble that seen in the general population (i.e. around 1%). This approach is valid regardless of whether genetic or non-genetic factors are responsible for the familial clustering of schizophrenia. Table III summarizes the studies done on data examining the frequency of schizophrenia in the first-degree relatives of patients with DD. These figures are life-time prevalence rates. They would increase slightly if age correction were used to produce morbid-risk figures. All but one study found the prevalence of schizophrenia in the relatives of patients with DD to be less than 2%. While these findings, especially when age corrected, show a slightly higher risk than that found in the general population, they uniformly show a much lower risk than that reported in families of schizophrenics. One problem with the earlier studies is that they contained no control group and that the diagnoses of the probands were not made blind to the status of the relatives. These potential methodological deficiencies were corrected in the study of Kendler and Hays’. In this study, 147 clinicahy diagnosed schizophrenics on whom systematic family history data had been collected where examined blindly and 12 were re-diagnosed as having DD. When the blind was broken, the prevalence of schizophrenia in the families of the schizophrenics was over 5 times higher than that found in the families of the patients with DD. This difference is statistically significant. Further evidence against a genetic link between schizophrenia and DD was provided by a reanalysis of the interviews by Kety et al. with relatives from the Danish Adoption Study of Schizophrenia’. Using DSM-III diagnoses, schizophrenia spectrum disorders (schizophrenia and schizotypal personality disorder) concentrated heavily in the biological relatives of the schizophrenic adoptees. This pattern was not seen for

Schizophrenia

relatives

Prcvalencc of Affcctivc

I .06 I .6%1.45

of patients

I.‘% o.xr/; I .7%

phrenia, the results of two studies**” showing that the risk of affective illness is actually lower in relatives of DD patients compared to schizophrenic patients is further evidence for the familial independence of DD and affective illness.

with

Re Is illness

1.1% . O.JV 4.93 ‘7.4%

IO I4

Diagnostic stability of delusional disorder

I7 I6 x

Nl 3.4%

1984

For patients with DD, far fewer longterm follow-up studies than family studies have been published. If DD were a subtype of schizophrenia, it would be cases of DD. The distribution of cases reasonable to expect that over time a of DD and schizophrenia spectrum dis- substantial proportion of cases of DD orders differed significantly in the would develop signs of classic schizophrenia. On the other hand, if DD were relatives. a subtype of affective illness, one would Fewer investigators have examined the familial relationship between DD expect a substantial proportion of cases and affective illness. These investiga- of DD to later display a full affective tions. the results of which are also seen in syndrome. Four studies, outlined in Table III, are somewhat more difficult Table IV, have examined the diagnostic to interpret than those regarding schizo- stability of DD over substantial periods phrenia because of the wide variation in of time. The diagnostic consistency of the reported prevalence of affective ill- DD in all four studies was high, i.e. ness in the general population. Dependbetween 78% and 93%. These figures ing on how affective illness is defined. compare favorably with the diagnostic the population prevalence of the dis- stability found for schizophrenia or affecorder ranged from 1.5% to 7%. The tive illness - usually found to be in the prevalence of affective illness in the range of 65-90%. However, in each first-degree relatives of patients with study a small percentage of patients with affective illness ranges from 12% to DD, between 3% and 22%) did develop around 30%, The frequency of affective schizophrenia on long-term follow-up. illness in the relatives of patients with Far fewer developed affective illness. DD resembles that found in the general These results suggest that in a small population and not in the relatives of percentage of cases, DD may represent patients with affective illness. For a prodromal manifestation of a schizoexample, the frequency of affective ill- phrenic psychosis. However, the vast ness found in the relatives of patients majority of cases of DD remain diagwith DD by Debray (i.e. 4.Y’C) (&rtle nostically stable and evolve neither gh!tiques des dt%res chroniques. thesis. schizophrenia nor affective illness. University of Paris, 1974) was exactly that found in a normal population, using Summary and future directions similar diagnostic criteria. While Wmokur In summary, the data outlined here found the rate of affective illness in (demographic family data and follow-up relatives of DD patients to be 2.4%, data) support Kraepelin’s viewpoint using similar methods he found the rate that DD is a syndrome that is not closely of affective illness in relatives of affec- related to either schizophrenia or affectively iIl patients to be 13.5%. Since tive illness. Other approaches, such as nearly all studies show no familial link comparing premorbid personality and between affective illness and schizo- performance on psychological testing TABLE Study

IV.

Diagnostic

stahility

Number patients

of

of delusional Follow-up period

disorder Slahility

Proportion later

0r patients dcvcloping Rcls

Schizophrenia Facrgeman Johanson Retterstol Winokur

9 52 I63 29

IS years Few months44 years S-15 years Few month+ 20 years

7x5 xxrir

22% 12%

8I%

13 R

943

w/r

Affective

illness 0% 0%

2 3

6% 6%

13. IS I7

TINS - Januaq~ 1984

17

Kendler. K. S. (1982) Arch. Gen. fsychiaWy (reviewed in Ref. 4) further support this response rate of this condition is un39. 89C-902 known, it is difficult to interpret these conclusion. While it is probable that a Kendler. K. S., Gruenberg, A. M. and Strauss, small subgroup of cases of DD may be a results. Nothing is known about the J. S. (1981) Arch. Gen. Psychiatry 38.985-987 prodromal manifestation of schizo- proper role of psychological or social Kendler. K. S. and Hays, P. (1981) Arch. Gen. therapies in treating patients with DD, phrenia, our current state of knowledge Psychiar? 38. 547-55 1 Kendler, K. S. and Twang. M. T. (1981) suggests that DD should be considered but again clinical experience suggests Schizophr. Bull. 7. 594-610 a third major form of ‘functional’ psycho- that it may be an important one. PlaceboKolle, K. (1931) Die frimare Verruckhei!, controlled treatment trials in DD of sis independent of both schizophrenia Thieme. Leipzig both pharmacological and non-pharmaand affective illness. Kraepelin. E. (1904) Clinical Psychiatry: While schizophrenia and affective ill- cological modalities are needed to proA Textbvok for Studem and Physiciams ness have been the focus of major re- vide clinicians with a scientific basis for (Delendorl. A. R.. trans.). Macmillan. New search efforts in the last several decades, the treatment of patients with this synYork E. (1976/reprinl) 12 Kraepelin. Manic-Depressive drome. Given good evidence that little research has been done on DD. lnsani~ and Paranoia (Barclay, R. M.. trans.). Although DD is rarer than either schizo- Kraepelin was correct in regarding DD Arno. New York as a distinct psychotic illness, our ignorphrenia or affective illness, the best Retterstol. N. (1966) Paranoid and Paranoiac estimates of the number of first psychi- ance regarding the etiology, diagnosis, Psychoses. Thomas. Springfield. IL atric admissions for DD in the USA per prognosis and treatment of this disorder Retterstol. N. (1967) Nord. Pxykiarr. Tidsxkr. year is around 3 000. Research in DD is is increasingly difficult to justify. 21. 185-194 particularly needed in four areas. First, Retterstol. N. (1970) Prognosis in Paranoid Psychoses. Thomas. Springfield, IL almost nothing is known about the etio- Reading list Watt. J. A. G., Hall. D. J., Olley. P. C.. logy of DD, from either a psychosocial 1 American Psychiatric Association (1980) DiugHunter, D. and Gardiner. A. 0. (1980) Acfa or a biological perspective. The increased nosric and Statistical Manual of Mental DbPsychiatr. Stand. 6 1. 4 13-426 rate of DD in immigrants suggests that orders. 3rd Edn. American Psychiatric Associ17 Winokur. G. (1977) Compr. Psychiarry 18, psychosocial factors may play a role in ation. Washington. DC 51 I-521 2 Faergeman. P. M. (1963) Psychogenic Psythe pathogen&s of this syndrome. While c/loses, Butterworth. London our increasing knowledge of neuro3 Johanson. E. (19&l) Am fsychiurr. Stand. Kenneth S. Kendler & at lhe Deparrtnenr of Psy biology has been enthusiastically applied Suppl. No. 177 chiat? and Schizophrenia Biologic Reseurch Cetrrer, to the production and testing of bioBrom Vererans’ Administration Medical Center 4 Kendler. K. S. (1980) Arch. Gen. PJychiurq logical theories on the etiology of schizo37. 699-706 and MI Sinai School of Medicine. Brons. NY phrenia and affective illness, no major 5 Kendler. K. S. (1980) Schizophr. Bull. 6. l-3 10468. USA. attempt has yet been made to identify neurobiological abnormalities in patients with DD. Second, there remain a number of important diagnostic issues about DD that need to be clarified. Such issues include the relationship between Frank Solomon remitting and chronic forms of DD; the relationship between the more common DD syndrome of persecutory delusions The singular shapes of neurons are the fundamental element of neuronal architecture. and the rarer DD syndromes that pre- We now have a significant body of experimental work, on neuronal and nonsent somatic, jealous or grandiose delu- neuronal cells, which suggests how those shapes might arise: the cellular machinery sions; and the precise diagnostic involved and how that machinery is guided to produce a particular form. Recent boundary between DD and paranoid studies have underscored the complexity of interactions within the cell, and between schizophrenia. A third area of research the cell and its environment, that we will need to understand, needed in DD is that of prognosis. Current evidence suggests that a small The morphological hallmarks of neuronal The formation of growth cones Experimental observations on cells in subgroup of patients presenting with cells are the processes they extend, the axons and dendrites. that form the func- culture enable us to form a description DD go on to develop schizophrenia. Since the treatment of such individuals tional connections between neurons and of the morphological events that lead to should probably differ from that given other cells. Their role in physiology the expression of their differentiated to other patients with DD, it is imporundoubtedly underlies the invariance of shape. All cells that are the products of tant to perform follow-up studies to form displayed by single identified cells mitotic fission begin as essentially spheridevelop means of identifying such from individual to individual. For the cal objects, except that in culture they patients. The fourth and most crucial student of neuronal architecture the are flattened along the ventral surface area in which research is needed in DD crucial issue is the nature of the informatouching the substratum. Spreading is that of treatment. No placebo-contion that specifies these patterns. Does begins with the extension of slender trolled, double-blind treatment study of it reside within the cell, or in its environfilopodia which wave about in the surany modality in DD exists in the psychi- ment? In what form is that information rounding growth medium. If in their atric literature. Uncontrolled studies stored and transmitted, and how is it waving they encounter another cell. the and clinical experience indicate that anti- translated into the events that produce filopodia frequently retract. This bepsychotic drugs are helpful in this condo- neuronal form? Approaches to these havior has led to the suggestion that the tion. Uncontrolled reports have also questions may be found in a detailed tilopodia serve a sensory function, explorsuggested that lithium or tricyclic anti- examination of the behavior of neuronal ing the substratum’. Attachment of the depressants may be helpful to some and non-neuronal cells as they elaborate filopodia is followed by spreading of patients with DD. Since the placebo their characteristic morphologies. larger projections of membrane called

Determinants of neuronal form