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PANIC/LOSS: an Innate Brain System

Although they surely interact in some way, in Affective Neuroscience: The Foundations of Human and Animal Emotions (1998), Jaak Panksepp explains that "as indexed by measures of separation calls in species as diverse as primates, rodents, and birds," PANIC/LOSS neurocircuitry is clearly distinct from FEAR neurocircuitry. Electrical stimulation to very specific brain areas, that we will refer to in this discussion as PANIC/LOSS neurocircuitry, produces the separation calls to which Panksepp refers. Although he considered both "sorrow" and "distress" as labels, he decided to call the neurocircuitry that generates feelings of loneliness, grief, and separation distress—as well as panic attacks in humans—the PANIC system. "LOSS" has been added to Panksepp's "PANIC" to draw attention to some of his observations that are found particularly meaningful.

The brain's PANIC/LOSS system and attachment:

Panksepp emphasizes that the PANIC/LOSS system "is especially important in the elaboration of social emotional processes related to attachment." He cites research that points to early childhood loss as a major risk factor for future depression and panic attacks. He proposes that one may be more vulnerable to depression and panic attacks "because of permanent developmental modification of the emotional substrates of separation distress." Indeed, in "Life Events Preceding the Onset of Panic Disorder" (1985) Faravelli writes that panic patients were more likely to have "underwent a major life event (death or severe illness, either personal or of a cohabiting relative) in the two months preceding the onset of symptoms."

Panksepp explains that "especially in intense forms such as grief," activation of PANIC/LOSS neurocircuitry "is accompanied by feelings of weakness and depressive lassitude, with autonomic symptoms of a parasympathetic nature, such as strong urges to cry, often accompanied by tightness in the chest and the feeling of having a lump in the throat."

chimpanzee family attachment

Panksepp explains: "To be a mammal is to be born socially dependent." When "young animals are socially isolated, they typically lose weight even if they have free access to lots of food. When the young are reunited with their kin, and a mood of apparent contentment is reestablished, appetite returns."

"Brain evolution has provided safeguards to assure that parents (usually the mother) take care of the offspring," writes Panksepp, "and the offspring have powerful emotional systems to indicate that they are in need of care (as reflected in crying or, as scientists prefer to say, separation calls)." Regarding such vocalizations, Panksepp points out that "specific locations in the auditory system, in both the inferior colliculi and the medial geniculate nuclei, are highly tuned to receive and process these primal communications." Panksepp provides a vivid example of the mother-infant bond in the animal world:

The life of a young sea otter is completely dependent on the care provided by its mother. After his sexual contribution, the father pays little heed to his young. It is the mother's job to be both caretaker and food provider, as often as not, on the open sea. The pup's life revolves around maternal devotion. When she dives beneath the dark surface of the water for food, being absent from her infant's side for many minutes at a stretch, the young otter begins to cry and swim about in an agitated state. If it were not for those calls of distress among the rising and falling waves, young otters might be lost forever. Their security and future are unequivocally linked to the audiovocal thread of attachment that joins them to their mothers. It is the same for all mammals. At the outset, we are utterly dependent creatures whose survival is founded on the quality of our social bonds—one of the remaining great mysteries, and gifts, of nature.

The PANIC/LOSS neurocircuitry that prompts separation distress "probably evolved from more ancient pain mechanisms of the brain," concludes Panksepp. He proposes that "social attachments emerge, in part, from environmental events activating brain chemistries that can reduce arousal in these [PANIC/LOSS] distress circuits."

The brain's PANIC/LOSS neurocircuitry:

In the laboratory, opioids were the first neurochemical discovered to "powerfully reduce separation distress," notes Panksepp And what in our environment stimulates opioid release naturally in the brain? Panksepp writes: "Love is, in part, the neurochemically based positive feeling that negates those negative feelings." More definitively, he points out that "neural circuits mediating separation distress are under the control of brain opioids… ." The role of opiates in decreasing activity in PANIC/LOSS neurocircuits also helps distinguish PANIC/LOSS circuitry from FEAR circuitry. Panksepp explains that "opiates are very effective in reducing separation distress but not fearful behaviors."

An important component of PANIC/LOSS neurocircuitry is the bed nucleus of the stria terminalis. According to MedlinePlus Dictionary, the stria terminalis is "a bundle of nerve fibers that passes from the amygdala along the demarcation between the thalamus and caudate nucleus mostly to the anterior part of the hypothalamus with a few fibers crossing the anterior commissure to the amygdala on the opposite side." In the illustration below left, the stria terminalis links to the hypothalamus which is hidden beneath the thalamus.

Brain stria terminalis Pre optic area

The illustration above right shows the position of the preoptic area within the hypothalamus. This image is from S.S. Nussey and S.A. Whitehead, Endocrinology, from the NCBI bookshelf (links to source). Regarding neural specifics for PANIC/LOSS neurocircuitry, Panksepp notes that there is a high density of active distress-vocalization sites "in the ventral septal area, the preoptic area [within the hypothalamus], and many sites in the bed nucleus of the stria terminalis [BNST] (areas that figure heavily in sexual and maternal behaviors)."

Brain Bnst Panic

The red circle on the image to the right (image links to source) indicates the general area within which the ventral septal area, preoptic area of the hypothalamus, and bed nucleus of the stria terminalis are nestled.

From the amygdaloid, hypothalamic, and BNST areas, PANIC/LOSS neurocircuitry runs "down through the dorsomedical thalamus to the vicinity of the PAG [periaqueductal gray in the midbrain]," explains Panksepp. Within the periaqueductal gray area, Panksepp notes that PANIC/LOSS neurocircuitry appears to arise from areas "very close to where one can generate physical pain responses." He writes: "Anatomically, it almost seems that separation has emerged from more basic pain systems during brain evolution… ."

Brain Midbrain Pag

As it does in other emotional neurocircuits, Panksepp points out that glutamate, an excitatory neurotransmitter, is probably the neurochemical that activates PANIC/LOSS neurocircuitry, thus generating distress vocalizations in young animals. In the laboratory, activating receptors for glutamate and corticotrophin releasing hormone (CRH) can dramatically increase distress vocalizations, even in the presence of other animals. In Part 1 of, we discuss the role of CRH in triggering the fight-or-flight response of the sympathetic nervous system, a component of the autonomic nervous system (see ANS—the autonomic nervous system). Panksepp emphasizes that CRH "arising from the paraventricular nucleus of the hypothalamus ... accompanies virtually all emotions and many psychiatric disturbances, especially depression." He points out that blocking receptors for glutamate and CRH dramatically decreases such vocalizations, even those induced by electrical brain stimulation.

Administration of opioids, oxytocin, and prolactin decreases activity in PANIC/LOSS neurocircuitry. Drugs that block transmission of glutamate and corticotrophin releasing hormone (CRH) also decrease PANIC/LOSS activity.

Depression and PANIC/LOSS neurocircuitry:

Panksepp asserts that "the major life factor in humans that precipitates depression is social loss." He explains that "the cascade of events during the initial protest phase of separation [marked by separation calls or crying] appears to establish the brain conditions for the subsequent despair phase [depression]." More specifically, he explains that when the stress response is activated, "a depletion of brain norepinephrine, serotonin, and certain dopamine reserves" follows. Panksepp points out that activity in PANIC/LOSS neurocircuitry is attenuated with tricyclic antidepressants such as imipramine and chlorimipramine. These antidepressants have no clear effect on FEAR-induced anxiety but have been "found to exert clear antipanic effects in humans and to also reduce separation distress in animals." Panksepp notes the interesting fact that although they experience far fewer panic attacks, people whose panic attacks have been attenuated with tricyclic antidepressants often still fear that the attacks will occur.

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