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The Sadness/Demoralisation dimension concerns core depressive symptoms that have long been the subject of clinical discussion. In fact, they have been described as key features of depression in ancient Greek medical texts. They are believed to result from functional abnormalities in cortical and subcortical regions involved in emotion regulation and reward processing. Besides deficiencies in noradrenergic and serotonergic function, other contributing neurobiological factors have been proposed (e.g. deficits in other neurotransmitters and neurotrophic factors, altered hippocampal neurogenesis, HPA dysregulation, and inflammation). This dimension displays a "cross-nosological" character, as it is often prominent in patients with diagnoses other than depressive disorders. Its neurobiology suggests treatment through the use of agents enhancing brain noradrenergic or serotonergic transmission, along with other agents and interventions. There are several effective psychotherapeutic treatments, which lead to observable changes in the brain. Antidepressants and psychotherapy may have distinct neural effects. Their combination seems to have some advantages.Apathy partially overlaps with depression, although it is considered a distinct construct. It also shows considerable overlap with the negative symptom domain of schizophrenia. Lesion-based and imaging data suggest that frontal-subcortical circuits involving the prefrontal cortex and basal ganglia are implicated in the neurobiology of Apathy. Among the neurotransmitters, dopamine has been the most researched, although others are likely involved. In depression, Apathy symptoms may respond poorly to serotonergic medication. Antidepressants that enhance catecholaminergic activity may offer some advantages. If response is poor, dopaminergic agents may be considered. Psychotherapy, particularly behavioural activation, may also be useful. In schizophrenia, Apathy poses severe challenges, as it is difficult to bring about substantial improvement in negative symptoms with any treatment.

DOI: 10.1007/978-3-319-78202-7_6

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