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Many of the studies exploring dopamine (DA) function in depression have produced inconsistent findings. Contributors to this inconsistency include the diagnostic heterogeneity of major depressive disorder (MDD); failure to control for age, bipolar disorder, and comorbid diagnoses; and variation in patient medication treatment status at the time of the study. Despite this variability, there is now a convergence of data from animal models, genetics, neuroimaging, and human clinical trials that strengthens the case for DA dysfunction in the pathophysiology of major depression, at least in a significant subgroup of patients. This chapter comprehensively reviews the current evidence, with subsequent recommendations for future studies of dopaminergic signaling in depression and its treatment.

The prevalence of diagnosable depressive disorders in children is 2.8% and in adolescents is 5.7%. This chapter reviews the evidence basis for the treatment of depressive disorders in youth. Cognitive-behavioral therapy has predominated in the research literature, with interpersonal therapy also receiving empirical support. In general, however, effects of intervention are small. Medication studies indicate that while antidepressants improve depression symptoms, they also increase suicidality in youth. Fluoxetine is the only SSRI with significant benefit for children, and sertaline and fluoxetine have significant benefits for adolescents. Large-scale studies on the differential efficacy of combining psychotherapy versus offering single treatments conflict in their findings. Interventions are evaluated against how well they address risk factors for the development of depression and adjustment for afflicted youth, and recommendations are advanced.

This chapter presents the evidence base for clinic and school-based interventions for four common childhood disorders or related symptom patterns: attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), disruptive behavior disorders, and anxiety disorders and related symptoms. It shows that within the existing base for each disorder, psychosocial interventions include an array of behavioral approaches. The psychopharmacology evidence base is strongest for ADHD, weaker for other disorders, and virtually nonexistent for anxiety disorders. Adjunctive studies examining a combination of psychosocial and psychopharmacological interventions were rare, with the largest and most sophisticated one for ADHD.

There is a clear need for biomarkers in neuro-degenerative and psychiatric disorders for both early and differential diagnosis, personalized prediction of treatment response, and in drug discovery. Non-invasive neuroimaging is a key area for biomarker development because it connects behavioural outcomes with structural, functional, and molecular mechanisms. This chapter discusses neuroimaging biomarkers in relation to dementia, schizophrenia, and mood disorders (bipolar and major depressive disorders). The current candidate biomarkers for each disorder are reviewed, across the full range of imaging modalities, followed by an evaluation of their future prospects. The chapter concludes that there has been substantial progress towards personalized neuroimaging-based biomarkers but much remains to be done. Such biomarkers must be validated for specific disorders and may include neuroimaging and non-neuroimaging components.

The symptoms of depression include persistent low mood, feelings of helplessness, hopelessness, or worthlessness, and anhedonia, or the inability to experience pleasure. Mood is influenced by a complex interaction of genetic, social, environmental, and other factors, such as substance abuse. Depression is further characterized by dysfunctional attitudes and negative automatic thoughts or ruminations. Psychiatric diagnostic criteria distinguish patients who experience only depressive episodes (unipolar depression or major depressive disorder, MDD) from patients who experience depressive episodes but also manic ones (bipolar disorder, BD). The symptoms of mania, on the other hand, include euphoria, over-activity, distractibility, socially inappropriate behaviour, increased appetite, and impaired insight. Thus, the emotional states of patients with depression and mania can be considered to represent two polar extremes on a mood spectrum. The states manifested in depression and mania are pathological in that they are extreme, disrupt quality of life, and are persistent and often recurrent. This chapter examines not only depression in MDD, but contrasts it with the, at times similar but at times diametrically opposed, symptoms of other disorders, such as BD, to achieve better insight. It also examines resilience in healthy individuals, i.e., how can mood remain normal despite factors such as adverse life events. Research on resilience has focused on determining the protective factors that allow some individuals to have more positive outcomes, despite being exposed to a variety of stressors.

Scientific commonsense would suggest that very young children cannot have psychiatric disorders such as bipolar disorder or major depression since they do not have the level of development to express the complex characteristics of these disorders. This chapter provides a detailed survey of current evidence supporting this common sense claim. The chapter first gives a general perspective on DSM that will be applied in looking at childhood psychiatric diagnoses and should be of some interest in its own right. I argue that there are some DSM based categorizations--those of major depressive disorder and bipolar disorder--that have substantial empirical support. I look at these two classifications as the best case for pediatric psychiatric disorders. I argue that this best case fails given our current state of knowledge, raising doubts in general about psychiatric diagnoses in small children. This conclusion has practical importance, since small children are increasingly being given powerful psychoactive drugs.

Major depressive disorder (MDD) affects more than 20 million people in the United States. Depression is comorbid with other psychiatric disorders and can increase risks of drug and alcohol abuse and suicide. Available antidepressants have limited efficacy and new therapeutic targets are needed. MDD and antidepressant responses are mediated via neurotransmitter signaling mechanisms and inflammatory responses involving an integrated network of limbic brain regions that include hippocampus, prefrontal cortex, and nucleus accumbens. Although this limbic circuit is broadly described, researchers do not understand how the properties of neurons within the circuit are altered in depression. The authors present the regulation of the p11 signaling module in this circuit, describe the diagnostic aspects of p11 function, and lay out a cellular and molecular framework for the understanding of MDD and the development of novel antidepressant therapies.

This chapter reviews the literature on treatment programs for people with severe mental illness (SMI), which includes schizophrenia and schizoaffective disorder, bipolar and major depressive disorder, posttraumatic stress disorder and panic disorder, and substance-related disorders. Several modalities of empirically supported treatments are covered to highlight the need for a multimodal approach to treating SMI. Emphasis is placed on the evidence related to brief, crisis, or acute phase treatment. The chapter also provides examples of therapeutic strategies used to address common symptoms of various severe mental illnesses. Most treatments are born out of a cognitive-behavioral or social learning theoretical framework. In conclusion, the severe mental illness treatment literature lends support to the popular notion that psychiatric problems are determined by multiple factors and therefore require multifaceted psychotherapy plans.

This chapter defines basic treatment guidelines through a cross-validation of the tentative suggestions provided earlier. The cross-validation relies on the mixed sample comprising the four samples described in this book. Two of the data sets consist of individuals who had been carefully and reliably diagnosed with major depressive disorders. Patients in these samples were treated with either group or individual cognitive therapy, group experiential therapy, individual psychodynamic therapy, antidepressant therapy, or a self-directed bibliotherapy. The chapter included two other samples in which depression was more broadly distributed. These samples included a general outpatient clinic sample on which was practiced the usual form of general outpatient care and a sample of patients being treated for alcohol abuse in a controlled clinical trial of cognitive therapy and family systems therapy.

The denial of death in contemporary American society can be found in bereavement policies, the reclassification of grief as a major depressive disorder, and the emerging popularity of grassroots memorialization. This chapter briefly traces the changing understanding of grief and examines newly emerging bereavement practices in light of these changes.