This thesis adopts a multidisciplinary approach, combining cognitive-experimental and physiological data, with quantitative and molecular genetic analyses, to investigate pathways from genes to ADHD behaviours. In chapter 2 we investigated socio-demographic factors as contributors of contrast effects (exaggeration of behavioural differences) in parental ADHD ratings. Gender moderated contrast effects, but only in opposite-sex pairs. Family size also contributed to contrast effects, which was further modified by gender. The reliance on rating scales and contrast effects may undermine gene-finding efforts. Accordingly, interest has been directed at objective ADHD- related measures. Promising candidates include heightened reaction time variability (RTV) and inhibitory deficits, indexed by commission errors (CE). Using a population-based twin sample we identified RTV and CE as separate cognitive pathways underlying inattention and hyperactivity-impulsivity (chapter 3). Molecular genetic investigations in the same sample (chapter 4) identified overlapping associations in line with these findings. However, no associations survived correction for multiple testing or were replicated in analysis of a clinical sample; we therefore cannot discount the possibility that they reflect chance findings. Behaviours that frequently co-occur with ADHD were investigated to elucidate shared versus unique pathways, and moderators. We found that social autistic-like traits (ALTs) largely underlie the covariation of ADHD behaviours and ALTs (chapter 5), and observed significant phenotypic and genetic covariation between RTV and social ALTs. In chapter 6, we investigated the aetiological covariation of ADHD and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, indexed by salivary cortisol. Using growth curve modelling, we identified an association between ADHD affection status and rate of change (declined faster). Further analysis suggested that this association was primarily driven by oppositional behaviours, and that there was a familial component underlying this covariation. Overall, the research summarised in this thesis will facilitate the further development of causal models linking genetic variation via mediating processes to ADHD behaviours.

This thesis aims to add to the literature on psychological factors in the development of OCD and the impact of paternal OCD on children. It is concerned with examining parenting style and behaviours in fathers with OCD as a potential route to OCD 'transmission' and psychological distress in their children as well as examining the perceived impact of having OCD on parenting. It follows from a preliminary study by Challacombe & Salkovskis (2009) examining these factors in mothers with OCD. Fathers have received little attention in psychological research, yet emerging evidence suggests their role in child rearing and effect on children in the case of psychological disorder may be different to that of the mother. 14 fathers with OCD were compared to 20 healthy control fathers. Perception of impact of OCD on parenting was ascertained by questionnaires given to fathers and mothers. Measures of general parenting behaviours and parenting in OCD-specific scenarios, involvement in parenting and levels of expressed emotion (ascertained using a speech sample) were compared to control fathers. Parents also completed questionnaires on their child's general well being, and children completed questionnaires measuring anxiety and OCD related symptoms. Findings revealed that fathers viewed OCD as having a significant impact on their parenting, to a greater degree than mothers. Fathers' perception of impact was unrelated to self-reported OCD severity. Although thematic analysis of speech samples revealed fathers' concern about the effect on their children, their offspring showed no elevated rate of OCD symptomatology. However they showed lower social and school competence, greater social problems, significantly increased internalising problems and increased anxiety, including separation anxiety and panic. Whilst fathers with OCD showed higher rates of expressed emotion, there were no differences in general or specific parenting behaviours, nor clear associations between aspects of parenting and child functioning. Findings are discussed in the context of social learning theory and the role of the father in facilitating social exploration and development. Clinical implications are also discussed.

Background and Aims: Early posttraumatic stress reactions are distressing and disabling for a significant minority of children and young people. We aimed to explore the relationship between posttraumatic stress reactions, cognitive variables implicated by an adult cognitive model of PTSD (Ehlers & Clark, 2000), and overgeneral autobiographical memory; a phenomenon linked to depression and trauma in adults, but rarely explored in children. Methods: Emergency department attendees (aged 8-18) and their parents were interviewed 2-6 weeks post-trauma. Children completed a diagnostic interview for acute stress disorder (ASD), and self-report depression and posttraumatic stress symptom severity questionnaires. Established statistical predictors of posttrauatmic stress reactions were measured using child and parent self-report questionnaires. The Autobiographical Memory Test (AMT) (Williams & Broadbent, 1986) was used to assess overgeneral autobiographical memory (OGM). Results: Among participants (N=43), 30.2% met ASD diagnostic criteria. Using step-wise linear regression analysis; avoidance, negative appraisals and, to a lesser extent, rumination accounted for over two-thirds of the variance of posttraumatic stress symptom severity scores in our sample. Rumination and to a lesser extent negative appraisals together accounted for 80% of the variance of scores in depression severity scores. AMT performance did not contribute significantly to these models. However, those with greater depression symptom severity retrieved fewer specific memories in response to positive cue words on the AMT (p = .022). Parental anxiety and depression did not significantly differ between ASD and non-ASD groups. Findings regarding prior emotional and behavioural difficulties were mixed. Conclusions: Avoidance, negative appraisals and rumination, variables identified in adult cognitive models relate to early responses to trauma in children. Overgeneral autobiographical memory appears less important in this respect, but findings remain tentative at this stage.

Background: TRD (Treatment Resistant Depression) patients have been shown to have hypercortisolemia and a hyperactive HP A (hypothalamo-pituitary-adrenal) axis. The Cortisol Awakening Response (CAR) is a naturalistic measure of the HP A axis activity. Although found to be elevated in depression, it has never been explicitly studied in TRD; furthermore, results have never been compared between Treatment Resistant Unipolar Depression (TRUD) and Treatment Resistant Bipolar Depression (TRBD). In addition, dehydroepiandrosterone (DHEA), the other main adrenal steroid, and which may counteract the effects of cortisol on the brain, has never been measured in TRUD or TRBD. Aims and Methods: To assess the state and relevance of HP A axis changes in treatment-resistant depression using the following methods: (a) salivary cortisol, DHEA and the ratio of Cortisol/DHEA, measured at several points of the day over 2 days; and (b) the CAR (AUCg and AUCi), measured over 2 days. These parameters were compared: between TRUD and TRBD; between patients in episode and in remission; and with matched healthy controls. Results: TRUD patients in episode had a higher CAR (AUCg) compared to controls, remitted patients and TRBD. They also exhibited hypercortisolemia throughout the day (AUCg), and on some measures an elevated Cortisol/DHEA ratio. TRBD patients in episode exhibited a lower CAR (AUCg and AUCi) than controls, remitted patients and TRUD, particularly on Day 1. The Cortisol/DHEA ratio was also lower than controls on some measures. However, patients with remitted TRBD had higher Cortisol/DHEA ratios (but not CAR) than controls.

Epidemiological studies highlight a robust association between advanced paternal age and risk for several neuropsychiatric disorders including autism, schizophrenia and bipolar disorder. In this study a mouse model was used to investigate behavioural and molecular effects of advanced paternal age on the offspring. C57BL/6J females aged 2 months were mated with fathers of the same strain of three different ages: 2 months to represent ’young’ fathers, 10 months to represent ’old’ fathers and 12 months to represent ’very old’ fathers. The offspring were subjected to behavioural tests to investigate their anxiety, locomotion, exploration, memory and social interaction. Significant reductions in exploratory, and particularly social, behaviours in the offspring of old fathers were observed. The deficit in social behaviour is interesting, given that social deficits are a common hallmark across the neuropsychiatric disorders associated with advanced paternal age. -- A variety of methods were utilised to investigate any molecular changes that might underlie the observed paternal age effect. Spermatozoa undergo multiple divisions throughout the male lifespan, potentially leading to a higher incidence of de novo genomic alterations in the offspring. To investigate whether copy number variation (CNV) was associated with advanced paternal age, DNA from the offspring was subjected to genome-wide CNV analysis using comparative genomic hybridisation (CGH) combined with high-resolution microarrays. No differences in the number or size of CNVs or the genes affected by CNVs between the offspring of young fathers and offspring of old fathers were observed. An alternative hypothesis is that epigenetic alterations may explain the relationship between advanced paternal age and behavioural alterations in offspring.

Background: Self-focused attention (S-FA), appearance-related comparisons (ARCs) and self-serving appearance-related biases are relevant to cognitive-behavioural models of, and therefore distress maintenance in, BDD despite them being underresearched. To the author’s knowledge, there are no previous published investigations looking at the nature and specificity of A-RCs, beliefs held about the functions of A-RCs, or experiments investigating self-serving A-RCs biases in people with BDD relative to healthy controls. It was also felt that a more fine grained investigation of self-esteem looking at self-competence and self-liking in people with BDD was warranted. Hypotheses: Hypothesis 1 explored the nature (frequency, direction (attractiveness of A-RCs targets) and automaticity) of A-RCs. More frequent, generally more upwards (to more attractive others) and more automatic A-RCs were hypothesised in people with BDD relative to healthy controls. Hypothesis 2 explored the specificity of A-RCs in people with BDD relative to healthy controls. It was hypothesised that the more frequent A-RCs would not be attributable to more general constructs related to comparing. Beliefs about the functions of A-RCs in people with BDD relative to healthy controls were also explored. Hypothesis 3 investigated a self-serving A-RCs bias, hypothesising that healthy controls, but not people with BDD, would hold this sort of bias contingent on S-FA. Hypothesis 4 investigated self-esteem, hypothesising that self-liking would be disproportionately lower than selfcompetence in people with BDD relative to healthy controls. Method: 23 people with BDD (10 females, 13 males) and 20 healthy controls (10 females, 10 males) matched approximately on age and sex were recruited while using rigorous screening criteria. Hypotheses 1 and 2 used standardised and newly devised questionnaires to explore A-RCs in people with BDD relative to healthy controls. Hypothesis 3 was tested (BDD, n=22; healthy controls, n= 20) using a novel mixed experimental design to investigate the self-serving A-RCs bias, which included employing a manipulation of implicit S-FA as a repeated-measures variable. Hypothesis 4 used the well-established Rosenberg Self-Esteem Scale, divided into self-competence and self-liking, to look at the extent of between group differences. Results: Hypothesis 1 was fully supported. A-RCs were significantly more frequent, generally more upwards, and more automatic in people with BDD relative to healthy controls. Hypothesis 2 was also fully supported. The significantly higher frequency of A-RCs in people with BDD, relative to healthy controls, could not be attributed to general social comparison orientation, upwards social comparison orientation, or self-esteem. People with BDD also held significantly stronger agreement with beliefs about A-RCs as serving functions of self-evaluation, self-loathing (a way to confirm beliefs about physical unattractiveness) and social threat management relative to healthy controls. Hypothesis 3 was not supported, with no A-RCs bias, contingent on S-FA, being found in healthy controls or people with BDD. Hypothesis 4 was also not supported with both self-competence and self-liking being found to be significantly and equally lower in people with BDD relative to healthy controls. Discussion: The author discusses results with particular reference to the theory of social comparison processes as well as literature on clinical anxiety and cognitive behavioural models of BDD. The discussed limitations of the present investigation include the absence of a clinical control group, not matching groups on objective attractiveness, and the study’s ecological validity. Clinical implications cover suggested guidance for addressing A-RCs in cognitive-behavioural therapy and with mindfulness. More comprehensive investigations of A-RCs biases in people with BDD are covered as future directions for research.

It has been well-observed in the literature that not every individual who experiences a traumatic event will go on to develop post-traumatic stress disorder (PTSD). Given this, a key focus within the field has been the examination of those factors which might serve to maintain PTSD symptomatology. In recent years, the potential role of rumination within disorder maintenance has been afforded greater attention, with accumulating evidence from clinical and non-clinical (analogue) studies to suggest its involvement. The evidence-base in this area thus far is outlined, with particular consideration given to the trauma-film paradigm, and the experimental induction of post-event rumination in consideration of symptom development and maintenance. It is noted that the few analogue studies to date utilising this paradigm have yielded mixed findings, and it is proposed that the one-off, brief periods of state rumination typically induced may have been insufficient to adequately parallel clinical rumination. As such, this study sought to make a key adaptation to previous methodological approaches by extending the duration of the experimental manipulation to a one-week period, with repeated daily task completion between two testing sessions. The impact of induced rumination (compared to distraction) on selected PTSD-type symptoms was considered, both following the initial in-session experimental induction and after the extended week-long manipulation: specifically, the impact upon negative affect, intrusive images and physiological arousal (heart-rate response) was assessed. Physiological response to trauma-reminders was also examined as an index of stimulus generalisation. As in previous analogue studies, results were mixed: contrary to hypotheses, a main effect of inducedrumination on intrusive memories, affective change, or in-session physiological arousal was not indicated (with theexception of non-significant trend-level increases specific to anxious and fearful specific toanxiousand fearful mood). gical responses to reminders of trauma (when previous medical experience was controlled for). Limitations regarding the interpretation and generalisability of the presented findings are outlined, and tentative indications as to the way in which these results may fit with current theoretical understanding are considered. Finally, the potential implications for clinical practice, and directions for future research, are discussed.

Background and aims: Evidence suggests that the mode in which traumatic events are processed may influence the development of PTSD, although experimental evidence is lacking. It is crucial to discover what could potentially protect against the development of symptoms such as intrusive memories, since this would allow for the development of evidence-based prevention programmes for at-risk groups. Using a trauma film paradigm (Holmes & Bourne, 2008), the current study investigated the effect of processing mode training (abstract versus concrete) during exposure to an analogue trauma on the subsequent development of intrusive memories, the hallmark feature of PTSD. It also investigated its effect on emotional reactivity to a subsequent traumatic stimulus and whether potential vulnerability factors (e.g. rumination, dissociation, sleep problems, self-reported proneness to intrusions) were related to the frequency of intrusions developed. Method: Fifty-one participants were trained to process traumatic films in an abstract or concrete mode. In the abstract condition, participants were trained to focus on the overall meaning and implications of the events and on questions such as ‘Why?’ and ‘What if?’ In the concrete condition, participants were trained to focus on contextual details and the sequence of events and on questions such as ‘What?’ and ‘How?’ Participants rated their emotional reactions to pre- and post-training test films. They then recorded in a diary the number of intrusive memories they experienced in relation to the film clips over the subsequent week and completed the Impact of Events Scale-Revised (IES-R; Weiss & Marmar, 1997) one week later. Results: As predicted, participants in the concrete group reported fewer intrusive memories in response to the film clips over the subsequent week and lower IES-R scores compared with the abstract group. They also showed reduced emotional reactivity (distress and horror) in response to a post-training film clip although this did not extend to subjective ratings of arousal and negative affect. Self-reported proneness to intrusive memories and pre-existing sleep difficulties significantly predicted intrusive memories, whereas trait rumination and dissociation did not. Conclusions: Overall, findings suggest that training people to adopt a concrete mode of processing during exposure to analogue trauma may protect against the development of intrusive memories and have important implications for the development of preventative programmes for at-risk occupational groups.

Re-experiencing symptoms are a hallmark feature of Post-Traumatic Stress Disorder (PTSD). They are postulated to result from the way in which a trauma memory is encoded, organised and retrieved (e.g. Ehlers, Hackmann, & Michael, 2004). Research has illustrated the effectiveness of exposure therapy (Foa et al., 1991) and Trauma-Focused Cognitive Behavioural Therapy (NICE, 2005) in the treatment of chronic PTSD, yet evidence for early intervention has been mixed. Reducing the fear response is a central aim in therapies for PTSD. Studies have shown that the fear response can be conditioned in humans in the laboratory, that it can return following extinction and that it can be prevented from returning (Schiller et al., 2008, 2010). This analogue study investigated methods to reduce the conditioned fear response, intrusion frequency and PTSD symptoms after viewing trauma films. The research used an experimental design that combined conditioning and trauma film paradigms. All participants underwent the same fear conditioning paradigm where trauma film stimuli (unconditioned stimuli) were paired with neutral stimuli (conditioned stimuli). Participants were randomly allocated to one of three US devaluation groups: ‘update’, ‘exposure’ and ‘neutral’. Exposure and updating techniques are frequently used as components of psychological therapy for PTSD but their relative effectiveness is unclear. This study aimed to compare the effects of updating the meaning of the trauma films (update group), further exposure to the trauma films (exposure group) and viewing non-traumatic films of related content (neutral group) on the reduction of the conditioned fear response and analogue PTSD symptoms. This study also investigated whether individual differences in fear conditioning are associated with the development of PTSD symptomatology. Overall, the findings suggest that adding a cognitive update to a US devaluation process significantly reduces subjective distress ratings to fear conditioned stimuli as well as intrusion frequency and PTSD symptoms. In this study, having a larger conditioned acquisition response predicted higher intrusion frequency and distress and more PTSD symptoms. However, in contrast to the hypotheses, adding a cognitive update to US devaluation increased skin conductance response to the conditioned stimulus compared to further exposure to the films. Theoretical and clinical implications are discussed as well as limitations and avenues for future research.

The highly complex and heterogeneous nature of overlapping neurodevelopmental disorders is likely to increase misspecification in group allocation and hinder the identification of the mechanisms involved. One strategy to facilitate gene identification and to improve understanding of the pathophysiological mechanisms underlying clinical co-occurrence is the investigation of intermediate phenotypes that lie between genes and behaviour. In particular, a neurophysiological perspective which utilises the exquisite time resolution of electroencephalography (EEC) allows objective quantification of the underlying mechanisms. Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are complex childhood-onset disorders that are traditionally treated as separate research fields, in part due to current diagnostic systems precluding a co-diagnosis. The past decade, however, has witnessed an increase in the awareness of significant behavioural, cognitive and genetic overlap between these disorders. The present thesis can be divided into two main objectives: (I) to examine the aetiological overlap between ADHD and quantitative EEG parameters, and (II) to identify shared and/or distinct cognitive-electrophysiological markers of ASD and ADHD and their common co-occurrence. This encompasses data collection in two samples: a community twin sample selected on the basis of consistently high or low ADHD symptoms, and a sample of clinically diagnosed children with ASD (n=19), ADHD (n=18), co-occurring ASD+ADHD (n=29) and typically developing controls (n=26). In Part I, structural equation modeling was used to demonstrate heritability of and substantial shared genetic influences between selected quantitative EEG measures and ADHD, supporting these measures as candidate intermediate phenotypes of the disorder. In Part II, ASD and ADHD were directly compared on these measures and ERP indices of attention and social cognition. Across these analyses, while it was possible to dissociate ASD-only and ADHD-only on their basis of cognitive-electrophysiological parameters, ASD+ADHD largely showed the unique deficits of both disorders, thus supporting an additive co-occurrence. Disentangling phenotypic variation in gene-brain-behaviour relationships is likely to aid the identification of susceptibility genes and other causal mechanisms underlying the complex aetiology of ADHD and ASD. In addition, elucidating the basis of comorbidity can help to refine classification systems and enhance the assessment of complex cases for more specific treatment strategies.