Schizophrenia is a chronic, severely debilitating psychiatric disorder that affects up to 1 % of the population worldwide. The N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP) can produce a syndrome in normal healthy humans that closely resembles the positive, negative and cognitive symptoms seen in schizophrenia and can exacerbate symptoms in patients with chronic schizophrenia. Furthermore, administration of PCP in animals results in behavioural, metabolic, neuropathological and electrophysiological changes modelling various aspects of schizophrenia symptomatology. The aim of these studies was to investigate the ability of a sub-chronic PCP treatment regime in adult rats to produce long lasting behavioural and neurochemical alterations with particular relevance to those observed in schizophrenia. Long term effects on behavioural, cognitive, and neuropathological endpoints were determined in adult Lister Hooded rats following sub-chronic PCP administration (7-days bi-daily dosing at 2mg/kg). Sub-chronic PCP treatment resulted in deficits in recognition memory using the novel object recognition (NOR) test, which reflects aspects of the cognitive symptomatology observed in schizophrenia. We observed deficits in social interaction using our existing methodology in the social interaction paradigm and also using a novel paradigm, the sociability and social novelty preference test, effectively mirroring some of the negative symptoms of schizophrenia. Behavioural sensitisation was firmly established following sub-chronic PCP treatment and co-administration with the antipsychotic risperidone was shown to attenuate the PCP-induced locomotor effect. Enhancement of locomotor activity is considered to be equivalent to certain aspects of the positive symptoms of schizophrenia. Deficits in parvalbumin immunoreactivity (PV-IR) were detected in the prefrontal cortex (PFC) but not in the hippocampus following sub-chronic PCP treatment. In conclusion, the results from these studies are supportive of sub-chronic PCP administration being a valid animal model for assessing a variety of the behavioural and neuropathological deficits associated with schizophrenia.

The aim of this thesis was to elucidate the nature of food craving and to examine the relationship between perimenstrual negative mood and food craving. It also aimed to examine the effect of intake of craved foods on mood and to assess the likely causes for any mood change observed. A retrospective questionnaire study including data from over 750 subjects assessed the qualitative experience of food craving, its relationship to negative mood and its link with psychosocial factors known to influence both eating behaviour and reporting of perimenstrual negative mood. In contrast to the link between perimenstrual mood change and past and present emotional state, food craving was unrelated to these variables. Neither was it associated with body mass index, satisfaction with body image or eating restraint. Significant relationships were observed only with measures of emotional eating and with reporting of perimenstrual negative mood and physical discomfort. Qualitative analysis of food craving suggested intake of craved foods, 90% of which were reported to be for carbohydrate-rich foods, to produce transient improvement in mood which appeared linked to the taste of craved foods. In conclusion, these findings support the previously suggested link between negative mood and food craving and confirm cravings to be for carbohydrate-rich, fat-rich, protein-poor foods. The effect on mood following satisfaction of a craving however appears primarily linked to sensory pleasure rather than to biological changes in serotonergic functioning. Instead of reflecting an attempt to counteract reduced serotonergic activity, carbohydrate craving may simply reflect the propensity to comfort eat in response to emotional and physical discomfort. These conclusions are discussed with reference to the therapeutic effects of antidepressants on premenstrual symptomatology.

The study aim was to identify the population of live patients in the Lothian area of Scotland, with presenile dementia of various aetiologies, and to describe the clinical profiles of each and the patterns of decline which occur, together with any genetic characterisation possible. Cases were identified using the Lothian Psychiatric Case Register. For the demographic data, the CAMDEX (The Cambridge Examination of Mental Disorders of the Elderly) informant interview was used. The behavioural assessment comprised the CAPE-BRS (Clifton Assessment Procedure for the Elderly, Behavioural Rating Scale), the Cornell Depression Scale and the MOUSEPAD, a new behavioural and psychopathological assessment. Of 290 potential cases, 164 (57%) were excluded. Reasons: Death 50 (31%), Unsuitable 40 (24%), Refused 40 (24%), Untraced 23 (14%), Out of area 11 (7%), Of the 126 (43%) seen, 112 (89%) met DSM3R (Diagnostic and Statistical manual of Mental Disorders, Third Edition, Revised) criteria for dementia. 63 (56%) of the 112 were rated as DSM3R severe type. 80 (72%) of the 112 fulfilled the McKhann criteria for Alzheimer's Disease. Full description of the group is available. The genetic testing included Apolipoprotein E, α-1 antichymotrypsin and Very Low Density Lipoprotein Receptor (VLDL-R) allele typing. Important data concerning the services provided and used by this group of patients and their carers has been collected and can be shared with organisations working to find funding for presenile dementia in the health service. This study will provide a thoroughly documented and clinically well worked-up sample. The analysis of the work will help to identify if subgroups exist, according to the patterns of various clinical features, the rates of decline and genetic variations. This would in turn, give a greater chance to plan appropriately for all those involved in caring for and managing these illnesses.

The study consisted of the examination of the phenomenological correlates of acting on delusions in a sample of 83 newly admitted psychotic subjects who demonstrated at least one non-mood congruent delusion. Subjects were screened to identify such beliefs using the P.S.E. and where several delusions were present one belief was selected for further study. This was termed the Principal Belief. Each subject was then interviewed using a newly designed instrument, the Maudsley Assessment of Delusions Schedule, in order to describe the phenomenology of the Principal Belief. Several areas of phenomenology were examined, namely, the degree of conviction with which the belief was held, the presence or absence of evidence supporting the belief, the affective content of that belief, its systematisation, the level of pre-occupation present and the level of insight demonstrated by the subject. In addition, information was obtained relating to two behavioural variables, one derived from the subject's own description and the other generated from information provided by informants. The phenomenological correlates of action defined in these two ways were then examined. When action was defined on the basis of information provided by informants, no such correlates were identified. It seems most likely that this reflects the lack of validity of the behavioural variable. When action was defined on the basis of information provided by the subjects themselves, several aspects of phenomenology were associated with such action. In particular, the ability to identify evidence supporting the belief, the presence of an affective component to that belief and the presence of a form of insight (a willingness, when challenged, to change the degree of conviction with which the belief was held) showed such an association.

This thesis begins with an exploration of the historical associations between learning disability and schizophrenia, which leads to the modern supposition that schizophrenia is commoner in people with learning disability than the normal population. A critical evaluation of both community and hospital epidemiological studies indicates that the point prevalence of schizophrenia in people with mild learning disability is around 3% i.e. around three times that expected in the normal population. Five possible mechanisms to account for this increase are postulated and discussed: a chance co-occurrence, a common aetiology, an epiphenomenon, a severe schizophrenia and a 'de novo' disease.

I have tested the hypothesis that infants are born with a capacity for social interacting and, that from an early age they can engage in an intersubjective relationship, not only with their mothers, but with other infants. I also investigated the sensitiveness of paired infants to the motives and feelings of their partners. I measured turn-taking, imitation, and both local and general bodily emotional expressions of their partners. I measured turn-taking, imitation, and both local and general bodily emotional expressions of a reciprocal or complementary form. Results show that 6 month-olds try to make contact, but, they do not sustain interaction. As a result, invitations for interactions occur frequently, but they are not always followed by appropriate responses. The infants are very interested and very friendly to one another, but as a result of their inability to keep attention, they often show indifference. At 8 months, infants show less indifference. They keep their interactions going for longer periods, and show much more interest in the other infant, with no irritation. At 9 months, another change is evident. Interactions and invitations are more balanced, meaning that the older infants are trying to give the partner turns in interactive strategies. At all ages, girls were more interactive, showing more emotional expressions than boys. Imitation is present in all ages, and at a very significant rate. It seems that infants use imitations to assist and regulate interaction: to start it, to keep it with more positive emotional expressions. This result is opposite to the differences between boys and girls observed in the Cross-Sectional and Longitudinal studies, where girls were more responsive. At all ages, infants are very attentive to their mirror images, which attract them and excite a richer variety of expressions than they display when faced with another infant. An important finding is that the 6-month-olds showed clear evidence of self-recognition in their emotional expressions and interactions.

This thesis presents a new model of unilateral neglect. The theory is based on novel empirical data collected in the current study which involved stroke patients with and without neglect. Halligan and Marshall (1992) have called for the exploration of "principles" of malfunction in neglect patients. In this thesis, we have provided such a principle. The core of the thesis is a new model of unilateral neglect, the "temporal diplopia" theory. It is strictly constrained by neuroanatomical and electrophysiological evidence. Our model claims that the underlying pathology in unilateral neglect is abnormal temporal integration and binding of information due to desynchronised neuronal activity. Disruptions in the temporal domain lead to impaired processing within the damaged hemisphere and between the two hemispheres. The empirical data presented in this thesis was interpreted as evidence for the "temporal diplopia" theory. We have provided support for the hypothesis that processing in the damaged hemisphere is slowed down by using a time perception, rhythm perception and inspection time paradigm. We have illustrated the explanatory power of our theory by unifying existing empirical evidence of neglect. Stimulus properties in neglect dyslexia were explored. Furthermore, we addressed the general 'binding' problem of body schemata and the disintegration of body schemata due to disrupted temporal neuronal processing. Our thesis is the first to investigate extensively the temporal aspects of information processing in unilateral neglect patients. Abnormal temporal processing appears to be a fundamental problem and it has been associated with a number of neurophysiological and psychiatric disorders such as dyslexia, dysphasia, autism and schizophrenia. Why temporal malfunction leads to different clinical pictures in different patient groups is a question that warrants future exploration.

The cannabis available in many countries has been changing in recent years to favour a product increasingly high in its main component, the cannabinoid Δ9-THC. Epidemiological studies have highlighted that early, persistent and heavy cannabis use, particularly for cannabis high in Δ9-THC, is associated with an increased risk of development of schizophrenia. However, cannabis is a complex plant which also produces over 100 other cannabis compounds, each with a unique pharmacological profile. Cannabinoids such as CBD and Δ9-THCV, which are virtually absent from cannabis sold on the black market in the UK today, may interfere pharmacologically with Δ9-THC and therefore protect against the negative effects associated with cannabis use. This thesis is comprised of two experimental studies in healthy volunteers where the cognitive, psychological and electrophysiological effects of Δ9-THC, CBD and Δ9-THCV are explored. Study 1: In the first part of study 1, the psychological and cognitive effects of Δ9-THC and CBD were explored in a placebo-controlled, between-subjects design with 48 healthy volunteers. Pre-treatment with CBD (600mg, oral) significantly inhibited IV Δ9-THCinduced (1.5mg) paranoia and impairments to delayed verbal recall. Also, significantly fewer participants experienced clinically significant psychotic symptoms following IV Δ9-THC if pre-treated with CBD compared to placebo. In the second part of study 1, the electrophysiological effects of Δ9-THC and CBD were explored in the same sample, although the data from three participants were excluded. I found that Δ9-THC significantly reduced theta amplitude and coherence, although these were not correlated with psychopathology or inhibited by CBD. However, Δ9-THC-induced increases of alpha and delta amplitude was significantly inhibited by CBD. Study 2: The second study was a within-subject, placebo-controlled, cross-over design study (N=10), exploring the effects of IV Δ9-THC (1mg) and Δ9-THCV (10mg/day oral for 5 days) in healthy male volunteers with minimal past cannabis use. I found that Δ9-THC did not produce significant increases in paranoia or psychosis, or impairments to immediate verbal recall. Δ9-THCV significantly inhibited Δ9-THC-induced heart-rate increase and impairments to delayed verbal recall. Δ9-THCV on its own produced a significant improvement in reverse digit span, and a trend towards increased anxiety. Together, these results highlight the important protective role that CBD and Δ9-THCV play in recreational cannabis use against the negative effects of Δ9-THC. It also raises the possibility that CBD and Δ9-THCV may hold therapeutic value for mental illness and cognitive impairment.

The debate regarding the relationship between epilepsy and mental illness started in Ancient Greece and has continued until the present. As a group, individuals with epilepsy tend to show increased rates of psychopathology compared to others. However this discrepancy disappears when compared to individuals with chronic physical illness. The psychopathology (maladaptive behaviour, psychiatric illness, personality disorder and overall mental disorder) of 150 individuals with a mental handicap and epilepsy both from hospital and the community was studied, and compared to an individually matched control group of 150 individuals with a mental handicap who did not sustain epilepsy. Fifty five percent of the total population, representing 58% of individuals with epilepsy and 53% of individuals without epilepsy, showed severe maladaptive behaviour. The difference between the groups with and without epilepsy was not significant. However, individuals resident in hospital showed significantly higher rates of severe maladaptive behaviour compared to individuals who were resident in the community. Nearly 25% of the whole group, representing 19% of the individuals with epilepsy and 31% of individuals without epilepsy, had a diagnosis of a psychiatric illness. The difference between those with epilepsy and those without was significant. Twenty-seven percent of mild to moderately mentally handicapped individuals with epilepsy, compared to 25% of individuals without epilepsy, had an abnormal personality. This difference was not statistically significant, although the hospital residents had a significantly higher rate of abnormal personality compared to individuals resident in the community.

No description available.