Disruptions in autobiographical memory processing in depression and the emergence of memory therapeutics

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Disruptions in autobiographical memory processing in depression and the emergence of memory therapeutics Tim Dalgleish and Aliza Werner-Seidler Medical Research Council Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge, CB2 7EF, UK

Depression is characterized by distinct profiles of disturbance in ways autobiographical memories are represented, recalled, and maintained. We review four core domains of difficulty: systematic biases in favor of negative material; impoverished access and responses to positive memories; reduced access to the specific details of the personal past; and dysfunctional processes of rumination and avoidance around personal autobiographical material. These difficulties drive the onset and maintenance of depression; consequently, interventions targeted at these maladaptive processes have clinical potential. Memory therapeutics is the development of novel clinical techniques, translated from basic research, that target memory difficulties in those with emotional disorders. We discuss prototypical examples from this clinical domain including MEmory Specificity Training, positive memory elaboration, memory rescripting, and the method-of-loci (MoL). Recollecting and reflecting upon our autobiographical past defines human mental life. Personal memories are the currency of social discourse, they mold and shape our emotions, help us plan our future, and provide candidate solutions for the problems that we face. Our library of autobiographical memories defines who we are, scaffolding our sense of self across time [1]. Systematic difficulties in the recollection of these past experiences, especially of emotionally evocative events, are a cardinal feature of affective disorders, and range from intrusive flashbacks of trauma in post-traumatic stress disorder (PTSD) to ruminations upon overgeneral negative personal themes in depression. These patterns not only define the mental lives of many patients but also drive the onset and maintenance of disorder [2,3]. Consequently, emerging clinical interventions that target and reverse these disrupted memory processes have enormous potential. In this review we discuss the often toxic problems faced by individuals with clinical depression (a description of depression is Corresponding author: Dalgleish, T. ([email protected]). Keywords: autobiographical memory; depression; overgeneral memory bias; suppression; method-of-loci. 1364-6613/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tics.2014.06.010

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given in Box 1) in the way that they process the autobiographical past and outline recent advances in the translational science of memory therapeutics that seek to address these difficulties. The four mnemonic horsemen of depression Sufferers of depression remember the past differently to their never-depressed peers. Their autobiographical memory processing is compromised in at least four distinct but interrelated ways that combine and interact to help maintain depressive episodes once they have begun, and to confer vulnerability to new episodes when sufferers are in remission (Figure 1). Biased recollection of negative memories The most striking feature when engaging with individuals in the grip of depression is the pervasively negative tone that sounds throughout their discourse about the past. Depression appears to be characterized by a systematic autobiographical recollection bias that favors negative experiences [4,5], with faster access to negative personal memories when prompted and a greater tendency to generate negative memories when recall is unconstrained [6]. Unbidden intrusive memories of negative, often traumatic, past experiences also characterize the disorder [7]. This facilitated negative retrieval is likely to be complemented by biases at encoding as a function of selective attention to negative personal experiences [4] and skewed interpretation of ambiguous personal scenarios in favor of negative resolutions [8]. Such pervasive preferential access to negative personal memories in depression contributes to the felt sense of a profoundly negative self, world, and future that depressed individuals describe [9]. Impoverished positive memories The day-to-day recollection of self-affirming positive experiences has been identified as a core adaptive emotion regulation strategy to counteract downturns in negative affect [10,11]. The biased recollection of negative memories in depression, described above, is also accompanied by impoverished access to such positive autobiographical past events [4]. Even when positive memories are successfully brought to mind, their recollection appears to have little

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Box 1. The nature of depression and cognitive theories of the disorder What is depression? In psychiatric terms, depression (defined as presence of a major depressive episode; MDE) is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) [70] as the presence of at least five symptoms from a set of nine, one of which must be consistent depressed mood or anhedonia. Additional symptoms may include changes in appetite or sleeping pattern, restlessness, fatigue, feelings of guilt or worthlessness, impaired concentration, and suicidal ideation. To fulfill criteria for an MDE the constellation of symptoms must be present for most of the day, nearly every day for a 2 week period or longer, and represent a change from previous levels of functioning. Symptoms must also interfere with functioning in social, occupational, or other important domains, or cause considerable distress to the individual. Epidemiological studies have established depression as a major public health concern that tends to run a chronic course [71]. The lifetime prevalence rate is approximately 16% [72], with more than 80% of individuals experiencing multiple episodes [71]. Each recurring episode predicts a higher risk of future recurrence [73], even after successful treatment of the current episode [74,75]. Depression currently costs the UK exchequer more than £9 billion annually [76] and is predicted by the World Health Organisation (see http://www.who.int/whosis/whostat/2008/en/index.html) to be the second leading cause of disability worldwide by 2020 [77]. Depression is a growing problem at both individual and societal levels, underscoring the need for more effective interventions not only to target the acute phase of disorder but also to reduce the likelihood of relapse/ recurrence.

beneficial impact on mood for those with a history of depression [12,13], and may even be detrimental [13]. This failure to improve mood may reflect the quality of recollected positive memories. For example, there is evidence that, when in a sad mood, individuals with a history of depression recall positive memories that are markedly less vivid [14] and less emotionally intense [15] than those retrieved by never-depressed peers. The lack of salient phenomenological memory features may very well make it more challenging for positive memory recall to confer emotional benefits (although whether this is also the case in currently depressed groups awaits confirmation). Another possibility is that reflecting on a past happier time, and making comparisons to current low mood, draws

Biased recollecon of negave memories

Impoverished posive memories

Depression

Overgeneral memory

Altered relaonship to emoonal memories TRENDS in Cognitive Sciences

Figure 1. The four mnemonic horsemen of depression. These four processes, characteristic of depression, interact and combine in ways that maintain depression and elevate the risk of recurrence even after remission.

Cognitive models of depression Cognitive approaches to depression provide a framework for understanding the psychological mechanisms involved in the onset, maintenance, and recurrence of the disorder. Perhaps the most influential cognitive model was provided by Beck who proposed that depression results from the activation of underlying dysfunctional schemas* that represent negative mental constructions about the self, the world, and the future (‘the negative cognitive triad’ [62]). Schemas are claimed to drive negative thinking and other cognitive biases and distortions (including biases in autobiographical memory processing) that serve to maintain schema integrity and thereby support and consolidate the cognitive foundations that drive the disorder [62]. Beck’s cognitive model and other related approaches [63] provide an overarching framework in which biases and distortions in a cognitive process such as memory are conceptualized as ‘rational’ and adaptive processes that are servicing maladaptive and dysfunctional underlying schemas. Cognitive behavior therapy (CBT), the intervention paradigm derived from such cognitive formulations of depression, seeks to identify and modify biases in thinking and cognitive processing and to reorganize and shift underlying schema to make them more adaptive and functional. The nascent memory therapeutics discussed here fall under the umbrella of this broad CBT approach.

*

Schemas are proposed to be cognitive structures which provide an internal representation of aspects of the self, the world, and of others, that derive from a lifetime of experience in encountering relevant exemplars from these categories and that shape the encoding, organization, and retrieval of information [62].

attention to the discrepancy between these states, thus spawning rumination that itself contributes to worsening mood [13]. There is some evidence supporting this account, with data showing that preventing rumination by instructing depressed and formerly depressed individuals to focus on the concrete and specific details of the memory leads to improved mood following memory recall [16]. Categorical memory A third striking feature of autobiographical recollection in depression is the focus on ‘categorical’ aspects of the past. In contrast to individual autobiographical episodes, these categorical recollections comprise general, often negatively-valent, themes that capture repetitions and regularities across many personal experiences. There is now good evidence that such categorical processing tends to override access to detailed memories of specific individual events in depression [3]. For example, on the widely-used autobiographical memory test (AMT) [17] – where specific, detailed memories are prompted by cue words – a depressed responder would be more likely to generate a categorical memory to a cue such as ‘party’ (e.g., ‘Every birthday party I’ve ever hosted has been a disaster!’) as opposed to the requisite recollection of a specific festive occasion. One likely reason why categorical autobiographical recollection is so potent in depression is the highly consolidated nature of negative categorical themes that underpin the disorder – an idea that lies at the heart of cognitive theories of depression with their emphasis on the role of negative schemas (Box 1). We used a novel ‘life chapters’ task to elucidate these emotionally salient categorical autobiographical themes in depression [18]. Participants constructed autobiographical timelines, dividing their life into discrete chapters (e.g., ‘student days’; ‘intimate 597

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relationships’), and subjectively allocated positive and negative descriptive information to each chapter. Those with depression showed increased coherence and repetition of negative information across chapters, and reduced coherence and repetition of positive information, whereas their never-depressed peers showed the opposite pattern. Greater depression entrenchment, indexed by number of prior episodes, was associated uniquely with lack of positive coherence, suggesting that a paucity of positive autobiographical themes is a cognitive marker of depression recurrence. There is now substantive evidence that the relative difficulty encountered by depressed individuals in accessing specific autobiographical memories, and their proclivity for dwelling on these categorical aspects of the personal past, is related to poorer prognosis [19]. One reason for this is that overgeneral recall can spur ruminative processes focused on the categorical themes that have been accessed. Rumination then consolidates these themes, further enhancing the tendency towards overgeneral memory (e.g., [20]). Another reason is that fluent processing of specific autobiographical memories is a core aspect of successful daily cognitive functioning involved in planning, problemsolving, and social discourse (Table 1). Consequently, impairment across these diverse cognitive operations has adverse downstream consequences concerning the course of depressive disorder [3]. Alterations in the mental relationship to emotional autobiographical memories The recollection of emotional past events can sometimes be painful, particularly for those struggling with mental health difficulties. Explicit and implicit efforts to avoid or suppress distressing personal memories and/or the emotions associated with them, perhaps unsurprisingly, have been shown to be more prevalent in depression [21,22]. However, such efforts are also more likely to be counterproductive, with greater intrusion of the unwanted memories following attempted suppression in individuals high in depressive affect relative to their less-depressed peers [23]. As well as being counterproductive, suppression focused on a given target upsetting personal memory appears to enhance subsequent access to other upsetting memories in depressed individuals, suggesting that suppression is a particularly toxic way of relating to the personal past when depressed [23]. Subtler forms of mental avoidance also appear to be at play in the way that those with depression relate to memories that have been recollected, especially when those memories are recalled in the form of mental images as

opposed to verbal narratives [24]. With image-based memories, depressed individuals have a greater tendency to adopt an observer perspective [25,26] – seeing themselves in the situation, but from the point-of-view of an outsider. This has been found to be the case for both negative and positive personal memories, and adopting an observer perspective generally reduces the affect associated with the memory in the short-term [27,28]. For distressing memories, it seems that adopting an observer perspective per se may be counterproductive in the longer-term because it mitigates successful emotional processing of the memory [24,29]. Similarly, in the case of positive memories, simply adopting an observer perspective may be unhelpful because it reduces the affective impact associated with the memory [27,28]. One strong motivating factor for such attempted (if unsuccessful) avoidance of the recollection of distressing aspects of the past is the fact that, when autobiographical memories do come to mind in depression, they have a greater tendency to spawn ruminative processes. These are either focused on the memories themselves or on relating those memories to the wider depressogenic categorical themes running through the individual’s autobiography, referred to in the preceding section [18,30]. The CaR-FA-X model of autobiographical memory processing in depression The CaR-FA-X model [3] (Figure 2) operationalizes the core disruptions in autobiographical memory processing associated with depression that we have outlined above. Within the model, difficulties accessing specific episodes from the past are characterized as resulting from the capture (Ca) of memory search efforts by highly consolidated categorical depressogenic themes, which then form the focus of maladaptive cycles of rumination (R). The likelihood of such capture is exacerbated by ingrained functional avoidance (FA) of specific details of past upsetting autobiographical events that itself diverts processing to the categorical level of autobiographical representation. The ability to override these dysfunctional processing imperatives is compromised as a function of the relatively impoverished executive (X) control that characterizes those suffering from depression [4,31]. Memory therapeutics and depression These advances in our understanding of the key roles that maladaptive aspects of autobiographical memory processing play in depression, and the CaR-FA-X framework that integrates them together, have prompted practitioner-researchers to explore new avenues of therapeutic

Table 1. Putative functions of specific memories and examples of impairment in affective contexts Function of specific memories Problem solving

Planning Emotional processing Reducing rumination 598

Examples of impairment in depression Reduced specificity is associated with impaired problem-solving in depression [78,79] and moderates the effect of a negative mood disturbance on problem-solving performance in previously suicidal patients [80]. Reduced specificity is associated with difficulty in imagining specific future events [81] with implications for effective future day to day planning [82]. Reduced specificity is associated with high scores on emotional avoidance measures [83,84] and predicts affective reaction to failure [85,86]. Reduced memory specificity is causally related to greater ruminative processing [87,88]

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Capture and ruminaon

Funconal avoidance

Non-specific autobiographical memory

Consequences E.g., impaired problem-solving

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Figure 2. The CaR-FA-X model of autobiographical memory processing in depression. Three processes contributing to overgeneral memory – capture and rumination (CaR), functional avoidance (FA), and impaired executive capacity and control (X) – can each have effects on cognition and behavior (e.g., problemsolving), either independently or through their individual or combined effect on autobiographical memory. Reproduced from [3], with permission, copyright ß (2007) American Psychological Association.

intervention which focus on changing patients’ processing of, and relationship to, their personal past. These emerging interventions sit against a broader backdrop of cognitive approaches to the treatment of depression and other emotional disorders which have historically focused on patient autobiographies as a rich source of therapeutic material (Box 1). We discuss here novel memory-based techniques addressing the four highlighted core domains of autobiographical memory disturbance in depression. Changing negative memory biases Cognitive bias modification (CBM) refers to a new range of interventions that seek to shift the pervasive maladaptive cognitive biases associated with clinical disorders through systematic, computerized training to recalibrate underlying processes in favor of positive or benign material, rather than negative information [32]. To date, CBM has been applied most effectively in anxiety [33]. However, recently the focus has shifted to evolving and evaluating CBM procedures in depression [34]. CBM for depression that has targeted initial attention to [35,36], and interpretation of [37–40], emotional events has produced mixed results [34]. However, CBM procedures that have directly targeted memory biases [41] by training depressed individuals to process mildly upsetting events in a specific and concrete way potentially show more promise, with the CBM participants experiencing decreased depressive symptoms relative to a control group [42]. Explicit rescripting of negative autobiographical memories to reduce their distressing impact, an approach with a history of successful application in anxiety syndromes [43], also shows potential as a clinical tool in depression. Wheatley et al. [44], in a clinical case series, reported benefits of rescripting in the form of reduced symptoms of depression and a decreased frequency of intrusive recollections of the rescripted events. Enhancing the recollection of positive autobiographical memories The affective impact of recalled positive and self-affirming memories can be enhanced through elaboration processes targeted at enriching the memories with affective, visual,

and sensory detail. For example, Werner-Seidler and Moulds [16] showed that, for individuals with depression, focusing on these detailed aspects of their memories (the moment-to-moment experience of the memories), instead of processing memories in an abstract way (reflecting on the causes, meanings, and consequences), enhanced the positive emotional impact of the memories. Commensurate with these findings is work from the imagery domain showing that, when positive material is elaborated using imagery, the impact on emotion is amplified [45,46]. These studies provide proof-of-principle that those with depression can derive affective benefits from suitably elaborated positive material. An entirely different challenge, however, is to facilitate day-to-day access to such elaborated memories when they are most needed (e.g., in the service of emotion regulation). One candidate solution is the MoL technique – a mnemonic device that relies on spatial relationships between familiar locations or routes to scaffold recollection of previously identified and stored information (Box 2). In the first study investigating the utility of the MoL in depression [47] we asked participants to generate and then elaborate a set of positive and self-affirming memories before practicing recalling the memories. Participants were divided into two practice conditions, using either a chunking-and-rehearsal technique or the MoL, and completed a week of retrieval training with their allocated method until they could recall all their identified memories without error. On the crucial surprise recall test after a further week (during which no further practice took place), recollection remained at ceiling only in the MoL group. These initial data suggest that the MoL has promise as a technique to allow easy access to sufficiently elaborated positive and self-affirming memories in depression. MEmory Specificity Training (MEST) The wealth of basic research suggesting a relative difficulty in accessing specific autobiographical memories in depression [3] suggests an elegantly simple intervention – training patients to become more specific in their emotional recollection (Box 3). To this end, Raes and colleagues [48] evaluated the effect of a group-based MEST program with depressed inpatients in an uncontrolled trial. The retrieval style of participants became significantly more specific (Figure I in Box 3), and improvements in specificity were significantly associated with reported improvements in processes important in day-to-day cognition (Table 1) including rumination, cognitive avoidance, and problemsolving skills. Building on this platform, we conducted the first randomized controlled trial (RCT) of MEST (versus a no-intervention control) with a sample of bereaved, depressed Afghan adolescent refugees living in Iran; importantly, this RCT also included a 2 month follow-up [49] (Figure I in Box 3). MEST successfully enhanced memory specificity, and specificity gains mediated subsequent improvements in depressive symptoms for adolescents in the MEST group, which were reduced into the non-clinical range. There is similar promising evidence for MEST as an intervention for sufferers of PTSD [50]. These early-stage trials suggest that, despite its simplicity, MEST is an efficacious intervention 599

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Box 2. The method-of-loci (MoL) The MoL is an ancient mnemonic device that relies on memorized spatial relationships between loci (e.g., locations on a familiar route such as the journey to work) that are used to arrange and recollect memorial content. The basic method uses visual imagery to mentally associate each to-be-remembered piece of information with one of the loci along the route (e.g., a particular building). By this means, material can be recollected simply by mentally retracing the route and using the loci and associated imagery on this imagined journey as prompts to cue the information from memory. The MoL was first described in Roman rhetorical treatises (e.g., [89]). It remains the favored strategy adopted by contemporary memory champions to store exceptionally large amounts of information, such as recalling the value of P to thousands of decimal places [90]. The MoL can be easily acquired by non-experts, and dramatically improves memory performance in naı¨ve participants [91–93]. The

Idenfy memories to be remembered

The birth of my first son

Elaborate memories to include rich and specific details

I was overcome with emoon – I remember his skin was so so as I held him for the first me

Idenfy a familiar route

The daily commute to work

features of the images used to combine the loci with the material to be remembered are crucially important – the more salient, vivid, and bizarre the imagery, the easier the material is to recollect [94]. The MoL is versatile; it can be readily used for the temporary storage of information (e.g., a shopping list), but also lends itself to the construction of more permanent mental repositories supporting access to the target material on repeated future occasions. Such repositories are commonly known as ‘memory palaces’ [95,96] because they often comprise elaborate and beautiful fictitious locations that the recollector has imagined solely for the purposes of information storage. Memory palaces of this kind have a long pedigree dating back to medieval times [97]. Our study utilizing the MoL to improve access to positive and selfaffirming memories in depression [47] extends the technique to clinical application; a worked example of this approach is illustrated in Figure I.

Idenfy loci along the route

The telephone box at the end of the street

Combine loci with memories using vivid imagery

Retrieve memories by mentally navigang along route

Instead of the telephone booth, I see that my infant son is holding the phone receiver chang away

By simply imagining my cycle to work, I pass the telephone booth and see my son gossiping away into the receiver... TRENDS in Cognitive Sciences

Figure I. Using the method-of-loci (MoL) to enhance recollection of positive autobiographical memories in depression [47].

that can alleviate depression (and other disorders), consistent with other novel depression interventions that focusing on enhancing concrete processing of personal material [42]. Changing relationships to memories Cognitive behavioral therapy (CBT) interventions for emotional disorders, including depression, that seek to change the way recipients relate to aspects of their mental life, such as their memories of the past, instead of trying to modify or challenge mental content itself, have been deemed the ‘third wave’ of behavior therapy [51]. Such treatments include acceptance and commitment therapy [52], dialectic behavior therapy [53], and, of most relevance to depression, rumination-focused cognitive behavioral therapy (RF-CBT [54]) and mindfulness-based cognitive therapy (MBCT [55]). RF-CBT is an adapted form of CBT designed to reduce residual symptoms of depression by directly targeting ruminative processes that we know are intimately linked to disruptions in autobiographical memory. There is preliminary support for this intervention, with RF-CBT proving efficacious in reducing symptoms relative to treatmentas-usual, although these effects need to be replicated in trials involving an active control group [54]. MBCT is a group intervention targeted at preventing relapse in currently well patients with recurrent 600

depression and has a strong database of supportive outcome data [56]. Although not targeted at memories per se, MBCT seeks to enhance affective executive control over mental life, including memory for the past, through the cultivation of mindfulness skills that promote the ability to psychologically ‘step back’ from distressing mental content. MBCT is a complex and intensive intervention requiring highly trained therapist input. More recently, researchers have endeavored to distil core cognitive elements of MBCT into simpler cognitive training protocols. Kross and colleagues investigated the benefits of self-distancing (SD) – the process of intentionally stepping back from an experience to reflect on it and reappraise it from the perspective of a distanced observer. It is important to note how this more reflective process is distinct from simply automatically adopting an observer perspective upon personal memories – something that by itself appears to be counterproductive (as discussed above [24,29]). Kross and colleagues have shown in a novel series of studies that analyzing the meaning of memories and experiences (e.g., thinking about why they may have occurred) from a selfdistanced perspective can reap mental health benefits in individuals with depression [57]. Similar work in our own laboratory has examined perspective broadening (PB) – the capacity to frame experiences within wider contexts. Preclinical work across four studies showed that a single

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Box 3. MEmory Specificity Training (MEST)

session of PB training reduced negative affect and psychophysiological responses to distressing film clips and upsetting personal memories and reduced subsequent memory intrusions [58]. Affective executive training Central to the CaR-FA-X framework is the idea that a core barrier faced by sufferers of depression when using autobiographical memory techniques in the clinic is a lack of executive capacity to work in complex ways with memories that are often emotive and resource-demanding [31]. To try to address this we developed an affective variant of an established working memory (WM) training protocol [59] that aimed to augment executive control in such affective contexts, and we used it to train affective WM over 20 days in healthy participants. We found that those exposed to training, unlike placebo-trained controls, showed enhanced performance on a measure of affective attention – the emotional Stroop task [60] – as well as on a quintessential index of affective executive control – the ability to downregulate negative affect in response to viewing distressing film clips [61]. Regulatory gains were associated with greater activity in the frontoparietal brain network as well as in other neural regions implicated in affective control, notably the subgenual anterior cingulate cortex

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MEST is designed to enhance the specificity with which depressed participants retrieve personal events from autobiographical memory with the aim of counteracting the difficulties associated with the disorder in accessing specific personal information [48,49]. MEST is delivered in small groups led by trained therapists and comprises the following five-session structure: Session 1: psychoeducation about memory difficulties common in depression is presented and discussed, and impairment in retrieving specific memories is provided as the rationale for MEST. As a group, participants practice recalling specific memories in response to positive and neutral cues, with demonstrations and support from therapists. For homework, participants identify specific memories in response to 10 cue words, and identify an additional specific event that has happened to them each day to bring to the subsequent session. Session 2: the second session commences with a brief summary of session 1 followed by a homework review. The remainder of the session follows the same format as session 1, focusing on memory retrieval for positive and neutral words. Additionally, participants are encouraged and assisted in retrieving multiple distinct memories in response to the same cue. For homework, participants identify specific memories in response to 10 cue words and identify two additional specific events each day. Session 3: in the third session, negative cues are introduced and participants practice retrieving specific memories in response to negative and positive cue words. As in session 2, participants retrieve multiple memories of a different nature in response to the same cue. Homework is identical to that of session 2 with the inclusion of negative cue words. Sessions 4–5: the fourth session involves further practice of memory retrieval in response to neutral words, and the fifth and final session involves retrieval to a variety of cues (e.g., positive, negative, and neutral), concluding with a summary and review of the program. The impact of MEST on memory specificity and depressive symptoms in the two published studies in depression is illustrated in Figure I.

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Figure I. The top panel shows mean of level specificity as measured by the autobiographical memory test (AMT) [17] at pre-training and post-training. Bottom panel shows mean depression scores as measured by the Beck Depression Inventory (BDI-II) for the single-group, uncontrolled pilot trial in the Raes et al. study (personal communication) and by the Mood and Feelings Questionnaire (MFQ) in the Neshat-Doost et al. controlled trial [49].

[61]. These initial studies suggest that affective executive training has potential to accrue transferable benefits to skills relevant to patients with affective disorders. Concluding remarks and future perspectives Cognitive theories of depression [62,63] emphasize the key role played by biases and perturbations across core cognitive faculties in the onset and maintenance of the disorder. Central to these is maladaptive processing of the emotional autobiographical past. We have reviewed four domains of such autobiographical memory dysfunctionality: systematic biases in favor of negative material, impoverished access and responses to positive memories, reduced access to the specific details of the personal past (overgeneral memory), and dysfunctional processes of rumination and avoidance around emotive personal autobiographical themes. These difficulties drive the onset and maintenance of depression; consequently, interventions targeted at these maladaptive processes have considerable clinical potential. Memory therapeutics is the development of novel intervention techniques, translated from basic research to autobiographical memory, that target memory difficulties in those with emotional disorders. We have presented prototypical examples from this clinical domain including MEST, positive memory elaboration, memory 601

Review rescripting, and the MoL, that have promise either as stand-alone low-intensity interventions for patients with milder forms of depression or as adjuncts to existing evidence-based interventions. In terms of the trajectory of intervention development [64], these techniques in autobiographical memory therapeutics are at an early stage. Although data from exploratory trials (e.g., MEST [48–50]) are encouraging, there is now a mandate for later-stage trials to provide definitive evidence of the clinical utility, feasibility, and costeffectiveness of these nascent approaches. There is also a need to build on emergent techniques that are still at the preclinical stage to explore their therapeutic utility in patients (e.g., [65]). Disturbances in autobiographical memory processing are of course not limited to depression, and there is good basic research evidence for the transdiagnostic relevance [66] of the major domains of difficulty reviewed here; for example, sufferers of PTSD also struggle to access specific details of the personal past [67] and there is encouraging evidence that memory specificity training delivers therapeutic benefits in this population [50]. Similarly, individuals with social anxiety disorder show impoverished recollection of positive personal experiences [68], and there is scope here to apply techniques to assist the elaboration and retention of memories for positive past events. This focus on working clinically to target underlying transdiagnostic processing difficulties that cut across traditional nosological divisions, rather than clusters of surface signs and symptoms, reflects a broader paradigmatic shift in our approaches to understanding mental health problems. Exemplified most clearly in the National Institute of Mental Health research domain criteria [69], this sea-change in the way that we seek to classify psychopathology provides an excellent context for the translation of novel process-focused interventions from basic research. References 1 Conway, M.A. and Pleydell-Pearce, C.W. (2000) The construction of autobiographical memories in the self-memory system. Psychol. Rev. 107, 261–288 2 Dalgleish, T. (2004) Cognitive approaches to posttraumatic stress disorder (PTSD): the evolution of multi-representational theorizing. Psychol. Bull. 130, 228–260 3 Williams, J.M.G. et al. (2007) Autobiographical memory specificity and emotional disorder. Psychol. Bull. 133, 122–148 4 Gotlib, I.H. and Joormann, J. (2010) Cognition and depression: current status and future directions. Annu. Rev. Clin. Psychol. 6, 285 5 Watts, F.N. et al. (1990) Memory deficit in clinical depression: processing resources and the structure of materials. Psychol. Med. 20, 345–349 6 Lloyd, G.G. and Lishman, W.A. (1975) Effect of depression on the speed of recall of pleasant and unpleasant experiences. Psychol. Med. 5, 173– 180 7 Patel, T. et al. (2007) Intrusive images and memories in major depression. Behav. Res. Ther. 45, 2573–2580 8 Dearing, K.F. and Gotlib, I.H. (2009) Interpretation of ambiguous information in girls at risk for depression. J. Abnorm. Child Psychol. 37, 79–91 9 Beck, A.T. (1976) Cognitive Therapy and the Emotional Disorders, Meridian 10 Erber, R. and Erber, M. (1994) Beyond mood and social judgment: mood incongruent recall and mood regulation. Eur. J. Soc. Psychol. 24, 79–88 602

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