kasus referat tentang delirium

8/12/2019 kasus referat tentang delirium

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Chapter 6

Reality d istort ion

Nat ure of hallucinat ions and delusions

Hallucinations and delusions, the phenomena that lie at the heart of psychosis,are perhaps the most enigmatic of all mental symptoms. Both entail a mismatchbetw een a compelling representat ion of reality produced by th e individuals ow nmind a nd t he representat ion supported by objective evidence. In ma ny psychoticillnesses they tend to occur together; they tend to follow a similar time course;and they respond similarly to antipsychotic medication. This suggests that theyshare ma jor aspects of th eir pathophysiology irrespective of t he illness in w hichthey occur. Studies employing factor analysis to examine the relationshipsbetween symptoms confirm that delusions and hallucinations usually load on a

single factor in various psychotic illnesses, including schizophrenia (Liddle,1987a; Malla et al , 1993) and affective psychosis (Maziade et al , 1995). Thischapter examines the evidence regarding t he nat ure of th e pathological processesthat give rise to these tw o core psychotic phenomena.

A hallucination can be defined as a perception with the quality of a sensoryperception but n ot derived from st imula tio n of a sense organ . Typically, apsychotic patient assumes falsely that the origin of the perception lies in theexternal world. In those instances where the patient recognises that theperception arises from within his/her mind, the experience may strictly bedescribed as a pseudo-hallucination. D uring the acute phase of illness, it is quit ecommon for hallucinations to be perceived as arising in the external world. Asthe acute episode resolves and insight returns, some patients recognise that it

arises from w ithin, w hile none the less st ill experiencing the abnormal perception.In this book we shall follow th e Di agnosti c and Stati sti cal M anual (DSMIV) of theAmerican Psychiatric Association (1994) in using the term hallucination forboth real and pseudo-hallucinations . However, the fact that this distinctioncan be made emphasises tha t a fully fledged hallucination involves both aberrantperception and impaired recognition of the o rigin of t he experience.

A delusion can be defined as a firmly fixed belief that is derived by erroneousinference or unjustified assumption, and that cannot be accounted for on thebasis of culture or religion. It is usually, but not necessarily, false. The essential


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issue is not the falsity of the belief but rather the lack of rational grounds for

holding it. The classic illustration of a situation in w hich a belief may in fact betrue, but n one the less delusional, is provided by the O thello syndrome, in w hichthe patient vehemently maint ains tha t his/her spouse has been unfaith ful on thebasis of irrational argument. The belief is sometimes held with such blindpassion that the spouse s life is in dang er. The condit ion is diagn osed on t he basisof the irrationality of the argument rather than t he question of whether or not thespouse has in fact been unfaithful.

Some delusions appear to arise via an unreasonable extrapolation fromevidence, such as I know the security services are spying on me because astranger looked at me in the st reet . Such instances, at first sight, suggest that theessential issue in delusional thinking is a faulty process of logical deduction.However, a psychotic individual does not exhibit a generalised failure of theprocesses of logical inference. As we shall discuss in greater detail in the sectionbelow concerned w ith n europsychological correlates of reality distort ion, logicalthinking is intact under many circumstances. In psychosis, it appears that a few ideas are mentally labelled in a way that makes them immune to the normalprocess o f evidential evaluation.

In an attempt to define the nature of the mental processes that underliedelusions and hallucinat ions, it is instructive to compare the distortion of realitythat is characteristic of psychotic illness with the distortions of thought andperception that can occur in non-psychotic illnesses. In many instances, a clearbasis for the distinction between psychosis and neurosis can be formulated,although in clinical practice the boundaries often become blurred. An adequateaccount of the mechanism o f psychosis must be able to account not only for thedistinguishing features but also for the frequency with which the boundaries

become blurred.

Comparison of psychotic and non-psychoticdistort ions of reality

In principle, a delusion can be clearly distinguished from the dist orted t hinkingthat occurs in neurotic conditions, such as obsessional disorder and non-psychotic depression, on the grounds t hat the neurotic patient recognises theirrationality of the belief, and the idea is at least partially amenable toexamination by rat ional argument.

Obsessional ruminations

Obsessional ruminations are intrusive thoughts that the patient experiences asalien, in the sense of being contrary to his/her own values or intentions, butwhich the patient none the less recognises as arising from within his/her own


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mind. The content of the ruminations can be quite bizarre in some instances.

None the less, the patient recognises them as an unwanted intrusion andusually resists them.For example, a conscientious young w oman , w hom w e shall call Jane, became

preoccupied by the fear that if she bought new clothes for herself she wouldbecome possessed by the devil. She had been brought up as a strict Christian,with a strong sense of right and wrong. In her childhood she believed that evilideas arose from t he prompting of t he devil. In early adultho od, she ha d rejectedthe simple piety of her childhood, and no longer a ttended church regularly. At asuperficial level, she no longer believed in the devil. However, she retained astrong sense tha t self-indulgence wa s w rong, and it is scarcely surprising tha t t hetemptation to spend money on clothes for herself rekindled her childhoodconviction that such temptations came from the devil. However, even sherecognised that the fear that she would become possessed by the devil was farbeyond the scope of her childhood beliefs. None th e less, despite recognising thatthis was a silly idea that arose from her own mind, she developed a state ofoverwhelming panic if she attempted t o go into any sort of sho p, even if only tomake quite mun dane purchases. Avoidance of shops seemed to be the only w ay tokeep the panic at bay. Ironically, her recognition of the irrationality of the ideacaused her to question her own sanity and she became intensely agitated by theprospect that she was going mad.

In contrast t o a deluded patient, Jane wa s able to identify the intrusive idea asa product of her own mind. She wa s even able to ascribe it, quite reasonably, to aninteraction betw een her overconscientious nat ure and puritanical aspects of herupbringing, but such rationalisation provided her with little consolation. Herrumination intruded with such force as to dictate her behaviour and dominate

her life. In a st ate of t orment, she eventually w ent t o see a psychiatrist. The factthat much of her torment arose from the fear of being eventually overwhelmedand unable to resist the idea of possession by the devil pointed to a diagnosis ofobsessional neurosis rather than psychosis. Treatment wit h t he serotoninreuptake inhibiter sertraline, augmented by cognitive behaviour strategies,directed at restoring her confidence in her ability to go shopping, led to a gra dualresolution of her symptoms.

Despite the difference in principle between obsessional ruminations anddelusions, the ability to recognise that an obsessional idea is unreasona ble variesbetw een individuals. In some insta nces an idea may be resisted at early phases ofthe illness but eventua lly the ability to discern what is real is lost. In a survey of475 patients with obsessive compulsive disorder (OCD), Eisen & Rasmussen(1993) found tha t 14% had psychotic sympt oms a nd 4% met the full diagnost iccriteria for schizophrenia. According to DSM IV, an additional diagnosis ofdelusional disorder, or psychotic disorder not otherwise specified, should bemade in cases of OCD with psychotic symptoms.

Conversely, in a substantial number of cases of schizophrenia, the patientexperiences unwanted, persistently intrusive ideas, and recognises them to beunreasonable. For example, betw een psychotic episodes, a conscientious youn gman w ith schizophrenia was torm ented by the fear tha t he might sexually molestthe child of a member of the congregation at the church he attended. Under-


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standably, this thought led him to question the nature of his own sexuality, but

he was quite able to distinguish his fear of molesting a child from reality.However, subsequently, at a time when the newspapers were dominated byaccounts of a sexually motivated murder, he suffered a psychotic relapse andturned himself in to the police, confessing to the murder. The police had nodifficulty in establishing t hat he could not h ave been t he murderer, and b roughthim to hospital.

Such cases imply that delusion formation involves both the mental (andneural) mechanisms by which ideas are generated and the mechanisms by w hichthey are evaluated, but the essential characteristic of delusional thinking is afailure of the mechanism for evaluating ideas. In OCD , compelling, unreasonableideas can arise, but t he individual none t he less correctly recognises that they areunreasonable. When th e ability to evaluate these ideas is lost, the borderline thatseparates OCD from psychosis is crossed.

Depression

Even in n on-psychotic depression, evaluation of on eself and the wo rld is usuallydistorted. Depressed people tend to see themselves as worthless and the futureas blea k. As Beck et al (1979) have emphasised, there is often a n all-or-nothing character to such depressive thoughts. However, a person with non-psychoticdepression can be engaged in debate about the basis for their beliefs. Confront-ationa l debate rarely alters th e depressed person s evaluation of t he evidence, butSocratic dialogue can produce a shift in that evaluation (Beck et al , 1979). Theproblem appears to be a bias in att ending to perceptions an d in the generation of

ideas; there is also evidence of a disorder of the evaluation of ideas, insofa r as adepressed person finds a negative interpretation of t he evidence more com pellingthan a positive interpretation. None the less, the patient with a milder form ofdepression is usually able to recognise that perceptions and ideas mu st pass a testof th eir plausibility before they can b e accepted. With increasing s everity, how ever,depressive thinking can become psychotic and no longer amenable to reason.Typically in depressive psychosis, the cont ent of delusio ns is an exaggera tion o fthe self-devaluing or guilty thoug hts characteristic of non -psychotic depression.The individual may also experience derogatory auditory hallucinations. Lesscommonly, the content of delusions and hallucinations can be non-congruentwith the depressive mood.

As in th e case of the relationsh ip between obsessional thinking and delusions,the relationship between depressive cognitions and delusions implies that themechanism involved in the generation of ideas and also that involved in theevaluation of ideas are implicated in t he format ion of delusions. In non-psychoticdepression, the mechanism of evaluation operates, but with a pronounced biastow ards negative evaluation. How ever, wh en the evaluation m echanism no longeroperates, the depression becomes psychotic. It is the failure of evaluation thatdefines it as psychosis.


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Reality distortion in psychosisDelusions and hallucinations commonly occur in schizophrenia, mania, psychoticdepression and in psychosis arising from overt brain injury or degeneration. It is a nintriguing fact tha t t he majority of delusions and h allucinat ions express ideas draw nfrom a limited set of approximately a dozen themes related to relationships withothers; self-identity an d w orth; a nd supernatural o r existential issues. These themesinclude persecution; alien control of thoughts, feelings or actions; religion;grandiosity; an d guilt. The them es tend t o differ betw een conditions. For example,delusions of guilt are especially common in depressive psychosis. Delusions ofreference, which entail the belief that the conversation or behaviour of nearbypeople, objects in the environment, or events, has a specific significance for oneself,

are also comm on. The specific content of a delusion or hallucination is influencedby contemporary cultural issues, but similar themes can be identified across timeand culture, and th is suggests tha t t hey reflect universal features of mental structure.

Schizophrenia

A diverse range of t ypes of delusion and hallucination occur in schizophrenia. Forexample, in t he Internat ional Pilot Study of Schizophrenia conducted by t he WorldHealth Organization (1978), second-person auditory hallucinations occurred in35.6% of sub jects; persecutory delusions in 51.8%; an d delusions o f reference in49.6%. Furth ermore, relat ively rare delusiona l themes, su ch as delusiona l

misidentification, delusions of parasitic infestation, and erotomania, occur inschizophrenia, even though they are perhaps more typically seen in instances ofovert brain injury or other special circumstances. The overall diversity of types ofreality distortion occurring in schizophrenia is consistent with the evidence,discussed in greater detail in Cha pter 11, tha t t he pathophysiology of schizophreniaentails a subtle ma ldevelopment affecting virtually all areas of t he cerebral cortex,resulting in the disruption o f an extensive range of aspects of ment al processing.

A particular type of delusion that is characteristic of schizophrenia, and w hichillustrates an important aspect of reality distortion, is the autochthonousdelusion, a delusional belief that arises without any identifiable mental ante-cedents. The belief arises as a fully formed not ion t hat has n ot been inferred inany discernible way from evidence. In particular, it is not possible to identify afault in logical deduction; rather, there appears to be a failure to recognise thatthe idea demands logical justification. For example, a schizophrenic patientmaint ained that his head had been split by an axe. He denied that this w as in anyway a figurative expression and insisted that it had really happened, despite hislack of ability to produce any grounds for his belief. The occurrence of autoch-thonous delusions suggests that the process of delusion formation can bypasslogic rather than distort it.


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Further evidence that delusions entail exemption from logic rather than

faulty logical deduction is provided by the clinical observation that, in manyinstances, schizophrenic patients can discern the logical inconsistency in theirbelief, and acknowledge that others would not accept it, but none the lesscontinue to believe it.

For example, an intelligent young man suffering from schizophrenia wasadmitt ed to hospital after stabbing him self. He reported tha t he had been stabbedby an evil person na med Michael, although h e himself had been t he only personpresent at the time, and he admitted that he had held the knife. He maintainedthat the act w as none t he less the act of Michael. He spoke of Michael as of a realperson who controlled his actions. Several mont hs later, when h e had recoveredfrom th e episode of acute psychosis, he still claimed tha t he ha d been stabbed byMichael. When presented wit h th e evidence that he had been alone and had heldthe knife himself, he readily acknowledged that , in light of this evidence, othersmight conclude that he had stabbed himself; this demonstrates that his capacityfor rational evaluation of the relevant evidence was intact. None the less, heappeared to assume that his explanation of the origin of his experience wasexempt from logical re-evaluation.

One of the clearest illustrations of the way in which the delusional beliefs ofschizophrenic patients a ppear t o be exempt from logic is provided by the h istoriccase of D aniel Schreber, a high-ranking judge from Leipzig who suffered a late-onset schizophrenic illness. Schreber s account (Schreber, 1955; see also Spitzeret al , 1989) is of special value for illustrating t he nat ure of delusions, because, byvirtue of h is keen intellect, w e have access to his ow n perceptions of his condit ion,in addition to det ailed accounts by his physicians. H is first psychotic episode wasat the of age 42. He subsequent ly suffered a more protracted episode in 1893, at

the age of 51, when facing a heavy burden of work after appointment as PresidingJudge at th e Appeal Court in D resden. He w as discharged from hospita l in 1902,but eventually suffered a th ird episode of illness, after his w ife suffered a st roke,and he remained in an uncommunicative, disorganised state until his death.

After obtaining a court order for his discharge from hospital in 1902, hepublished his memo irs in a volume tha t includes his ow n account o f his beliefs,and also the report prepared by the asylum director, Dr Weber, opposing hisdischarge. Schreber believed that he had a mission to redeem the world andrestore mankind to its lost state of bliss. His system of delusions included thebelief that he w as being transformed into a voluptuous female partner of God. D rWeber reported that, in 1902, Schreber continued to maintain his delusionalbeliefs in a manner that would accept no contrary argument, although heexhibited a lively interest in h is social environment an d had a w ell informed mindand sound judgement. Schreber himself agreed that his beliefs were unchange-able. He considered that t hey belonged to a domain t hat w as exempt from normallogic. I could even say w ith Jesus Christ: My kingdom is not o f this w orld; my so-called delusions are concerned solely with Go d and t he beyond.

In man y instances, the delusions of schizophrenia appear to arise from an alt eredexperience of self or of external reality. The phenomena identified by the Germanpsychiatrist Kurt Schneider (1959) as the first-rank symptoms of schizophrenia(discussed in greater deta il in Chapter 11) include several symptoms tha t ent ail an


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aberrant experience of ownership of one s own thought, will, action, emotion or

bodily function, which the patient attributes to alien influence.The experience of alien control of action in schizophrenia can be remarkablysimilar to the experience reported by individuals who have suffered an injury tothe supplementary mot or area located on the m edial surface of the brain ant eriorto the primary motor area. For example, Mellor (1970, p. 18) describes a schizo-phrenic patient who reported: my fingers pick up the pen but I don t controlthem I sit there watching them move but they are quite independent. Whatthey do has nothing to do with m e. Compare this with a n account of a patientwit h a lesion of the supplementary moto r area: at one point it w as noted that thepatient ha d picked up a pencil and begun scribbling with the right hand. She t henindicated that she had n ot h erself initiated t he original action. She experienced afeeling of dissociation from th e actions of th e right arm, st ating o n several occasionsthat it will not do what I w ant it to do (Goldberg et al , 1981, pp. 684 685).

It appears that in both the psychotic individual and in the patient with aninjury to t he supplementary m otor area t here is a disruption of t he neural circuitryresponsible for identifying on eself as the source of one s own actions. However,whereas the patient with traumatic injury to the supplementary motor area canusually recognise tha t he/she is suffering an abnorm al, albeit compelling, experiencethat has arisen from an injury, the psychotic patient not o nly suffers the abnorm alexperience of alien influence, but also has an impaired ability to identify thesource of that experience, and does not subject it t o a t est of its veracity.

Although studies employing factor analysis to delineate the relationshipsbetw een schizophrenic symptoms demon strat e that delusions and hallucinat ionshave some factor in common, there is also substantial evidence that particularsubgroups of delusions and hallucinations can be distinguished on facto r analytic

grounds. In particular, within the range of reality distortion symptoms that areprevalent in schizophrenia, tw o ma jor subgroups load on distinguishable factors(Liddle, 1987a). One fa ctor ha s high loadings on Schneiderian first-rank symptom s,such as delusions of control, audit ory hallucinations in the t hird person, as w ellas bizarre delusions. Most of the items loading on this factor are related to theissue of aut onomy, and are fairly specific to schizophrenia. The second factor hashigh loadings on persecutory delusions, grandiose d elusions and second-personhallucinat ions. The phenomena a ssociated w ith t his second factor are concernedwit h the relationship between self and others, and are relatively commo n in otherpsychotic illnesses. The tw o factors are moderat ely correlated w ith each other.

Thus examinat ion of the relationships betw een reality distort ion symptom s inschizophrenia supports the proposal that there is a pathological feature commonto all manifestations of reality distortion, but, in addition, a distinct factor,possibly associated w ith disorders of th e experience of autonom y, contributes t oa subgroup of symptoms that is relatively specific for schizophrenia.

Affective psychosis

As mentioned previously, t he delusions a nd hallucinat ions of affective psychosistend t o be mood congruent . In depression, delusions focus on them es of low self-


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worth, guilt or pessimism, while auditory hallucinations tend to be critical.

Conversely, during m anic episodes, delusions of grandiose identity or ability a recommon. The content of hallucinations often serves to confirm the exaggeratedself-esteem characteristic of mania.

While the existence of mood-incongruent delusions might give grounds forquestioning a diagn osis of a ffective psychosis, the occurrence of psychotic illnessdominat ed by mood disturbance but including mood-incongruent delusions and/or hallucinations undoubtedly occurs. Persecutory delusions are relativelycommon. Schneiderian first-rank symptoms occur in about 10 20% of cases(O G rady, 1990), compared w ith a prevalence of abo ut 60% in schizoph renia(Mellor, 1970). According to the DSM IV criteria, a diagnosis of m ood disorderwith psychotic features is made when delusions and/or hallucinations occurduring an illness dominat ed by a m ajor mood disorder, irrespective of wheth er ornot t he content is mood congruent, un less there is a period of at least tw o w eekswhen delusions or hallucinations are present in the absence of major mooddisturbance.

It is important to note that reality distortion in affective psychosis does notappear merely to be an inevitable consequence of severe mood disturbance,although t he bias in thinking associated wit h the mood disturba nce can shape itscharacter. Many patients suffer repeated episodes of severe unipolar depression,perhaps w ith gross psychomot or retardation or w ith marked agitation, yet do notdevelop delusions or hallucinations. The mood disorder and reality distort ion aredistinguishable dimensions of psychopathology that none the less interact.

Alzheimers disease

Various hallucinations and d elusions are encountered in a subst antial m inority ofcases of Alzheimer s disease. In a thorough study of 56 patients who wereassessed clinically in life and received a definitive diagnosis of Alzheimer sdisease at post-mortem examination, Forstl et al (1994) found the most commonform of psychotic symptom was delusional misidentification, which occurred in25% of t heir cases. Visual ha llucinatio ns occurred in 18%, para noid d elusions in16% and audit ory h allucinat ions in 13%.

The category of delusional misint erpretat ion embraced several similar types ofphenomena, of which the most common was the misidentification of otherpeople. It is likely that it reflects a disorder of the circuitry specialised for therecognition of familiar faces. O nly 29% of th e cases exhibiting delusionalmisidentification exhibited paranoid delusions, which indicates a relatively low degree of overlap in the pathophysiology of delusional misidentification andparanoid delusions. On the other hand, among t hose with audit ory hallucinations,57% had visual hallucinat ions an d 57% had paranoid delusions, w hich show sthat there is a tendency for hallucinations in one modality to be associated withhallucinations in a different modality and also with paranoid delusions.

Thus, in Alzheimer s disease as in schizophrenia, a diverse range of psychoticphenomena occur, although they are somewhat less prevalent in Alzheimer sdisease. Some phenomena, such as paranoid delusions and audit ory hallucinations,


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are common in other psychotic illnesses; others, especially delusional mis-

identification, are common in Alzheimer s disease and relatively rare in otherconditions. It is of interest to note that the neuropathology of Alzheimer sdisease, like that of schizophrenia, appears to affect w idespread areas of t he cerebralcortex, with t he most severe tissue loss in the medial temporal regions, particularlyin the para hippocampa l gyrus (Hubba rd & Anderson, 1981). How ever, in contra stto schizophrenia, w here the path ology is quite subt le and possibly involves lossof neuropil rather t han cell bodies (Ch apter 11), Alzheimer s disease is character-ised by progressive degeneration of both cell bodies and neuropil.

Overt brain injury and epilepsy

There is a great deal of overlap between the phenomena of schizophrenia andpsychosis arising from overt brain damage or degeneration, although at leastsome stu dies indicate t hat visual hallucinations are more prevalent in psychosisarising from overt cerebral damage t han t hey are in schizophrenia (Goodw in et al ,1971). The possibility of identifying t he relationsh ip betw een form and /or contentof reality distortion an d th e site of cerebral damage in cases of focal brain injuryhas prompt ed man y clinical reports. In a comprehensive review of such reports,Davison & Bagley (1969) concluded that lesions of the temporal lobe anddiencephalon are particularly significant in t he genesis of psychosis.

Tempora l lobe epilepsy, a condit ion chara cterised by aberra nt n eural activit yrather than a deficit in neural activity, is associated with a schizophrenia-likepsychosis characterised by delusions and hallucinations, including Schneiderianfirst-rank symptoms, but with less of the disorganisation and psychomotor

poverty seen in schizophrenia. Of th e 69 patients w ith psychosis associated withtemporal lobe epilepsy studied by Slater et al (1963), 67 had delusions in clearconsciousness an d 52 suffered ha llucinations in clear consciousness, but only 31exhibited forma l thou ght disorder and 28 exhibited loss of affective responses.

Conclusions from clinical observations

The pat tern of occurrence of delusions and hallucinations in various conditionssupports the proposal t hat these core features of psychosis share a cardinal aspectof th eir pathophysiology. The similarities betw een delusions and h allucinationsoccurring in diverse disorders, and t he fact th at a ntipsychotic medication can beeffective in treating these symptoms irrespective of diagnosis, implies that theshared cardina l pat hophys iological feature can occur in several different disorders.None t he less, the differences in t he frequency of specific types of delusions andhallucinations in various conditions suggest that there are aspects of theirpathophysiology that are more strongly associated with the specific pathologicalprocesses causing particular illnesses.

In general, the evidence suggests that psychotic reality distortion involves atleast two stages. The first is the generation of a specific aberrant mental event.The neuronal system involved in this stage would be that specialised for


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processing th e relevant type of informa tion. The second sta ge, w hich is specific to

psychotic illness, appears to be a failure of the mechanism th at evaluates mentalevents a s they ent er consciousness. Such a failure might enta il malfunction of aneural system specialised for the evaluation of mental events, or result from amiscommunication between the neural system in which the aberrant mentalevent was generated and the neural system mediating conscious awareness.

With regard to specific brain loci in the network, the temporal lobe isimplicated not only by the specific association of these symptoms with overttemporal lobe lesions and t emporal lobe epilepsy, but also because the t emporallobe is heavily involved in the n europathology of schizophrenia (see Chapter 11)and Alzheimer s disease (Hubba rd & Anderson, 1981), tw o conditions in w hicha diverse range of reality dist ortion phenomena o ccur.

Neuropsychological correlat es ofreality distort ion

In many individuals exhibiting psychotic reality distortion, there is a markedcontrast between the dramatic mental aberration generating the delusional ideaor hallucinatory experience and t he patient s ability to perceive and think in anapparently normal man ner in other doma ins. Furthermore, various studies haveshow n tha t deluded schizophrenic patients do n ot differ significantly from normalindividuals in their ability to make rational deductions (e.g. Williams, 1964).

Thus t he cardinal abno rmality is unlikely to be a generalised failure of reasoning.Although it appears that impaired deductive reasoning is not relevant, various

investigators have proposed that delusions are associated with a deficit in theability to m ake judgements based on probabilistic evidence. In a stud y designedto t est this hypothesis, Huq et al (1988) presented deluded schizo phrenic patient swith beads drawn one at a time from a jar containing unequal numbers of beadsof tw o colours, and asked them to predict the colour of the majority of the beadsin the jar. The schizophrenic subjects tended to reach their conclusion after beingshown fewer beads but made no more errors than healthy controls. On average,the schizophrenic patients ma de their choice when th ey had enough informat ionto give a 95% probab ility of being correct, a level eq ual to t he probabilit ythreshold conventionally accepted by statisticians, whereas healthy controlswaited until the probability of error was less. Thus, this study indicates thatdeluded schizophrenic subjects are competent at judgements based on probabil-istic evidence, but tend t o be less conservative in reaching decisions t han healthycontrol subjects. Unfortunately, the design of the study did not rule out thepossibility that this difference was due to greater impulsiveness, unrelated todelusional thinking, in the patients.

A variety of deficits or biases in the processing of information have beenreported to be associated with features of reality distortion, and these arediscussed under separat e headings below.


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Peripheral sensory processes

Clinical observation suggests an association between deafness and paranoidpsychosis in t he elderly. Formal testing of audit ory acuity reveals an a ssociationbetween subtle hearing impairment and auditory hallucinations in patients withsevere persistent schizophrenia (Matt hew et al , 1993). H ow ever, m ost psychoticpatients are not deaf, and th is is unlikely to be the principal factor leading to t hegeneration of hallucinations.

Attributional style and biased processing of information

In a series of studies of the at tributiona l style of patients suffering from paranoidpsychosis, Bentall (1994) has found evidence that patients with persecutorydelusions tend to attribute negative outcomes to causes external to themselves.This bias appears to reflect selective processing of information, as revealed bytypes of error on memory and attentional tasks.

Disturbance of figureground perception

Several studies have found an association of moderate strength between realitydistortion an d an impaired ability to distinguish a line draw ing of a figure from adistr actin g ba ckground (Robert son & Taylor, 1985; Liddle, 1987b). Evidencefrom studies of animals indicates that the hippocampus plays an important rolein distinguishing figure from ground (G ray, 1982).

Monitoring of self-generated mental activity

Heilbrun (1980) found that patients with auditory hallucinations have animpaired ability to recognise the origin of thoughts that they themselves havegenerated. Collicut & Hemsley (1981) proposed t hat hallucinat ions arise from abias in the attribution of the origin of mental events such that unexpected,internally generated experiences are attributed to external events. In a studydesigned to test t he hypothesis that hallucinations are associated with a t endencyto judge internally generated stimuli as arising from external sources, Bentall &Slade (1985) compared schizophrenic subjects suffering from hallucinations w ithnon-hallucinating schizophrenic subjects in their ability to distinguish auditorystimuli consisting of a voice plus noise from stimuli conta ining noise alone. Thetw o groups of pat ients achieved a similar level of correct identifications, but thepatients w ith ha llucinations w ere more likely to report stimuli as voices than asnoise alone. The authors interpreted this finding as evidence that patients withhallucinat ions are mo re likely to report imagina ry events as real.

Implicit in the hypot hesis that hallucinations arise when int ernally generatedmenta l events are att ributed to an external source is the assumption t hat t here isa mechanism for monitoring internally generated mental activity. Frith & Done


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gyrus and hippocampus. Furthermore, the area of parahippocampal activity

coincided with an area that is activated in normal individuals during theperformance of a n ovel eye movement t ask designed to place heavy demand s onthe need for internal m onitoring of self-generated movements ( Frith et al , 1992).Liddle et al (1992) also found evidence for aberrant activity at several othercerebral sites. In particular, they found overactivity in the ventral striatum andleft ventrolat eral prefrontal cortex, together w ith underactivity in the left lateraltemporal/parietal cortex and posterior cingulate.

In a subsequent SPET study of acutely ill schizophrenic patients, Ebmeier et al (1993) confirmed the observation that reality distortion is associated withunderactivity in t he left lateral temporal cortex, but t hey did not find evidence ofoveractivity in t he hippocam pus. This ma y be because SPET is less sensitive th anPET, especially for activity in st ructures deep in the bra in, alt hou gh it is alsopossible that the discrepancies between studies reflect differences in studydesign, wh ich we sh all consider later.

In a SPET study of patients with auditory hallucinations, imaged during theexperience of hallucinations and then in the a bsence of hallucinations, McGuireet al (1993) found that the presence of auditory hallucinations was associatedwit h significantly increased activity in Broca s area (the left ventrolateral frontalcortex), consistent w ith the hypoth esis that th e genesis of auditory hallucinationsinvolves the aberrant production of internal speech. Furthermore, t he increasedactivity in Brocas area wa s part of a pattern of activity in a distributed netwo rk ofcerebral areas, including t he left medial temporal lobe and the a nterior cingulatecortex. The magnitude of the increase in rCBF in the medial temporal lobe wasactually greater tha n tha t in Broca s area, but ow ing to t he noisiness of this regionof the im ages this increase did not by itself achieve stat istical significance.

In a PET study of hallucinating schizophrenic subjects, Silbersweig et al (1995)found tha t t he occurrence of auditory ha llucinations w as correlated w ith increasedrCBF in the hippocampus and parahippocampal gyrus, and also in the cingulategyrus, thalamus and ventral striatum.

Conclusions from functional imaging

The most consistently reported abnormality associated with reality distortion isoveractivity in t he medial t emporal lobe, especially in t he parahippocampal gyrusand hippocampus (Musalek et al , 1989; Liddle et al , 1992; McGuire et al , 1993;Silbersweig et al , 1995). Other replicated findings include overactivity in theventral striatum (Liddle et al , 1992; Silbersweig et al , 1995); overactivity in theleft ventrolateral frontal lobe (Liddle et al , 1992; McGuire et al , 1993); andunderactivity in the left superior tem poral gyrus (Liddle et al , 1992; Eb meier et al ,1993).

The observation of overactivity in the medial temporal lobe is likely to be ofspecial relevance, because it is engaged during several aspects of mentalprocessing that were implicated in reality distortion by the neuropsychologicalevidence we considered above. In particular, the hippocampus is involved inmemory for context (Chun & Phelps, 1999). In addition, the site of aberrant


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parahippocampal activity w hich Liddle et al (1992) found to be associated with

reality distortion coincided with t he site that Frith et al (1992) found to be activeduring a task designed to place heavy demands on internal monitoring of thesource of intended action .

Oth er sites at w hich overactivity has been reported include loci that might beexpected to be involved in the generation of t he specific menta l acts tha t form t hecontent of the delusions or hallucinations. In particular, some of the evidenceindicates that Broca s area, w hich is specialised for the production of speech, isactivated in patients with auditory hallucinations. Furthermore, areas related tothe selection of mental activity, including the anterior cingulate and medialprefrontal cortex, are also implicated. As will be discussed in Chapter 7, theseareas are also implicated in the disorganisation syndrome, perhaps accountingfor the moderate overlap between the occurrence of reality distortion anddisorganisation reported in som e stud ies (Liddle & Barnes, 1990).

The finding that reality distortion is associated w ith overactivity in t he ventralstriatum is potentially of particular significance for understanding th e mechanismof antipsychotic treatment . Studies of the induction of immediat e early genes byvarious pharmacological agents in the brains of animals indicate that all knownantipsychotic agents, both typical and atypical, act on the ventral striatum(Robertson & Fibiger, 1992). Immediate early genes, such as c-fos , are expressedrapidly after the pharmacological stimulation of a cell. The functional significanceof the expression of these genes is not know n.

Despite the substantial level of agreement between the various studies ofregional cerebral activity associated with reality distortion, not all studies haveobserved the same abnormalities. One possible explanation is that, due todifferences in study design, some studies might be expected to detect the

abnormalities associated with the actual occurrence of reality distortion, whileothers might be more sensitive to the trait abnormalities that predispose toreality distortion. For example, the st udies by Susuki et al (1993), McGuire et al (1993) and Silbersweig et al (1995) were all longitudinal st udies that comparedcerebral activity during the occurrence of hallucinations with that in the samepatients when hallucinations were absent. Therefore, these studies would beexpected to identify feat ures associated w ith t he occurrence of hallucinat ions. Allof these studies reported cerebral overactivity, but not sites of cerebral under-activity.

The study of Ebmeier et al (1993) was a cross-sectional one that determinedthe correlation betw een severity of reality distort ion and rCBF, across subjects.Such a study would be more sensitive to the trait t hat d etermines the propensityto suffer reality distortion. Ebmeier et al observed underactivity in the lateraltemporal cortex. The study by Liddle et al (1992) w as a lso cross-sectional but itincluded only patients with persistent symptoms, so that it is likely that thepatients w ere experiencing sympto ms during scanning. Thus th is study w ould beexpected to reveal sites associated w ith bot h th e predisposing trait and the actua lexperience of reality distortion. Liddle et al observed underactivity in t he lateraltemporal lobe, as observed by Ebmeier et al , but also overactivity at the diversesites found t o be overactive in the st udies of McGuire et al (1993) and Silbersw eiget al (1995). Thus it is plausible that sites of cerebral underactivity reflect the


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propensity to suffer reality distortion, whereas the sites of cerebral overactivity

reflect the actual occurrence of reality dist ortion.

Neurochemistry and pharmacology ofreality distortion

The success of antipsychot ic drugs tha t block dopamin e D 2 receptors in a lleviat ingdelusions and h allucinat ions provides strong circumstant ial evidence implicatingdopamine in the pat hophysiology of reality distortion. Indirect dopamine agon istssuch as amphetamine tend to exacerbate delusions and hallucinations inschizophrenic patients. Furthermore, in a study using SPET w ith t he specific D 2ligand iodobenzam ide (IBZM), Laruelle et al (1996) obtained evidence indicatingthat the exacerbation of psychotic symptoms induced in schizophrenic patientsby the administration of amphetamine is associated with increased levels ofintrasynaptic dopamine. When amphetamine is administered, endogenousdopamine displaces IBZM from receptors in the basal ganglia. Laruelle et al observed that t he amount of displacement of IBZM w as greater in schizophrenicsubjects than in healthy subjects. Furthermore, in the patients, the amount ofIBZM displaced following the administration of amphetamine was correlatedstrongly wit h the magnit ude of the transient exacerbation of psychotic symptoms(lasting for a few hours after t he procedure).

However, not all psychotic patients respond to treatment with D 2-blocking

medication. For example, in a study of first-episode schizophrenic patients, only83% achieved remission after on e year of treatment wit h a ntipsychotic medication(Lieberman et al , 1993). Of those who did not achieve remission, many hadpersisting delusions or hallucinations. Among patients experiencing their secondor subsequent episode, th e proportion achieving a sat isfactory remission is evenlower. A substantial minority of patients who do not respond to typicalantipsychotic medication respond to clozapine. Clozapine is effective against theentire spectrum of schizophrenic psychopathology, including reality distortion(Meltzer, 1992). As clozapine blocks a variety of types of receptor, it is uncertainwh ich aspect o f its complex pharmacological action is responsible for its enhancedtherapeutic effect. Comparison with other atypical antipsychotic drugs suggeststhat blockade of 5-HT 2 receptors ma y play a part (Meltzer et al , 1989).

The fact that antipsychotic drugs induce the expression of the gene c-fos inthose neurons with which they interact provides a tool for identifying the likelysites of their action. In rats, t ypical ant ipsychotics such as h aloperidol induce c-fos in both the dorsal and ventral striatum. The induction of c-fos in the dorsalstriatum is consistent with the widely accepted view that haloperidol generatesparkinsonism by blocking dopamine receptors there. Atypical antipsychoticssuch as clozapine do not induce c-fos in the dorsal striatum, consistent w ith thelack of parkinsonian side-effects of these drugs, but they do induce c-fos in theventral striatum and prefrontal cortex (Robertson & Fibiger, 1992). Thus


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circumstant ial evidence indicates tha t t he ventral striatum is the most likely site

for the t herapeutic actions shared by t ypical and atypical antipsychotic drugs. Italso suggests that the enhanced therapeutic effects of clozapine might arisethrough action in the prefrontal cortex. It is of interest to note that thepharmacological destruction of dopamine neurons abolishes the induction of c- fos by typical and atypical antipsychotics in the ventral striatum, but does notabolish its induction by clozapine in the prefrontal cortex, implying that theeffect in the prefrontal cortex does not involve dopaminergic neurons. Asdiscussed above, t he circumsta ntial evidence provided by t he observation o f c-fos induction in the ventral striatum and prefrontal cortex is consistent with theevidence from P ET stu dies (Liddle et al , 1992; Silbersw eig et al , 1995) implicatin gthese areas in t he experience of reality distortion.

While dopamine is the neurotransmitter most heavily implicated in realitydistortion, ot her neurotransmitt ers are also implicated. Agents tha t interact w ithserotonin receptors, such a s t he ha llucinogenic drug lysergic acid diethylamide(LSD), w hich is a serotonin 5-HT 2 receptor agonist, have a hallucinogenic effect.LSD stimulat es autoregulato ry presynaptic 5-HT 2 receptors in the ra phe nucleus,thereby inhibiting neuronal firing. The net effect is decreased cerebral serotonergictransmission. It is noteworthy that serotonin inhibits dopamine release in somebrain areas, by acting at presynaptic heteroreceptors located on dopaminergicneurons (see Chapt er 5). Thus reduced serotonergic transmission might promotedopaminergic release. However, it is not certain that diminished serotonergictransmission due to reduced firing in the raphe nucleus is responsible for thehallucinogenic effect of LSD. Direct st imulation of cortical 5-HT 2 receptors m ightalso play a role.

Drugs that block glutamatergic receptors, such as the psychotogenic anaes-

thetic agent ketamine, can produce symptoms of reality distortion, t ogether wit hother symptoms typical of schizophrenia. Carlsson & Carlsson (1990) haveargued that blockade of glutamatergic input to the indirect cortico-striato-thalamo-cortical feedback loop would promote psychosis. The indirect loopprovides negative feedback to the cortex (see Chapter 4), and reduction intransm ission through th is loop w ould lead to disinhibition of input to th e cortexfrom the thalamus. Since dopamine acts to inhibit transmission through theindirect loop, glutamate and dopamine have potentially opposing effects ontransmission in this pathway. Thus, according to the hypothesis proposed byCarlsson and Carlsson, psychosis arises from a shift in the balance betweenglutamatergic and dopaminergic activity in the indirect pathway, in favour ofexcess dopaminergic activity.

Synthesis and hypothesis

Examination of t he clinical characteristics and neuropsychological correlates ofdelusions and hallucinations indicates th at t he mechanism of reality distortion islikely to involve the failure to label internally generated mental events correctly.


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A delusion is an internally generated idea that is labelled as if it were an

externally validated fact, and therefore exempt from logical analysis. A hallucin-ation is an int ernally generated perception t hat is labelled as if it had been derivedvia the external senses. The content of th e delusions and hallucinat ions is likelyto be determined by th e cerebral area in which the relevant menta l event arises.For example, it is probable tha t o veractivity in th e left ventrolateral fronta l cortexis associated with the generation of verbal hallucinations (McGuire et al , 1993).The primary ment al events might in them selves be either pathological, as in t hecase of ideas that are distorted by depressed mood, or norma l, as in the case of anew untested idea, or normal inner speech. The essential feature of realitydistortion appears to be a failure to label such an event appropriately.

In this section we shall draw upon our understanding of the role of thehippocampus in memor y for contextual information (see Cha pter 3) and the roleof th e cortico-striato -tha lamo-cortical feedback loops (see Cha pter 4) to proposea mechanism for the generation of delusions and hallucinations, and for theaction of ant ipsychotic medication.

The relevance of context for the evaluation of ideas and perceptions

Memories for items of information ( declarative memories ) are either episodicor semantic. Episodic memories are memories of specific events experienced bythe subject. Their credibility is usually determined by contextual information.Semantic memories are memories for facts w hose validity transcends the contextwithin which they were learned. For example, an individual might know thatParis is th e capital city of France with out remembering the specific circumstances

in w hich he first learned th is fact. Novel ideas are initially evaluated in relation t othe context in which they arose. Eventually an idea may be sufficiently consoli-dated (perhaps by cross-reference to other accepted information) that it isaccepted without reference to the context of its origin. At that point it becomesan a ccepted item in semant ic memory. This implies that the cerebral represent-ation of a novel idea is normally linked to t he representation of t he context of itsorigin.

The role of the hippocampus in the processing of context

The observation that bilateral damage to the hippocampus abolishes recentepisodic memory (Milner, 1966) without damaging semantic memory suggeststhat the hippocampus may play a role in the linking of an idea to its originalcontext. This hypothesis is strengthened by the subsequent observation thathippocampal da mage impairs t he ability to employ previously presented contextualinformation to locate a target in a visual search task (Ch un & Phelps, 1999). Asdiscussed in C hapter 3, Rolls (1989) has proposed a model based on the connec-tions of t he hippocampus, according to w hich the CA3 region of the hippocampusacts as an auto-association memory device. An auto-association memory deviceis a neural network in which memories are stored by strengthening the


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connections within the network in such a manner that re-exposure of the

netw ork to part of a previously presented patt ern of inputs reactivates the entirepattern of activity evoked by the previous pattern of inputs. Since inputs frommany a reas of the n eocortex converge on pyramidal neurons in th e CA3 region ofthe hippocampus, th ese neurons w ould be expected to fire w henever a previouslyencountered pattern of distributed cortical activity occurs.

Hippocampal neurons project via glutama tergic fibres to t he corpus striatum,wh ere they synapse on G ABA-ergic spiny interneurons, w hich are components o fthe cortico-striato-thalamo-cortical feedback loops that regulate frontal corticalactivity (see Chapter 4). As demonstrated by Grace et al (1998), input from thehippocampus to the striatum facilitates feedback via these loops. Thus theconnections and architecture of the hippocampus provide it w ith th e capacity toidentify and reinforce specific patterns of cerebral activity.

When the patt ern of cerebral activity associated w ith a particular mental eventcoincides with a pattern of cerebral activity that represents its appropriatecontext, hippocampal firing would tend to reinforce that pattern of mentalactivity. Thus, under normal circumstances, hippocampal firing may act toreinforce mental events that are contextually appropriate. If the pattern ofcerebral activity represented an incidenta l menta l event one occurring withoutany supporting context it would be less likely that the pattern of cerebralactivity would be adequately reinforced. On the other hand, once an idea hasbeen repeatedly reinforced, its cerebral representation might be reinvokedwithout reference to context.

What might happen in pathological conditions in w hich aberrant hippocampalfiring occurred? One possibility is that concurrent mental activity would beexperienced as if it had occurred before. This is the phenomenon of d j vu,

which occurs in temporal lobe epilepsy. However, less massive aberrant firing ofhippocampal neurons might produce more subtle effects. Patterns of neuralactivity representing incidental thoughts might be reinforced irrespective ofcontext. Thus reality might become distorted in one of several w ays.

One possibility would be that an incidental idea would become firmly linkedwit h concurrent perceptual processing. By such a means, delusional perceptionsmight arise. A delusional perception is the misinterpretation of a normalperception as proof of an unrelated idea. For example, in a case reported byMellor (1970), a young Irishman at breakfast in a lodging house correctlyperceived his companion pushing the salt cellar towards him, and interpretedthis as evidence that h e should return hom e since the Pope was about to visit hisfamily because one of the young man s sisters was about to give birth to theChrist child.

In situations where a thought related to concurrent mental activity wasreinforced inappropriately, such as excessive reinforcement of ideas of unworthi-ness during an episode of depression, t he reinforced idea might achieve delusionalintensity. In other circumstances, the fleeting idea that a situation contained athreat to one s safety might be reinforced so as to become a delusion ofpersecution. H allucinat ions might arise if aberrant hippocampal firing occurredduring the production of subliminal internal speech. For example, if aberranthippocampal firing occurred during the formation of an internally directed


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utterance such as You fool! , the pattern of cerebral activity corresponding to

that utterance might be reinforced without reinforcement of the precedingmental events. Thus the utterance might enter consciousness without anyawareness of its internal origin.

These speculations imply that the cardinal event leading to the genesis ofdelusions and hallucinations is aberrant hippocampal activity. However, thetendency to reality distortion might be greatly enhanced if the aberrant hippo-campal activity occurred in association with dopaminergic hyperactivity, whichtends t o promot e positive feedback via the cortico-striato-thalam o-cortical loops(Alexander & Crutcher, 1990a). As discussed in Chapters 7 and 8, dopaminergicoveractivity would also be expected to promote other symptoms, such asdisorganisation and psychomotor excitation. Individuals prone to dopaminergicoveractivity at t imes of stress (see Chapter 5) w ould be expected to be prone toacute psychotic episodes in w hich reality disto rtion occurred in association w ithpsychomotor excitation and disorganisation.

The action of antipsychotic drugs

For typical antipsychotics, the level of dopamine D 2 receptor occupancy in thebasal ganglia is correlated with the therapeutic effect (Nordstrom et al , 1993).Dopamine blockade would be expected to diminish the excessive positivefeedback via cortico-striato -tha lamo-cortical circuits tha t is presumed to underlienot only delusions and hallucinations, but also symptoms of disorganisat ion andpsychomotor excitation. However, in some cases, psychotic symptoms persistdespite a high level of D 2 receptor blockade (Wolkin et al , 1989). Our hypothesis

implies tha t full remission of reality distortion in acute psychosis will occur onlyif dopamine blockade is accompanied by suppression of aberrant hippocampalfiring (possibly mediated by a decrease in activity in the abundan t gluta mat ergicprojections from th e frontal cortex to t he hippocampus). In individuals in w homaberrant hippocampal firing persisted despite dopaminergic blockade, delusionsand hallucinations would be resistant to treatment with typical antipsychotics.

Even in individuals in whom aberrant hippocampal firing was alleviated byantipsychotic treatment, the patterns of cerebral activity representing mentalevents that had previously been inappropriately reinforced might still bemaintained via normal hippocampal activity, but would be amenable to rationalscrutiny and would be expected to fade with time. However, in cases with aprolonged duration of psychosis before treatment, it would be anticipated thatdelusions w ould be firmly entrenched and, therefore, more resistant t o treatm ent.

The dorsal striatum is principally involved in feedback to the premotor cortex,wh ile the ventral st riatum is m ore strongly involved in feedback to t he prefronta lcortex, which is involved in higher mental functions (Alexander et al , 1986).Therefore, it would be expected that dopaminergic modulation of the ventralstriatum rather than the dorsal striatum would be relevant to the relief ofpsychotic symptoms. This expectation is supported by the observation byRobertson & Fibiger (1992) t hat both typical and a typical antipsychotics inducethe imm ediate early gene c-fos in the ventral striatum in rat s, wh ereas only typical


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antipsychotics, w hich are prone to produce movement disorders as side-effects,

induce c-fos in the dorsal striatum.

Summary

The principal postulates of the proposed mechanism for the generation ofdelusions and hallucinations are:

(1) Under normal circumstances, hippocampal firing acts to reinforce mental eventsthat are contextually appropriate.

(2) Aberrant firing of hippocampal neurons leads to reinforcement of mental eventsirrespective of context, t hereby leading to delusions or hallucinations.

(3) Dopaminergic overactivity w ill increase the propensity to delusions and hallucin-ations by virtue of promoting positive feedback via the cortico-striato-thalamo-cortical loops. Therefore, delusions and hallucinations are most likely to ariseduring periods of acute dopaminergic overactivity.

(4) Antipsychotic drugs decrease the severity of a psychotic episode by diminishingexcessive positive feedback to the front al cortex via the cortico-striato -tha lamo-cortical loops, but the cardinal requisite for a lleviation of delusions and hallucin-ations is th e abolition of aberrant hippocampal firing.

Thus it m ight be predicted th at, d uring the treat ment of a cute psychosis, therewould be a reduction in neural activity in the cortico-striato-thalamo-corticalloops, and also in the hippocampus. Furthermore, the degree of reduction ofhippocampal activity w ould predict t he degree of resolution of reality distortion.

To t est t hese hypotheses, my colleagues and I performed a st udy using P ET tomeasure changes in regional cerebral metabolism during treatment with theantipsychotic risperidone in first-episode schizophrenic patients (Liddle et al ,2000). We performed PET scans before the start of t reatment , 90 minutes afterthe administration of the first dose of risperidone and again after six weeks oftreatment. Reduced activity in the frontal cortex, ventral striatum and thalamuswa s discernible after the first dose (P late 15) and became more extensive after sixweeks treatment. This reduction was not preferentially correlated with areduction in severity of a ny specific group of symptoms. In addit ion, w e observedthat reduction in hippocampal metabolism following the first dose was stronglypredictive of the degree of subsequent a lleviation of delusions and ha llucinationsafter six w eeks treatment (Plate 16).

These findings provide strong support for the hypothesis that reduction ofhippocampal activity is essential for the alleviation of delusions and hallucin-ations. They provide indirect support for the hypothesis that delusions andhallucinations arise as a consequence of aberrant hippocampal firing, whichreinforces concurrent m ental activity irrespective of context.

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