Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial.

After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced in number by an intervention involving a computer game with high visuospatial demands (Tetris), via disrupting consolidation of sensory elements of trauma memory. The Tetris-based intervention (trauma memory reminder cue plus c. 20 min game play) vs attention-placebo control (written activity log for same duration) were both delivered in an emergency department within 6 h of a motor vehicle accident. The randomized controlled trial compared the impact on the number of intrusive trauma memories in the subsequent week (primary outcome). Results vindicated the efficacy of the Tetris-based intervention compared with the control condition: there were fewer intrusive memories overall, and time-series analyses showed that intrusion incidence declined more quickly. There were convergent findings on a measure of clinical post-trauma intrusion symptoms at 1 week, but not on other symptom clusters or at 1 month. Results of this proof-of-concept study suggest that a larger trial, powered to detect differences at 1 month, is warranted. Participants found the intervention easy, helpful and minimally distressing. By translating emerging neuroscientific insights and experimental research into the real world, we offer a promising new low-intensity psychiatric intervention that could prevent debilitating intrusive memories following trauma.

Imagine the bright side of life: A randomized controlled trial of two types of interpretation bias modification procedure targeting adolescent anxiety and depression.

INTRODUCTION: Anxiety and depression are highly prevalent during adolescence and characterized by negative interpretation biases. Cognitive bias modification of interpretations (CBM-I) may reduce such biases and improve emotional functioning. However, as findings have been mixed and the traditional scenario training is experienced as relatively boring, a picture-based type of training might be more engaging and effective. METHODS: The current study investigated short- and long-term effects (up to 6 months) and users' experience of two types of CBM-I procedure in adolescents with heightened symptoms of anxiety or depression (N = 119, aged 12-18 year). Participants were randomized to eight online sessions of text-based scenario training, picture-word imagery training, or neutral control training. RESULTS: No significant group differences were observed on primary or secondary emotional outcomes. A decrease in anxiety and depressive symptoms, and improvements in emotional resilience were observed, irrespective of condition. Scenario training marginally reduced negative interpretation bias on a closely matched assessment task, while no such effects were found on a different task, nor for the picture-word or control group. Subjective evaluations of all training paradigms were relatively negative and the imagery component appeared particularly difficult for adolescents with higher symptom levels. CONCLUSIONS: The current results question the preventive efficacy and feasibility of both CBM-I procedures as implemented here in adolescents.

Mental Imagery-Based Training to Modify Mood and Cognitive Bias in Adolescents: Effects of Valence and Perspective.

Mental imagery has a powerful impact on emotion and cognitive processing in adults, and is implicated in emotional disorders. Research suggests the perspective adopted in mental imagery modulates its emotional impact. However, little is known about the impact of mental imagery in adolescence, despite adolescence being the key time for the onset of emotional dysfunction. We administered computerised positive versus mixed valence picture-word mental imagery training to male adolescent participants (N = 60, aged 11-16 years) across separate field and observer perspective sessions. Positive mood increased more following positive than mixed imagery; pleasantness ratings of ambiguous pictures increased following positive versus mixed imagery generated from field but not observer perspective; negative interpretation bias on a novel scrambled sentences task was smaller following positive than mixed imagery particularly when imagery was generated from field perspective. These findings suggest positive mental imagery generation alters mood and cognition in male adolescents, with the latter moderated by imagery perspective. Identifying key components of such training, such as imagery perspective, extends understanding of the relationship between mental imagery, mood, and cognition in adolescence.

Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series.

Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP).

Good prognosis cytogenetics in B-cell chronic lymphocytic leukemia is associated in vitro with low susceptibility to apoptosis and enhanced immunogenicity.

Chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) have been shown to correlate with prognosis. Little is known about the relationship between chromosomal abnormalities and biological behavior of B-CLL cells in vitro. The present study was designed to explore the impact of chromosomal abnormalities determined by interphase fluorescence in situ hybridization (FISH) on the in vitro survival and immunogenicity of B-CLL. Considerable heterogeneity was noted in the in vitro survival and expression of costimulatory, adhesion, and antigen-presenting molecules by B-CLL cells. Spontaneous apoptosis of B-CLL cells in vitro was significantly lower in samples with good prognosis cytogenetics when compared to samples with poor prognosis cytogenetics. In contrast, B-CLL cells from samples with good prognosis cytogenetics exhibited higher basal expression of molecules involved in costimulation, cellular adhesion, and antigen presentation, and induced significantly more T-cell proliferation in mixed lymphocyte cultures. We conclude that chromosomal aberrations of B-CLL cells correlate with the in vitro biological behavior of B-CLL. Our data indicate that good prognosis cytogenetics correlates with less spontaneous apoptosis but greater in vitro immunogenicity. These findings could have significant implications on the design of future therapeutic approaches in patients with CLL, and the likelihood of response based on cytogenetics.

Construction of a human chromosome 4 YAC pool and analysis of artificial chromosome stability.

In order to construct a human chromosome 4-specific YAC library, we have utilized pYAC4 and a mouse/human hybrid cell line HA(4)A in which the only human chromosome present is chromosome 4. From this cell line, approximately 8Mb of chromosome 4 have been cloned. The library includes 65 human-specific clones that range in size from 30kb to 290kb, the average size being 108kb. In order to optimize the manipulation of YAC libraries, we have begun to investigate the stability of YACs containing human DNA in yeast cells; these studies will also determine if there are intrinsic differences in the properties of chromosomes containing higher eukaryotic DNAs. We are examining two kinds of stability: 1] mitotic stability, the ability of the YAC to replicate and segregate properly during mitosis, and 2] structural stability, the tendency of the YAC to rearrange. We have found that the majority of YACs examined are one to two orders of magnitude less stable than authentic yeast chromosomes. Interestingly, the largest YAC analyzed displayed a loss rate typical for natural yeast chromosomes. Our results also suggest that increasing the length of an artificial chromosome improves its mitotic stability. One YAC that showed a very high frequency of rearrangement by mitotic recombination proved to be a mouse/human chimera. In contrast to studies using total human DNA, the frequency of chimeras (i.e., mouse/human) in the YAC pool appeared to be low.