Psychotic states with their classic symptoms of delusions, hallucinations, illogical thinking and formal thought disorders, encompass a broad range of psychiatric illness -the prototype being schizophrenia-, but also various neurological disorders and toxic-metabolic disturbances. Psychiatric symptoms are common in Alzheimer’s disease (AD), with psychosis -as evidenced by hallucinations and delusions- present in approximately 50% of affected patients. This propensity toward psychosis coupled with the prevalence of AD in the population renders it second only to schizophrenia as a source of psychotic states. Various clinical and biological features are shared by both schizophrenic and demented older patients such as AD. Without entering into an extensive review of the similarities and the differences between both diseases (see e.g., White and Cummings, 1996), the following common characteristics should be noticed. As previously mentioned, positive psychotic symptoms are common in AD. Delusions occur more frequently than hallucinations. Alike in schizophrenia, the delusions of dementia tend to be unsystematized and loosely held, with the majority being of a simple persecutory type. Importantly, delusions in AD are not correlated with the severity of dementia and are an independent manifestation of brain dysfunction (Flynn et al., 1991). Contrastingly, visual hallucinations are more frequent than auditory ones in AD, the reverse pattern being observed in schizophrenia. Neuroimaging studies have evidenced a lateral/third-ventricular enlargement associated with hippocampus and temporal lobes atrophies in both diseases, along with a reduced glucose metabolism in frontal lobes. Roughly speaking, neurochemical studies have evidenced a disturbed dopamine/acetylcholine balance in both diseases, which seems to result from an overactivity of the central dopaminergic systems in schizophrenia, and from an under activity of the presynaptic cholinergic systems in AD. Finally, psychotic symptoms in both diseases are treated using mainly dopamine-blocking agents, even if the therapeutic efficacy of these agents in AD is modest compared with that seen in schizophrenia. Surprisingly with regard to the original description of schizophrenias as a group of Dementia Praecox (Bleuler, 1911/1966), such clinical analogies between schizophrenic patients and demented older ones have attracted only a limited amount of researches. Since several years, our group was interested by these similarities, but focusing mainly on delusion disorders (Oberling & Carnicella, in press). Delusion is defined as a false belief based on incorrect inferences and interpretation about external reality (DSM III-R). Despite their semantic contents (persecutory, grandiosity, bizarre, etc), delusion disorders seem to be characterized by the spreading activation and maintenance of erroneous causal relationships between events. More precisely, deluded patients exhibit a particular and somewhere specific pattern of hasty decision making, the so-called ‘jump to conclusion’ effect (Garety & Hemsley, 1997). With regard to non-deluded (non-deluded schizophrenic, depressed, obsessive-compulsive or anxious) patients, deluded patients need fewer information to reach a decision, a finding which is reliably observed throughout studies. This pattern of response does not seem to rely on affective bias, such as a poor motivation to engage into the tasks or the urge to finish them as quickly as possible (for a review, see e.g. Garety & Freeman, 1999). On one hand, deluded patients have a strong tendency to bind both together information that simply co-occurs randomly. This leads to spontaneously generated abnormal causal relationships (Chapman and Chapman, 1973), and is referred as the ‘data-gathering bias’ (Hemsley & Garety, 1997; Garety & Freeman, 1999; but see Kaney & Bentall, 1989). On the other hand, when they are facing reasoning tasks, deluded patients tend to proceed normally, except that they require fewer information while doing more errors, but with a level of conviction in the correctness of their choice being higher than the one of normal subjects (Linney et al., 1998). It should be clear from the abovementioned data that the psychological features of deluded disorders are not yet fully captured. It is thus tempting to try having a further insight into the psychological and biological mechanisms of delusion disorders. This is the purpose of the present article.

Using an associative word recall task, Nestor and his colleagues (1998) evidenced that schizophrenia was characterized by faulty modulation of associative links, but within an apparently spared lexicon. In their task, both the connectivity (associative strength) and the network size (number of associates) of the words varied in such a way that the list contained equal proportions of four types of words: 1/ high connectivity-small network size (HC-SN), 2/ low connectivity-small network size (LC-SN), 3/ high connectivity-large network size (HC-LN), and 4) low connectivity-large network size (LC-LN). The schizophrenic patients showed a particularly pronounced effect of the connectivity of the to-be-remembered words. Regardless of network size, recall improved substantially for words of high connectivity and declined dramatically for words of low connectivity. By contrast, the normal comparison subjects showed the usual best recall for words of HC-SN, followed by words of LC-SN, then by words of HC-LN, and finally by words of LC-LN. Connectionist simulation evidenced that modeling the schizophrenic response pattern led to aberrant activation and network instability that could account for thought intrusion and delusional thinking (Han et al., 2003). Whether the schizophrenic pattern is primarily driven by the dominance of strong associations over weak ones, or the occurrence of competitive distracting relationships that might interfere, remains to be determined. In line with previous studies using associative tasks (e.g. Chapman and Chapman, 1973; O’Carrol, 1995; Nestor et al., 1998), Han et al. (2003) hypothesized that the schizophrenic response pattern might be primarily driven by the relative absence of weak associations.

Using tasks that allow the independent assessment of memory for item and for associative information, Naveh-Benjamin (2000) evidenced in older adults, considerable difficulties in binding together unrelated components of an episode into a cohesive entity. Older adults are particularly deficient in tasks that require the binding of information to contextual elements, that is, background information that can disambiguate the meaning of a target event (Baddeley, 1982). More precisely, older adults show context activation/updating impairments, context maintenance starting to be altered in the oldest adults (age > 75 years), a phenomenon that is further exacerbated in adults suffering from early stage of AD (Braver et al., 2001; 2005). Deficit in the use of contextual information processing constitutes a striking analogy between dementia in older adults and schizophrenia. Bleuler (1911/1966) first observed the intrusion of dominant but contextually inappropriate associations in schizophrenic thought. Direct experimental evidence came from the rigorous work of Chapman and Chapman (1973) who demonstrated a pronounced schizophrenic bias for dominant meanings of homonyms (e.g., “pen” as a writing instrument) even when preceding sentential context called for secondary meanings (e.g., “pen” as an enclosed fence). In line with several studies (e.g. Rizzo et al., 1996; Oberling et al., 1999; Bazin et al., 2000), Cohen and his colleagues (Cohen & Servan-Schreiber, 1992; Cohen et al., 1999) provided compelling evidence that context updating and maintenance was altered in schizophrenic patients in a way similar to what was observed in older adults and AD (Braver et al., 2005).

Based on the abovementioned observations and keeping in mind that not every schizophrenic or older demented patients are deluded, we propose the following hypothesis to account for delusion disorders in these pathologies: The core neuropsychological alteration in both schizophrenia and dementia relies on a dysfunction of the associative processes, patients experiencing difficulties to bind both together information. The deficit of binding concerns primarily weak associations such as contextual ones (Cohen & Servan-Schreiber, 1992; Oberling et al., 1999; Braver et al., 2005). Thus, the bulk of information coming from patients’ past, present and future cannot be organized into a coherent entity. This results to an incoherent internal speech which can lead to disorganized external behaviors (verbalization, action, etc.). The associative deficit appears suddenly in schizophrenia at a post-pubertal stage, when the frontal cortices are supposed to connect to other structures. It appears progressively in older adults when the brain start to engage into neurodegenerative mechanisms. At the neuro-anatomical level, such a disconnection induces a global hypo-activity of the frontal cortex which affects its most rostral part, namely the prefrontal cortex, a region which is involved in many cognitive functions such as reasoning, planning, or executive functions (Ramnani & Owen, 2004). From a neurochemical point of view, schizophrenia is characterized by an overactivity of the mesolimbique dopaminergic system, whereas dementia is characterized by a loss of the forebrain cholinergic neurons. These facts lead in both cases to a disturbed dopamine/acetylcholine (DA/Ach) balance, or more precisely stated, to an altered DA/Ach ratio. In both cases (schizophrenia and dementia) the DA/Ach ratio is higher than the one in normal subjects. To the extent that the DA/Ach ratio follows a simple Weber’s law, increasing the level of DA or decreasing the level of Ach, should produce similar outcomes. Simply put, the central dopaminergic system is involved (among other functions) in the detection of newly formed associations (for a review, see e.g. Young et al., 2005), whereas the forebrain cholinergic system supports attentional and mnesic processes (Everitt & Robbins, 1997). On this ground, increasing the DA/Ach ratio leads to the formation of new and strong, albeit irrelevant, associations, either by increasing the dopaminergic flow or by decreasing the cholinergic one. Associative processes must be impaired enough to generate abnormal behaviors that lead to the clinical diagnostic of schizophrenia or dementia. When those processes are less severely impaired, individuals are clinically classified as schizotypal-prone or pre-demented. This emphasizes that the associative processes can be intact (normal young and older individuals), mildly impaired (schizotypal traits and pre-dementia) or severely impaired (schizophrenia and dementia), therefore suggesting a progressive gradient of deterioration as the diseases are exacerbated. If one is ready to accept the associative deficit as the core neuropsychological process in both schizophrenia and dementia, it remains to consider that not all schizophrenic and older demented patients suffer from delusion disorders. We here suggest that the demented (praecox or late-onset) pattern results from an initial lost a weak associations (such as evidenced by the contextual deficit observed in these pathologies), followed latter on, as the diseases are more salient from a clinical point of view, by a net dominance of strong associations over weak ones (Escobar et al., 2002), leading thus to disorganized internal speech and external behaviors. In this framework, delusions would result from the intrusion of competitive distracting associations that will interfere with the primarily established and aberrant strong associations. We acknowledged that our hypothesis constitutes a simple, not to say a simplistic, view of delusion disorders. Nevertheless, it provides the tremendous advantage of being experimentally testable.

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