Glannon, W - Depression as Mind-Body Problem (Plus Comments), (2002) 9 PPP 243

GLANNON / DEPRESSION AS A MINDBODY PROBLEM 243

2003 by The Johns Hopkins University Press

Walter Glannon

Depression as aMindBody Problem

ABSTRACT: Major depression is a disorder of the mindcaused by dysfunction of both the body and the brain.Because it is a psychiatric illness and psychiatry is abranch of medicine, the question of how mind andbody interact in depression should be treated as amedical rather than metaphysical mindbody prob-lem. The relation between mind and body as it per-tains to this illness should be construed in teleologicalrather than causal terms. Mental states like beliefsand emotions serve an adaptive purpose by constrain-ing the physiologic systems involved in the bodysstress response, thus preserving homeostasis and pro-tecting us from various disorders. Depression resultswhen the mind fails it its constraining role.

KEYWORDS: Depression, mind, body, teleology, con-straint, homeostasis.

MANY PSYCHIATRISTS CONCEPTUALIZE severemental illnesses like schizophrenia,bipolar disorder, and severe depres-sion as disorders of the mind arising from dys-functions in the brain (Andreasen 1997; APA1994, 273392). Schizophrenia is characterizedas a disorder of cognition (hallucinations, deliri-um), emotion (affective blunting), and volition(inability to initiate and complete goal-directedbehavior); bipolar disorder as an affective disor-der involving radical swings between mania anddepression; and chronic depression as an affec-tive disorder involving negative moods such assadness, hopelessness, and listlessness. Most neu-robiologists believe that some varieties of brain

dysfunction underlie serious mental illnesses.Whereas neurotransmitters such as acetylcho-line, dopamine, noradrenaline, and serotonin mayplay a role in these illnesses, there are additionalfactors that may account for them as well.

The mind consists in the capacity for cognitivestates like beliefs and affective states like emotions,as well as unconscious affective states like emo-tional memories that can cause conditioned fear andphysiologic responses when triggered by externalevents.1 Our mental states are generated andsustained by the brain. In their conscious mode,however, there are qualitative and intentionalaspects of our beliefs, emotions, and memories.Neither the subjective nature of these mental statesnor their representational content (what they areabout) can be explained in terms of the brainalone. Diagnostic measures such as functionalmagnetic resonance imaging and positron emis-sion tomography scans can reveal the underlyingpathophysiology of a mental disorder by showingreduced glucose metabolism, reduced blood flow,and structural abnormalities in the cortex. Butthese objective measures cannot explain what itfeels like to hear voices or to have negative moods.Nor can they account for the contents of thesemental states. In these respects, the first-personperspective of being schizophrenic or depressedis ontologically distinct from and irreducible tothe third-person perspective of brain science.

These considerations invite the two main ques-tions at the core of the mindbody problem: (1)

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How can conscious mental states like beliefs andemotions arise from physical processes in thebody and brain? (2) If the mental and the physi-cal are ontologically distinct domains, then howcan there be causal interaction between the mindand the body? These metaphysical questions havevexed philosophers since antiquity. Yet, even ifthe metaphysical mindbody problem remainsinsoluble, it does not follow that we cannot makeprogress in coming to a better understanding ofthe medical mindbody problem: how mind andbody interact in maintaining health or causingdisease. It is the second question raised abovethat is germane to psychiatry in general anddepression in particular, especially regarding theidea that the mind can affect the brain and body,and vice versa. By analyzing depression as amedical rather than a metaphysical mindbodyproblem, we can gain a better understanding ofhow psychological and physiologic processes in-teract. This can shed light on the etiology ofdepression and other mental disorders and leadto more effective therapies to alleviate the suffer-ing of the people who experience them. Meta-physics is inadequate in this regard because ittends to locate the mind in the brain. The medi-cal model more closely captures the idea that themind is not located in any one place but is dis-tributed among the brain, the body, and theenvironment.

Depression results not only from dysfunctionof the brain but from mental states as well. Be-cause the mental states that figure in its etiologyhave a subjective quality and representational con-tent that reflect the social and natural environ-ment, factors external to the brain must be con-sidered to properly diagnose and treat the disorder.Indeed, in physiologic terms alone it is not onlythe brain or central nervous system that play a rolein depression, but endocrine and immune sys-tems as well. By explaining how these physiolog-ic systems are interconnected, and how mentalstates can influence and be influenced by them, Iwill show that depression is a psychoneuroim-munologic disorder consisting of four dimen-sions, one psychological and three physiologic.

Furthermore, because the mind serves an adap-tive purpose by enabling a human organism to

process sensory information more accurately andefficiently and thus enhance its survival, it ismore plausible to construe the relation betweenmind and brain (and body) in teleological terms.The causal question of how brain and mind in-teract should be subsumed under the teleologicalquestion of why they interact. From the perspec-tive of evolutionary medicine, I will take issuewith the idea that depression can be an evolu-tionary tool for human survival. On the basis ofa teleological model, I will explore the ethicalimplications of the mindbody relation for treat-ment of depressed patients by psychiatrists. Be-cause depression is a disorder with interdepen-dent physiologic and psychological dimensions,it requires both pharmacology and psychothera-py as complementary forms of treatment.

Theories of MindIn addressing a mental disorder like depres-

sion, it is necessary to frame it by a satisfactorytheory of the relation between mind and body.Descartes raised the problem of causal interac-tion between the mind and body by arguing thatthey were ontologically distinct substances. Hislegacy of substance dualism says that, althoughmind and body causally interact through thepineal gland in the brain, the metaphysical rela-tion between these substances is contingent rath-er than necessary. It is possible for the mind toexist and function independently of the body andbrain. Few philosophers today defend substancedualism; most agree that the mind necessarilydepends on the body and brain to generate andsustain it. Instead, many philosophers defendreductive materialism. This theory says that con-sciousness and other forms of mentality are notsimply caused by neural processes in the brain;mental states just are neural processes or neuralstates (Dennett 1991; Churchland 1995; Church-land 1989). This form of materialism is reduc-tionist because it says that mental states can beexplained entirely in terms of the material orphysical structures and functions of the brain.

But insofar as our mental states have a subjec-tive phenomenology, and insofar as their contentinvolves features of the social and natural envi-ronment, the mind cannot be explained entirely

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in terms of the objective physical properties ofthe brain and body. The qualitative experience ofpain underscores the inadequacy of materialism.There is something that it is like to feel pain thatcannot be explained away by neurophysiology.As neurologist Todd Feinberg puts it, From theoutside, we cannot ultimately reduce the experi-ence of pain to the neural state that creates itbecause there is nothing material from the out-side perspective to reduce . . . Our visions, ourminds, our pains, are personal and have no ma-terial existence for anyone but ourselves (Fein-berg 2001, 146). The first-person ontology ofthe mind is irreducible to the third-person ontol-ogy of the physical structure and functions of thebrain (Feinberg 2001; Searle 1992, 122).

This seems to introduce another version ofdualism, however. The distinction is not betweenmental and physical substances, but betweenmental and physical properties that are relatedcontingently rather than necessarily. It still leavesus with the problem of explaining how the mindcan interact with the brain if it is ontologicallydistinct from it. The nonreducibility of the men-tal to the physical seems to entail epiphenome-nalism, the view that the physical affects themental but not vice versa. The mind does notcause our behavior and makes no difference towhat happens in the world. Jaegwon Kim spellsout the problem of the explanatory exclusion ofthe mental thus: If mental properties are physi-cally irreducible and remain outside the physicaldomain, then, given that the physical domain iscausally closed, how can they exercise causalpowers, or enjoy any kind of causal relevance, inthe physical domain? (Kim 1998, 58).

The main metaphysical theory advanced tosolve this problem is supervenience, which speci-fies a relation of dependence of mental proper-ties on physical properties. Every mental proper-ty has a physical base in the brain that guaranteesits instantiation. For example, if a person experi-ences pain, then the mental property of havingthe experience is an instantiation of some under-lying physical property in the brain and nervoussystem that regulates pain (Kim 1998, Chapter1). But there are at least two problems withsupervenience.

First, it suggests the idea of linear causationbetween particular physical events or states inthe brain and particular mental events or states.But this is based on a mistaken view of how themind arises from the brain. The conscious men-tal state of fear, for example, may be triggered bya belief about an environmental stimulus. Fearand belief are mental states generated by popula-tions of neurons in many different brain regions.These neurons are regulated by feedback loopsbetween the amygdala and thalamus on a lowerlevel, and between the prefrontal cortex and theamygdala on a higher level. In addition, the phe-nomenological quality of the mental state de-pends partly on physical processes in the hippoc-ampus, brain stem, hypothalamus, and limbicsystem. Because so many neurons and brain re-gions are involved in generating and sustainingmental states and events, it is implausible tothink that there can be a one-to-one correspon-dence between a particular physical event in thebrain and a particular mental event. Instead,there is a stream of neural activity with diverserelations to moments of conscious experience(Gillett 1999, 288 ff.).

Second, like any other metaphysical theory,supervenience locates the mind in the brain. Evenif it does not limit it to one brain region, itignores the interaction of the brain with the bodyas well as with the environment in explaining thenature of the mind.2 As Antonio Damasio (1994,1999) and others (Clark 1997; Schechtman 1997)have argued, the mind is a function of the inter-action of the entire organism, not of the body aloneor the brain alone, with the environment. Damasiosays that, for the mental state of the self to occur:

numerous brain systems must be in full swing, asmust numerous body-proper systems. If you were tocut all the nerves that bring brain signals to the bodyproper, your body state would changes radically, andso consequently would your mind. Were you to cutonly the signals from the body proper to the brain, yourmind would change too. Even partial blocking ofbrainbody traffic, as happens in patients with spinalcord injury, causes changes in mind state. (1994, 227).

A more promising theory consistent with thedistributed view of mind is emergentism. On thistheory, mental states emerge as higher-level prop-

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erties from lower-level physical properties in thebrain and body. There are two distinct types ofhierarchy that explain how mentality emergesfrom the brain: nested and non-nested. In a non-nested hierarchy, although successive levels ofproperties causally interact, each emerging levelis independent of the others. And once it emergesat the top of the hierarchy, the mind is indepen-dent of the lower physical levels that generate it.In what Feinberg (2001, Chapter 8, Eccles 1966)calls a compositional or, nested, hierarchy, theproperties comprising the lower physical levelsare inextricably intertwined with, or nested with-in, the properties of the higher mental level.3

This theory best captures the medical model ofthe mindbody relation. By holding that lower-level physical properties and higher-level mentalproperties are interdependent, the nested viewavoids the problem of property dualism in thenon-nested view. It does not have to explain howmental properties can be self-sustaining and caninteract with physical properties if they are onlycontingently related to them.

Feinbergs position is similar to what JohnSearle (1992, 1999) calls biological naturalism.Consciousness is a biological phenomenon. Itdoes have subjective features, and unlike the neu-rons from which it arises, it is intentional, direct-ed toward states of affairs external to the brain.But it is a higher-level feature of the brain in thesame way that digestion is a higher-level featureof the stomach, or liquidity is a higher-level fea-ture of the system of molecules that constitutesour blood. The mental and the physical are notindependent categories, but two interdependentaspects of one biological system of a humanorganism interacting with the environment.

A critical notion in the nested hierarchy modelof mind is constraint. Feinberg explains mentalconstraint on the brain and body by analogywith the human lung. At a higher level, the lungdisplays emergent features not possessed by andthus not reducible to the mitochondria in itscells. If the lung did not breathe, the body wouldnot have oxygen, and if it did not have oxygen,the mitochondria would not be able to carry oncellular respiration. In this manner, the higher-level property of breathing constrains the activi-

ty of the mitochondria. When the system is con-sidered as a whole, the mitochondria contributeto the emergence of the lung. And the lung inturn constrains the mitochondria. (Feinberg2001, 1289)

Similarly, the higher-level properties of themind constrain the lower-level properties of thebrain and body. But this relation can be under-stood only in terms of the purpose the mindserves for a human organism as a whole. Inevolutionary terms, the mind serves an adaptivepurpose by enhancing the survival of the organ-ism by protecting it from external threats andpreventing various physiologic disorders. Strictlyspeaking, the mind as such is not adaptive.4 Rath-er, mental states like beliefs and emotions areadaptive when they enable the organism to dis-criminate between threatening and benign eventsby processing sensory information from the envi-ronment accurately and efficiently. When theyaccurately represent these events to the organ-ism, the relevant mental states modulate physio-logic systems in the body so that they are neitherunderstimulated nor overstimulated. By constrain-ing or modulating bodily systems, the mind playsa critical role in maintaining homeostasis of thesystems that constitute the organism. Consistentwith this role, the mind cannot be so inattentiveto environmental stimuli that it renders the brainand body unable to sense and respond appropri-ately to real threats. At the same time, the mindcannot be so overly attentive to external eventsthat beliefs misrepresent benign situations asthreats and emotions are out of proportion tothe problems at hand. In these instances, themind becomes maladaptive and can trigger patho-logic processes in the brain and body.

The model of the mind as an emergent featureof a nested hierarchy serving an adaptive pur-pose has several advantages over both superve-nience and non-nested models. First, because itspecifies interdependence among different levelsand different regions of physical and mental or-ganization, it provides a more accurate picture ofmindbrain interaction than the linear causationin supervenience, which treats this interaction asa one-to-one relation between particular physi-cal events and particular mental events. Second,

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it assumes that the mind emerges from the inter-action of the body and brain of the entire organ-ism in interaction with the environment. Third,as a teleological rather than causal model, itoffers a more helpful way of understanding howthe mind plays a role in preserving bodily ho-meostasis and maintaining health or generatingdisease in human organisms. Fourth, by focusingon purposive rather than causal processes, andthus on evolutionary biology rather than phys-ics, the nested hierarchy model sidesteps worriesabout physical events causally determining men-tal events in accord with psychophysical laws. Italso sidesteps worries about how the mind in anon-nested hierarchy could interact with physi-cal properties from which it emerges but of whichit presumably becomes independent. Given thatmind and brain are two aspects of one biologicalsystem, we can account for interaction betweenthem. But we can only do this provided that anycausal explanation of the interaction betweenphysical and mental events is subsumed under amore general teleological explanation specifyingtheir role in terms of the organism as a whole ininteraction with the environment.

MindBrain Interaction andthe Etiology of Depression

Let us focus on psychological and physiologicstress responses to environmental stimuli as causesof chronic depression. Strictly speaking, mooddisorders like chronic depression and anxietydisorders are differentiated in psychiatry. Butbecause both are emotional disorders tied to ex-cessive fear, involve a stress response, and impli-cate many of the same brain structures, path-ways, and processes, I will speak of anxiety asone of the emotions that can trigger depression.PTSD should be treated separately. Unlike mostcases of depression, which involve a chronic stressresponse, PTSD can result from a single severetraumatic experience. The severity of the traumacan cause different physiologic reactions fromthose implicated in depression.

A psychological stress response can occur inthe form of fear or anxiety activated by traumaor a belief about a real or imagined threat from

the environment. This can initiate a physiologicstress response by first triggering the amygdalain the limbic system, which controls emotions.The amygdala activates one subsystem of thebodys autonomic nervous system, the sympa-thetic nervous system. This subsystem preparesthe body for action to protect it against externalthreats, while the other subsystem, the parasym-pathetic nervous system, counteracts this responseonce the perceived threat has passed. In thisbalanced way, these two subsystems contributeto bodily homeostasis. The amygdala activatesthe hypothalamus, which controls the autonom-ic nervous system and prepares the body for asustained stress response. The hypothalamus doesthis by producing corticotropin-releasing hor-mone (CRH), which then stimulates the pituitarygland to secrete adrenocorticotropin hormone(ACTH), which in turn stimulates the adrenalglands to secrete cortisol. Now the hypothalam-icpituitaryadrenal (HPA) axis is in a full phys-iologic stress response: the fight-or-flight re-sponse (Conlan 1999, McEwen 1999; Sternberg1999, 2000; LeDoux 1996, 1999).

Under ordinary circumstances, when a realthreat to the organism has ended, the bodyssensory processing system relays this informa-tion from beliefs and conscious emotions to theparasympathetic nervous system, which shutsdown the production of the stress hormones.Cortisol acts as a complex feedback loop regu-lating production of CRH. But when the percep-tion of real or imagined danger is constant, andthere is a psychological stress response in theform of chronic fear or anxiety, this signals thebody, specifically the adrenal glands, to continueproducing cortisol. The HPA axis also functionsabnormally in people with PTSD, although forsome unknown reason they tend to exhibit un-usually low cortisol levels. It may be due to thestrength of the original unconditioned stimulus,such as the acute stress of a military battle or anautomobile accident (Hobson and Leonard 2001,1445). Perhaps the less severe stress of chronicfear and anxiety has the opposite effect on corti-sol. In any case, with our mental states telling thesympathetic nervous system and its auxiliarystructures that there is a persistent threat to the

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organism, the body is put on the constant defen-sive. As a consequence, the feedback loop be-tween cortisol and CRH is disrupted. The mindfails to constrain the central nervous, endocrine,and immune systems, disrupting homeostasis andthereby working against the adaptive purposefor which it is designed. An adaptive mechanismturns into a maladaptive response. The psycho-logical and physiologic stress responses persistbeyond the point where they are useful in en-hancing the survival of the organism.

Overproduction of cortisol adversely affectslevels of the neurotransmitters noradrenaline andserotonin by disrupting the presynaptic reuptakeof them. This appears to be the major physiolog-ic cause of chronic depression. In addition, over-production of cortisol can prompt the immunesystem to release cytokines and immune mole-cules such as interleukin I and II, which can alsoadversely affect the relevant neurotransmittersand contribute to or exacerbate depression. Al-though the underlying mechanisms are still un-clear, research suggests that impaired feedbackregulation of the HPA axis found in many de-pressed patients is positively correlated with im-mune activation of cytokines (Krionfel andRemick 2000; Ader et al., 2001). Chronic psy-chological and physiologic stress responses cantrigger the release of cytokines from leukocytesin the blood circulation, which can penetrate thebloodbrain barrier and combine with cytokinereceptors in the hypothalamus and pituitary. Byaltering normal hormone secretion in these twostructures, cytokines can disrupt modulation ofnoradrenaline and serotonin, leading to depres-sion. The links among nervous, endocrine, andimmune systems may help to explain why de-pression is often correlated with suppressed im-mune function and increased susceptibility toinfectious diseases in patients who have the dis-order. Too much cortisol suppresses the immunesystem and increases susceptibility to infection.Too little cortisol overstimulates the immune sys-tem and increases susceptibility to autoimmunediseases like rheumatoid arthritis. This illustrateshow an imbalance in or between bodily systemsinvolved in the stress response can disrupt ho-meostasis and lead to disease.

All of these points suggest that the mind is oneof four interrelated systems in human organismsdesigned to preserve homeostasis. The other threeare the nervous, endocrine, and immune systems.As an emergent feature of lower-level physiolog-ic systems in a human organism, the mind isneither independent of nor reducible to, but ratherinterdependent with these three other systems. Inits role as a highly refined sensory processor ofinformation from the external world, the mind isnaturally designed to constrain these systems sothat they are not over- or understimulated. Inthis way, the mind contributes to the preserva-tion of homeostasis and the survival of the or-ganism by protecting it from various disorders.In depression, overstimulated cognitive and af-fective mental states in the psychological stressresponse to external events can initiate a pro-longed physiologic stress response. This in turncan manifest in the negative moods that are symp-tomatic of the disorder. The pathway goes frommind, to brain and body, then back to mind. It isimportant to emphasize that the mind cannot bereduced to the brain and body in accounting forthis sequence of events; the intentional and qual-itative aspects of beliefs and emotions cannot beexplained in terms of physical processes in thebrain and body alone. In particular, the eventstoward which these mental states are directed, aswell as the phenomenological quality of thesestates, are critical to the initiation of the stressresponse.

The fourfold psychoneuroimmunologic mod-el that I have described has important medicaland ethical implications for antidepressant ther-apy. It points to the combination of biomedicineand psychotherapy as the most effective meansof treating depression. It also suggests that psy-chiatrists should treat their depressed patientswith different varieties of these interventions,depending on the extent to which the one psy-chological and the three physiologic systems fig-ure in the way that depression affects each patient.

An Adaptive Response?There are fewer stressors on humans from the

natural environment now than there were centu-ries ago, largely because we are better able to

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control its effects on us. Arguably, there are nowmore stressors from the social environment. Giv-en a higher standard of living than what ourremote ancestors enjoyed, there are greater so-cial expectations to achieve more in life. Corre-spondingly, there is increased pressure to set high-er goals for ourselves. The gap between theseexpectations and the failure to meet them maylead to the perception of expectations as stres-sors and to negative beliefs about ones abilities,both of which can contribute to depression. De-pression thus can be characterized as an adaptivedisorder. The problem is not with adapting to thenatural environment, but instead to the socialenvironment.

Some psychiatrists consider certain forms ofdepression as an evolutionary tool for survivalthat may have developed as a useful human re-sponse to situations in which a desired goal isunattainable (Nesse 1999, 2000; Stevens and Price2000). In some cases, depression as a limitingcondition may help one to disengage from projectsin which one puts considerable effort but throughwhich one achieves nothing. In other cases, itmay protect one from taking on or abandoningprojects too impulsively, making one deliberatemore carefully before acting. Understood in thisway, depression is a defense mechanism that canprotect us from harming ourselves and othersand thereby enhancing our ability to adapt toand survive in the social environment. If this iscorrect, then, contrary to what I have claimed,depression is not an adaptive disorder but anordered, adaptive, response to social circumstances.

Those who endorse this view see depression asanalogous to certain physical responses in thebody that should be described as defense mecha-nisms protecting the organism, rather than asdisorders. Coughing is not a disorder, but thebodys way of ridding itself of bacteria in thelungs and bronchial tubes. Diarrhea and vomit-ing serve as defenses in eliminating potentialpathogens from the stomach and intestine. Painprotects the body from injury by acting as amechanism alerting it to objects that can damageit. This is borne out in the limb deformities ofpeople with leprosy (Hansens disease), whereperipheral neuropathy caused by the bacterium

Mycobacterium leprae destroys nerve endings thatordinarily enable us to feel pain in our limbs.

There are important disanalogies between theseconditions and depression, however. Depressioninvolves both psychological and physiologic re-sponses, not just a physiologic one. The processof perceiving and internalizing social expecta-tions is much more complicated than coughingor vomiting. Moreover, unlike the acute physio-logic responses of coughing and vomiting, whichend once the threat to the organism has beenremoved, the stress that results in depression is achronic response setting off a cascade of eventsthat disrupt bodily homeostasis. Once the pro-cess begins, it is difficult to reverse it and thedamage that has already been done. As I willexplain in the next section, this is because de-pression and other mental disorders often in-volve emotional memories embedded in an over-active amygdala, which is difficult to modifybecause it is such a hard-wired feature of thehuman brain. Although it may be plausible tothink of depression as a limiting condition ongoals that are unattainable, there is no singleevent or set of events leading to the conditionthat can alert us to when that limit has beenreached. Many people go beyond the limit andonly realize it once they have the full-blownsymptoms of the condition.

In the light of these considerations, we shoulduphold the claim that depression is an adaptivedisorder consisting in an individuals inability toadjust to the social environment. It is not a de-fense mechanism serving an adaptive purpose forthe survival of the organism. Ordinarily, the minddoes serve such a purpose. But when the mind isdisordered, as in chronic depression, it worksagainst this purpose. Depression results when anadaptive mechanism turns into a maladaptiveresponse. The key to treating depression may bein adjusting ones perception of and relation tothe environment so that ones goals and expecta-tions from others are set within reasonable limits.

Treatment Modalities:Biomedicine and Psychotherapy

Antidepressant therapy should be tailored tofit the relative causal roles that the four systems I

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have discussed play in depression. For example,if the immune system and cytokines have a majorrole in the disorder, then tricyclic antidepressantsor monoamine oxidase inhibitors (MAOIs) maybe indicated as appropriate drug therapy. This isbecause these classes of drugs have been shownto modulate immune response and the release ofcytokines more effectively than other classes. Still,this point must be weighed against the fact thatthe drugs can have adverse side effects. In partic-ular, people who take MAOIs must adhere to anumber of dietary restrictions to prevent poten-tially life-threatening hypertension from the drugs.

On the other hand, the newer class of selectiveserotonin reuptake inhibitors (SSRIs) can boostserotonin levels and moderate mood to a normallevel or even elevate it. SSRIs are important be-cause they allow the prefrontal lobes to havemore control over the amygdala. This is the re-gion of the brain where the negative consciousemotions and unconscious emotional memoriesthat figure prominently in the cascade of eventsleading to depression are generated or embed-ded. These drugs can enhance the effect of cogni-tive psychotherapy, for example, because the be-liefs that are altered or moderated to break achronic stress response are generated from theprefrontal lobes and relay sensory informationback to them (Hobson and Leonard 2001, 156ff.).As the probable role of the immune and endo-crine systems in depression indicates, though,proper treatment of the disorder requires an un-derstanding of more than the brain or centralnervous system. Restoring normal levels of sero-tonin and noradrenaline requires ensuring theproper balance of the endocrine and immunesystems that also modulate these neurotransmit-ters. In PTSD, for example, overproduction ofadrenaline may serve to embed the emotionalmemory of a traumatic event in the amygdala.

Biomedicine is limited in its therapeutic valuein treating chronic depression, however. It is anecessary but not a sufficient intervention. Psy-chiatric drugs like SSRIs only treat the symptomsof mental disorders; they do not treat the under-lying causes. Furthermore, psychiatric drugs arenot always specific enough to precisely target thecritical neuronal receptors in the brain that regu-

late neurotransmitter levels in each patient. Ow-ing to this lack of precision, they do not alwayseffectively stabilize mood in all patients, andthey may cause debilitating side effects. Eachpersons brain has a great degree of plasticity anddevelops uniquely in response to the social andnatural environment as the person develops overthe course of his or her life. Our brains aresystems that are in dynamic interaction with theenvironment and as such facilitate our related-ness to it (Edelman 1992; Gillett 1999). Also,antidepressants can positively modulate neu-rotransmitters and the qualitative aspects of be-liefs and emotions and thereby influence how weperceive their representational content. But anti-depressants cannot completely determine this con-tent. The nature of the states of affairs towardwhich our mental states are directed is indepen-dent of our minds and brains. Because this con-tent can elicit a psychological stress response inour beliefs and emotions, there are causes ofdepression that are not located in the brain andbody.

Given the role that beliefs and emotions playin the sequence of events leading to depression,biomedicine is insufficient because therapeuticintervention must also take place at the mentallevel where the sequence is initiated. Behaviortherapy, for example, can help to block stimulithat prompt a conditioned response involving anunconscious memory that can generate consciousfear or anxiety out of proportion to the problemat hand (McCullough 2000). In constructiveavoidance, patients are taught to develop appro-priate responses to stimuli by working throughharmless to gradually more difficult stimuli untilthe stimuli become manageable. Ideally, the con-ditioned signals that prompt attacks will be elim-inated. This is difficult to achieve in practice,though, because it is extremely difficult to re-wire the amygdala, where unconscious emo-tional memory is entrenched. Emotional memo-ry is distinct from conscious memory of emotion,which is controlled by the hippocampus. Becausethe amygdala is hard-wired as a defense mecha-nism that responds automatically to stimuli aspotential threats to the organism, psychotherapythat utilizes more recently evolved (soft-wired)

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brain regions such as the cerebral cortex is likelyto have only limited success. It is much moredifficult to work backward and alter the path-way between the cortex and the amygdala be-cause of the more primitive role that the thala-musamygdala pathway plays in sensoryprocessing. Once a fear- or anxiety-inducing emo-tional memory becomes embedded in the amygda-la, it cannot be easily dislodged (LeDoux 1996).This problem is even more acute in PTSD. Yet, itis now believed that administering beta-blockersimmediately after a traumatic incident to blockthe excessive release of adrenaline may preventthe emotional memory from becoming lockedinto this region of the brain.

Cognitive therapy operates on the level of thesubjects beliefs about him- or herself or aboutevents he experiences in the social and naturalenvironment. The therapy aims to enable thesubject to become more consciously aware of hisor her beliefs and thereby achieve a better matchbetween the qualitative features of the beliefsand their actual contents. This can give one morecontrol over events or situations that otherwisewould be perceived as stressors or threats. Ifones beliefs are such that an event is not per-ceived as a threat, then the cerebral cortex sus-taining the belief will not relay the informationto the thalamusamygdala pathway in threaten-ing terms. This can prevent a psychological andphysiologic stress response that would be out ofproportion to the real nature of the event.

Yet the same problem that plagues behaviortherapy plagues cognitive therapy as well. Indepression and anxiety disorders, the force of theamygdala outweighs the force of the cerebralcortex. Unconscious emotions are more recalci-trant than conscious beliefs because, in evolu-tionary terms, the amygdala and the emotions itsustains (fear, anxiety) are more crucial to thesurvival of the organism than the cerebral cortexthat sustains beliefs. Moreover, our minds areunconscious to a much greater extent than theyare conscious; most of our emotions occur out-side of our conscious awareness. So, developingconscious control over unconscious emotions isno easy task. The role of transference in a neuro-dynamic approach might be one way of reconfig-

uring the unconscious. But it is unclear how thiscould modify the most hard-wired regions of thebrain. Although the precise mechanism is stillnot completely understood, research suggests thattrauma, grief, and other forms of prolonged stresscan prompt depression by causing the amygdalato overbalance the prefrontal lobes and conse-quently lower levels of the critical neurotrans-mitters. Nevertheless, the prefrontal lobes of thecerebral cortex can serve as a counterweight tothe amygdala and its role in depression and anx-iety because it is through the former that thelatter receives sensory information.

Beliefs are not just generated and sustained bythe prefrontal lobes; beliefs also relay sensoryinformation, which is then relayed to the amygda-la. Recall that there are two levels of sensoryinformation processing: from the thalamus tothe amygdala at a lower level, and from thecortex to the amygdala at a higher level. It is atthe higher level that beliefs are critical. If thecontent of ones beliefs is perceived in a positiveor benign way, then it is less likely that the cortexsustaining these beliefs will cause the amygdalato interpret their content as a threat to the organ-ism. By focusing on positive intentional and qual-itative aspects of a patients beliefs, cognitivetherapy may help to restore the balance betweenthe two regions of the brain at issue and thecognitive and affective states that depend on them.

But cognitive therapy is not likely to accom-plish this on its own. Indeed, research points tothe efficacy of combining pharmacologic use ofantidepressants with psychotherapy as comple-mentary treatment modalities (Keller et al. 2000).It is worth noting, however, that although thiscombination treatment makes the most sense fordepression, it may not be generalized to all psy-chiatric conditions. It is not proven for schizo-phrenia and bipolar disorder, for which drugssuch as clozapine and lithium are much moreeffective. For depression, SSRIs can increase theactivity of the prefrontal lobes in the cerebralcortex, which in turn can enhance the ability ofthe cortex to modulate the functions of theamygdala. At the mental level, antidepressantscan enable conscious beliefs to more effectivelycontrol unconscious emotional memories that

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otherwise might prompt a conditioned fear oranxiety response. The functional relation betweenthe cortex and beliefs, on the one hand, and theamygdala and emotions, on the other, is a goodexample of mindbody interaction in preservinghomeostasis.

Earlier, I said that psychiatrists should treatdepression as a physiologic disorder involvingnot only the brain and central nervous system,but endocrine and immune systems as well. Anti-depressant medication should be tailored to fitthe role that each of these systems plays in thedisorder, depending on the extent to which CRH,ACTH, cortisol, and cytokines are implicated.As a mental disorder, psychiatrists also have anobligation to address the qualitative and inten-tional aspects of the depressed patients psychol-ogy. These include the patients feeling of help-lessness, dread, or fear, and the states of affairstoward which these emotions and associated be-liefs are directed. This requires helping the pa-tient to reestablish a more salutary relationshipwith the environment, enabling him or her tonormalize his or her perception of it and elimi-nating or neutralizing any real or potential stres-sors. Psychiatrists also have an obligation to ex-plore the history of a patients beliefs and emotionsto gain a better understanding of the role thesemental states play in the etiology of depression.It is these mental states, and the environmentalstressors that are their contents, that often trig-ger the cascade of events resulting in brain dys-function and mood disturbance. This means al-lowing the patient to express his or her uniquefirst-person experience of past and present events,and listening to this narrative and interpreting itin terms of the patients life as a whole (McHughand Slavney 1986). Attention to these features ofthe patients psychology can yield clues into howthe pathologic sequence of events began. More-over, it can point toward ways of reestablishingthe balance between the patients cognitive andaffective mental states and the balance betweenthe brain and body that ultimately will restorethe patient to mental and physical health.

To be sure, psychotherapy is labor intensive,time consuming, and expensive and thereforenot likely to be looked upon favorably by any

health care system. Pharmacologic interventionis comparatively much more cost efficient; butby itself it is not more cost effective. Failure tocombine biomedicine with psychotherapy can bequite costly, especially when one considers thesocial and economic consequences of the home-lessness, crime, and suicide that all too oftenresult from inadequately treated mental illness.A neurodynamic approach, combining biomedi-cine and psychotherapy, may be the most medi-cally and economically effective long-term courseof treatment (Hobson and Leonard 2001, Chap-ter 12). Accordingly, psychiatrists may have amedical and ethical obligation to adopt this ap-proach in treating their depressed patients, andhealth care systems may have an ethical obliga-tion to support it.

ConclusionMind and body (and brain) are not indepen-

dent substances. The mind is generated and sus-tained by the body and brain and could not existwithout them. Nor is the mind reducible to them.For the qualitative and intentional aspects ofmental states cannot be explained entirely interms of physical processes in the body and brain.Mind and body are interdependent higher- andlower-level features of a nested hierarchy in abiological system that is a human organism. Mindand body interact as part of an adaptive purpose,which is to maintain homeostasis of bodily sys-tems and thereby enhance the survival of theorganism by protecting it from disease.

With the help of the cerebral cortex that sus-tains it, the minds role is to process sensoryinformation in a more refined way than the com-paratively primitive processing of the thalamusand amygdala in the brain. By distinguishingbetween threatening and benign events and re-laying this information to the relevant bodilysystems, the mind constrains these systems andprevents the body from undergoing a chronicstress response that can lead to physical andmental disorders. Chronic depression is a psy-choneuroimmunologic disorder that results whenthe mind fails in its constraining role. Negativebeliefs or emotions relay information to the ner-vous, endocrine, and immune systems in such a

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way as to trigger a stress response with patholog-ic consequences for these systems and the organ-ism as a whole. Against the evolutionary hypoth-esis that depression is a defense mechanismpreventing us from pursuing unattainable goals,I have argued that it is an adaptive disorder.Mental states that are designed to serve as anadaptive mechanism become part of a maladap-tive response to the social environment.

We do not know, and perhaps never will know,precisely how the mind arises from the brain. Yetby explaining mindbody interaction in terms ofa medical rather than metaphysical model,progress can be made toward achieving a betterunderstanding the psychological and physiologicmechanisms of depression and other mental andphysical disorders. Psychiatrists treating patientswith this disorder must try to enable them toreestablish a normal connection between mindand environment. Ultimately, the aim of all psy-chiatric interventions is to restore the balancebetween the mind and the body so that theyinteract in accord with the adaptive purpose forwhich they are naturally designed in preservingthe health and life of human organisms.

AcknowledgmentI am grateful to George Graham and two

anonymous reviewers for this journal for veryhelpful comments on earlier versions of this paper.

Notes1. Damasio (1994, 1999) and LeDoux (1996, 1999)

distinguish between feelings and emotions. Feelings arethe conscious manifestations of emotions, which arelargely unconscious. I ignore this complication for theissue at hand and simply distinguish between con-scious and unconscious emotions.

2. Most philosophers in the analytic tradition de-fend the localized view of mind, especially Dennett(1991) and Kim (1998), as do most cognitive scientists.

3. According to the non-nested view, once higher-level mental properties emerge at the top of the hierar-chy, they become independent of lower-level physicalproperties. This is a form of property dualism. It isdefended by, among others, Sperry (1966) and Scott(1995).

4. There has been much discussion of whether themind is or is not adaptive, as well as of the different

senses in which it might be adaptive. For a good criticaldiscussion of this idea, see Buller and Hardcastle (2000).

ReferencesAder, R., Felten, D., Cohen, N. 2001. Psychoneuroim-

munology, 3rd ed, 2 vols. San Diego: AcademicPress.

Andreasen, N. 1997. Linking mind and brain in thestudy of mental illnesses: A project for scientificpsychopathology. Science 275, 158693.

Buller, T., and Hardcastle, V. G. 2000. Evolutionarypsychology, meet developmental neurobiology:Against promiscuous modularity. Brain and Mind1, 30725.

Churchland, P. 1995. The engine of reason: The seatof the soul. Cambridge, Mass.: MIT Press.

Churchland, P. S. 1989. Neurophilosophy: Toward aunified science of the mind/brain. Cambridge,Mass.: MIT Press.

Clark, A. 1997. Being there: Putting brain, body, andworld together again. Cambridge, Mass.: MIT Press.

Conlan, R., ed. 1999. States of mind. New York:Wiley.

Damasio, A. 1994. Descartes error: Reason, emo-tion, and the human brain. New York: Grosset/Putnam.

Damasio, A. 1999. The feeling of what happens: Bodyand emotion in the making of consciousness. NewYork: Harcourt Brace.

Dennett, D. 1991. Consciousness explained. Boston:Little Brown.

Diagnostic and Statistical Manual of Mental Disor-ders, 4th ed. (DSM-IV). 1994. Washington, D.C.:American Psychiatric Association.

Eccles, J. C. 1966. Brain and conscious experience.New York: Springer-Verlag.

Edelman, G. 1992. Bright air, brilliant fire: On thematter of the mind. New York: Basic Books.

Feinberg, T. 2001. Altered egos: How the brain cre-ates the self. New York: Oxford University Press.

Gillett, G. 1999. The mind and its discontents: Anessay in discursive psychiatry. Oxford: Oxford Uni-versity Press.

Gillett, G. 1999. Philosophy, neuroscience, and thehuman soul. Unpublished.

Hobson, J. A., and Leonard, J. 2001. Out of its mind:Psychiatry in crisis. Cambridge, Mass.: Prometheus.

Keller, M., McCullough, J. P., Klein, D. N., Arnow, B.,Dunner, D. L., Gelenberg, A., Markowitz, J. C.,Nemeroff, C. B., Russell, J. M., Thase, M. E.,Trivedi, M. H., and Zajecka, J. 2000. A compari-son of nefazodone, the cognitive behavioral analy-sis system of psychotherapy, and their combinationfor the treatment of chronic depression. New En-gland Journal of Medicine 342:146270.

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Kim, J. 1998. Mind in a physical world: An essay onthe mindbody problem and mental causation.Cambridge, Mass.: MIT Press.

Krionfel, Z., and Remick, D. 2000. Cytokines and thebrain: Implications for clinical psychiatry. Ameri-can Journal of Psychiatry 157:68394.

LeDoux, J. 1996. The emotional brain. New York:Simon & Schuster.

LeDoux, J. 1999. The power of emotions. In States ofMind (pp. 12349), ed. R. Conlan. New York:Wiley.

Nesse, R. 1999. What Darwinian medicine offers psy-chiatry. In Evolutionary medicine (pp. 35174),ed. W. R. Travathan, Smith, E., and McKenna J.New York: Oxford University Press.

Nesse, R. 2000. Is depression an adaptation? Archivesof General Psychiatry 57:1420.

McCullough, J. P. 2000. Treatment for chronic de-pression: Cognitive behavioral Analysis systems ofpsychotherapy. New York: Guilford.

McEwen, B. 1999. Stress and the brain. In R. Conlan,ed. States of mind (pp. 81101). New York: Wiley.

McHugh, P. R., and Slavney, P. R. 1986. The perspec-tives of psychiatry. Baltimore: The Johns HopkinsUniversity Press.

Schechtman, M. 1997. The brain/body problem. Philo-sophical Psychology 10:14963.

Scott, A. 1995. Stairway to the mind: The controver-sial new science of consciousness. New York:Springer-Verlag.

Searle, J. 1992. The rediscovery of the mind. Cam-bridge, Mass.: MIT Press.

Searle, J. 1999. Philosophy in the real world. London:Weidenfeld & Nicolson.

Sperry, R. 1966. Brain Bisection and the Mechanismsof Consciousness. In J. C. Eccles. Brain and con-scious experience (pp. 298313). New York: Spring-er-Verlag.

Sternberg, E. 1999. Emotions and disease. In R. Con-lan, ed. States of mind (pp. 10321). New York:Wiley.

Sternberg, E. 2000. The balance within: The scienceconnecting health and emotions. New York: W. H.Freeman.

Stevens, J., and Price, J. 2000. Evolutionary psychia-try, 2nd ed. London: Routledge.

Travathan, W. R., Smith, E., and McKenna J. 1999.Evolutionary medicine. New York: Oxford Uni-versity Press.

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MARTIN / THE EVOLUTION OF DEPRESSION 255


Mike W. Martin

On the Evolution ofDepression

KEYWORDS: Depression, morality, mental disorders, psy-chobiology, evolutionary psychiatry.

IN DEPRESSION AS A MINDBODY PROBLEM,Walter Glannon outlines a psychosocial-phys-iological explanation of depression as a psy-chological response to chronic stresstoday, es-pecially social stressin which cortisol imbalancesdisrupt neurotransmitters. Accordingly, treatmentfor depression should combine psychopharma-cology and psychotherapya valuable reminderin light of the current restrictions on funding forhealth care (Hobson and Leonard 2001). Mycomments focus, however, on Glannons objec-tions to evolutionary theorists who explain ourcapacity for depression as adaptive to the naturaland social environment. His objections are im-plausible because he fails to distinguish depres-sion as a mood and a disorder.

What Is Depression?Explaining the psychology, sociology, physiol-

ogy, and evolution of depression presupposesknowing what depression is and hence what isbeing explained. As a blunt but important dis-tinction, let us contrast depression as a moodand as a mood disorder.

As a mood, depression is a state of low spirits,typically involving painful and low affect (of akind needing further specification). Not all nega-tive low moods are depressions. It is notoriously

difficult to distinguish depression from grief, sad-ness, gloom, and a host of additional ways to feeldownespecially because today many people useIm depressed as a blanket expression for vir-tually any low mood. For the purposes of thispaper, it is not necessary to attempt a full-blownanalysis of depressed moods (and emotions). Iwould emphasize, however, that depressed moodsinvolve values. They involve negative evaluationsof ourselves, major events in our lives, life in itsentirety, or the values that have been guiding us.Typically, to be depressed is to experience suchthings as feelings of worthlessness, dejection aboutfailures, despair and hopelessness, and loss ofcaring and commitment. Thus, we might be sador grieving but not depressed because we retain asolid grip on what is valuable and worthwhile. Inany case, there should be no general presump-tion that depressed moods are all bad or undesir-able. Instead, we should be prepared to appreci-ate the importance of depressed moods inconnection with questions of value, identity, andeven moral insight (Martin 2000). Depressed per-sons are not necessarily sick.

In contrast, depression as a mood disorder is,by definition, pathologic. Moreover, usually it isnot a depressed mood, although it involves de-pressed moods. On the one hand, depression as adisorder is defined as pathologic, a notion that isitself understood in terms of valuesthe valuesof health and, indirectly, moral values that definewhat is culturally acceptable. Thus, even severe

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grief can be nonpathologic, even though it in-volves depressed moods, when it is within therange of culturally-sanctioned responses (APA2000, xxxi). On the other hand, only sometimesis depression a single pathologic mood, as inmajor depressive episodes that can strike with aterrifying and suicidal severity (APA 2000, 375).Usually, however, the pathology is not a singledepressed mood, but instead a longer-term stateinvolving recurring depressed moods and addi-tional features, such as poor concentration, in-somnia, poor appetite or overeating, and so on.For some purposes, such as research funding andbilling insurance companies and governmenthealth providers, these pathologies can be equat-ed with what is currently in the DSM. Yet, thereare many additional states of suboptimal health,in which the DSM criteria are only partly met.

What does Glannon mean by depression? Hedoes not define it, but he makes it perfectly clearthat he intends depression as a disorder. Or rath-er, it is a set of mental disorders, including thedepressive disorders of major depressive dis-order, dysthymic disorder, depressive disordernot otherwise specified, and a variety of bipolardisorders and some anxiety disorders. Glannonsometimes indicates his primary topic is severedepression, which of course is not a DSM cate-gory (nor always a mark of pathology). For themost part, however, he says his topic is chronicdepression, which might suggest dysthymia, achronically depressed mood for most of the day,for more days than not, as indicated either bysubjective account or observation by others, forat least 2 years (APA 2000, 380). I suspect,however, that Glannon intends something broaderthan dysthymia, perhaps including most patholog-ic states that significantly involve depression thatis severe and recurrent. Such a broader conceptionwould allow him to bypass the vagaries of theDSM classifications, which fluctuate as its editionschange. Nevertheless, he seems to target disor-ders that involve primarily depressed moods, rath-er than bipolar disorders, and he explicitly setsaside posttraumatic stress disorder. In any case,because parts of his paper are concerned with thephysiology of depression, it might be helpful tomore fully specify the disorders being explained.

My main concern, however, lies elsewhere. Ina brief section titled An Adaptive Response?Glannon calls for a sweeping rejection of expla-nations developed by evolutionary psychiatrists andpsychobiologists to explain why we have evolvedas creatures who suffer depression (and lots of it).According to these evolution theorists, depres-sion serves various adaptive purposes. Glannonargues that these theorists are mistaken becausedepression is a set of maladaptive disorders: de-pression is an adaptive disorder consisting in anindividuals inability to adjust to the social envi-ronment. It is not a defense mechanism servingan adaptive purpose for the survival of the or-ganism. In making this claim, he assumes thatthe evolution theorists mean what he means bydepressionnamely, mental disorders. Do they?

Maladaptive Disorders VersusAdaptive Defenses

Are the evolutionary theorists trying to ex-plain (a) the evolutionary purposes of depressedmoods (both healthy and unhealthy ones) or (b)the evolutionary purposes of depression as a mooddisorder only? Glannon assumes (b), but (a) iscloser to the truth. I say closer to the truthbecause evolutionary psychiatrists also sometimesfail to distinguish (a) and (b). Even so, Glannonfails to engage the evolutionary theorists on theirown terms, and sometimes he seems to attack astraw man.

As an example of someone who clearly in-tends (a) rather than (b), consider Randolph M.Neeses Is depression an adaptation? (2000),an essay that Glannon explicitly targets. Afternoting the unclarity about what depression means,Neese stipulates that for his purposes depres-sion will refer to severe states of negative affectthat are often but not necessarily pathologic, andlow mood will refer to states in the commonrange of normal experience (Nesse 2000, 15).He notes the intuitive starting point that muchlow mood and depression are normal and be-come pathologic only in some forms and undersome conditions. Then he seeks an explanationof both depression and low mood, concludingthat although many depressions are pathologic(maladaptive), many other depressions and low

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moods are adaptive in helping us deal with de-feat and danger.

It seems likely that low mood and relatednegative affects were shaped to help organismscope with unpropitious situations. Some nega-tive and passive aspects of depression may beuseful because they inhibit dangerous or waste-ful actions in situations characterized by com-mitted pursuit of an unreachable goal, tempta-tions to challenge authority, insufficient internalreserves to allow action without damage, or lackof a viable life strategy (Neese 2000, 18).

In Evolutionary Psychiatry, another work tar-geted by Glannon, Anthony Stevens and JohnPrice (2000) give credence to attachment theoryexplanations of depression, as well as to Neesesescape-and-avoidance theory that focuses on com-petition and rank conflicts. Attachment theoryemphasizes that love and other deep bonds ofaffection involve (as one mark of depth) grief,sadness, guilt, shame, and other forms of distresswhen the love is lost or threatened. These emo-tions can easily degrade into pathologic states.Stevens and Price are less careful than Neese indefining depression, but it is clear they are ex-plaining a wider range of low-mood states andthen subsuming pathology as a maladaptive dis-tortion. Depressive disorders, they tell us, arebest understood as chronic exaggerations ofinnate behavioural potentials with which all hu-man beings are equipped by virtue of their hu-manity (2000, 48).

Glannon is not accurate, then, when he says,tout court, that evolutionary theorists portrayand explain pathologic depression as adaptive.The theorists are not saying there is pathology inevery depressed-mood withdrawal from compe-tition and response to the loss of love. Instead,the theorists are explaining how humans came topossess general capacities for depressed moodsthat enter into a continuum from adaptive tomaladaptive. These general types of explanationshave great interest and promise, in my view, andGlannon provides no reason to reject them. Stat-ed more positively, Glannons psychophysiologicexplanation of depression as a disorder is com-patible with the work of the evolutionary theo-rists.

To confuse (or clarify?) matters further, let mesuggest that evolutionary psychiatrists often in-terweave two different types of explanation ofmood disorders, what I will call adaptive-sick-ness explanations and malfunctioning-defenseexplanations. Adaptive-sickness explanationsexplain why mood disorders sometimes servepurposes beneficial to individuals and groups.These explanations seem paradoxical, becauseby definition disorders are maladaptive or dys-functional. In fact, the paradox is superficial. Adisorder can be maladaptive in some ways (indi-cated in its defining criteria) and adaptive inother ways (given serendipitous circumstances).It is commonplace, but interesting, that maladiesof many kinds can have good side effects (Sand-blom 1995). For example, the maladies that takeaway a writers ability to walk might provoke thewriter into greater commitment and concentra-tion that result in an explosion of creativity (Price1995). Similarly, it is amply documented thatmood disorders sometimes play creative roles inthe lives of artists (e.g., Lord Byron), leaders(e.g., Abraham Lincoln), and others (Jamison1993).

Malfunctioning-defense explanations seek toexplain a broader category of moods (or othermental states) as frequently adaptive psychologi-cal defenses against stress and anxiety, and thenthey portray mood disorders as breakdowns ordistortions of those defenses. That is, they do notportray pathologies as adaptive; on the contrary,the disorders are maladaptive perversions of pro-cesses and states that normally functions adap-tively. Glannon, too, provides explanations ofthis sort. (In doing so, I might add, he distin-guishes psychological defense mechanisms, whichhe says help us to avoid harm and social realities,and disorders. Yet, defense mechanisms, the ideaintroduced by Freud and refined by neo-Freud-ians, can serve healthy or unhealthy purposes.)

One Cheer for DepressionClarity about definitions and distinctions, I

have suggested, is essential in gaining clarity aboutwhat is being explained and assessed in evolu-tionary psychiatry and psychobiology. It is alsoimportant in connection with therapy and self-

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understanding, in determining what is unhealthyor not, and in understanding the continuum be-tween health, suboptimal health, and full-blowndisorders. Indeed, our choice of terminology al-ready reflects our attitudes. If we think of nega-tive low moods as inherently undesirable thenwe will tend to use the word depression to con-note sickness. If we discern value in many nega-tive low moods we will be more likely to use theword depression to refer to a broad range ofmoods, most of which are normal and some ofwhich are pathologic (Neese 2000, 15).

Furthermore, if we view all depressed moodsas bad, we will have to usurp some other term toconnote the wider range of healthy emotions.For example, Lewis Wolpert (1999) stipulatesthat (all) depression is pathologic and then usessadness for wider range of emotions: depressionis malignant sadness. For reasons I gave earlier, Ithink we should keep the broader sense of de-pression, and not equate depressed moods withsadness. No doubt that reflects both my attitudesand my idiolect.

Historically, attitudes toward depression (mel-ancholy, acedia, etc.) have varied greatly (Rad-den 2000). At one extreme, much everyday de-pression is defended and even celebrated, a viewassociated with Romanticism. (I still rememberthat in an undergraduate course on English Ro-manticism I was graded down for failing to ap-preciate how much the Romantics value statesthat today we pathologize.) Some philosopherscontinue that positive emphasis on the desirableaspects of depression as part of a value-guidedlife (Solomon 1976). At the other extreme arethe pathologizers, not just some Prozac-profli-gate psychiatrists but also many up-beat Ameri-cans who require steady and ever-increasing statesof augmented cheerfulness to get through theweek. In between are a variety of nuanced atti-tudes, including Susanna Kaysens (2001) aptlyexpressed realism in giving one cheer for mel-ancholy as unpleasant but often useful.

Evolutionary explanations of depression blurover most of the nuanced roles of depression inindividual lives and cultures. Their broad-brushedexplanations focus on only one value, howeverimportant: survival. Evolutionary theory is tele-

scopic: it observes big and complicated terrain froma great distance. In contrast, physiology is micro-scopic: it sees big and complicated terrain fromclose up. Telescopes and microscopes reveal much,but they also neglect much that is important inappreciating the nuances of the value-permeatedworld of human beings. Worse, they carry thedanger of reducing complex value dimensions ofhuman life to something simplera danger towhich sociobiology fell prey (Midgley 1995).

Glannons interest is mental health, but evenour conceptions of mental health are immersedin a broader set of values than survivalvaluesabout morality and meaningful life. Furthermore,many psychologists have come to appreciate theneed for focusing not only on disorders andthreats to survival, but also on positive concep-tions of health as well-being beyond the mereabsence of disease (Snyder and Lopez 2002). Isuspect that psychologists current explorationsin positive health will yield new insights into thepositive contributions of depressed moods tomeaningful life. In any case, depression as a moodraises important questions about moral values atseveral junctures: the value judgments internal tothe mood (e.g., self- or world-denigration); thevalues under assault by the mood (e.g., loss ofcaring); defining the line (blurry) line betweenhealthy moods and depressive disorders; thera-peutic judgments about the best course of treat-ment for depressive disorders and suboptimal health.

ReferencesAmerican Psychiatric Association (APA). 2000. Diag-

nostic and statistical manual of mental disorders.4th ed. Text Revision. Washington, DC: Author.

Edwards, R. B. 1997. Value dimensions of mentalillness and mental health. Ed. R. B. Edwards.Ethics of psychiatry (pp. 1721). Amherst, NY:Prometheus Books.

Hobson, J. A., and Leonard, J. A. 2001. Out of itsmind: Psychiatry in crisis. Cambridge, Mass: Per-seus Publishing.

Jamison, K. R. 1993. Touched with fire: Manic-de-pressive illness and the artistic temperament. NewYork: Free Press.

Kaysen, S. 2001. One cheer for melancholy. Ed. N.Casey. Unholy ghost: Writers on depression. NewYork: William Morrow.

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Martin, M. W. 2000. Depression: Illness, insight, andidentity. Philosophy, Psychiatry, and Psychology6:27186.

Midgley, M. 1995. Beast and man. Revised ed. NewYork: Routledge.

Nesse, R. M. 2000. Is depression an adaptation? Ar-chives of General Psychiatry 57:1420.

Price, R. 1995. A whole new life: An illness and ahealing. New York: Plume.

Radden, J. (ed.). 2000. The nature of melancholy:From Aristotle to Kristeva. New York: OxfordUniversity Press.

Sandblom, P. 1995. Creativity and disease: How ill-ness affects literature, art and music. New York:Marion Boyars.

Snyder, C. R., and Lopez, J. S., eds. 2002. Handbookof positive psychology. New York: Oxford.

Solomon, R. C. 1976. The passions. Notre Dame, IN:University of Notre Dame Press.

Stevens, A., and Price, J. 2000. Evolutionary psychia-try: A new beginning, 2d ed. London: Routledge.

Wolpert, L. 1999. Malignant sadness: The anatomy ofdepression. New York: Free Press.

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FUCHS / MIND, MEANING, AND THE BRAIN 261


Thomas Fuchs, MD, PhD

Mind, Meaning, andthe Brain

KEYWORDS: Mind, brain, meaning, translation, depres-sion.

A Systemic View of the Mind

PROGRESS IN BRAIN RESEARCH over the pasttwo decades demonstrates the power ofthe neurobiological paradigm. However,this progress is connected with a restricted fieldof vision typical of any scientific paradigm. Thepsychiatrist should be aware of this restriction,because, unlike the brain scientist, he deals withpatients, not with brains. The restricted viewmay be described by the terms of (1) reduction-ism, (2) reification, and (3) isolation.

Reductionism: Neurobiology tends to regard sub-jectivity as a mere by-product of the brains ac-tivity as a symbol-manipulating machine or aninformation processor. Consciousness becomesan epiphenomon of the neuronal machinery that,operating behind our back, creates the illusion ofa continuous self and of an autonomous will(Churchland 1995; Roth 1996).Reification: Mental or subjective states seem tobe localizable in the brain; thoughts or feelings,it appears, may be observed in the colored illu-mination of cortical and subcortical structures.This results in the belief that brain images couldalso show the cause of a mental illness, or eventhe illness itself, which then manifests, for in-stance, in a reduced metabolic activity in certainareas of the cortex.

Isolation: As a further consequence, this viewisolates the individual patient and considers hisillness separated from the interconnections withhis environment. However, on these interconnec-tions his personal experiences and dispositionsare founded, and it is the actual interpersonalsituation that has triggered his present illness.

Walter Glannons paper successfully countersthese tendencies toward a neurobiological reduc-tionism with an extended view of the mind: . . .the mind is not located in any one place but isdistributed among the brain, the body, and theenvironment. Of course, who observes some-ones brain will never see his thoughts, his pain,or his anxiety. For consciousness is not a localiz-able object or state at all but a process of relatingto something: a perceiving of, remembering of ,wishing for, aiming at, and so on. Thus on thephenomenological level, there is nothing like amental event that could be isolated from theworld and from the stream of conscious experi-ences. The mind exists only embedded in theworld and in the temporal process of life.

The same applies to the biological level: Con-sciousness is based on the continuous interactionof the brain with the organism, and of the organ-ism as a whole with the environment. The role ofthe brain for mental phenomena is thus compa-rable to the role of the heart in the circulatorysystem or of the lung in the respiratory system.Of course, the lung is the central organ of breath-ing, but respiration may not be restricted to the

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lung, nor to the organism as a whole. It meansconstant exchange with the environment, andthere is no sense in asking whether the air takenin still belongs to the surroundings or already tothe organism. The same systemic unity is foundin the circle of perception and action mediatedby the brain: When I am writing a letter, there isno place in the unity of action where my selfends and the world begins, no border thatseparates inner and outer worlds.

There is another argument to be raised againstthe reification of the mind if we consider theaspect of a historical biology. From birth on, ourmind as well as the correlated brain structuresare essentially formed by social and cultural in-fluences. The brain is not inserted into the worldas a prefabricated apparatus but through its plas-tic development in and from the world. Thus itadapts epigenetically to its specific natural andsocial environment like a key to a lock. Thiscomplementarity makes it impossible to restrictones view to the anatomic organ and requires aninterdisciplinary approach to brain-environmentinvestigation, as for example, under the headingof a social cognitive neuroscience (Ochsnerand Lieberman 2001).

As Glannon goes on to argue, to overcomeneurobiological reductionism, more is requiredthan a defense of subjective consciousness and itsirreducible intentional or qualitative aspects; forthis impregnable refuge of subjectivity wouldalso remain sterile. An adequate theory of mindrather ought to grasp its function in the systemicunity of organism and environment; and an ade-quate theory of the brain should be able to repre-sent not single objects, events, or states but rela-tions and interactions.

However, Glannons teleological explanationof the mind seems not quite sufficient. Certainlyits adaptive function amounts to more than themere enhancement of survival by adequately re-acting to threatening stimuli, triggering a fight-or-flight response, and so on. The decisiveprogress brought about by the evolution of themind is not just an improved reaction to stimuli(this could better be performed by a mindlessbrain alone) but gestalt formation; that is, thegrasping of complex wholes or situations. Be-

cause the human organism itself is an integratedwhole, it has to act and react as such, whichpresupposes an integrated or gestalt-like repre-sentation of itself (the body), the environment(the world), and its own relation to the environ-ment (meaning). This is mainly brought about(1) by a synthesis of sense experiences, creatingour embodied being in the world; (2) by anintegrated evaluation of the meaning and theoptions of a given situation, which we experi-ence as emotion; and (3) by the iconic and sym-bolic representation of the world, that is, byideas and language. The mind creates wholes,such as body, feeling, self, ideas, and concepts.This allows the human organism to internallymodel its relation to the environment, and thusto act not merely in an automatic, but in a mean-ingful way.

The Brain as an Organ of TranslationIf we now try to describe the role of the brain

on this systemic basis, we may conceive it as anorgan of transformation or translation, whichtranslates the relations between single elementsof a given situation (stimuli) into wholes or ge-stalt units. The constantly changing patterns ofsynchronized neuronal excitations correspond tothe wholes emerging in subjective experience.We may illustrate this transformation by the syn-thesis of single letters to a word (such as book),which we grasp immediately through its compo-nents, without even being aware of the letters.Of course, we once had to learn this word letterby letter (b-o-o-k), but by stabilizing the patternor picture in our subjective experience, our brainwas induced to form a corresponding neuronalpattern (in systems theory, an attractor) in such away that the constellation of single letters re-ceived the new meaning of book.

Following this line, we cannot regard subjec-tive experience as a merely epiphenomenal pic-turing of underlying neuronal processes. On thecontrary, it plays an essential role in the systemicinteraction of organism and environment. For itis only by conscious experience that the organ-ism is able to enter into a relationship with theenvironment on the higher level of meaning, ofintegrated perceptive and cognitive units or ge-

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stalten; and these subjective, meaningful units inturn influence the plasticity, the structuring andfunctioning of the brain. A historical biologyimplies the continuous formation and reconstruc-tion of the brain via subjective experience. Theconstraint that the mind in a nested hierarchy(Feinberg 2001) exerts on the lower-level proper-ties of the brain and the body consists mainly informing, maintaining, and connecting meaning-ful units of experience that stabilize correspondingneuronal activity patterns and thus trigger, ac-cordingly, physiologic reactions of the organismas a whole.

As Glannon rightly points out, there is nodualistic causality involved here: The brain trans-forms configurations of single elements or eventsinto higher-order patterns or units, and vice ver-sa. It may be addressed by input on the differenthierarchical levels and translates them into eachother. This means that any process concerningthe etiology and symptoms of mental illness is ofa biological as well as psychological nature. Thetranslation only runs top-down in the one casefrom subjective experience (e.g., a perceived so-cial situation, a psychotherapeutic intervention)to the level of neuronal and biochemical processes,and it runs bottom-up in the other case, for exam-ple, from pharmacologic effects on transmittermetabolism to a change in emotional experience.

Depression and SubjectivityObviously this systemic concept of the brain is

opposed to any biomedical reductionism operat-ing in claims like depression really is a chemicalimbalance, or responsible psychiatrists shouldfocus on the real causes of psychiatric illness, i.e.,damaged brains. The bottom-up explanation ofmental disorders as products of specific geneticor physiologic etiologies is inadequate to thecausal complexity of most disorders. Whateverthe genetic basis of, as an example depression is,it can be only one precondition of a complex,interactive process that ends up as a psychiatricdisorder. The final disorder is the product of acascade of subjective, neuronal, social, and envi-ronmental interactions in which the brain acts asa mediating, translating, and amplifying relaystation, but not as the cause.

Glannon regards depression as a psycho-neuroimmunologic disease involving psycholog-ical as well as physiologic stress responses. In asimilar approach, I have described depression asa psychophysiologic desynchronization (Fuchs2001): a perceived backlog or gap between onesexpectations and achievements is translated bythe brain into a neurobiochemical pattern associ-ated with depressed mood. It also entails anuncoupling of rhythmic physiologic (e.g., endo-crine) processes otherwise synchronized to eachother and to the environment. In the course ofthis desynchronization, the production of stresshormones and, subsequently, immunologic pro-cesses may become autonomous and inadequate,resulting in negative feedback loops and, in turn,increasing depressed mood. Thus the subjectivereactions to the disorder become intertwined withthe disorder itself. Psychosocial and physiologi-cal desynchronization influence each other.

As we can see, subjective experience is morethan a mere by-product of an underlying real orbrain depression. Depressed mood, distortedthinking, or perceived insufficiency, are not justaccidental or epiphenomenal symptoms whoseonly importance is to give cause to consult apsychiatrist (who actually is rather a brain doc-tor). Depression, on the contrary, is triggered bythe subjective perception of meaningful, mainlyinterpersonal situations, and it is also to a highdegree maintained or worsened by negative feel-ing, thinking, and interacting with others.

Finally, given the inadequacy of monocausalaccounts that invoke specific brain abnormali-ties, it would be inappropriate for the psychia-trist to treat the brain exclusively. Instead, atherapeutic pluralism is required. One could ar-gue here that because the brain translates inputin both directions, a biochemical or bottom-uptreatment suffices to attain the desired purpose.However, in view of the limited effectiveness ofpharmacologic treatment, it would be imprudentto neglect the top-down options on the psycho-therapeutic level. But what is more important,we do not have any biochemical means to changethe maladaptive dispositions of perception andbehavior that have led to depression and maylead to relapse in the future. Such dispositions

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are only accessible to change by new and repeat-ed subjective experiencesemotional, verbal, andinterpersonal processes of learning that stabilizenew attractors of perception and behavior in thebrain. Only conscious experience is able to cor-rect the corresponding dysfunctional patterns ofneuronal activity. Because the brain is a histori-cal organ, there will probablyand hopefullynever be a way to create new views of the selfand the world by brain manipulation.

ConclusionI have briefly outlined a systemic view of mind

and brain as embedded in the relation of organ-ism and environment. There is no such thing as abrain for itself, as long as it is not separated fromthe living organism by autopsy. Its role may beseen in the mutual translation of single elementsof a given situation into higher-order units thatare experienced as meaningful wholes and viceversa. Only subjectivity contains the gestalt-likewholes that for the organism represent an inte-grated model of reality. And it is only subjectiveexperience that is capable of gradually changingthe dysfunctional patterns of perception and be-havior that may lead to mental disorders.

A psychiatry of the brain, when adequatelyunderstood, would have to become a systemicor ecological psychiatry (Fuchs 2002). Psychi-atry needs an ecology of the brain to bettergrasp the interconnection of psychological, so-cial, and pharmacologic approaches adequate forits subject. For this subject is not the brain, butthe mentally ill patient.

ReferencesChurchland, P. M. 1995. The Engine of Reason, the

Seat of the Soul. Cambridge, Mass: The MIT Press.Feinberg, T. 2001. Altered Egos: How the Brain Cre-

ates the Self. New York: Oxford University Press.Fuchs, T. 2001. Melancholia as a desynchronization.

Towards a psychopathology of interpersonal time.Psychopathology 34:17986.

Fuchs, T. 2002. The Challenge of Neuroscience. Psy-chiatry and Phenomenology today. Psychopathol-ogy 35:319326.

Ochsner, K. N., and Lieberman, M. D. 2001. TheEmergence of Social Cognitive Neuroscience. Amer-ican Psychologist 56:71734.

Roth, G. 1996. Das Gehirn und seine Wirklichkeit.Frankfurt: Suhrkamp.

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GLANNON / THE PSYCHOLOGY AND PHYSIOLOGY OF DEPRESSION 265


Walter Glannon

The Psychology andPhysiology of

Depression

TRAUMA AND STRESSFUL EVENTS can disruptthe physiologic homeostasis of our bod-ies and brains. The physiologic stress re-sponse consists of neural and endocrine mecha-nisms whose function is to reestablish homeostasis.These mechanisms include the secretion of glu-cocorticoids (cortisol) and catecholemines (epi-nephrine and norepinephrine). Once an externalevent has ceased to be a stressor or threat to ahuman organism, an integrated system of nega-tive feedback loops inhibits the continued pro-duction of these hormones and effectively shutsdown the stress response. These mechanisms areadaptive in the sense that they ensure the surviv-al of the organism by reestablishing homeostasis.But prolonged exposure to real or perceived stres-sors can trigger prolonged secretion of stresshormones, thereby disrupting the feedback sys-tems and causing a cascade of pathogenic events.The stress response is a double-edged sword. Anacute stress response can protect an organismfrom external threats and reestablish homeosta-sis. But a chronic stress response can cause thebodys defenses to become damaging rather thanprotective and to result in various disorders. Acutestress responses are adaptive. Chronic stress re-sponses are often maladaptive and pathogenic.

In Depression as a MindBody Problem, Icharacterized major clinical depression as a dis-order resulting from a maladaptive chronic stress

response (Glannon 2003). Specifically, I arguedthat depression often results when our beliefsand emotions are out of proportion to the truenature of external events. The mind prolongsrather than constrains the physiologic stress re-sponse. Depression is not a disorder of the brainalone or the mind alone, however. Endocrine andimmune dysfunction can contribute to the dys-function in the brain and central nervous systemthat are involved in depression. Moreover, thecontents of the mental states that initiate thesequence of events leading to depression are re-flections of the persons natural and social envi-ronment. Thus, a satisfactory account of depres-sion requires an analysis of the interconnectionsamong the central nervous, endocrine, and im-mune systems, as well as the mind and the envi-ronment. All of these factors support the descrip-tion of depression as a psychoneuroimmunologicdisorder.

Mike Martin (Martin 2003) and Thomas Fuchs(Fuchs 2003) discuss important aspects of de-pression that I did not elaborate in my paper.Martin argues that I fail to distinguish betweendepression as a mood and depression as a disor-der. This is pertinent to the distinction evolution-ary psychiatrists draw between moods that areadaptive and moods that are maladaptive. Incontrast to my negative characterization of de-pression, Martin also makes a case for the posi-

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tive contributions of depression to meaningfullife. Fuchs explores the notion of the brain as anorgan of translation enabling patients to havemeaningful subjective experience. The emphasison subjectivity has important implications forpotential preventive and therapeutic interventionsfor depression. For whether a person perceivesan external event as a stressor may play a crucialrole in the physiologic stress response. I willaddress the main points of these two authors inturn.

Contrary to what Martin claims, I explicitlydefined chronic depression as an affective (mood)disorder. My focus was on the clinical definitionof major depression as a moderately severe tosevere chronic disorder. It consists of affective,cognitive, and even physical dysfunction that in-terferes with a persons ability to carry out thenormal tasks of daily life. This characterizationof major chronic depression distinguishes it frommilder forms of depression, such as dysthymia.Because these milder forms do not involve thesame type or degree of dysfunction as more se-vere forms, they are not appropriately character-ized as pathologies. For this reason, I focused onNesses (2000) discussion of depression ratherthan on his discussion of low mood. In fairnessto Nesse and Stevens and Price (2000), not allforms of depression are pathologic according tothe evolutionary view they defend. Some passiveaspects of mild depression may be useful in alert-ing us to dangerous or wasteful behavior. It doesseem plausible to describe depressed moods asfalling along a continuum from those that areadaptive to those that are maladaptive. Yet mostcases of chronic depression are pathologic ratherthan useful or adaptive precisely because of themental and physical dysfunctions that are symp-tomatic of them. Moreover, it is difficult to knowwhen one has crossed the threshold separatingmoods that are useful from those that are patho-logic.

As I explained in my earlier paper, this diffi-culty is due to the fact that the mental statesinvolved in the psychological stress response arelargely nonconscious. Emotions such as fear andanxiety, as well as the physiologic processes thatunderlie them, occur to a considerable extent

outside of our conscious awareness. The slidefrom adaptive to maladaptive beliefs and emo-tions cannot be easily controlled because we can-not always be aware of the process. JosephLedoux explains the problem with implicit(nonconscious) memory of stored informationabout stressful or traumatic situations as fol-lows: If we dont know what it is we are learn-ing about, those stimuli might on later occasionstrigger fear responses that will be difficult tounderstand and control, and can lead to patho-logic rather than adaptive consequences (Ledoux2002, 225). In evolutionary terms, perhaps ourpsychological and physiologic stress responseshave not yet adjusted to the noise and air pollu-tion in the modern natural environment, or tothe crime and higher expectations in the modernsocial environment. These chronic stressors arevery different from the more acute stressors oftemporary food shortages and threats from ani-mals that typified the environment of our ances-tors.

Martin maintains that mood disorders canhave good side effects. He cites the creative rolethat mood disorders have played in the lives ofartists. Although there may be a correlation be-tween bipolar disorder and artistic creativity, asimilar correlation between depression and cre-ativity is questionable. Even in bipolar disorder,it is during the manic, not depressed, phase thatartists and writers with this condition do theircreative work. More importantly, the lost oppor-tunities and suffering of people afflicted withthese and other mental illnesses far outweigh anypositive effects they might have. Martins roman-ticized view of depression applies to a very smallsubset of people wit

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Glannon, W - Depression as Mind-Body Problem (Plus Comments), (2002) 9 PPP 243