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KEY CONCEPTS

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  • Emotions activate physiologic, cognitive, and behavioral outputs that facilitate adaptive responses to salient external and internal stimuli.

  • A crucial emotion, important in several mental disorders, is fear. The neural circuitry of fear is well understood because fear can be reliably elicited in animal models, and because its effects can readily be measured.

  • Information about threatening stimuli is transmitted from the thalamus and cerebral cortex to the amygdala where it is processed; neurons carrying fear-related information then project to diverse downstream sites in the brain responsible for adaptive responses.

  • Anxiety, a state characterized by arousal, vigilance, physiologic preparedness, and, in humans, negative subjective states, may share some critical circuits with fear.

  • Because of the evolutionary conservation of key neural circuits, animal research on fear has relevance to humans. Several anxiety disorders may involve abnormal regulation of amygdala-based fear circuitry.

  • Mood disorders are divided into unipolar disorders, which are characterized by depression only, and bipolar disorder, which is diagnosed if the person has ever had an episode of mania.

  • Mood disorders are influenced by both genes and environment, with genes playing a greater role in bipolar than in unipolar disorders.

  • Animal models to study mood regulation and mood disorders are far from perfect. However, in concert with human experiments involving functional neuroimaging, studies of postmortem brain tissue, and clinical trials of deep brain stimulation, a picture of mood-regulating circuits is emerging.

  • A subset of individuals with major depression exhibit excessive activation of the hypothalamic–pituitary–adrenal axis; thus, certain cases of depression share some physiologic mechanisms with chronic stress.

  • Most of the effective pharmacologic treatments for depression act on protein targets within monoamine synapses, generally enhancing neurotransmission by norepinephrine, serotonin, or both. A similar role for dopamine is postulated but unproven.

  • Although the initial molecular targets of antidepressants are well characterized, the actual mechanism of action is not understood. The several-week latency of onset of therapeutic effects suggests that slowly developing adaptive responses to initial enhancement of monoamine neurotransmission are required for efficacy.

  • Current research aimed at developing more effective antidepressants with novel mechanisms of action is focused on several forebrain regions and the actions of numerous neurotransmitter systems, neurotrophic factors, cytokines, intracellular signaling pathways, and transcriptional regulatory mechanisms.

  • The discovery of ketamine, an NMDA glutamate receptor antagonist, as a rapidly acting antidepressant has opened up new avenues in depression and antidepressant research.

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INTRODUCTION

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Emotions are critical to survival and represent transient physiologic, cognitive, and behavioral outputs that constitute adaptive responses to survival-relevant or otherwise salient stimuli. Mood is a term used to characterize the predominant emotional state over time. Moods (eg, happy, sad, irritable) interact bidirectionally with emotional responses to particular stimuli.

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Although there are many subtle forms of emotion, they may be divided into two broad categories by their valence. Negative emotions, such as fear, are elicited under normal circumstances by stimuli that connote danger, pain, or other noxious conditions and generally lead ...

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