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.

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.

Dynamics and control of delayed rumor propagation through social networks.

Investigation of rumor spread dynamics and its control in social networking sites (SNS) has become important as it may cause some serious negative effects on our society. Here we aim to study the rumor spread mechanism and the influential factors using epidemic like model. We have divided the total population into three groups, namely, ignorant, spreader and aware. We have used delay differential equations to describe the dynamics of rumor spread process and studied the stability of the steady-state solutions using the threshold value of influence which is analogous to the basic reproduction number in disease model. Global stability of rumor prevailing state has been proved by using Lyapunov function. An optimal control system is set up using media awareness campaign to minimize the spreader population and the corresponding cost. Hopf bifurcation analyses with respect to time delay and the transmission rate of rumors are discussed here both analytically and numerically. Moreover, we have derived the stability region of the system corresponding to change of transmission rate and delay values.

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.

Dynamics of COVID-19 transmission with comorbidity: a data driven modelling based approach.

An outbreak of the COVID-19 pandemic is a major public health disease as well as a challenging task to people with comorbidity worldwide. According to a report, comorbidity enhances the risk factors with complications of COVID-19. Here, we propose and explore a mathematical framework to study the transmission dynamics of COVID-19 with comorbidity. Within this framework, the model is calibrated by using new daily confirmed COVID-19 cases in India. The qualitative properties of the model and the stability of feasible equilibrium are studied. The model experiences the scenario of backward bifurcation by parameter regime accounting for progress in susceptibility to acquire infection by comorbidity individuals. The endemic equilibrium is asymptotically stable if recruitment of comorbidity becomes higher without acquiring the infection. Moreover, a larger backward bifurcation regime indicates the possibility of more infection in susceptible individuals. A dynamics in the mean fluctuation of the force of infection is investigated with different parameter regimes. A significant correlation is established between the force of infection and corresponding Shannon entropy under the same parameters, which provides evidence that infection reaches a significant proportion of the susceptible.

Mathematical model of COVID-19 with comorbidity and controlling using non-pharmaceutical interventions and vaccination.

Pandemic is an unprecedented public health situation, especially for human beings with comorbidity. Vaccination and non-pharmaceutical interventions only remain extensive measures carrying a significant socioeconomic impact to defeating pandemic. Here, we formulate a mathematical model with comorbidity to study the transmission dynamics as well as an optimal control-based framework to diminish COVID-19. This encompasses modeling the dynamics of invaded population, parameter estimation of the model, study of qualitative dynamics, and optimal control problem for non-pharmaceutical interventions (NPIs) and vaccination events such that the cost of the combined measure is minimized. The investigation reveals that disease persists with the increase in exposed individuals having comorbidity in society. The extensive computational efforts show that mean fluctuations in the force of infection increase with corresponding entropy. This is a piece of evidence that the outbreak has reached a significant portion of the population. However, optimal control strategies with combined measures provide an assurance of effectively protecting our population from COVID-19 by minimizing social and economic costs.

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.

Herbometallic nano-drug inducing metastatic growth inhibition in breast cancer through intracellular energy depletion.

Cancer cells need extensive energy supply for their uncontrolled cell division and metastasis which is exclusively dependent on neighboring cells, especially adipocytes. Herein, we have introduced a novel herbometallic nano-drug, Heerak Bhasma nanoparticle (HBNP) from natural resources showing high potential in the reduction of energy supply thereby promoting cell death in breast cancer cells. Inductively coupled plasma optical emission spectra (ICP-OES), atomic absorption spectra (AAS), Raman spectra, X-ray diffraction analyses confirmed the physicochemical properties of HBNP. The differential light scattering (DLS) and field emission scanning electron microscope (FESEM) analyzed the cell-permeable size of HBNP, whereas, cell viability assay confirmed the non-toxic effect. Seahorse energy efflux assay, apoptotic cell quantification, ROS, mitochondrial membrane potential, in vivo oxidative stress etc. were measured using standard protocol. The notable changes in cancer energy metabolism investigated by cellular Mito and Glyco-stress analyses confirmed the HBNP induced intracellular energy depletion. Also, a significant reduction in mitochondrial membrane potential and subsequently, extensive reactive oxygen species (ROS) generations were observed in presence of HBNP followed by the induction of cell apoptosis. The cell invasion and wound healing assay followed by reduced expression both protein (MMP 2, MMP 9) and cytokine (IL6, IL10) had signified the effectiveness of HBNP against cancer metastasis. In addition, HBNP also showed an excellent antitumor activity in vivo followed by developing healing characteristics due to oxidative stress. All these findings strongly suggest that HBNP has the potential to be the new cancer therapeutic. A schematic phenomenon represents the overall HBNP mediated anticancer activity via limitation of both fatty acid uptake and energy metabolism.

Exploring dynamical complexity in a time-delayed tumor-immune model.

The analysis of dynamical complexity in nonlinear phenomena is an effective tool to quantify the level of their structural disorder. In particular, a mathematical model of tumor-immune interactions can provide insight into cancer biology. Here, we present and explore the aspects of dynamical complexity, exhibited by a time-delayed tumor-immune model that describes the proliferation and survival of tumor cells under immune surveillance, governed by activated immune-effector cells, host cells, and concentrated interleukin-2. We show that by employing bifurcation analyses in different parametric regimes and the 0-1 test for chaoticity, the onset of chaos in the system can be predicted and also manifested by the emergence of multi-periodicity. This is further verified by studying one- and two-parameter bifurcation diagrams for different dynamical regimes of the system. Furthermore, we quantify the asymptotic behavior of the system by means of weighted recurrence entropy. This helps us to identify a resemblance between its dynamics and emergence of complexity. We find that the complexity in the model might indicate the phenomena of long-term cancer relapse, which provides evidence that incorporating time-delay in the effect of interleukin in the tumor model enhances remarkably the dynamical complexity of the tumor-immune interplay.

Metabolic adaptability in liver and gastrocnemius muscle of mice following subacute lead toxicity.

Lead (Pb) is one of several environmental pollutants that adversely affect human health by producing toxicity at the tissue level. The aim of the study was to understand the effects of Pb on the metabolic profiles of liver and gastrocnemius muscle of mice in relation to carbohydrate and fat metabolisms. Swiss albino mice were chosen and divided into two groups, control and Pb-treated. The Pb-treated animals were exposed to Pb at a dose of 5 mg/kg body weight for 30 days orally, which resulted in hypoglycemia, glycosuria, and increased glycogenolysis in the liver and gastrocnemius muscle of treated mice. Pyruvic acid, the end product of glycolysis decreased in muscular tissue and increased in the liver. Additionally, the activity of G-6Pase was depressed in the liver, whereas lactate dehydrogenase activity was increased in skeletal muscle only. An adaptive mechanism was initiated by stimulating glycogenolytic and retarding glycolytic activity in the liver and also by alteration of liver and muscle pyruvate dehydrogenase activity along with increased activity of malate dehydrogenase in skeletal muscle. There was enhancement of succinate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activities in the studied tissues. Interestingly, cholesterol, high-density lipoprotein, and low-density lipoprotein levels were elevated, whereas those of triglycerides were decreased in Pb-treated mice serum. The activities of fatty acid synthase and glyceraldehyde 3 phosphate dehydrogenase were depressed in Pb-treated mice livers. Pb also significantly altered the morphological features of the liver, skeletal muscle, and pancreas. These data suggested that subacute Pb exposure was responsible for metabolic modulation in an adaptive fashion in the liver and skeletal muscle of mice.

Treatment-resistant depression: problematic illness or a problem in our approach?

Treatment-resistant depression is widely defined as non-response to two 'adequate' courses of treatment. However, the definitions of treatment and depression are inconsistent reflecting gaps in our understanding. We argue that a failure to respond is often the result of administering inappropriate treatment, which occurs principally because of paradigm failure.Declaration of interestNone.

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.

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.

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.

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.

Atom-economical selenation of electron-rich arenes and phosphonates with molecular oxygen at room temperature.

Organoselenium and selenophosphorus compounds are ubiquitously found in biologically active compounds, agrochemicals, functionalized materials etc. Although selenium is a micronutrient and an essential trace element, its contamination/consumption in higher concentrations is extremely dangerous. However, most of the previous selenation reactions generate toxic selenium waste as a by-product. Thus development of green synthetic protocols of these compounds is in high demand. We report herein a mild base-catalyzed cross-dehydrogenative coupling (CDC) between electron-rich arenes and phenylselenol to afford 3-selenylindole or selenylated phenols under air at room temperature. Interestingly, in the presence of a base and oxygen, the phenylselenol is converted into the diphenyldiselenide and provides almost quantitative yield. Similarly, a mild synthesis of selenophosphates was also achieved from the corresponding diorganyldiselenide or phenylselenols and nucleophilic phosphonates in a "dump and stir" manner under an oxygen balloon without a base or catalyst. From the preliminary mechanistic studies for selenation of indoles and phosphonates with TEMPO and EPR of the reaction mixture, it was evident that the reaction proceeds through the anionic pathway, which is in sharp contrast to the previous literature. The present reactions proceed smoothly under the mild conditions, furnishing high to almost quantitative yields in several cases. The reaction is easily scaled up to gram scale and has been demonstrated for the synthesis of an anti-HIV zidovudine (AZT) analogue.

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.