We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing.
Methods
Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic (n = 77), hypophagic (n = 66), and euphagic (n = 42) MDD groups and a healthy comparison group (n = 38). We examined fALFF and SBC in a mask restricted to reward [nucleus accumbens (NAcc), putamen, caudate, ventral pallidum, and orbitofrontal cortex (OFC)] and interoceptive (anterior insula and hypothalamus) regions and also performed exploratory whole-brain analyses. SBC analyses included as seeds the NAcc and also regions demonstrating group differences in fALFF (i.e. right lateral OFC and right anterior insula). All analyses used threshold-free cluster enhancement.
Results
Mask-restricted analyses revealed stronger fALFF in the right lateral OFC, and weaker fALFF in the right anterior insula, for hyperphagic MDD v. healthy comparison. We also found weaker SBC between the right lateral OFC and left anterior insula for hyperphagic MDD v. healthy comparison. Whole-brain analyses revealed weaker fALFF in the right anterior insula, and stronger SBC between the right lateral OFC and left precentral gyrus, for hyperphagic MDD v. healthy comparison. Findings were no longer significant after controlling for body mass index, which was higher for hyperphagic MDD.
Conclusions
Our results suggest hyperphagic MDD may be associated with altered activity in and connectivity between interoceptive and reward regions.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
Methods
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Results
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
Conclusion
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
The number of people living with dementia (PWD) is increasing worldwide, corresponding with an increasing number of caregivers for PWD. This study aims to identify and describe the literature surrounding the needs of caregivers of PWD and the solutions identified to meet these needs.
Method:
A literature search was performed in: PsycInfo, Medline, CINAHL, SCIELO and LILACS, January 2007–January 2018. Two independent reviewers evaluated 1,661 abstracts, and full-text screening was subsequently performed for 55 articles. The scoping review consisted of 31 studies, which were evaluated according to sociodemographic characteristics, methodological approach, and caregiver’s experiences, realities, and needs. To help extract and organize reported caregiver needs, we used the C.A.R.E. Tool as a guiding framework.
Results:
Thirty-one studies were identified. The most common needs were related to personal health (58% emotional health; 32% physical health) and receiving help from others (55%). Solutions from the articles reviewed primarily concerned information gaps (55%) and the education/learning needs of caregivers (52%).
Conclusion:
This review identified the needs of caregivers of PWD. Caregivers’ personal health emerged as a key area of need, while provision of information was identified as a key area of support. Future studies should explore the changes that occur in needs over the caregiving trajectory and consider comparing caregivers’ needs across different countries.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Methods
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Results
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
Conclusions
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Dialectical behavior therapy (DBT) is a form of cognitive behavior therapy (CBT) for mood disorders. There are three categories of core strategies employed in DBT: change strategies, acceptance and validation strategies, and dialectical strategies. Change strategies in DBT, for the most part, are based on learning principles. One rationale for using DBT to treat mood disorders is the significant co-morbidity between borderline personality disorder (BPD) and mood disorders. Adapting DBT is different from adopting DBT. In the latter, DBT, e.g. the modes of treatment delivery, may be changed to meet the needs of the setting or target population. Programs which adopt comprehensive DBT benefit from the existing evidence base. DBT is an efficacious treatment proven to reduce suicidal behavior and nonsuicidal self-injury. DBT has been adapted for both bipolar adolescents and geriatric patients with treatment-resistant depression or depression co-morbid with BPD.
This chapter deals with brain imaging techniques. MRI and computer tomography (CT) scans have been used to identify changes in brain morphology in major depressive disorder (MDD). Functional MRI (fMRI), positron emission tomography (PET), and single photon emission computer tomography (SPECT) have all been utilized to identify regions of the brain that are differentially activated in MDD when compared to healthy control subjects. Altered correlation of activity between the frontal lobe and the amygdale has been reported during fMRI studies of patients with MDD. Both bipolar disorder and MDD are likely heterogeneous conditions with different molecular, cellular, genetic, or environmental causes that produce the same clinical phenotype of the disorder. Technical advances in neuroimaging techniques may allow for new questions to be asked into the biological underpinnings of mood disorders and may be used to predict responses to treatments.
There has been considerable controversy over the correct diagnosis for patients with mood disorder associated with the lifetime occurrence of hypomanic symptoms which are sub-threshold for the diagnosis of bipolar disorder. Extrapolating from the accelerating accumulation of knowledge of the biology of psychiatric disorders over the last several decades, it is easy to anticipate that this trend will continue and that such knowledge will define the molecular pathways whereby genes and environment affect the risk for mood disorders. There are early efforts to apply proteomic methods to mood disorders. Electrophysiology, primarily in the form of electroencephalographic recording, has shown significant promise in application to mood disorder therapeutics. An important intellectual trend is that the rapidly advancing technologies of quantitative neuroscience and molecular genetics appear to be making enormous progress toward demonstrating a neurobiological substrate of mood disorder.
This chapter discusses potential mechanisms of antidepressant action and outlines areas of active research in electroconvulsive therapy. Electroconvulsive treatment (ECT) remains the most effective treatment for major depression. During the seizure itself, and for a period of hours afterward, there is higher sympathetic tone with markedly elevated heart rate and blood pressure during ictus and for several minutes postictally. Pre-existing seizure disorder is generally not a contraindication for ECT; however, in patients with seizures, it should be ascertained that the seizure is not caused by a mass lesion or vascular malformation which could constitute higher risk with ECT. ECT requires the consent of the patient or, in the event that the patient lacks capacity, a ruling from a legal authority regarding procedures for substituted consent if available. The most common adverse effects of ECT are headache and myalgia.
Diagnosis of major depressive disorder is entirely clinical at present, and based on criteria such as DSM-IV. The classes of medications include antidepressants, selective serotonin reuptake inhibitors (SSRIs), older dual-action reuptake inhibitors, newer dual-action antidepressants, norepinephrine reuptake inhibitors (NRIs) and monoamine oxidase inhibitors. Successful treatment of major depression may require a multi-modal approach including pharmacotherapy, education, and psychotherapy. Patient response to treatment needs systematic monitoring, not only to improve compliance, but to make sound decisions about the need to raise the dose to achieve an optimal antidepressant effect and to monitor side effects. A history of episodes lasting more than 6 months require longer continuation treatment of up to 12 months, and generally continuation treatment will be longer for psychotic depression. Antidepressant and adjunctive pharmacological agents allow successful acute treatment and prevention of future episodes of major depression in most patients.
This chapter discusses models of unipolar mood disorder that incorporate both current neuroscience and clinical research. Severe major depressive disorder (MDD) is associated with higher basal cortisol secretion and higher peak levels, as well as dexamethasone resistance, indicating failure of feedback inhibition at both the higher stimulated cortisol levels and the lower resting cortisol levels. Post-traumatic stress disorder (PTSD) is associated with lower basal cortisol and increased glucocorticoid receptor (GCR) expression, indicating that the response to stress can be different in different disorders. The fundamental concept of the gene-environment interaction model is that whether a result of genes or early environmental trauma, or both, early life stress results in functional and structural changes in the brain that confer a life-long hyperactive stress response mediated by the hypothalamic pituitary adrenal (HPA) axis. Direct genetic effects or purely environmental effects may result in depressions.
This chapter focuses on a member of a much larger family of interventions known as cognitive behavior therapy (CBT). Cognitive therapy (CT) was first developed as a time-limited treatment of depression. Dysfunctional cognitions about medication can be modified with CT, and behavioral interventions, such as reminder systems and behavioral plans to overcome obstacles to adherence, can be used. The efficacy of CT has been subjected to hundreds of controlled investigations across a wide range of disorders. CT is the most exhaustively studied psychosocial intervention for depressive disorders. The primary analyses of six subsequent studies, all making greater efforts to ensure that pharmacotherapy was adequately administered, found CT and pharmacotherapy to be comparably effective across 12-16 weeks. It is noteworthy that the two most recent studies used selective serotonin reuptake inhibitors and, hence, have greater generalizability to contemporary practice.
Diagnosis of major depressive disorder is entirely clinical at present, and based on criteria such as DSM-IV. The classes of medications include antidepressants, selective serotonin reuptake inhibitors (SSRIs), older dual-action reuptake inhibitors, newer dual-action antidepressants, norepinephrine reuptake inhibitors (NRIs) and monoamine oxidase inhibitors. Successful treatment of major depression may require a multi-modal approach including pharmacotherapy, education, and psychotherapy. Patient response to treatment needs systematic monitoring, not only to improve compliance, but to make sound decisions about the need to raise the dose to achieve an optimal antidepressant effect and to monitor side effects. A history of episodes lasting more than 6 months require longer continuation treatment of up to 12 months, and generally continuation treatment will be longer for psychotic depression. Antidepressant and adjunctive pharmacological agents allow successful acute treatment and prevention of future episodes of major depression in most patients.
This chapter discusses models of unipolar mood disorder that incorporate both current neuroscience and clinical research. Severe major depressive disorder (MDD) is associated with higher basal cortisol secretion and higher peak levels, as well as dexamethasone resistance, indicating failure of feedback inhibition at both the higher stimulated cortisol levels and the lower resting cortisol levels. Post-traumatic stress disorder (PTSD) is associated with lower basal cortisol and increased glucocorticoid receptor (GCR) expression, indicating that the response to stress can be different in different disorders. The fundamental concept of the gene-environment interaction model is that whether a result of genes or early environmental trauma, or both, early life stress results in functional and structural changes in the brain that confer a life-long hyperactive stress response mediated by the hypothalamic pituitary adrenal (HPA) axis. Direct genetic effects or purely environmental effects may result in depressions.