Significant age by childhood trauma interactions on grey matter volumes: A whole brain VBM analysis.

BACKGROUND: Childhood trauma is deleterious to long term brain development. The changes are variable, and depend on gender, age and the nature of the trauma. In this exploratory analysis, we investigated the effects of exposure to emotional trauma on grey matter (GM) volumes in adolescent females. METHODS: We explored GM volumes in non-clinical females aged 12-17 years who had been exposed to either higher (HET; N = 75) or minimal (MET; N = 127) emotional trauma. High-resolution T1-weighted structural images were analysed with an optimised FSL-VBM protocol. The General Linear Model was run on HET versus MET with continuous age as an interaction. Mean GM volumes were extracted from significant corrected age interaction statistical maps and scrutinised with SPSS®. RESULTS: We observed greater HET*age than MET*age interactions (corrected p-value = 0.0002), in 4 separate bilateral cortical regions associated with mood disorders. Scrutiny of these regions showed significant GM volume enlargements in the early adolescent HET group (p = 0.017) and reductions in the late adolescent HET group (p < 0.0001). Notably, there were no differences in middle adolescence (p > 0.05). LIMITATIONS: Causality cannot be inferred from this cross-sectional study and the onset of trauma cannot be determined using retrospective measures. CONCLUSIONS: Whilst GM volumes diminish from early adolescence onwards, our results show that HET impacts this brain development, perhaps first via unstable adaptative mechanisms, followed by maladaptive processes in late adolescence. This suggests that compromises of emotional and cognitive self-regulation in mood disorders may underpin the structural abnormalities observed across multiple brain regions in these teenage girls.

Eating disorder features in bipolar disorder: clinical implications.

BACKGROUND: Bipolar disorder (BD) is associated with elevated rates of eating disorders (EDs), but the nature and impact of specific ED features are unclear. AIMS: This study sought to identify which ED features are common in BD, and whether these relate to quality of life (QoL) impairment and body mass index (BMI). METHOD: A clinical sample of 73 adults with BD completed self-report measures of health, ED features, emotion regulation ability, impulsivity, and QoL. RESULTS: Binge eating (45%), excessive dietary restriction (39%), overvaluation of weight/shape (51%), purging (16%) and driven exercise (27%) were common, and associated with a poorer clinical picture, including poorer QoL and poorer emotion regulation. Furthermore, regular binge eating episodes explained a significant proportion of variance in QoL impairment after controlling for other significant predictors. The best predictors of BMI were number of medical conditions, impulsivity and positive beliefs about binge eating. CONCLUSIONS: ED features that may not meet criteria for a fully diagnosable ED - particularly overvaluation of weight/shape and binge eating - warrant greater attention, as they may still significantly worsen QoL. Future research should focus on modifying existing psychological interventions to better target ED features among individuals with BD and thereby improve clinical outcomes.

An fMRI examination of the neural basis of suicide attempts: The role of mentalizing in the context of mood.

OBJECTIVES: Facial emotion recognition (FER) deficits in depressed mood disorder patients contribute to suicidality. Prior research shows that intrinsic brain activity patterns are altered by attempting suicide. Therefore, we investigated in depressed patients whether differences in FER contribute to their clinical symptoms of suicide. METHODS: Neural activity in response to an FER task was compared across three groups: healthy controls (HCs, N = 66), suicide non-attempter (SNA, N = 50), suicide attempter (SA, N = 25). Modulation of brain networks by the task and functional connectivity (FC) within (using spatial map, spectral power) and between (using functional network connectivity; FNC) were examined. The contribution of these differences to suicidal symptoms in each group was also examined. RESULTS: Patient groups displayed impaired FC both within and between networks but differed in nature and networks involved. They also showed differential modulation of networks by task, such that compared with both HC and SNA, SA displayed impaired FC within the default-mode network (DMN) and also its task modulation. In the SA group, FC within the DMN and FNC between two lateral prefrontal networks, and its interaction with the basal ganglia network contributed significantly to the clinical symptoms of suicide. CONCLUSIONS: This study affirms differences between SA and SNA brain activity patterns and suggests that suicidal activity probably emanates via different mechanisms in these patient groups. Perhaps, over-attribution of emotion impairs one's self-referential thought processes and coupled with diminished emotional control this makes depressed individuals vulnerable to suicide.

The impact of torture on interpersonal threat and reward neurocircuitry.

OBJECTIVE: Torture adversely influences emotional functioning, but the neurophysiological mechanisms underpinning its impact are unknown. This study examined how torture exposure affects the neural substrates of interpersonal threat and reward processing. METHODS: Male refugees with (N = 31) and without (N = 27) torture exposure completed a clinical interview and functional magnetic resonance imaging scan where they viewed fear, happy and neutral faces. Between-group activations and neural coupling were examined as moderated by posttraumatic stress disorder symptom severity and cumulative trauma load. RESULTS: Posttraumatic stress disorder symptom severity and trauma load significantly moderated group differences in brain activation and connectivity patterns. Torture survivors deactivated the ventral striatum during happy processing compared to non-torture survivor controls as a function of increased posttraumatic stress disorder symptom severity - particularly avoidance symptoms. The ventral striatum was more strongly coupled with the inferior frontal gyrus in torture survivors. Torture survivors also showed left hippocampal deactivation to both fear and happy faces, moderated by trauma load, compared to controls. Stronger coupling between the hippocampus and frontal, temporoparietal and subcortical regions during fear processing was observed, with pathways being predicted by avoidance and hyperarousal symptoms. CONCLUSION: Torture exposure was associated with distinct brain activity and connectivity patterns during threat and reward processing, dependent on trauma exposure and posttraumatic stress disorder symptom severity. Torture appears to affect emotional brain functioning, and findings have the potential to guide more targeted interventions for torture survivors.

"The Food Matches the Mood": Experiences of Eating Disorders in Bipolar Disorder.

Approximately 33% of those with bipolar disorder (BD) have a comorbid eating disorder (ED). However, the trajectory of these conditions has received little research attention. Nine participants who met criteria for BD and an ED participated in qualitative interviews exploring experiences of illness onset, the interaction of these conditions, and service provision. Almost all participants in the sample reported minimal to no screening of ED problems, despite their health professionals' frequent discussion of obesity. Findings suggested that ED features were diverse and evolved over time. Mania and depression were connected to ED features such as overeating and restricting, but this differed between and within participants. Most participants disclosed historic trauma which they considered central to their mental health concerns. This clinical group appears to be underserviced. Clinicians and researchers should routinely screen for ED features when treating and diagnosing BD to inform their physical and mental health interventions.

Role of self-focussed reappraisal of negative emotion in emergence of emotional symptoms in adolescent girls.

BACKGROUND: Adolescent subthreshold emotional symptoms arise from impaired self-referential information-processing and approach-avoidance behaviour network integration, which compromises goal evaluation and pursuit strategies. AIMS: We investigated whether impairment of negative emotion (goal) reappraisal strategies (self-focussing and self-distancing) generates emotional symptoms (emotional disorders precursors). METHOD: Using functional magnetic resonance imaging and a triple-network model (default mode, executive control and salience), functional connectivity differences within and between networks, and their modulation by task and relationships with emotional symptoms were determined in healthy adolescent girls (N = 202) grouped by presence or absence of emotional symptoms. RESULTS: The groups differed in spectral power distribution and in dorsal default mode network and right executive control network modulation when self-focussing and self-distancing, respectively. Girls without emotional symptoms had greater spectral power and less network modulation. Greater spectral power was associated with reduced emotional symptoms and less dorsal default mode network modulation when self-focussing. CONCLUSIONS: The early phases of anxiety and depressive disorders in adolescence are marked by emotional symptoms that usually emerge in the context of negative life events. To contend with the negative effect of such events, a typical reappraisal strategy is to distance oneself and switch the focus of one's thinking. This brain-imaging study in adolescent girls prone to the development of emotional disorders has found functional changes in key neural networks that are involved in reappraisal and shown that this process is impaired. This is important because it provides an early indication of these common disorders and a potential target for psychological interventions.

Default mode dysfunction underpins suicidal activity in mood disorders.

BACKGROUND: Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention. METHOD: Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity. RESULTS: Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA. CONCLUSIONS: DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.

Lithium therapy and its interactions.

Lithium is one of the most effective mood stabilisers for people with a mood disorder. However, many of these patients are also taking other medicines that could potentially interact with lithium To minimise the risk of relapse, it is usually necessary to maintain the lithium serum concentration between 0.6 mmol/L and 0.8 mmol/L Lithium clearance is easily influenced by drugs that alter renal function such as ACE inhibitors, angiotensin receptor antagonists, diuretics, and non-steroidal anti-inflammatory drugs It is therefore prudent for prescribers to monitor and adjust the lithium dose to avoid adverse effects or loss of efficacy

Resting-state neural network disturbances that underpin the emergence of emotional symptoms in adolescent girls: resting-state fMRI study.

BACKGROUND: Subsyndromal emotional symptoms in adolescence may represent precursors for full-blown emotional disorders in early adulthood. Understanding the neurobiological mechanisms that drive this development is essential for prevention. AIMS: Self-referential processing and emotion regulation are remodelled substantively during adolescence, therefore this study examined integration of key neural networks involved in these processes. METHOD: At baseline, clinical and resting-state functional magnetic resonance imaging data were collected for 88 adolescent girls (mean age 15 years), and 71 of these girls underwent repeat clinical assessment after 2 years. These 71 girls were then partitioned into two groups depending on the presence (ES+) or absence (ES-) of emotional symptoms, and differences in dynamic functional network connectivity were determined and correlated with clinical variables. RESULTS: The two groups displayed a differential pattern of functional connectivity involving the left lateral prefrontal network (LPFN). Specifically, in the ES+ group this network displayed positive coupling with the right LPFN but negative coupling with the default mode network, and the inverse of this pattern was found in the ES- group. Furthermore, the coupling strengths between left and right LPFN at the irst time point predicted follow-up depression and state anxiety scores. CONCLUSIONS: Our findings suggest that in adolescent girls, emotional symptoms may emerge as a result of impaired integration between networks involved in self-referential information processing and approach-avoidance behaviours. These impairments can compromise the pursuit of important goals and have an impact on emotion processing and finally may lead to the development of emotional disorders, such as anxiety and depression in adulthood. DECLARATION OF INTEREST: None.

The effects of childhood trauma on adolescent hippocampal subfields.

OBJECTIVE: Mood disorders are more common among girls and typically emerge during adolescence. The precise reasons for this are unknown, but among the many mechanisms implicated are stress-induced hippocampal structural changes during this developmental stage. The hippocampus is a complex structure comprised of subfields that develop differentially and respond variably to stress and childhood adversity, both of which are risk factors for mood disorders. To better understand vulnerability to mood disorders, we investigated a cohort of adolescent girls and determined volumetric changes in their hippocampal subfields to elucidate the potential effects of childhood trauma. METHODS: Of the 229 participants, 201 girls (aged 12-17 years) fulfilled our analysis inclusion criteria. Of these, 76 had been exposed to higher emotional trauma (emotional abuse or neglect). The girls underwent high-resolution structural magnetic resonance imaging scans, and hippocampal subfield volumes were measured using FreeSurfer. We compared hippocampal subfield volumes in those exposed to higher emotional trauma and those exposed to minimal emotional trauma, at three time-points of adolescent development: early (12-13 years), mid (14-15 years) and late (16-17 years). RESULTS: Mid-adolescent girls exposed to higher emotional trauma had significantly smaller left CA3 volumes than minimal emotional trauma girls ( p = 0.028). Within the minimal emotional trauma group, mid-adolescents had significantly larger left CA3 volumes than early ( p = 0.034) and late ( p = 0.036) adolescents. Within the higher emotional trauma group, early adolescents had significantly larger left CA3 volumes than late adolescents ( p = 0.036). CONCLUSION: In our exploratory study, we observed higher emotional trauma-induced volume changes in the left CA3 hippocampal subfield, which varied depending on age, and may ultimately produce deficits in behavioural, cognitive and emotional processes. We propose that these changes (1) may provide a mechanism through which vulnerability to mood disorders may be increased in adolescent girls, and (2) may signal the best times to implement targeted prevention interventions.

Effect of stress gene-by-environment interactions on hippocampal volumes and cortisol secretion in adolescent girls.

OBJECTIVE: Adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. Genes interacting with the environment (G × E) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. In this study, we assessed the effects of stress system G × E interactions on hippocampal volumes and cortisol secretion in adolescent girls. METHODS: We recruited 229 girls aged 12-18 years, and scans were obtained from 202 girls. Of these, 76 had been exposed to higher emotional trauma (abuse or neglect). Hippocampal volumes were measured using Freesurfer and high-resolution structural magnetic resonance imaging scans. Saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: FKBP5, NR3C1 (both N = 194) and NR3C2 ( N = 193). RESULTS: Among girls with the 'G' allelic variant of the NR3C1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes ( N = 44; mean = 4069.58 mm3, standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant ( N = 69; mean = 4222.34 mm3, standard deviation = 366.74). CONCLUSION: In healthy adolescents, interactions between emotional trauma and the 'protective' NR3C1 'GG' variant seem to induce reductions in left hippocampal volumes. These G × E interactions suggest that vulnerability to mood disorders is perhaps driven by reduced 'protection' that may be specific to emotional trauma. This novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.

Modeling suicide in bipolar disorders.

INTRODUCTION: Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence. METHODS: A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide" and "suicide models". Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance. RESULTS: Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis-stress model, the bipolar model of suicide and the ideation-to-action models, the interpersonal theory of suicide, the integrated motivational-volitional model, and the three-step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action. CONCLUSION: Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only for research purposes, but also for future real-world clinical practice.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: major depression summary.

INTRODUCTION: In December 2015, the Royal Australian and New Zealand College of Psychiatrists published a comprehensive set of mood disorder clinical practice guidelines for psychiatrists, psychologists and mental health professionals. This guideline summary, directed broadly at primary care physicians, is an abridged version that focuses on major depression. It emphasises the importance of shared decision making, tailoring personalised care to the individual, and delivering care in the context of a therapeutic relationship. In practice, the management of depression is determined by a multitude of factors, including illness severity and putative aetiology, with the principal objectives of regaining premorbid functioning and improving resilience against recurrence of future episodes. Main recommendations: The guidelines emphasise a biopsychosocial lifestyle approach and provide the following specific clinical recommendations: Alongside or before prescribing any form of treatment, consideration should be given to the implementation of strategies to manage stress, ensure appropriate sleep hygiene and enable uptake of healthy lifestyle changes. For mild to moderate depression, psychological management alone is an appropriate first line treatment, especially early in the course of illness. For moderate to severe depression, pharmacological management is usually necessary and is recommended first line, ideally in conjunction with psychosocial interventions. Changes in management as a result of the guidelines: The management of depression is anchored within a therapeutic relationship that attends to biopsychosocial lifestyle aspects and psychiatric diagnosis. The guidelines promote a broader approach to the formulation and management of depression, with treatments tailored to depressive subtypes and administered with clear steps in mind. Lifestyle and psychological therapies are favoured for less severe presentations, and concurrent antidepressant prescription is reserved for more severe and otherwise treatment-refractory cases.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: bipolar disorder summary.

INTRODUCTION: In December 2015, the Royal Australian and New Zealand College of Psychiatrists published a comprehensive set of mood disorder clinical practice guidelines for psychiatrists, psychologists and mental health professionals. This guideline summary, directed broadly at primary care physicians, is an abridged version that focuses on bipolar disorder. It is intended as an aid to the management of this complex disorder for primary care physicians working in collaboration with psychiatrists to implement successful long term management. Main recommendations: The guidelines address the main phases of bipolar disorder with a particular emphasis on long term management, and provide specific clinical recommendations. Mania: All physicians should be able to detect its early signs so that treatment can be initiated promptly. At the outset, taper and cease medications with mood-elevating properties and institute measures to reduce stimulation, and transfer the patient to specialist care. Bipolar depression: Treatment is complicated and may require trialling treatment combinations. Monotherapy with mood-stabilising agents or second generation antipsychotics has demonstrated efficacy but using combinations of these agents along with antidepressants is sometimes necessary to achieve remission. Commencing adjunctive structured psychosocial treatments in this phase is benign and likely effective. Long term management: Physicians should adjust treatment to prevent the recurrence of manic and/or depressive symptoms and optimise functional recovery. Closely monitor the efficacy of pharmacological and psychological treatments, adverse effects and compliance. Changes in management as a result of the guidelines: The guidelines position bipolar disorder as part of a spectrum of mood disorders and provide a longitudinal perspective for assessment and treatment. They provide new management algorithms for the maintenance phase of treatment that underscore the importance of ongoing monitoring to achieve prophylaxis. As a first line treatment, lithium remains the most effective medication for the prevention of relapse and potential suicide, but requires nuanced management from both general practitioners and specialists. The guidelines provide clarity and simplicity for the long term management of bipolar disorder, incorporating the use of new medications and therapies alongside established treatments.

Is "early intervention" in bipolar disorder what it claims to be?

BACKGROUND: The notion of early intervention is understandably appealing for conditions such as bipolar disorder (BD), a chronic life-long illness that increases risk of suicide and diminishes quality of life. It is purported that intervening early in the course of the illness with suitable interventions could substantially alter the trajectory of BD and improve outcomes. However, while there are obvious benefits to the prompt commencement of treatment, it is important to consider the gaps in our understanding regarding the aetiopathogenesis of bipolar disorder-upon which the paradigm of early intervention is predicated. METHODS: A literature search was undertaken using recognized search engines: PubMed, PsycINFO Medline, and Scopus, along with auxiliary manual searches. RESULTS: This review first examines how the unpredictable nature of BD creates substantial difficulties when determining an optimal therapeutic target for early intervention. Second, the challenges with identifying appropriate populations and apposite times for early intervention strategies is discussed. Finally, the risks associated with intervening early are examined, highlighting the potential harmful effects of initiating medication. CONCLUSION: Early intervention for BD is a potentially useful strategy that warrants investigation, but until the emergence and trajectory of the illness are definitive, and a clear view of key targets is achieved, a more conservative approach to treating nascent BD and its antecedent symptoms is needed.

Exclusion of overlapping symptoms in DSM-5 mixed features specifier: heuristic diagnostic and treatment implications.

This article focuses on the controversial decision to exclude the overlapping symptoms of distractibility, irritability, and psychomotor agitation (DIP) with the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier. In order to understand the placement of mixed states within the current classification system, we first review the evolution of mixed states. Then, using Kraepelin's original classification of mixed states, we compare and contrast his conceptualization with modern day definitions. The DSM-5 workgroup excluded DIP symptoms, arguing that they lack the ability to differentiate between manic and depressive states; however, accumulating evidence suggests that DIP symptoms may be core features of mixed states. We suggest a return to a Kraepelinian approach to classification-with mood, ideation, and activity as key axes-and reintegration of DIP symptoms as features that are expressed across presentations. An inclusive definition of mixed states is urgently needed to resolve confusion in clinical practice and to redirect future research efforts.

Lithiumeter: Version 2.0.

BACKGROUND: The Lithiumeter was developed as a visual and practical guide for determining lithium levels in the management of bipolar disorder (BD). It appears to have been well received, as evidenced by its increasing popularity amongst doctors as a deskside clinical aide, and adoption and reproduction of the schematic in clinical guidelines and texts. However, since its publication 5 years ago, key basic neuroscience and clinical research developments pertaining to lithium have significantly advanced our understanding, necessitating further refinement of guidance concerning the practicalities of lithium therapy. METHODS: Literature concerning the indications for, and therapeutic levels of, lithium and the associated acute and chronic risks of therapy was scrutinized as part of updating clinical practice guidelines. We have reviewed these updates and identified significant areas of change with respect to the previous Lithiumeter (version 1.0). RESULTS: Since 2011, updated clinical practice guidelines have narrowed the indicated plasma lithium concentration for maintenance therapy, suggesting that additional guidance is necessary for optimizing treatment. Relevant updated clinical guidance was integrated to constitute the Lithiumeter 2.0, which provides a more comprehensive overview of the practical aspects of lithium therapy while maintaining a focus on optimization of lithium levels, such as differential titration of lithium depending on the current mood state. CONCLUSIONS: The Lithiumeter 2.0 is an update that clinicians will find useful for their practice. By addressing some of the issues faced in clinical practice, translational clinical research will continue to inform the Lithiumeter in future updates.

The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder.

OBJECTIVE: The aim of the present study was to characterize the neurocognitive effects of lithium in bipolar disorder to inform clinical and research approaches for further investigation. METHODS: Key words pertaining to neurocognition in bipolar disorder and lithium treatment were used to search recognized databases to identify relevant literature. The authors also retrieved gray literature (e.g., book chapters) known to them and examined pertinent articles from bibliographies. RESULTS: A limited number of studies have examined the effects of lithium on neurocognition in bipolar disorder and, although in some domains a consistent picture emerges, in many domains the findings are mixed. Lithium administration appears to reshape key components of neurocognition - in particular, psychomotor speed, verbal memory, and verbal fluency. Notably, it has a sophisticated neurocognitive profile, such that while lithium impairs neurocognition across some domains, it seemingly preserves others - possibly those vulnerable to the effects of bipolar disorder. Furthermore, its effects are likely to be direct and indirect (via mood, for example) and cumulative with duration of treatment. Disentangling the components of neurocognition modulated by lithium in the context of a fluctuating and complex illness such as bipolar disorder is a significant challenge but one that therefore demands a stratified and systematic approach, such as that provided by the Lithium Battery. CONCLUSIONS: In order to delineate the effects of lithium therapy on neurocognition in bipolar disorder within both research and clinical practice, a greater understanding and measurement of the relatively stable neurocognitive components is needed to examine those that indeed change with lithium treatment. In order to achieve this, we propose a Lithium Battery-Clinical and a Lithium Battery-Research that can be applied to these respective settings.

Mood disorders: neurocognitive models.

OBJECTIVES: In recent years, a number of neurocognitive models stemming from psychiatry and psychology schools of thought have conceptualized the pathophysiology of mood disorders in terms of dysfunctional neural mechanisms that underpin and drive neurocognitive processes. Though these models have been useful for advancing our theoretical understanding and facilitating important lines of research, translation of these models and their application within the clinical arena have been limited-partly because of lack of integration and synthesis. Cognitive neuroscience provides a novel perspective for understanding and modeling mood disorders. This selective review of influential neurocognitive models develops an integrative approach that can serve as a template for future research and the development of a clinically meaningful framework for investigating, diagnosing, and treating mood disorders. METHODS: A selective literature search was conducted using PubMed and PsychINFO to identify prominent neurobiological and neurocognitive models of mood disorders. RESULTS: Most models identify similar neural networks and brain regions and neuropsychological processes in the neurocognition of mood, however, they differ in terms of specific functions attached to neural processes and how these interact. Furthermore, cognitive biases, reward processing and motivation, rumination, and mood stability, which play significant roles in the manner in which attention, appraisal, and response processes are deployed in mood disorders, are not sufficiently integrated. The inclusion of interactions between these additional components enhances our understanding of the etiology and pathophysiology of mood disorders. CONCLUSIONS: Through integration of key cognitive functions and understanding of how these interface with neural functioning within neurocognitive models of mood disorders, a framework for research can be created for translation to diagnosis and treatment of mood disorders.