The NMDA receptor is crucial for the induction of neuronal plasticity throughout the central nervous system. Although traditionally thought of as relatively stable compared to AMPA receptors, recent evidence suggests that synaptic NMDA receptors are in fact quite labile. In this study, the NMDA receptor-mediated synaptic responses of two pathways onto CA1 neurones were studied. Stimulating electrodes were placed in the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) to stimulate the Schaffer collateral (SC) and temporoammonic pathways (TA) of the hippocampus, respectively. Whole-cell voltage-clamp recordings were obtained from CA 1 principal neurones. Each pathway was alternately stimulated and pharmacologically isolated NMDAR-mediated EPSCs were recorded. Application of the group I mGlu receptor agonist DHPG caused L TD of NMDA receptor-mediated responses of the SC, but not the TA pathway. DHPG-L TDNMDA did not appear to influence the postsynaptic NMDA receptor subunit composition as assessed by the decay time constant of the NMDA receptor-mediated EPSC and the efficacy of R025-6981, an antagonist of GluN2B-containing NMDA receptors. Also, a 5 Hz 20-second stimulation protocol was again shown to evoke L TD of NMDA receptor-mediated responses of the SC, but not the TA pathway. This 'theta frequency-evoked' L TD was also mediated by mGlu receptors but, in contrast to DHPG-L TDNMDA, did cause a change in the decay time constant of the NMDA- receptor mediated EPSC. 5 Hz 20 seconds stimulation did not cause L TD of AMPA receptor-mediated transmission but induced metaplasticity in extracellular field recordings, as it inhibited the subsequent induction of L TP of field EPSPs. These results demonstrate two forms of plasticity that are both expressed at one synapse of CA1 principal neurones but not another. The downregulation of NMDA receptor-mediated transmission in this manner may have functional consequences for synaptic transmission and plasticity within the hippocampus. 2

The main aim of the present thesis was to investigate the effects of depression on the creation of false memories. Across four experiments the parameters of the Deese (1959), Roediger and McDermott (1995) paradigm (DRM) were manipulated. The DRM paradigm is a robust method for inducing false memories in participants and has been used widely to investigate false memory over the past 20 years (see Gallo, 2006). In the first experiment an effect of induced mood on performance in the DRM/ was established. That is, participants in an experimentally induced positive mood were more likely to falsely recognise neutral words than participants in an experimentally induced negative mood. This provided further justification for investigating mood and the creation of false memories and led onto expanding the research to participants diagnosed with depression. Experiment 2 used a recognition task with positive, negative and depression relevant word lists and compared participants diagnosed with depression and matched controls. This experiment demonstrated that participants with depression were no less accurate for true recognition than matched controls, across all word types. However elevated levels of false recognition for depression relevant words in participants diagnosed with depression was discovered. Experiment 3 used a directed forgetting task in combination with the DRM paradigm. Here it was discovered that participants diagnosed with depression were more likely to falsely recall the critical lure if they were directed to forget the related word list, significantly more so than matched controls. In addition participants diagnosed with depression were significantly more likely to recall the critical lure later in the recall sequence than matched controls under forget instructions only. The final empirical study investigated personal relevance and arousal of the particular words and lists used. Participants diagnosed with depression produced lowered levels of true recognition compared to non- depressed matched controls, but no significant difference between false recognition levels was found. There was a trend towards mood congruent effects however, where participants were more likely to misidentify depression relevant critical lures if they were diagnosed with depression. Overall, participants were also more likely to correctly and falsely recognise words if they were negatively valenced. The over arching conclusions of the research conducted within this thesis are that participants with depression are not necessarily displaying global deficits in terms of memory production, however their memory traces are vulnerable to certain manipulations of experimental design, particularly for tasks that require greater levels of cognitive control. In addition, it appears that mood congruent words and concepts may be more vulnerable to false memory errors in participants diagnosed with depression.

Much research has shown both cognitive deficits and negatively valenced cognitive biases to be present in depression. Rumination - the tendency to think repetitively about ones own thoughts feelings, symptoms and problems - has also been linked to cognitive deficits and biases. It has been proposed that rumination which is a risk factor for degression and is consistently found to be elevated in currently depressed patients, may cause cognitive deficits in depression by overwhelming cognitive resources. Rumination may also cause negative cognitive biases by focussing attention onto negative over positive information and therefore causing it to be over-consolidated into memory.

No description available.

No description available.

A growing body of evidence suggests that mindfulness is a useful treatment for reducing alcohol use, yet little is known about the relationship between trait mindfulness and alcohol misuse. Furthermore, the variation in the measurement of mindfulness means that the existing evidence is difficult to interpret and the prevalent use of student samples greatly limits generalisability. It has been proposed that mindfulness may bring more awareness and acceptance to depression symptoms and craving leading to reduced alcohol use. The present study aimed to examine the relationship between the individual facets of mindfulness and alcohol misuse, taking into account the role of depression and craving. A cross-sectional, correlational design was used to explore these relationships in individuals seeking treatment for alcohol misuse. Seventy seven participants completed self-report measures on depression, craving, mindfulness and alcohol misuse. The results showed that depression symptoms were positively associated with alcohol misuse and negatively correlated with mindfulness, thus supporting previous findings. The mindfulness abilities of bringing full awareness to present moment activities and adopting a non-judgemental and a non-reactive attitude were associated with less alcohol misuse. The ability to bring full awareness to present moment activities was also associated with less craving. However, mindfulness did not moderate the association between depression and alcohol misuse, disconfirming the hypothesis. Higher levels of craving were associated with higher levels of alcohol misuse suggesting that craving represents a cognitive marker that precedes alcohol use. The results provide valuable evidence of the association between certain mindfulness facets and alcohol misuse in a sample of individuals with moderate to severe alcohol misuse problems and suggest that these mindfulness abilities may be a useful focus for interventions for both depression and alcohol misuse.

No description available.

Autobiographical memories are memories from one's personal past. They are distinguished from other forms of memory by their self-referent nature. studies of voluntary autobiographical memory recall have repeatedly found that individuals with depression are prone to retrieve fewer specific autobiographical memories than non-depressed controls (for a review see Williams et al, 1996). This phenomenon Is commonly referred to as the over- generality effect. Over-general recall has been found to be highly correlated with failure to recover from depression. It has been found to be present prior to the onset of a depressive episode and also after the depression remits. It seems that over-generality may be a trait marker which could possibly be indicative of vulnerability to persistent depression (Brittlebank, Scott, Williams & Ferrier, 1993). The over-generality effect therefore appears to be a clinically relevant feature of depression.

Positive Interpretation Training (PIT) refers to computerised procedures designed to instil in the user a more positive cognitive bias. This study aimed to investigate the potential for PIT to modify the negative cognitive biases of people with depression, and thus improve their mood and mental health. The limitations to the current research meant that a single case series design was most appropriate at this stage.

Objectives: Biological approaches to depression have been dominated by the serotonin theory, which suggests that clinical depression is associated with low serotonin function in the brain. However, the way in which serotonin might lead to mood change is still unclear. The relationship between serotonin dysfunction and psychological mechanisms identified by cognitive theories as being fundamental in the development of depression (e.g. core beliefs, cognitive distortions, negative automatic thoughts,) is particularly unclean The low dose tryptophan paradigm will be used to examine whether or how impaired serotonin function produces cognitive changes that map directly onto the clinical cognitive constructs that are targeted in CBT for depression.