According to the DSM-IV, hallucinations can be described as a sensory perception that has the compelling sense of reality of a true perception but occurs without external stimulation of the relevant sensory organ (American Psychiatric Association, 1994, p. 767). It is often thought that hallucinations occur amongst patients with a mental illness or those who are experiencing high levels of stress (Kaufman et al., 1997), drug abuse (F’nelon & Hamdani 2010),and other factors which suppose an abnormal situation (Freeman & Garety, 2003). However a number of studies have reported the existence of hallucinations not only in individuals with mental disorders but also in members of the healthy, general population (Johns, 2005; McGee, Williams, & Poulton, 2000) including children and adolescents (McGee, Williams & Poultron, 2000).
The prevalence of at least one hallucinatory experience amongst the general population is well-supported with an incidence of approximately 10% (Slade & Bentall, 1988). Hallucinatory experiences in the normal population provide support for the notion that psychotic phenomena exist on a symptomatic continuum (Verdoux & Os, 2002). There is growing research into what causes hallucinations and how these individuals differ to those who do not hallucinate.
Researchers have attributed the causes of hallucinations to physiological disorders such as sensory deprivation, central nervous disorders and most commonly mental disorders such as schizophrenia, parkinsons disorder and affective psychosis (Guillem et al., 2002; Rietkerk et al., 2008). Others hypothesise that hallucinations are related to functional personality disorders (Barrett & Etheridge, 1994; Millon, 1986) and biological explanations (Kety, 1974; Schiebel & Schiebl, 1962; West, 1975). One theory suggests hallucinations are due to a failure in ‘discrimination reality process’, whereby the individual attributes an internally generated experience to an external one (Bentall, 1990; Slade & Bentall, 1988; Seal, Aleman & McGuire, 2004).
Studies reveal hallucinatory experiences in the normal population share close resemblance to the neural substrates’ of hallucinations experienced in schizophrenia (Barkuset al., 2007). For example non-clinical auditory hallucinations (AH) share the same underlying cognitive mechanisms as auditory hallucinations in clinical individuals (Honig et al., 1998;Waters et al., 2003). Although some authors argue that there are significant differences in the features of AH in schizophrenia and non-schizophrenia populations, such as the frequency and complexity of the experience (Choong, Hunter, & Woodruff, 2007), there remains an important foundation to further investigate hallucinations in the general population as they may potentially lead to the development of clinical hallucinations.
It has been reported that subjects who hallucinate often make premature, erroneous judgements when told to guess the meaning of perceptually vague words (Heilbrun and Blum, 1984). A later study revealed that subjects with high positive schizotypy were also more likely to have false perceptual experiences (Tsakanikis & Reed, 2005). Although there is inconclusive research that unusual perceptual experiences refer to hallucinations, it can be argued that unusual perceptual experiences are the precursor to the development of hallucinations (V. Bell, Halligan, & Ellis, 2006). Nonetheless there remains a lack of studies in the literaure to demonstrate a relationship between schizotypy and hallucination proness if any. As hallucinations are a prominent positive symptom of schizophrenia, the current study will investigate whether they occur in non-clinical schizotypy subjects.
Meehl (1962) initially proposed the notion of schizotypy as a genetic diathesis-stress model for psychosis-proneness and schizophrenia (Meehl, 1990). Other views describe schizotypy as non-pathological personality traits which occur on a continuum including non-clinical individuals of the normal population (Claridge, 1994; Goulging, 2004) as opposed to the categorical view of psycho (Claridge, 1997). According to numerous studies, cognitive and personality traits in schizotypy are qualitatively similar yet quantitatively less prominent to those in schizophrenia (Claridge, 1997; Rawlings et al. 2008; Silere & davis, 2004).
In reference to the DSM-IV criteria, an individual with social and interpersonal deficits and cognitive or perceptual distortions along with at least five other criteria (e.g. magical ideation, unusual perceptual experiences, paranoid ideation, odd speech, lack of close friends and inappropriate affect) meet the symptoms of schizotypy. However factor analytical studies reveal that positive symptoms are the most common factors reported in schizotypy (Vollema & van den Bosch, 1995). These include unusual perceptual experiences’ in high schizptypy individuals which debatably is analogous to hallucinations (Liddle, 1987).
Although schizotypy individuals experience attenuated symptoms of schizophrenia, they often have the potential to develop schizophrenia (Chapman et al., 1994; Meehl, 1990). This further supports the notion that psychotic phenomena lie on a continuum which incorporate the general population. In addition there are various reports on the prevalence of schizotypy in the general population. One study estimates 10% of the population (Blanchard et al., 2000), while others report 0.006-2.4% (Torgersen, Kringlen, & Cramer, 2001) and others (Goulding, 2005; Johns & van Os, 2001; Verdoux et al., 1998) suggest an approximately 40% incidence. Research also indicates a close epidemiology between schizotypy and schizophrenia, particularly factors such as age and gender differences (Spauwen et al., 2003).
When studying schizophrenia and the associated symptoms, there are a number of limiting factors to the overall validity of the research as the individuals’ are subject to medication side-effects, hospitalization and the generalised deficit confound commonly seen in schizophrenics. Therefore the use of non-clinical schizotypal individuals’ eliminates such confounding variables in light of achieving results that can be applied as primary features.
It is a well documented that schizophrenia patients exhibit cognitive deficits which require attention, and executive functions (Almeida et al. 1995; Bartok et al. 2005; Hutton et al., 1998; Turner et al., 2004). These findings have been replicated in schizotypal samples and indeed cognitive impairments have been reported in all domains of cognition and executive functioning (Trestman et al, 1995; Dinn et al, 2002). However poor inhibition and attentional deficits have specifically and consistently been posed as key difficulties (Ascome, 1987; Cadenhead and Braff, 1995; Gray, 1998). For example neuropsychological deficits, namely inhibitory impairments have been reported in subjects with visual hallucinations with Parkinsons Disease (Barnes & Boubert, 2008). For example AH in schizophrenia are implicated in terms of a combination of contextual memory binding and intentional inhibition deficits (Badcock et al. 2005). Other studies by the same authors looked at high hallucinating healthy individuals who exhibited deficits in intentional inhibition (Paulik, Badcock, & Maybery, 2007) and found that these were related to that observed in schizophrenia (Badcock et al., 2003).
Other aspects of impaired cognition seen in acute schizophrenia have been hypothesised to arise from disturbances in the ability to use past references to guide current information processing (gray et al., 1991; Hemsley, 1987; Weiner, 1990).
The significance of the impact of cognitive symptomatology in schizophrenia requires neuropsychological assessments for accurate identification of the cognitive domain affected (Joyce et al., 2005). The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a battery of neuropsychological tests, administered on a personal computer with a touch sensitive screen (Sahakian and Owen, 1992), which has gained both empirical and clinical credit for successfully parsing test performance into primary cognitive processes and associating these to neuroanatomical structures (Levaux et al., 2007). Studies of schizophrenia employ CANTAB for testing memory, attention and executive functions. Elliot & Sahakian (1995) reported that cognitive dysfunctions found in schizophrenia with CANTAB and those documented using conventional neuropsychological tests such as the Wisconsin Card Sorting Task (WSCT) were alike.
Although encouraging, the results from these studies must be replicated by other research teams before it can be concluded that CANTAB is useful for schizophrenia’s cognitive profile subtyping.
A review of CANTAB studies reveal that executive functioning deficits are the most commonly reported amongst schizophrenia patients, which correspond to the fronto-striatal impairments of schizophrenia (Levaux et al., 2007). Research has highlighted that impairments in executive functions are particularly useful for detecting individuals at high risk of developing psychosis (Wood et al., 2003). The Intradimensional’Extradimensional Shift (ID/ED) test assesses attentional set shifting (Owen et al., 1991) as well as problem solving and reasoning (Roberts et al., 1988). Participants are required to switch attention from stimuli within the same dimension (intradimensional shift, IDS) to a new previously irrelevant dimension (extradimensional shift, EDS). The test is usually assessed by the number of trials completed and the error score (Pantellis et al., 1999). In comparison to controls, schizophrenia patients were significantly impaired on the perseveration (intra-dimensional shift stage) which indicates particular difficulties in set-shifting and the inhibitory mechanisms of executive function in schizophrenia indicative of fronto-striatal impairments (Hutton & Huddy, 2004; Jazbec et al., 2007; Tyson et al., 2004). In contrast Hilti et al. (2010) found poor performance on attention ability on the ID/ED task while set-shifting abilities were unimpaired in first episode schizophrenia. Thus it was propsed that performance gradually decreases as the illness progresses.
Furthermore the CANTAB Stop-Signal Task (SST) is a useful test for directly measuring response inhibition (Logan et al., 1984, 1997; Nigg, 2000; Quay, 1997). Previous studies have employed the SST as a measure of inhibitory control in schizophrenia studies (Rubia, Russell, Bullmore, et al. 2001; Badcock et al. 2002; Rubia 2002). Recent reports have demonstrated that response inhibition on the SST lead to higher reaction times in schizophrenia patients compared to controls, supporting the notion that response inhibition is impaired in schizophrenia (Nolan, D’Angelo & Hoptman, 2010). Specifically the SST assesses the time required to inhibit an already initiated motor response. Reports show that the Stop-Signal Task is distinct from the Stroop task as they are not well correlated (Avila et al. 2004; Friedman and Miyake 2004).
Nicotine smoking has been extensively studied in the schizophrenia spectrum primarily due to the well-documented, notably high incidence of smokers in both schizophrenic and schizotypy individuals (Adler et al., 1998; Dinn et al., 2004; Glynn & Sussman, 1990; Kollaikou & Joseph, 2000; Roick et al., 2007). On average, reports indicate Schizophrenic patients to be 5.3 times more likely of being a smoker compared to the general population and approximately 62-88% of schizophrenic patients are reportedly current smokers (de Leon et al., 2002; de Leon & Diaz, 2005; Chapman et al., 2009).
Furthermore schizophrenic patients are documented to have higher nicotine dependence (the psychiatric diagnosis which entails tolerance, withdrawal, and associated problems; APA, 2000; McChargue et al., 2002) and have a greater nicotine extraction from smoking (Olincy et al., 1997) compared to the normal population (de Leon & Diaz, 2005). This has been supported by findings of higher levels of nicotine or cotinine which is a key metabolite of nicotine (O’Leary et al., 2008) which is associated with attention enhancing, in blood and saliva samples of schizophrenic smokers (Bozikas et al., 2005; Strand & Nyback, 2005; Williams et al., 2005; Weinberger et al., 2007). Furthermore research has indicated that smokers score higher on schizotypy scales in comparison to non-smokers (Esterberg et al., 2007).
Nonetheless the literature shows an inconsistent consensus on smoking and facets of schizophrenia. For instance there are reports of an association between smoking and positive symptoms (Ziedonis et al., 1994), negative symptoms (Patkar et al., 2002), both positive and negative symptoms (Goff et al., 1992), and no associations with positive and negative symptoms (e.g., Dalack et al., 1999). Likewise numerous studies in schizotypal samples revealed a relationship between smoking and increased positive symptoms (Allan et al., 1995; Burch et al., 2008; Esterberg et al., 2007; Esterberg et al., 2009; Joseph et al., 2003; Wan et al., 2007), increased negative symptoms (Burch et al., 2008; Esterberg et al., 2007) and increased disorganization symptoms (Esterberg et al., 2007; Esterberg et al., 2009; Wan et al., 2008).
Theories for smoking rates in the schizophrenia spectrum
In humans (Buccafusco, 2004, Terry et al., 2005a, Riveles et al., 2008; O’Leary et al., 2008). This model has also been applied to the relationship between smoking and executive function deficits (Dinn et al., 2004). Smoking may also improve cognitive function and attentional performance.
To explain the staggering smoking rates in the schizophrenia spectrum various theories have been posited. Some authors sugges that nicotine may lead to the development of schizophrenia or psychosis (Abi-Dargham et al., 1998; Montgomery et al., 2007; Moore et al., 2007; Murphy et al., 2002; Smith et al., 2009) while others propose that individuals may use nicotine for self medication (Adler et al., 1993; Kumari & Postma, 2005; Zabala et al., 2009; Zammit et al., 2003) to increase cognitive processes including concentration and mood (Levin et al., 2006; Gurpegui et al., 2007; Ripoll et al., 2004).
More specifically the self-medication hypothesis (Adler et al., 1998), puts forth that schizophrenic individuals smoke to manage unpleasant medication side effects and cognitive deficits including poor attention and thought disorder, disorganisation and negative symptoms (Aguilar et al., 2005; Nisell et al., 1995) which ultimately reinforces its use. Studies which demonstrate enhanced performance on selective attention tasks in smokers, relative to non-smokers support this theory (eProvost, S.C. & Woodward, R., 1991). Likewise smoking as a means of sustaining cognitive functioning has gained support from studies that found a link between nicotine and enhanced cognitive functioning (Dinn et al., 2004; George et al., 2006; Kumari & Postma, 2005; Taiminen et al., 1998; Lyon, 1999).
Contrary to the self-medication properties of nicotine, studies have found a positive relationship between smoking and an increase in positive and negative symptoms of schizophrenia. Others have shown that smoking cessation or reduction did not have a significant impact on the symptoms of schizophrenia. Furthermore tobacco companies promote and fund research supporting the self-medication hypothesis to campaign that schizophrenic patients are less vulnerable to the damaging effects of smoking (Prochaska et al., 2008a).
Alternative views from Barr et al. (2008a) advocate that this population may smoke to counter balance medication side-effects such as loss of motivation (Barr et al., 2008a; Glassman,1993). However an estimated 80% of schizophrenia patients were found to be smokers prior to symptom onset (Beratis et al., 200; de Leon et al., 2006; Esterberg et al., 2007) suggesting there may be other undocumented processes such as premature cognitive challenges involved, which lead to high smoking rates before the onset of clinical symptoms in this population.
To date there is insufficient findings to explain the elevated smoking rates amongst the schizophrenia spectrum despite controlling for confounds such as socioeconomic status, hospitalisation and medication, elevated smoking rates persisted (Lyons et al., 2002; Aguilar et al., 2005; Kumari & Postma, 2005).
Cholinergic system in schizophrenia
Nicotinic Receptors (nAChR), activated by nicotine, are responsible for reward and nicotine dependence. Alpha-7 (a-7) nicotinic receptors, a subset of nAChR, are highly implicated in schizophrenia due to its crucial role in cognition and have increasingly become a target for improving cognitive function (Friedman, 2004; Raedler et al., 2007). Alterations in nicotinic receptors have frequently been reported in schizophrenia and post-mortem studies have revealed a decrease in the expression of a-7 nicotinic receptors in several brain areas of schizophrenics ([Freedman et al., 1995], Court et al., 1999; Guan et al., 1999; Martin-Ruiz et al., 2003; Adams & Stevens, 2007; Olincy & Stevens, 2007).
It is thought that reduced a-7 nicotinic receptors in the thalamus may be involved in triggering hallucinations (Behrendt, 2006). However the above literature lead researchers to predict an upregulation of the a-7 nicotinic receptors in schizophrenic smokers compared to non-smokers (Freedman et al., 1995; Court et al., 1999), thus nicotine use may manage hallucinatory experiences as well as cognitive disturbances. In support for this research highlighted nicotine treatment alone lead to nicotinic receptor upregulation similar to that seen in antipsychotic medication and nicotine combined (Breese et al., 2000; Hansen et al., 2007; Ochoa & Lasalde-Dominicci, 2007). Lee et al. (2001) however found that the combined treatment was associated with a decrease in a-7 nicotinic receptor upregulation compared to receptor upregulation induced by nicotine treatment alone (Lee et al., 2001).
Sensory gating can be defined as the brains ability to filter irrelevant sensory stimuli for efficient information processing (Braff and Geyer, 1990). According to Adler et al. (1998) this happens by preventing irrelevant sensory information from entering the higher cortex. Deficits in sensory gating may lead to cognitive fragmentation and an overwhelm of external and internal information which then affect correct sensory information processing (Croft et al., 2001), as observed in schizophrenia and schizotypy (Adams and Stevens, 2007; Turetsky et al., 2007; McGhie & Chapman, 1961; Freedman et al., 1983; Cadenhead et al., 2000).
Commonly used experimental paradigms to assess sensory gating include: 1) the P50 paradigm (Adler et al., 1982; Freedman et al., 1983), 2) prepulse inhibition (PPI) and 3) Eye tracking tests (Turetsky et al. 2007). In the P50 paradigm the a-7 nicotinic receptor is mainly accountable for P50 auditory gating (Freedman et al., 1994). Schizophrenic patients had higher P50 ratios in comparison to healthy subjects (Adler et al., 2004, Martin and Freedman, 2007, & Turetsky et al., 2007).
Previous literature presents mixed findings between schizotypy, smoking and sensory gating and attention. Croft et al. (2001) showed that individuals with high schizotypy, have poorer suppression on the p50 paradigm. Similarly, individuals with high reports of abnormal perceptual experiences had poorer p50 suppression. On the other hand advanced sensory gating has been revealed amongst chronic smokers (Crawford et al., 2002 and Croft et al., 2004) possibly from the temporary enhancing effect of nicotine on attention and sensory gating via a-7 nicotinic receptors (Adler et al. 1993; Adler et al., 1998). Moreover Wan and colleagues (2006) found that high schizotypy non-smokers demonstrated poorer sensory gating compared to low schizotypy non-smokers whereas high schizotypy smokers displayed better sensory gating than low schizotypy smokers. This suggests that high schizotypy participants with high nicotine dependence are likely to perform better at inhibitory cognitive tasks compared to low schizotypy, non-smokers.
This inhibitory failure is associated with poor sustained attention, as measured by tests of attentional dysfunction (Cullum et al., 1993; Yee et al., 1998).
In prepulse inhibition, smoking prior to testing resulted in better test performance than not smoking (Kumari et al., 2001).
Reduced _7 subunit levels have been noted in frontal lobe regions (Guan et al., 1999), including the dorsolateral prefrontal cortex (Martin-Ruiz et al., 2003).
Positive schizophrenia and schizotypy symptoms including hallucinations are particularly associated with inhibitory deficits in information processing (Hemsley, 1993; 1994). For example anatomical studies have revealed that the hippocampus and the prefrontal cortex (PFC) are primary areas associated to the P50 task (Turetsky et al., 2007). Decreased a7 nAChRs in the hippocampus in schizophrenia suggest that this nicotinic receptor plays an important role in the correct functioning of auditory gating (Adams and Stevens, 2007; De Luca et al., 2006a, De Luca et al., 2006b; Leonard et al., 1998; Olincy et al., 2007; Zammit et al., 2007). Therefore decreased levels of a-7 AChR in the thalamus is thought to be involved in the onset of hallucinations (Behrendt, 2006). Research has been carried out to investigate whether these phenomena hold true in a nonpsychiatric sample.
The role of a7 subunits in schizophrenia is further supported by rodent studies, which exhibit decreased a7 nAChR expression in the hippocampus in conjunction with auditory gating deficits (Martin and Freedman, 2007). Studies have shown that as well as some antipsychotics, nicotine improves P50 deficiencies in schizophrenia (Ripoll et al., 2004; Martin & Freedman, 2007; Turetsky et al., 2007) as well as sensory gating in rodents (Levin et al., 2006; Olincy et al., 2007). In summary these findings emphasize that nicotine may have positive effects on the correct functioning of sensory gating in schizophrenic patients (Olincy et al., 2007).
PPI AND LATENT INHIBITION (LI)
Furthermore several schizophrenia studies have generally proposed weak contextually-driven inhibitory processes such as latent inhibition (Jones et al., 1992).
It has been established that one of the core facets of schizophrenic patients are attentional and inhibitory deficits (Cadenhead and braff, 1995; Gray, 1998). In addition to sensory gating tasks, these individuals are impaired on prepulse inhibition (PPI) tasks (Thaker, 2007 &Turetsky et al., 2007]), latent inhibition and the Stroop test (Lezak, 1995).
LI is the repeated presentation of a stimulus which then becomes irrelevant (Fern’ndez & De la Casa, 1989), latent inhibition, the ability to reduce attention to previously presented irrelevant stimuli ([Lubow and De la Casa, 2002] and [Lubow et al., 2001]). LI refers to a process in which noncontingent presentation of a stimulus attenuates its ability to enter into subsequent associations, and it has received much attention because it is widely considered to relate to the cognitive abnormalities that characterise acute schizophrenia. High schizotypy subjects also demonstrate significantly low LI compared to low schizotypy subjects (Baruch, 1988; De la Casa, Gray et al., 2002; Ruis & Lubow, 1993; Lubow et al., 1992). Furthermore Hemsley (1987; 1993; 1994) has consistently suggested that reduced latent inhibition (LI) functioning may lead to the positive symptoms found in schizophrenia. These findings provide revelvant support to suggest that high schizotypy as opposed to low schizotypy and particularly high hallucinating individuals may be at greater risk of impairments on inhibitory and selective attention tasks.
Response inhibition can be defined as the intentional prevention of a behavior that is underway or that is otherwise automatically evoked (i.e., ‘pre-potent’). Experimentally, it can be studied with stop-signal task (SST) and other inhibitory tasks
Furthermore the literature there appears to be an intricate link between schizotypy, hallucinations and smoking (or nicotine dependence). Therefore it is highly anticipated that individuals with a high score on one measure will be predisposed to having high scores on all measures. In further the majority of high schizotypy subjects will hypothetically also be high hallucinators and likewise high in nicotine dependence and therefore will be simultaneously studied.
The results have been attributed to the inability to ignore irrelevant stimuli (LUBOW, 2005).
Furthermore it can be argued that PPI impairment also indicates extraneous information filtering difficulties (Van den Buuse et al., 2003). It has also been proposed that nicotine in patients with schizophrenia (Carls & Ruehter, 2006] & Hong et al., 2008]).