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Is Sadness an Evolutionarily Conserved Brain

Mechanism to Dampen Reward Seeking? Depression
May Be a “Sadness Disorder”
a
Peter Freed
a
Division of Neuroscience, Columbia University Medical Center, New York, NY, U.S.A.
Published online: 09 Jan 2014.

To cite this article: Peter Freed (2009) Is Sadness an Evolutionarily Conserved Brain Mechanism to Dampen Reward Seeking?
Depression May Be a “Sadness Disorder”, Neuropsychoanalysis: An Interdisciplinary Journal for Psychoanalysis and the
Neurosciences, 11:1, 61-66, DOI: 10.1080/15294145.2009.10773595

To link to this article: http://dx.doi.org/10.1080/15294145.2009.10773595

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 Depression: An Evolutionarily Conserved Mechanism? • Commentaries
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Is Sadness an Evolutionarily Conserved Brain Mechanism to Dampen Reward
Seeking? Depression May Be a “Sadness Disorder”
Commentary by Peter Freed (New York)
Downloaded by [Gazi University] at 17:46 17 August 2014
Keywords: sadness; depression; attachment; emotion; yearning; incentive salience
Douglas Watt and Jaak Panksepp’s article addresses
two fundamental questions in behavioral neurosci-
ence:
1. How is the protest phase of separation distress adap-
tively terminated?
2. What is the evolutionary purpose of depression?
Their innovative response is to use each question to
answer the other. Separation distress is terminated by
depression, and depression evolved to terminate sepa-
ration distress.
In analyzing this appealing, if somewhat circular,
argument, I will draw contrasts between it and a model
addressing the same questions recently published by
myself and John Mann (Freed & Mann, 2007), to
which it bears many similarities, but from which it
departs in several key aspects.
Freed and Mann suggest that the core problem in
separation distress is the persistent incentive salience,
or reward-value, of the missing love object. This in-
centive salience drives four key features of the protest
phase: (1) attention toward reminders of the missing
attachment, (2) yearning for the missing attachment,
(3) motivation to seek out the missing attachment, and
(4) crying behavior.
In our model, the opportunity cost of protest is its
most serious downside. While a period of heightened
incentive salience may adaptively promote reunion
Peter J. Freed: Division of Neuroscience, Columbia University Medical
Center, New York, NY, U.S.A.
© 2009 The International Neuropsychoanalysis Society
61
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dation of the Dysfunctional Attitudes Scale: A Preliminary
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bauer, S., & Ehlert, U. (2007). Perfectionism and the corti-
sol response to psychosocial stress in men. Psychosomatic
Medicine, 69: 249–255.
with a missing object, attention/yearning/seeking/cry-
ing comes at the expense of pursuing other strategies
toward adaptive fitness. At a certain break-point the
opportunity cost of protest becomes too high relative
to other avenues toward regaining function, and, for
adaptive fitness to be maximized, it must be down-
regulated.
As in the Watt–Panksepp model, Freed and Mann
suggest that the despair phase of separation distress is
a likely candidate for facilitating the downregulation of
protest. But which parts of despair are targeting which
aspects of protest? Rather than suggest that the entire
despair phase performs some function with respect to
the entire protest phase, we focus on the core “positive
symptom” of despair—sadness—and its relationship
to the core positive symptom of protest—yearning. We
hypothesize that sadness may be a subjective correlate
of neural events in which dopaminergic yearning and
seeking mechanisms, geared toward obtaining oxyto-
cin and opioid rewards, are downregulated. We suggest
that sadness facilitates the rapid onset of what I will call
the adaptive “negative symptoms” of despair: amotiva-
tion, immobility, introversion, depressive affect, and
anhedonia. We summarize our model as follows:
When the desire for reunion with a deceased loved
one is both overpowering and maladaptive, a mecha-
nism that inhibits reward seeking and downregulates
yearning and attentional bias [towards the attachment]
is useful. Sadness may be such a mechanism. How-
ever, if sadness does not perform such a function, fur-
ther inquiry is needed into the mechanisms by which
• http://www.neuropsa.org
 62
bereaved persons decouple outdated stimulus–reward
associations. [Freed & Mann, 2007, p. 32]
As reviewed below, Watt & Panksepp have nominated
depression where we put forth sadness.
Finally, as with Watt & Panksepp, we suggest that
adaptive hope-renouncing mechanisms in the human
brain—in the case of our model, sadness—can become
disordered, giving way to depression.
If sadness is shown to reduce incentive salience and
the neurocircuitry of minutes-long episodes of sadness
overlaps with that of sustained periods of depression,
it may be plausible that depression is in part a “sadness
disorder” in which incentive salience, hopefulness,
motivation, and goal-directed activities are all reduced
as a result of the inappropriate triggering of this sad-
ness mechanism. [Freed & Mann, 2007, p. 32]
In short, the Freed–Mann and Watt–Panksepp models
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both are concerned with how protest is dampened
when it becomes maladaptive; both suggest that de-
spair plays some downregulatory role; and both sug-
gest that despair can become disordered and give way
to depression. Furthermore, both emphasize that at-
tachment figures provide homeostatic regulation and
are experienced as rewarding and that the dampening
of reward seeking and return of homeostasis must be
end products of any adaptive process in despair. Given
these many similarities, readers may wonder how the
two models differ. Watt & Panksepp do not address this
question in their article, and in fact for unclear reasons
our paper and model are only referenced in passing. As
such, I must offer my own analysis of the distinction
between their framework and ours—I look forward to
learning whether they agree with it.
In my view, the core difference is that Freed &
Mann attribute to the emotion of sadness the same
protest-dampening functions that Watt & Panksepp
attribute to depression, a term they use to describe the
despair phase of separation distress.
Before examining their model in detail, I would em-
phasize that the overriding reason that Freed & Mann
did not suggest that depression (despair) per se was
adaptive is that in our view despair is a heterogeneous
state combining adaptive and maladaptive features of
various etiologies. As such the phase cannot be use-
fully attributed a singular function as a whole and in-
stead, we believe, must be broken down and analyzed
in terms of distinct processes (e.g., helplessness, anhe-
donia, stress). This point is implicit in our suggestion
that attachments provide homeostatic regulation and,
therefore, that when they die, dysregulation of the or-
ganism maladaptively follows, including a protracted
Peter Freed
stress response and neurovegetative symptoms. This
dysregulation takes time to emerge and does not ap-
pear prominently during protest. The term “phase” in
the phrase “despair phase” gives the false impression
that all the characteristics of this phase are somehow
orchestrated, when in fact many are likely homeostatic
breakdown pathologies that take time to emerge.
However, implicit in our model is also the idea that
despair does contain adaptive processes which can be
conceptually parsed from the maladaptive ones. In par-
ticular, we believe it is downregulation of the incentive
salience of the deceased that is the crucial adaptive
process during the despair phase.
This brings me to the positive hypothesis of our
article, which is our answer to the question “how does
downregulation of incentive salience occur?” Here we
suggest that sad emotion—a minutes’- to hours’-long
actively generated state—plays a key role in reducing
incentive salience. I emphasize here that we purposely
focus on this brief emotion because it helps to explain
the defining temporal signature of normal grief: “pangs
of grief.” Pangs of grief may be loosely defined as brief
but intense amalgams of yearning, sadness, anhedonia,
and preoccupation with the missing object.
Of crucial importance, these pangs are interspersed
with periods of normal function. Following in a long
tradition of analytic thinking from Freud onwards, we
emphasize that this sinusoidal nature of grief bestows a
singular, and incalculably beneficial, adaptive function
over that attributed to depression in Watt & Panksepp’s
article. It is this: grief permits the maintenance of nor-
mal social function and all the adaptive benefits that
attend it. To argue that depression is the evolutionarily
conserved process by which protest is dampened is,
implicitly, to argue that it bestows some adaptive ad-
vantage that is greater than the loss of social function it
requires, relative to grief.
In contrast to Watt & Panksepp, we believe that
chronic negative affect is rarely adaptive, while brief
bursts of negative affect that rapidly alter an organ-
ism’s orientation, priorities, and behaviors are. This
is seen with normal versus pathological anxiety and
anger, and we see no reason that this should not also
be the starting assumption about sad emotion as well.
We therefore start by hypothesizing that any adaptive
negative affect during despair should be rapidly revers-
ible, thereby granting the organism maximal behav-
ioral flexibility.
Pangs of grief grant behavioral flexibility. The
hours- to days-long periods of euthymia in grief allow
the mourner to continue to maintain his or her work
and social relationships, to continue to provide value to
 Depression: An Evolutionarily Conserved Mechanism? • Commentaries
any group he or she is a part of, to continue to eat and
sleep and pursue the activities of daily living, and to
retain access to peak cognitive functioning. However,
the acute pangs themselves facilitate important deca-
thexis. Importantly, we believe the burst-like nature of
the decathexis in grief is likely more adaptive than the
tonic and global decathexis in which all pleasure and
normal social function is lost in depression.
Having now outlined the Freed–Mann model and
its overall differences from the Watt–Panksepp model,
I now proceed to analyzing their model per se. I will
subsequently critique the Freed–Mann model in the
hope of anticipating (and in several places I suspect
agreeing with) their critiques. I will close with a sug-
gestion that the two models may be usefully combined
in an effort to find a way forward to understanding the
important but mysterious connections between mourn-
ing and melancholia.
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Summary of Watt & Panksepp’s argument
Watt & Panksepp’s work embodies an inspirational
and sorely needed conviction that a review of “bot-
tom-up” brain changes in depression, combined with
a sophisticated “top-down” evolutionary and psycho-
logical model, may meet in the middle to create an in-
tegrated model of depression. They correctly note that
only such a broad model can hope to do justice to the
lived experience of the disorder and its neuroanatomy.
Furthermore, only such a model can point the way to
new research paradigms and novel treatments for de-
pression. Their focus on dynorphin, a product of their
review, is an example of the concrete progress that can
come from such an effort.
The authors are rightly critical of pure bottom-up
models, which they demonstrate to be insufficient to
produce an explanation of depression. They review
the inadequacy of models based purely on findings
regarding norepinephrine, serotonin, dopamine, opi-
oids, GABA, glutamate, dynorphin, substance P, CRF,
BDNF, cortisol, and many other small molecules. Each
is shown to contribute important elements to an un-
derstanding of the DSM-IV symptoms of depression,
but to be insufficient on its own to explain the illness.
They perform a similar review, though less extensive,
of brain regions involved, including PAG, PFC, amyg-
dala, and ACC (including BA25). Throughout they
emphasize that the brain may be too complex to allow
depression to be explained by any single overriding
theory.
However, despite these caveats, and consistent with
63
the article’s bold title, they seek to combine key fea-
tures of the data to create an organizing model of de-
pression. In addition to the model implied by the title,
to my reading they imply two other models. Because
these are presented separately, and briefly, and are not
explicitly reconciled to one another, I shall discuss
them separately.
All three models begin with a common set of obser-
vations. First, attachment is pleasurable, is mediated
by oxytocin and opioids, and promotes homeostasis
with low allostatic load. Separation from caregivers
deprives the organism of this pleasurable attachment
and homeostatic regulation, leading to high allostatic
load. A stress cascade ensues that is metabolically
demanding and gives rise to many of the symptoms of
the protest phase of separation distress. To name but a
few highlighted by the authors, the HPA axis is acti-
vated, with cortisol and CRF having various effects on
cognition, anxiety, and mood. Dysphoria is produced
as a function not only of the reduction of oxytocin
and opioids, but of the effects of CCK and dynorphin.
Brain regions involved in executive functions become
hypoactive and may process negative stimuli more
readily, while limbic and paralimbic regions such as
BA25 demonstrate increased processing that may be
related to negative affect. Brain regions implicated
in separation distress, and regulated by oxytocin and
opioids, are also active, including the PAG and BNST.
They note that “normal” separation distress is adaptive
but, if not self-limiting, can progress to depression.
They are not specific about what criteria help to define
when an organism has crossed the line from adapta-
tion to pathology. Nevertheless, they make clear that
over time the distress response becomes pathological.
BDNF decreases, there is atrophy of hippocampus and
other brain regions, social function suffers, and the
metabolic demands placed on the organism are incon-
sistent with optimal health.
It is from these data that each of the three models
takes their cue.
What might be called their “decathexis” model,
and the topic of the paper’s title, follows the uncited
Freed–Mann model closely, although it is possible
that my reading of their model is unduly influenced
by my familiarity with my own. However, as I read it,
it explains the data above by focusing on the adaptive
risk of remaining attached to a caregiver who no longer
provides care. Decathexis is necessary when caregiv-
ers are absent. For this purpose, the despair phase of
separation distress (which the authors appear to de-
scribe as depression at some points) evolved to “shut
down” attachment seeking seen in protest. This model
 64
accounts for the decline in opioids and oxytocin and
for the dysphoric effects of dynorphin. It also makes
sense of psychoanalytic contributions, described at the
article’s close, in which depression reflects an inability
to attain goals. It is also consistent with theoretical
work on goal renunciation done by Nesse (2000) and
others. Watt & Panksepp state that the despair phase
lasts long enough to accomplish the decathexis goal,
at which point it “self-limits”; people with deficits in
this self-limiting mechanism, possibly as a function
of early-life difficulties, may be prone to pathology.
As discussed below, they are not specific about when,
why, and how this self-limitation occurs.
What might be called the “social brake” model—
though less developed than the decathexis model—
suggests that subtypes of depression may be adaptive
shutdown mechanisms for other social emotions be-
sides separation, including sex, play, and status. Status
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is the best explained of these. They suggest that when
efforts to climb status gradients are assessed to be too
dangerous, despair may save the physical body from
attack by others, even as it renders the psyche sorrow-
ful. Again, a loss of motivation and pleasure experi-
ences are adaptive in this context.
Finally what might be called a “stress model” ap-
pears in pieces throughout the article and seems to be
only partially overlapping with the separation-distress
model. Here, Watt & Panksepp imply that if adaptive,
the despair phase should dampen rather than increase
the stress of protest. I was not sure they explained how
the despair phase might do this; most of their emphasis
was on the dangers of stress, rather than its downregu-
lation.
Critique of the Watt–Panksepp model
Having summarized their model as I understand it, I
now highlight four trouble spots that require clarifica-
tion.
What separates the despair phase from
depression?
First, the term “depression” seems sometimes to be
used to describe the apparently adaptive despair phase
of separation distress and at other times to describe
frank psychopathology, consistent with the DSM. Be-
cause the premise of the article requires despair to
be an evolutionarily conserved adaptation, I think it
would be advisable to avoid conceptual drift by clearly
Peter Freed
segregating it from psychopathology. I believe their
argument would be greatly clarified if they were to use
two words (“despair” vs. “depression”) to describe the
distinct adaptive and pathological conditions to which
they now apply the single term “depression.” This
would require that the title of their article be changed
to “Despair: an evolutionarily conserved mechanism
to terminate protest; depression: a pathology of de-
spair?”
Terminology aside, the question arises as to what,
exactly, divides despair from depression. Throughout
the article the authors refer to the “self-limiting” nature
of despair, but they do not describe the mechanism of
limitation. The details of this limitation are a crucial
piece of the puzzle that needs more clarification. I
think that three questions should be answered:
1. What precisely is the brain mechanism that termi-
nates despair and returns the person to normal func-
tion?
2. How does the brain “decide” when to trigger this
mechanism? What process must be complete (e.g.,
decathexis) before it is triggered, and how is this
completion detected?
3. What pathologies (e.g., early initiation, late termi-
nation, excessive intensity) of this mechanism may
permit pathological depression to develop?
Depression as decathexis: turning off one bulb
by blowing every fuse in the house
It is possible that the article’s main argument embod-
ies something of a logical fallacy. Let us say that it
is true that depression terminates separation distress.
Does this mean that this is its purpose? I think some
improvements to the argument might attend a discus-
sion of all the candidate processes by which protest
might be terminated, followed by a review of the
relative strengths and weaknesses of each. As im-
plied above, I think such a review would reveal that
grief—a process hardly discussed in this article—is
an excellent candidate to which depression must be
compared. I will discuss this more below. However,
as the heading of this section indicates, while de-
pression dampens all reward seeking—akin to blow-
ing every fuse in the house—is it possible that some
other process might more elegantly reduce yearning
for the missing attachment, while preserving general
reward processes crucial to survival—akin to turning
the switch on a single lamp?
 Depression: An Evolutionarily Conserved Mechanism? • Commentaries
The problem of stress
I was not sure that the stress story was a complete
one, as presented. The authors offer two pieces of
what I think needs to be a three-piece model explain-
ing the role of stress in depression. First, they show
that attachment is protective against stress, and, con-
sistent with this, separation from caregivers triggers
stress that characterizes the protest phase. Second, they
show—and do so admirably—that stress is a gateway
into depression and, indeed, that control of stress at the
biological level may in the future play a crucial role in
resolving pathological depression.
But at this point they face a choice, and I was
not sure that they made one. One option is that they
can show that the despair phase of separation distress
adaptively terminates protest-phase stress. This would
provide an evolutionary purpose for despair distinct
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from decathexis. If this is the case, we need more de-
tail, as the vast bulk of their review of this topic indi-
cates that stress worsens, rather than improves, during
despair. The second option is that, given that stress
worsens in despair, it represents a pathological com-
ponent of the despair phase. This then puts pressure
on their model to adjust to the fact that the despair
phase, per se, does not have an adaptive function but,
rather, must be subdivided into adaptive and maladap-
tive components.
Subtypes of depression
A final critique is over the “social brake” model of
depression, which though mentioned briefly deserves
a foundational place in the neuroscience of depression.
The authors raise the provocative—and for psychoana-
lysts, laudable—idea that depression terminates forms
of social reward other than attachment reward. For
followers of Sidney Blatt’s work on introjective versus
anaclitic depression (Blatt, 2004), the suggestion that
depression may facilitate disengagement from status
conflicts and be experienced subjectively as a failure
of the self—rather than the loss of an object—was
quite welcome, and a harbinger of a hopefully fruitful
intellectual collaboration between psychoanalysis and
neuroscience. However, I thought that this suggestion
inadvertently poses problems for the decathexis model,
as it takes the purpose of despair—which in the article
is presented as a response to protest—as possibly be-
ing to address problems that are not related to protest
at all. This raises the question of whether despair is
an “independent module” not inextricably tethered to
65
attachment. The details of this will be important. For
example, are oxytocin and opioid systems the final
common pathway for status pleasure?
Critique of the Freed–Mann model
The Freed–Mann model makes three claims that the
Watt–Panksepp model may correctly dispute; empiri-
cal study will be necessary to do so.
The first is that sadness, the “positive symptom”
of despair, triggers depression, which I believe can
be considered the “negative symptoms” of despair—
amotivation, anhedonia, anergia, introversion—as
they represent the absence of normal function. Watt
& Panksepp describe these as a fundamental loss of
hopefulness in the face of adversity. In our model,
these symptoms are brief—on the order of minutes to
hours—and dissipate rapidly, allowing the return of
normal function. Therefore, our focus is on functional
brain changes rather than on neurobiological ones. I
think this is a matter for empirical study, and critics
would be well within their rights to argue that the posi-
tive and negative symptoms of despair are not causally
connected. I suspect that this is what Watt & Panksepp
believe, and I think that if this is the case, they have
clinical evidence on their side: many periods of depres-
sive affect consist, simply, of the absence of normal
function, without the involvement of sad affect. If this
is the case, then work must be performed separately on
sadness and depressive affect.
Second, we clearly locate sadness in the despair
phase of separation distress. However, I believe that
critics—and personal conversation with Panksepp and
a review of his work leads me to believe he is one
of them—might place sadness squarely in the pro-
test phase of separation distress. In the Freed–Mann
2007 article, we suggest that this question should be-
come an item for empirical study. However, if sadness
is properly understood as a protest-phase behavior,
then it is likely that some other process in depression
accomplishes the decathexis of stimuli from reward
predictions—which is to say, negative reward–pre-
diction errors. A region not discussed by Watt and
Panksepp—the habenula—is currently emerging as
just such a candidate region; it may detect the absence
of predicted rewards and dampen VTA production of
dopamine, thereby reducing incentive salience and en-
coding negative reward-prediction errors.
The third and final claim—and the one closest to
psychoanalysis proper—that may be disputed is that
pangs of grief allow the targeted decathexis of love
 66
objects while preserving normal reward seeking in
other areas of life, thereby preserving normal social
function. Watt & Panksepp may believe that depres-
sion—which essentially produces a decathexis field
that robs the reward value of any stimulus entering it,
be it sexual, nutritive, aspirational, interpersonal—is
necessary to accomplish the decathexis task. Here,
however, I believe the burden remains on those sug-
gesting that depression is adaptive to prove that grief
does not produce the main effect needed without the
nasty side effects of depression.
In closing, I want to draw attention to a crucial dif-
ference between grief, including episodes of sadness,
versus depression, that deserves a longer exposition.
Negative emotion during grief comes in waves. These
waves of intense pangs of yearning, sadness, and think-
ing about the deceased are interspersed with prolonged
period of relative euthymia. During these periods the
Downloaded by [Gazi University] at 17:46 17 August 2014
bereaved person is able to prosecute normal social re-
lationships in a way that promotes integration with his
or her social world, increases his or her attractiveness
to others, and keeps available rewards within reach.
This stands in contrast to the extended dysfunction of
depression, in which social dysfunction and reward
insensitivity are interminable. What makes the wave-
form of grief possible is the brain’s capacity to rapidly
dampen—just as it rapidly generates—strong negative
affect. I think for these reasons, and as elaborated on
above, grief—and in particular, sadness—must be con-
sidered the most likely natural process for terminating
separation distress.
Phasing out phases?
I want to suggest that, moving forward, we should dis-
card the phase model of separation distress and substi-
tute in its stead a task framework. This would have the
immediate benefit of allowing us to rapidly distinguish
between adaptive and maladaptive features of despair,
rather than seeking to explain the phase as a whole. In-
stead, we should ask what tasks must be accomplished
Peter Freed
by a person who has lost the homeostatic regulation of
an attachment figure and for whom protest has failed.
In the Freed–Mann model reviewed here, the answer is
that the rapid encoding of negative reward-prediction
errors, leading to a downregulation of dopaminergic
seeking/incentive salience, is necessary, as it can free
the bereaved person from the mandate to pursue opioid
or oxytocin rewards in the form of the deceased and,
instead, to seek them elsewhere. Or as Freud would
call it, decathexis. Or as Watt & Panksepp would call
it, the loss of hopefulness in the face of adversity. Key
questions that then remain are these:
1. whether this loss of hopefulness, which certainly
occurs at some point during despair, occurs as a
result of sadness or regardless of it;
2. whether the loss of hopefulness occurs in bursts
seen in pangs of grief or requires a sustained period
of depression;
3. how the loss of hopefulness is itself terminated—
whether through adjustment to a negative reward-
prediction error, as in my own thinking, or some
other mechanism.
On these questions depends the manner in which the
known biological and emerging functional changes in
depression should be interpreted. Watt & Panksepp’s
clarion call for synthetic bottom-up plus top-down em-
pirical-evolutionary models is sorely needed and with
little doubt represents the way forward on this tricky
problem.
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American Psychological Association.
Freed, P. J., & J. J. Mann (2007). Sadness and loss: Toward a
neurobiopsychosocial model. American Journal of Psychia-
try, 164 (1): 28–34.
Nesse, R. (2000). Is depression an adaptation? Archives of Gen-
eral Psychiatry, 57: 14–20.