Brain, Behavior, and Immunity xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

Brain, Behavior, and Immunity

journal homepage: www.elsevier.com/locate/ybrbi

Review Article

Depression subtyping based on evolutionary psychiatry: Proximate

mechanisms and ultimate functions
Markus J. Rantala a,b,⇑, Severi Luoto c,d, Indrikis Krams e,f, Hasse Karlsson g,b
a
Department of Biology, University of Turku, FIN-20014 Turku, Finland
b
Turku Brain and Mind Center, University of Turku, FIN-20014 Turku, Finland
c
English, Drama and Writing Studies, University of Auckland, 1010 Auckland, New Zealand
d
School of Psychology, University of Auckland, 1010 Auckland, New Zealand
e
Institute of Ecology and Earth Sciences, University of Tartu, 51014 Tartu, Estonia
f
Department of Zoology and Animal Ecology, University of Latvia, 1004 Riga, Latvia
g
Department of Psychiatry, University of Turku and Turku University Hospital, FIN-20014 Turku, Finland

a r t i c l e i n f o a b s t r a c t

Article history: Major depressive disorder constitutes one of the leading causes of disability worldwide. However, it is not
Received 1 July 2017 a unitary disease—it is a heterogeneous syndrome, with patients differing remarkably in symptom profile,
Received in revised form 11 October 2017 pathophysiology and treatment responsiveness. Previous attempts to subtype major depressive disorder
Accepted 15 October 2017
have showed limited clinical applicability. We present a classification of major depressive disorder epi-
Available online xxxx
sodes based on the proximate mechanisms that led to the original mood change that caused the depressive
episode. We identify discrete depression subtypes that are induced by: 1) infection, 2) long-term stress,
Keywords:
3) loneliness, 4) traumatic experience, 5) hierarchy conflict, 6) grief, 7) romantic rejection, 8) postpartum
Depression
Evolutionary psychopathology
events, 9) the season, 10) chemicals, 11) somatic diseases and 12) starvation. We further examine the ulti-
Inflammation mate functions of these subtypes and show that not all types of mood changes that trigger depression are
Epidemiology adaptive. Instead, some are clearly maladaptive and some are byproducts of other adaptations. In modern
Proinflammatory cytokines societies, low mood after adverse life events may turn into a pathological depressive state. Modern life-
Modernization style increases susceptibility to inflammatory dysregulation and chronic stress, both of which increase
Obesity the amount of proinflammatory cytokines in peripheral blood, leading to low mood and sickness beha-
viour. Proinflammatory cytokines may aggravate the previously adaptive short-term mood changes to
a chronic maladaptive depressive state by preventing the normalization of mood after adverse life events.
Subtyping depression enables an effective and intelligent long-term treatment of patients in each subtype
by treating the underlying causes of depression.
Ó 2017 Elsevier Inc. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Why depression has become a disease of modernity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Subtypes of depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Infection-induced depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Depression induced by long-term stress (previously melancholy) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.3. Depression induced by loneliness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.4. Depression induced by traumatic events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5. Depression induced by hierarchy conflict . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6. Depression induced by grief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.7. Depression induced by romantic rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.8. Postpartum depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

⇑ Corresponding author at: Department of Biology, University of Turku, FIN-20014

Turku, Finland.
E-mail address: markus.rantala@utu.fi (M.J. Rantala).

https://doi.org/10.1016/j.bbi.2017.10.012
0889-1591/Ó 2017 Elsevier Inc. All rights reserved.

Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
2 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx

3.9. Season-related depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

3.10. Chemically induced depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.11. Depression induced by somatic diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.12. Starvation-induced depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. The problem with diagnosing clinical depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Proximate mechanisms and ultimate functions of depressive symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.1. Emotional pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.2. Proneness for suicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.3. Rumination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.4. Change in appetite: Significant mass gain or loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.5. Anhedonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.6. Sleep disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.7. Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.8. Anxiety. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.9. Psychomotor agitation or retardation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.10. Pessimism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.11. Self-accusations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5.12. Low self-esteem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

1. Introduction problems, diseases, substance use, medication, long-term stress

Major depressive disorder is among the leading causes of dis-
ability worldwide (Vos et al., 2015), imposing an annual economic
burden of $210.5 billion in the US alone (Greenberg et al., 2015).
With substantial advances made in evolutionary psychology in
recent decades, multiple hypotheses have been proposed to
explain the evolutionary origins of major depressive disorder and
the possible adaptive functions of its symptoms (Anders et al.,
2013; Andrews and Thomson, 2009; Badcock et al., 2017; Nettle,
2004). Although many evolutionary explanations may seem plausi-
ble and logical, none of them has received full acceptance in the
field. What is more, most clinicians think that an evolutionary
approach is irrelevant to their clinical practice, because there is
no evolutionarily based treatment for depression (Troisi, 2012).
We think that the main reason for the failure of evolutionary
explanations to provide an adequate theoretical framework for
depression is that most of the authors who have suggested or crit-
icized evolutionary explanations for depression have seen it as a
single disorder (see e.g. Badcock et al., 2017; Nesse, 2000;
Sharpley and Bitsika, 2010). Likewise, major depressive disorder
is routinely diagnosed based on the number of reported symptoms
and a threshold score of their sum-score. This diagnostic tool in
itself is based on the assumption that depression is a single condi-
tion and that all symptoms are interchangeable and equally good
indicators of one underlying disorder (Fried and Nesse, 2015b).
The evidence that major depressive disorder is a group of sepa-
rate syndromes comes from the observations that patients with
major depressive disorder not only have many hundreds of unique
symptom profiles (see e.g. Fried and Nesse, 2015a), but many of the
symptoms often have opposite features such as insomnia and
hypersomnia, increased and decreased appetite, or psychomotor
agitation and retardation. We argue that the occurrence of symp-
toms (or patterns of symptoms) depends on the subtype of the
depressive episode. Different adverse life events lead to different
patterns of depressive symptoms (Keller et al., 2007; Keller and
Nesse, 2006) and the particular manifestation of depressive symp-
toms may have more to do with what triggered the depression
than the personality of the patient (Keller et al., 2007). It is proba-
ble that different adverse events trigger different psychological
adaptations that are designed by natural selection as a response
to the adaptive problem in question. What is more, certain health
and several other factors may trigger major depression disorder
episodes. Thus, a single explanation covering all cases of depressive
episodes is not plausible.
Evolutionary explanations for a trait or a behaviour focus on
two different levels: 1) what is the proximate mechanism underly-
ing the trait: how does it work?—and 2) what is the ultimate reason
it evolved: what fitness benefit, if any, does it provide for the
organism? (Bateson and Gluckman, 2011; Laland et al., 2011;
Luoto and Rantala, 2017). In this article, we suggest a novel evolu-
tionary subtyping of depression based on proximate mechanisms
and ultimate functions underlying specific depression episodes.
2. Why depression has become a disease of modernity
Anthropologists have documented the rarity of major depres-
sive disorder episodes (that fulfil the diagnostic criteria of DSM-5
or ICD-10) in hunter-gatherer societies (Hollan and Wellenkamp,
1994; Keyes, 1986; Schieffelin, 1986). Depression is more common
in hunter-gatherer societies that have shifted to agricultural prac-
tices—a phenomenon reported for example among the Ik people in
Uganda (Stevens and Price, 2000). Likewise, indigenous people in
the arctic areas that changed to a modern lifestyle experienced
tripled suicide rates in a decade (Shephard and Rode, 2008).
Cross-cultural analyses of women living in developing and devel-
oped parts of the world have found that the degree of moderniza-
tion correlates with a higher prevalence of major depressive
disorder in a dose-dependent manner (Colla et al., 2006). Chinese
people born after 1966 are 22.4 times more likely to suffer from
a depressive episode than Chinese people born before 1937 (Lee
et al., 2007). The prevalence of major depressive disorder is only
1% among Old Order Amish people (who still live without electric-
ity and plow their fields with horses) in the US (Egeland and
Hostetter, 1983), compared with the almost sevenfold overall
prevalence of depression in the US (6.8% according to Greenberg
et al., 2015). Needless to say, the low prevalence of major depres-
sive disorder does not mean that hunter-gatherers and Old Order
Amishes do not have tragic events in their life. For example,
approximately 47.5% of hunter-gatherer children fail to survive
to puberty (Volk and Atkinson, 2013). For some reason, however,
in hunter-gatherers and Old Order Amishes the periods of low

Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
mood, sadness and grief after adverse events in life does not seem
to transform to episodes of major depressive disorder that fulfil the
diagnostic criteria of DSM-5 or ICD-10.
There are many possible factors that may increase the risk that
low mood or sadness exacerbates to a major depressive disorder
episode in modern societies. These include sedentary lifestyle,
overfeeding, reduced food quality, reduced sunlight exposure,
sleep deprivation and social isolation (reviewed in Hidaka, 2012,
see also Saeri et al., 2017). These lifestyle factors generally lead
to poor physical health, inflammation and an increased susceptibil-
ity to stress (Miller & Raison 2016). Thus, in a modern lifestyle,
adverse life events hypothetically lead to chronic stress or ‘‘a run-
away stress response” more often than in traditional cultures
(Ilardi, 2009). Modern lifestyle also brings forth ‘‘diseases of
modernity”, which include obesity, atherosclerosis, hormone-
related and gastrointestinal cancers, type 2 diabetes and osteo-
porosis (Lindeberg, 2010). Common to all of these is that they are
associated with inflammatory dysregulation and increased levels
of proinflammatory cytokines (Shoelson et al., 2007) and that they
are conspicuously absent in traditional hunter-gatherer societies
(Lindeberg, 2010). Furthermore, there is a strong reciprocal con-
nection between depression and obesity (Luppino et al., 2010;
Schwartz et al., 2016), which is driven by inflammation (Berk
et al., 2013; Kiecolt-Glaser et al., 2015; Rethorst et al., 2014).
The inflammatory dysregulation common to modern lifestyle
seems to increase the likelihood of developing major depressive
disorder after adverse life events. This hypothesis is supported by
the finding that the risk of major depression increases by 44% for
each standard deviation increase in log c-reactive protein (Pasco
et al., 2010). Likewise, patients with coronary heart disease—in
which inflammation is one of the major contributing factors—have
a threefold risk to suffer from major depressive disorder compared
with the general population (Frasure-Smith and Lesperance, 2006).
Interestingly, alleles associated with an increased risk of depres-
sion are also associated with known effects on immune function
(Raison and Miller, 2013). Likewise, many studies have found that
interventions that are known to alleviate depression—e.g. physical
exercise, mindfulness or psychotherapy—also reduce peripheral
inflammatory biomarkers (Blumenthal et al., 2005; Kohut et al.,
2006; Zautra et al., 2008). Taken together, current evidence sug-
gests that the inflammation dysregulation caused by a modern life-
style may prevent the normal rise of mood after an adaptive mood
change.
On the other hand, childhood maltreatment is known to
increase vulnerability to major depressive disorder and other men-
tal illnesses (Maccari et al., 2017; Saleh et al., 2017). Childhood
maltreatment increases the likelihood of suffering from chronic
stress in adulthood: this happens by epigenetic mechanisms such
as altering DNA methylation (DNAm) levels of the hypothalamic-
pituitary-adrenal (HPA) axis genes (Bustamante et al., 2016). It
has been suggested that chronic stress in childhood also affects
the microbiome in such a way that an altered, suboptimal micro-
biome could predispose individuals to increased stress
(O’Mahony et al., 2016). In addition to childhood maltreatment,
maternal obesity, unhealthy maternal diet, maternal stress and
inappropriate nutrition in childhood may all increase vulnerability
to mood disorders later in life by modulating HPA-regulatory com-
ponents (Cirulli, 2017). More generally, all adverse conditions in
life potentially lead to epigenetic changes which prepare the body
to face similarly harsh conditions later in life—if similar conditions
are subsequently not met, these epigenetic changes may have mal-
adaptive consequences (Cirulli, 2017). For example, if a pregnant
rat is given a restricted diet, her pups will be smaller at birth. How-
ever, if the offspring subsequently have access to unrestricted food,
they become more obese than the offspring of dams that were fed
an unrestricted diet during pregnancy (reviewed in Bateson et al.,
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
3
2014; see also Andrews et al., 2015a). Early life events can there-
fore have a substantial effect on susceptibility to disease in adult-
hood (Andersen, 2015; Gluckman et al., 2007; Hanson and
Gluckman, 2014).
Not all depressed patients, however, have suffered from early
life adversity nor do they necessarily suffer from chronic stress.
After all, only about half of all severely depressed patients have ele-
vated levels of cortisol (Hale et al., 2010). Likewise, not all
depressed individuals have increased proinflammatory cytokine
concentrations in peripheral blood (Penninx et al., 2013), suggest-
ing that not all depressed patient have inflammation dysregula-
tion. In a sample of 585 depressed patients, for example, 47% had
CRP levels 3.0 mg/L, and 29% had CRP levels 5.0 mg/L
(Rethorst et al., 2014). Therefore, not only do depressive episodes
differ in their symptom profiles but also in the physiological state
of the body. In addition, a recent study using functional magnetic
resonance imaging (fMRI) found that depressed patients belong
to at least four different neurophysiological subtypes, that is, clus-
ters of individuals who have different symptom-linked brain fea-
tures (Drysdale et al., 2017). These clusters of individuals differed
in responsiveness to transcranial magnetic stimulation therapy
(Drysdale et al., 2017). These findings on the physiological hetero-
geneity of depression provide further empirical support for the
argument that depression should not be treated as a single
disorder.
From the point of view evolutionary psychology, a depressive
episode may be (1) an adaptation against the specific adaptive
problem (adaptive mood change), (2) a maladaptive state due to
an environmental mismatch as a result of modern lifestyle, (3) a
byproduct of other adaptations or (4) a pathological state without
any adaptive function (cf. Del Giudice, 2014, 2016; Lewis et al.,
2017). To provide effective treatment, it is crucial to define which
of these classes a given depressive episode belongs to. This analysis
is facilitated by a classification of depressive episodes into discrete
subtypes based on evolutionary psychiatry. In the following sec-
tions, we suggest a new classification of depression episodes to dif-
ferent subtypes based on proximate mechanisms that triggered the
mood change and the ultimate function that the mood change is
likely to serve.
3. Subtypes of depression
Categorising depression into subgroups is not a new idea—re-
searchers have tried to subtype major depression disorder episodes
based on the symptoms (e.g. atypical, melancholic or psychotic
depression), onset (e.g. early versus late in life), course (single,
recurrent, chronic), neurophysiology or severity (Rush, 2007).
These classifications, however, have not been unified by a convinc-
ing theoretical framework. In addition, there is no common agree-
ment as to the number or validity of these subtypes (Harald and
Gordon, 2012; Lichtenberg and Belmaker, 2010) and they have lim-
ited clinical applicability (van Loo et al., 2012). In contrast, evolu-
tionary and neurobiological approaches provide a convincing
theoretical framework for subtyping depression episodes.
We classify depression to 12 subtypes based on proximate
mechanisms and ultimate functions that trigger the mood change
that may lead to depression (Fig. 1). All of the proximate mecha-
nisms that we list below are commonly known as potential causes
of low mood and depression episodes, but they have not been pre-
viously identified as contributing to different depressive subtypes.
Nevertheless, some of the subtypes are already identified in The
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
(DSM-5) as separate causes of depression (American Psychiatric
Association, 2013), but this subtyping has not been adopted into
clinical treatment of depression. The present subtyping based on
4 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
Fig. 1. Depression subtypes based on evolutionary psychiatry.
evolutionary psychiatry could help find more effective treatments
because it allows treating the underlying reasons (triggers) of
depression instead of merely focusing on the symptoms, which is
how traditional psychiatry treats depression (e.g. Fried et al.,
2017). In addition, the subtyping helps to develop treatments that
are more intelligent and effective for each depressive subtype.
3.1. Infection-induced depression
Due to selective pressures caused by parasites and pathogens,
natural selection has equipped humans (at the ultimate level of anal-
ysis) with an immune system and many other adaptations to com-
bat parasites and pathogens (Schmid-Hempel, 2011). One of these
adaptations is sickness behaviour, which includes somatic, cogni-
tive and behavioural changes that help individuals overcome infec-
tion by conserving metabolic resources for the use of the immune
system, thus avoiding further infections (Anders et al., 2013). The
behavioural patterns of sickness behaviour include anorexia, psy-
chomotor retardation, sleep disturbances, anergy, anhedonia, weak-
ness, malaise, listlessness, hyperalgesia and impaired concentration
(Dantzer, 2001). Sickness behaviours are observed in humans dur-
ing acute infections (the proximate level of causation), but also after
an experimental and therapeutic administration of proinflamma-
tory cytokines (Bonaccorso et al., 2001; Capuron et al., 2002), endo-
toxins (Eisenberger et al., 2010; Reichenberg et al., 2001) and
vaccination against typhoid (Harrison et al., 2009). Furthermore,
cytokine antagonists and anti-inflammatory agents block the devel-
opment of sickness behaviour / depression symptoms following
immune activation (Dantzer et al., 2008).
All symptoms in behavioural changes induced by sickness seem
to be adaptations against infection, helping the immune system
work more effectively (Anders et al., 2013). If the infection is con-
tagious, the social withdrawal caused by the sickness behaviour
may reduce the likelihood that an individual will infect their
kin—a behavioural feature which increases an individual’s inclu-
sive fitness (cf. Gardner and West, 2014). Social withdrawal caused
by anhedonia, fatigue, hypersomnia and psychomotor retardation
reduce mobility and help to conserve energy for immune defence
(Anders et al., 2013).
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
3.2. Depression induced by long-term stress (previously melancholy)
Short-term stress can be beneficial due to its performance-
boosting effect. Stress constitutes a problem when the factor caus-
ing it is not eliminated, lengthening the duration of stress. Stress is
known to activate the immune system, causing an increase in
proinflammatory cytokine levels that influences mood if stress
becomes chronic (Berk et al., 2013). In our evolutionary history,
stress was statistically associated with a higher probability of
being wounded and thus our immune system is designed to be
upregulated as a response to stress (Slavich and Irwin, 2014).
Unfortunately, if stress becomes chronic, this response leads to
inflammation and production of proinflammatory cytokines (Berk
et al., 2013). Another mechanism with which stress upregulates
the immune system is associated with the gut. Chronic stress
causes the gut to leak non-pathogenic commensal bacteria into
the peripheral circulation which activates the immune system
and causes an increase in proinflammatory cytokines in blood
(reviewed in Miller and Raison, 2016). This increase in proinflam-
matory cytokine levels triggers sickness behaviour and may result
in a maladaptive state of clinical depression. The symptoms of
depression induced by chronic stress include reduced mood, fati-
gue, self-blame, appetite problems, concentration problems, sui-
cide ideation, sleep problems, psychomotor problems and
anhedonia (Fried et al., 2015).
Prolonged stress is not necessarily caused by a life-threatening
danger or an imaginary threat; even modern-day working life may
be stressful enough to cause a prolonged stress response. For
example, a medical internship (which is a particularly stressful
time for medical students) has been shown to increase depression
levels from 3.9% at baseline to 25.7% during an internship (Sen
et al., 2010). In many jobs, rotating night shift work causes chronic
stress (Korompeli et al., 2009) by causing ‘‘constant jet lag”,
because workers’ circadian rhythms never adjust to irregular
working hours. Likewise, insomnia may lead to a state of chronic
stress in the body (Motivala et al., 2005), doubling the risk that a
non-depressed individual will develop clinical depression
(Baglioni et al., 2011). In modern societies, personal financial stress
and indebtedness may cause chronic stress that leads to depression
(Ferrie et al., 2003). Depression induced by chronic stress does not
appear to be an adaptation to a specific problem. Instead, it seems
to be a maladaptive byproduct of prolonged stress response, occur-
ring because of a mismatch between the current environment and
the ancestral environment.
3.3. Depression induced by loneliness
Humans are highly social primates; separation from the social
group and family has been a major fitness threat in our evolution-
ary history. A solitary individual is more vulnerable to predators,
hostile conspecifics and other forces of nature than individuals in
social groups. It is therefore not surprising that loneliness makes
people feel unsafe (Cacioppo et al., 2014), causing a lonely person’s
brains to be in a highly alert state. Since it is especially dangerous
to sleep in absence of a safe social surrounding, loneliness influ-
ences the quality of sleep by increasing the amount of microawak-
enings. This makes sleep less restful and leads to daytime fatigue
(Cacioppo et al., 2002). The aversive feeling of loneliness seems
to be an adaptation that motivates an individual to seek the com-
pany of others, much like hunger motivates one to eat and thirst to
drink. For example, isolated rats increase their locomotor activity
(Garzon and Delrio, 1981), and other studies in non-human ani-
mals have shown that loneliness leads to depressive-like behaviour
(reviewed in Cacioppo et al., 2015).
Although in humans it is easy to see that the awareness of lone-
liness may be an adaptation to signal that one’s connections to
 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
others are frayed, motivating an individual to repair those connec-
tions (Cacioppo et al., 2006), it is less easy to see how loneliness-
induced depression episodes might be adaptive. Depression caused
by social isolation is likely to be a pathological state, not an adap-
tation. Experimental studies in humans and non-human animals
have shown that social isolation increases hypothalamic-
pituitary-adrenal (HPA) axis activation and decreases inflamma-
tory control (reviewed in Cacioppo et al., 2011). Thus, loneliness
is a stressor which may lead to a chronic stress state. This causes
low-grade peripheral inflammation that the body misinterprets
as an infection, leading to sickness behaviour that can ultimately
be maladaptive. Loneliness possibly even increases social isolation
because it may decrease self-esteem and social ability, leading to a
vicious cycle of further social withdrawal. It is important to note
that although a depression episode itself may cause loneliness,
studies suggest that loneliness appears to have a stronger effect
on symptoms of depression than depression has on loneliness
(Cacioppo et al., 2006).
3.4. Depression induced by traumatic events
Traumatic events, such as a severe injury or a dramatic threat to
life, lead to a stress response which in the majority of cases disap-
pears in a matter of weeks. Studies carried out in hospitals imme-
diately after a traumatic event have reported that patients with
low stress hormone levels were more likely to develop post trau-
matic stress disorder (PTSD) than patients with high stress hor-
mone levels (Aardal-Eriksson et al., 2001; Mouthaan et al., 2014).
This indicates that those who react to a traumatic event with a
fight or flight response are not inflicted with PTSD. Fight or flight
response is not the only possible way for animals to react to dan-
ger. If an animal experiences and survives a danger which it cannot
overcome with a fight or flight response, it is better for the animal
to avoid situations in which the danger can reoccur. Natural selec-
tion has favoured organisms which efficiently record dangerous
situations, thus decreasing the likelihood of ending up in a similar
situation again. It has even been suggested that nightmares pre-
pare the mind to react to threatening situations (Valli et al.,
2005), and so traumatic events may be replayed in memories
and dreams, maintaining the prevalence of the threat. PTSD seems
to have developed as a facultative adaptation which guides indi-
viduals to avoid similar situations that caused the trauma.
A study on 677 randomly selected patients with depression
found that 36% suffered from PTSD (Campbell et al., 2007). Clini-
cally depressed patients with PTSD had more severe symptoms
than clinically depressed patients without PTSD (Campbell et al.,
2007). A large meta-analysis composed of 57 studies reported a
comorbidity rate of 52% of depression among both military and
civilian persons suffering PTSD (Rytwinski et al., 2013). Thus, PTSD
seems to be an important trigger of major depressive disorder that
has substantial comorbidity and overlapping symptoms with PTSD
(Breslau et al., 1991; Gros et al., 2012; Kessler et al., 1995). Why
has natural selection produced a mind that makes traumatic events
trigger PTSD but results in some people suffering from it chroni-
cally? It is possible that in the environment of evolutionary adapt-
edness (EEA) of humans (see e.g. Lewis et al., 2017), PTSD did not
become chronic. Indirect support for this hypothesis is provided
by findings on how evolutionarily novel lifestyle choices, such as
smoking, obesity and low physical activity, increase the risk of
chronic PTSD (Buckley et al., 2004; Olff et al., 2006), while
micronutrient intake may actually decrease it (Rucklidge et al.,
2012). Although PTSD is associated with hypocortisolism (Bicanic
et al., 2013), PTSD patients have an elevated concentration of
proinflammatory cytokines (Gill et al., 2009), which explains why
PTSD often takes on features of sickness behaviour and leads to
depression. Although PTSD per se seems to be an adaptation caused
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
5
by natural selection to avoid the cause of the trauma, the depres-
sion triggered by PTSD may be a pathological consequence of an
increased concentration of proinflammatory cytokines. This makes
it necessary to classify PTSD-induced depression as a separate,
non-adaptative phenomenon distinct from the original, adaptive
nature of PTSD.
3.5. Depression induced by hierarchy conflict
Humans and many other group-living animals have a need to
climb the social hierarchy of the group, since a higher position
improves reproductive success in both sexes and leads to several
other positive life outcomes (Miller, 2009; Nelissen and Meijers,
2011). In many non-human animals, social defeat causes
depressive-like behaviour and physical responses that are similar
to those seen in depressed humans (Rygula et al., 2005; Shively
et al., 1997). Depression functions as a signal that an individual
has given up after a hierarchy conflict. Decreased self-esteem pre-
vents the defeated individual from challenging more highly ranked
conspecifics, helping the individual conserve their bioenergetic
resources. Depression functions as an honest signal that the
defeated individual does not pose a threat anymore, which can pre-
vent them from being expelling from the social group, conserving
their life in most extreme cases (Price et al., 1994).
Unemployment may be a sufficient trigger for modern humans
to experience a strong negative feeling of hierarchy conflict, which
can lead to depression (Stolove et al., 2017). Exclusion from a social
group may also trigger depression. Bullying, either at school or
work, can constitute a hierarchy conflict and induce depression
(see e.g. Kaltiala-Heino and Frojd, 2011). It has long been known
that depression is especially common in people who are pursuing
unreachable goals in their life (Davis, 1970). Because career goals
are often associated with climbing in the social hierarchy, the neg-
ative mood which results from not reaching them can be classified
as depression induced by hierarchy conflict. One of the conse-
quences of depression is that it makes the individual reassess their
goals to meet their de facto abilities or realistic possibilities.
What has traditionally been classified as ‘atypical depression’
seems to be clinical depression caused by hierarchy conflict. This
is because the symptoms of ‘atypical depression’ include social
ineptitude, which is caused by fear of rejection (Angst et al.,
2002). Other symptoms of atypical depression include hypersom-
nolence, increased appetite, weight gain and lethargy (O’Keane
et al., 2012). Unlike in other types of depression, this subtype is
characterized by mood reactivity: patients are able to experience
elevated mood as a consequence of positive events, yet they are
still sensitive to negative feedback (O’Keane et al., 2012). It is espe-
cially interesting that patients with atypical depression often also
have hypocortisolism (Gold and Chrousos, 2002). Likewise,
research on mice has shown that social defeat leads to elevated
stress hormone levels in most individuals, but a subset of individ-
uals get depressed after repeated social defeat and show adreno-
cortical hyporesponsiveness and hypocortisolism (Bowens et al.,
2012). It therefore seems that individuals with atypical depression
do not react to conflict hierarchy with a fight or flight response—in-
stead, they give up and become susceptible to ‘atypical depression’
(as it has been named in prior research) or to depression caused by
hierarchy conflict (as we identify it). The fundamental difference in
cortisol concentrations discussed above—i.e. hypocortisolism in
patients suffering from this depressive subtype—facilitates the
diagnosis of depression induced by hierarchy conflict.
Taken together, the existing evidence suggests that depression
induced by hierarchy conflict (at the proximate level of explana-
tion) may in fact be an adaptation caused by natural selection (at
the ultimate level of explanation). However, this does not mean
that depression induced by hierarchy conflict is adaptive for all
6 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
depressed individuals who have a modern Western lifestyle. For
example, inflammation (common to Western lifestyle) may mix
features of sickness behaviour to symptoms of depression induced
by hierarchy conflict, which can escalate the mood change episode
to be maladaptive. Thus, any given adaptation may have low ‘cur-
rent utility’ in a modern environment that is vastly different from
the EEA (Bateson and Laland, 2013; Del Giudice and Ellis, 2016).
3.6. Depression induced by grief
Forty-two per cent of individuals whose spouse had passed
away fulfilled the diagnostic criteria of clinical depression a month
after the spouse’s death; after a year, the percent of clinically
depressed widows was 16% (Zisook and Shuchter, 1991). The
symptoms of such a grief response differ from those typical for a
clinically depressed patient: grief is characterized by momentary
mood decreases, while clinically depressed patients typically suffer
from a constant low mood. Grief also does not usually result in
lowered self-esteem or suicidal ideation (Assareh et al., 2015). An
estimated 10–20% of people who lost a loved one develop clinical
depression (Middleton et al., 1996). This depression subtype may
be further exacerbated if the individual suffers from loneliness that
results from the loss of a loved one (Cacioppo et al., 2006).
Because of the costliness of grief, it has been suggested that
grief functions as an honest indicator of commitment and signals
a person’s propensity to form strong non-utilitarian bonds and
commitment to group (Winegard et al., 2014). Although studies
suggest that those who grieve more intensely are perceived as
nicer, more loyal and more trustworthy than low grievers
(Reynolds et al., 2015), the ‘grief as an adaptation’ hypothesis is
not able to explain why grief exists also in non-social species like
prairie voles (Sun et al., 2014). Grief as a response to experiencing
a loss of a mate, sibling or offspring has been reported in numerous
nonhuman animal species (King, 2013). In non-social animals, the
grief and possible depression that result from losing a loved one do
not seem to increase an individual’s fitness in any way, and so they
are unlikely to be adaptations caused by natural selection. Grief
leading to depression is more likely to be a byproduct of the
attachments that humans are naturally inclined to make with
other people, although it might have acquired a signalling function
in social communication in humans (Reynolds et al., 2015). In evo-
lutionary psychology, this signalling function that grief has
acquired in a social species such as humans would be classified
as a spandrel. That is because it is a feature that did not arise as
an adaptation through natural selection but rather as a side effect
of other adaptive processes, which have subsequently been co-
opted for a novel function (Buss et al., 1998; Gould, 1991). To the
extent that grief has a social function in humans (Reynolds et al.,
2015; Winegard et al., 2014), pharmacological interventions to
relieve the symptoms should only be made when grief does not
fulfil its social purpose (say, in the absence of a social support net-
work) and instead escalates into a pathological depressive state
that causes more harm than benefit for the patient.
3.7. Depression induced by romantic rejection
The trauma of romantic rejection is commonly known to cause
clinical depression and, in extreme cases, even suicide or homicide.
A study on 114 men and women who had been left by their roman-
tic partners within the last two months found that 40% had symp-
toms comparable to clinical depression (Mearns, 1991). Because
romantic love is comparable to drug addiction, its withdrawal
symptoms resemble those associated with drugs (Fisher et al.,
2016). Although some of the symptoms associated with romantic
rejection can be withdrawal symptoms, some seem to be adapta-
tions caused by natural selection. For example, ruminating on the
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
cause of the rejection can help an individual avoid repeating the
same mistakes in future relationships (Andrews and Thomson,
2009). Furthermore, the lowered self-esteem associated with
romantic rejection makes an individual lower their self-assessed
mate value, leading to future mate choices that are better aligned
with the individual’s de facto mate value. It is also possible that
depression may work as an honest signal to the rejecting partner
that the rejected person truly loved the rejecting partner, helping
to win back the lost love.
3.8. Postpartum depression
Postpartum depression occurs in 10–15% of women in the six
months following childbirth (Brummelte and Galea, 2010). In addi-
tion to regular depressive symptoms, mothers who suffer from
postpartum depression typically feel a loss of interest in their baby
and may even develop harmful intentions towards them. Other
symptoms include crying, suicidal ideation, bouts of anger and
hopelessness (Brummelte and Galea, 2016). In modern societies,
only a fraction of mothers end up deserting or killing their baby,
since infanticide carries an enormous social stigma and legal con-
sequences. In the EEA of Homo sapiens, however, infanticide or
desertion has likely been a far more common solution for mothers
suffering from postpartum depression than it currently is. For
example, Ayoreo Indian mothers (whose lifestyles represent a clo-
ser approximation to our ancestral conditions than modern Wes-
tern lifestyles) kill 38% of the babies they give birth to (Hausfater
and Hrdy, 1984).
Several studies indicate that postpartum depression is linked to
the mother feeling that she is receiving inadequate childcare sup-
port from the father or from kin (reviewed in Hagen, 1999). This
can lead to despair and a feeling that she cannot cope with the par-
ental duties (Hagen, 1999). A situation in which a mother was left
to raise her child by herself would have been catastrophic in
humans’ EEA and would have likely meant that the mother is
unable to raise the child to a viable adulthood. A woman who con-
tinued investing in a child whose survival is unlikely would have
had fewer copies of her genes in the next generation than a woman
who ceased her investment and postponed reproduction to a more
propitious moment in time. Since the child’s health affects their
chance of survival, it is not surprising that poor health in the child
predicts postpartum depression in the mother (Hagen, 1999).
Mothers who had complications during pregnancy or delivery
were eight times more likely to suffer from postpartum depression
(Hopkins et al., 1984).
The primary function of postpartum depression does not seem
to be the desertion of the child. Rather, postpartum depression
may function as a signal to kin and the spouse that the mother
requires more support (Hagen, 1999). Women with postpartum
depression have been found to have downregulated HPA axis activ-
ity, lower salivary stress hormone levels and lower levels of proin-
flammatory cytokines in serum compared to non-depressed
mothers (Groer and Morgan, 2007). Thus, the symptoms of post-
partum depression are not associated with sickness behaviour.
Instead, it seems that postpartum depression is an adaptation
which might not be adaptive in all cases due to the environmental
mismatch between the EEA and modern conditions.
3.9. Season-related depression
Seasonal affective disorder (SAD) is a mood disorder that affects
an individual the same time each year (Rosenthal et al., 1984). In
temperate and northern latitudes, the most common form of SAD
is winter depression, in which the symptoms often begin in
autumn and abate in spring and summer. It is often associated with
mild hypomania in spring and summer (Partonen and Rosenthal,
 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
2001). A typical feature of SAD is that the symptoms intensify in
the afternoon. SAD is characterized by general fatigue, decreased
libido, increased need to sleep and increased appetite, especially
for carbohydrates and starchy foods (McCarthy et al., 2002;
Rohan et al., 2003).
It has been suggested (at the ultimate level of explanation) that
SAD is an adaptation to northern latitudes to conserve energy dur-
ing historically predictable periods of dwindling food supply (Davis
and Levitan, 2005; Eagles, 2004). However, we are not convinced
that SAD is an adaptation to seasonal changes in food supply, nor
to northern (or southern) latitudes. An abundance of empirical evi-
dence supports this view. First, studies done in Finland (latitudes
60 °N to 70 °N) have found that variation in SAD is not explained
by latitude (Grimaldi et al., 2009; Partonen et al., 1993; Sandman
et al., 2016), suggesting that the Nordic population would have
adapted to changes in their photoperiod without developing SAD.
Second, SAD is more common among individuals migrating to
northern latitudes from tropical and subtropical regions than
among native populations, which have adapted to the local envi-
ronment (Saheer et al., 2013; Suhail and Cochrane, 1997). If SAD
had developed as an adaptation to a northern environment, people
migrating from tropical and subtropical regions should not become
afflicted with it.
It has been found that SAD is more common in people with eve-
ning chronotypes (Sandman et al., 2016) and that light therapy is
an effective treatment for it (as well as for other depression types)
(Golden et al., 2005). Since the circadian system of evening chrono-
types is more sensitive to light and temperature than that of morn-
ing chronotypes (Sandman et al., 2016), the most plausible
explanation is that SAD is just a maladaptive byproduct of the fail-
ure of a person’s circadian rhythm to match the reduced daytime
length. In addition, it has been found that inflammation and
chronic stress may disrupt the function of circadian rhythm
(Mavroudis et al., 2013).
Since reduced sunlight in winter causes more negative mood in
so many people in temperate and northern latitudes, it sounds
counterintuitive that some individuals feel more depressed during
spring and early summer. People who experience spring / early
summer depression sleep less, wake up earlier and their mood is
worst in the morning; they also have decreased appetite and
weight (Boyce and Parker, 1988). This subtype of depression has,
however, not been studied adequately: more research is needed
before spring / early summer depression can be formally cate-
gorised as a subtype of its own. Nevertheless, in countries with a
temperate climate, the prevalence of suicides peaks in spring /
early summer, while suicide rate is lowest during the time of win-
ter depression (Reutfors et al., 2009). In addition, suicide seasonal-
ity is more evident in violent than in non-violent suicide methods
(Reutfors et al., 2009). A lower or absent seasonality effect in sui-
cide rates has been found in regions close to the equator
(Benedito-Silva et al., 2007; Chew and McCleary, 1995; Heerlein
et al., 2006; Parker et al., 2001). Thus, there is something in spring
/ early summer that lowers mood in many people.
Since spring is the time of year when many people develop
allergic reactions due to an increased amount of pollen, it has been
suggested (at the proximate level of explanation) that the increase
in proinflammatory cytokines induced by the allergy aggravates
depressive symptoms by intensifying inflammation in the body
(Manalai et al., 2012). This is supported by a study on bipolar dis-
order patients which found that depressive symptoms correlated
positively with immunoglobulin E in plasma (Manalai et al.,
2012). On the other hand, in many cases depressed patients have
upregulated serotonergic system (Andrews et al., 2015b). Since
light is shown to interact with brain serotonergic system
(Lambert et al., 2002), it is possible that in individuals with upreg-
ulated serotonergic system, the increase of sunlight in spring ele-
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
7
vates the brain’s serotonin levels to an excessive degree, making
depressive and anxious symptoms stronger. This rationale is sup-
ported by the observation that the hours of daily sunshine corre-
late with daily suicide rates after mathematically removing the
effect of season (Vyssoki et al., 2014). In sum, it seems that, at
the ultimate level of analysis, season-related depressive episodes
are maladaptive byproducts of seasonal changes in the amount of
daylight. At the proximate level, season-related depressive epi-
sodes may be exacerbated by a rise in proinflammatory cytokines
as well as an upregulated serotonergic system.
3.10. Chemically induced depression
At the proximate level of causation, depression may be a conse-
quence of substance abuse (e.g. alcohol and cocaine) or a side effect
of medication (e.g. corticosteroids, benzodiazepine tranquilizers)
(American Psychiatric Association, 2013). There is a wealth of
experimental evidence to suggest that the long-term use of alcohol
reduces mood and may cause depression (reviewed in Schuckit,
2006). More than 40% of alcoholics fulfil the criteria for major
depressive disorder and as many as 70% of these cases are classi-
fied as substance-induced depression (Schuckit, 2006). In contrast
to many other subtypes of depression, alcoholics suffering from
substance-induced depression are not depressed all day every
day (Schuckit, 2006). Thus, they do not fulfil the DSM-5 criteria
for major depressive disorder. They are likely to experience insom-
nia, problems in concentrating and irritability (Schuckit, 2006). In
contrast to other depression subtypes, the symptoms of
substance-induced depression decrease or disappear rapidly with
abstinence (Schuckit, 2006), which makes the identification of
the subtype easier. We suggest that, besides changing neurotrans-
mitter functioning (Chastain, 2006; Kertes et al., 2011), one possi-
ble mechanism how alcohol may cause depression is by causing
the leak of non-pathogenic commensal bacteria from the gut into
the peripheral circulation (see Bjarnason et al., 1984), which trig-
gers the production of proinflammatory cytokines and leads to
symptoms of sickness behaviour.
Depressed individuals often self-medicate themselves with
alcohol and other drugs. Although alcohol and other drugs may
temporarily elevate mood and reduce anxiety, substance use typi-
cally does not help an individual resolve the adaptive problem that
led to the original mood change. Instead, substance use has poten-
tially hazardous consequences for mental health (Leeies et al.,
2010). In addition, it may be that the previously adaptive mood
change turns to a maladaptive state of clinical depression due to
an increase in the production of proinflammatory cytokines that
causes symptoms of sickness behaviour.
There is also some evidence that depression may be caused by
environmental toxins, like heavy metals, pesticides, plasticizers
and other endocrine-disturbing or neurotoxic compounds
(Genuis, 2008; Rauh and Margolis, 2016; Stallones and Beseler,
2016). However, more studies are needed on this topic to verify
the proximate mechanism at play. At the ultimate level of analysis,
chemically induced depression seems to be a maladaptive state,
the symptoms of which do not help to avoid or combat the chem-
ical that triggers it.
3.11. Depression induced by somatic diseases
Depression is frequently comorbid with many somatic diseases.
Neurological conditions like Alzheimer’s disease, Parkinson’s dis-
ease, migraine, epilepsy, stroke and traumatic brain injury are
associated with an increased risk of depression (Bulloch et al.,
2015). Several neuroendocrine conditions, such as Cushing’s dis-
ease and hypothyroidism, may also induce depression (Kim et al.,
2015). In multiple sclerosis—an inflammatory, demyelinating
8 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
disease of the central nervous system—the lifetime prevalence of
depression may even exceed 50% (Beal et al., 2007; Schubert and
Foliart, 1993). Almost two-thirds of women with breast cancer suf-
fer from depression (Reich, 2007), with similar figures reported for
other types of cancers (Reich, 2007). There are three main proxi-
mate causes why cancer may induce depression: 1) finding out
that you have cancer may cause chronic stress and anxiety that
may lead to depression (McDaniel et al., 1995), 2) chemotherapy,
radiotherapy and surgery may lead to depression induced by sick-
ness behaviour or 3) cancer itself may raise proinflammatory cyto-
kine levels in blood, leading to sickness-induced depression. There
is substantial evidence both in experimental animal studies and in
clinical work on humans for causes 2 and 3 (Coussens and Werb,
2002; Egeland et al., 2017; Lamkin et al., 2011; Pyter et al.,
2009). Cancer itself may therefore induce depression. In many
cases, depression induced by somatic diseases appears ultimately
to be a maladaptive state because it impairs recovery from illness
and increases mortality (Pinquart and Duberstein, 2010).
3.12. Starvation-induced depression
Famines have been common in our evolutionary history, which
is why natural selection has equipped humans with physical and
psychological adaptations to outlast food shortages (Prentice,
2005). In starvation, the body begins to reduce investment in the
body functions that are not necessary for immediate survival. For
example, investment in growth and immune function are reduced.
Starvation increases slow wave sleep and reduces REM sleep
(Macfadyen et al., 1973), probably to save energy during the night.
It also increases physical activity, which increases the odds to find
food (Exner et al., 2000). Starvation reduces mood, causes irritation
and anhedonia and diminishes sexual interest (Keys, 1950). Starva-
tion declines the ability to concentrate on tasks that require major
cognitive processing due to the obsession to find food (Keys, 1950).
Prolonged starvation leads to apathy and social withdrawal (Keys,
1950). Starvation-induced depression can be an adaptation to save
energy in order to increase the odds of surviving through a famine.
4. The problem with diagnosing clinical depression
With some subtypes of depression, it is problematic to identify
when a possibly adaptive state of low mood has escalated to patho-
logical clinical depression which requires treatment. From the
point of view evolutionary biology, an adaptive state of low mood
turns into pathological clinical depression when the patient’s
symptoms do not serve the purpose that natural selection has
shaped them to serve. In contrast, a depressive episode becomes
maladaptive when the environment has changed so much that
the depressive symptoms do not lead into the outcome which they
were designed to achieve.
In practice, although subtyping depression is not always
straightforward (because sometimes depression may be caused
by several factors), the present subtyping will nevertheless facili-
tate assigning proper treatments for each patient. This cannot be
done by focusing merely on the symptoms, but requires an analysis
of the patient’s life history. The importance of subtyping depres-
sion is highlighted by the presumed reoccurrence of depressive
symptoms when treating the symptoms is discontinued. To cus-
tomise treatment, it is necessary to identify the cause of depres-
sion. For example, if depression induced by loneliness is treated
with antidepressants instead of removing its underlying cause, it
is to be expected that the depressive symptoms reoccur when
the treatment is discontinued.
To be able to understand the logic of using evolutionary psychi-
atry for subtyping depression, it is important to analyze why
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
depressive symptoms exist in the first place. In the following sec-
tion, we therefore discuss the proximate mechanisms and ultimate
functions of depressive symptoms.
5. Proximate mechanisms and ultimate functions of depressive
symptoms
While different adverse events lead to different patterns of
depressive symptoms (Keller et al., 2007; Keller and Nesse,
2006), major depressive disorder is routinely diagnosed based on
the number of reported symptoms (American Psychiatric
Association, 2013). We argue that this is an ill-founded diagnostic
tool; instead, an improved understanding of the proximate mech-
anisms and ultimate functions of the symptoms of a specific
depressive episode is more important for optimal treatment and
recovery. For example, since many individuals with major depres-
sive disorder have increased levels of proinflammatory cytokines
when compared with groups of nondepressed individuals, some
symptoms of depressed patients may in fact be symptoms of sick-
ness behaviour that are caused by peripheral inflammatory
response (Miller and Raison, 2016). These include changes in appe-
tite, anhedonia, social withdrawal and proneness for suicide, as
discussed below. While some depressive symptoms are maladap-
tive byproducts of normally functioning physiological or psycho-
logical adaptations, other depressive symptoms are adaptations
against specific adaptive problems.
5.1. Emotional pain
As with physical pain, one of the functions of emotional pain is
to make an individual avoid the behaviour which caused the pain
(Keller and Nesse, 2005). Emotional pain could be expected to
occur in response to a fitness-relevant loss of resources (Nesse,
2000). In the evolutionary history of humans, social relationships
have provided crucial resources not only for reproduction but also
for survival. The collapse of social relationships with people close
to us causes emotional pain and grief. Rather than providing an
actual fitness benefit to an individual, emotional pain may simply
be the price humans pay for forming emotional bonds with others.
On the other hand, experiencing emotional pain motivates individ-
uals to cherish their social relationships and to take care of the
people with whom they have formed an emotional bond.
Crying is a common symptom of depression especially when
social relationships are in danger of being broken or have already
done so (Keller and Nesse, 2006). It seems that the main functions
of depression-induced crying are to request aid, receive empathy
and social support and to solidify social bonds. On the other hand,
tears and crying are not only a visual and an auditory signal of sad-
ness, but tears also contain pheromones, i.e. chemical substances
that cause physiological or behavioural changes in conspecifics
(Gelstein et al., 2011). It has been found that exposure to emotional
tears reduces testosterone levels in men (Gelstein et al., 2011).
Thus, tears can reduce the aggression of a dominant individual in
a hierarchy conflict. Crying and tears may not be mere functionless
behaviours but can in fact be a means of manipulating and affect-
ing conspecifics’ behaviour.
5.2. Proneness for suicide
Suicidal ideation occurs frequently in depressed individuals.
Although this may seem maladaptive in a modern environment,
suicide may in fact have increased an individual’s inclusive fitness
under certain circumstances in our evolutionary history. Suicide
can facilitate the success of one’s genes in a situation in which
an individual’s own reproductive prospects are slim or nonexistent
 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
and the individual has become a burden to their kin. Suicide can
improve the reproductive success of kin and therefore the prolifer-
ation of the individual’s genes when relatives need not feed or take
care of the sick individual (Decatanzaro, 1986). Studies have
indeed shown that suicide ideation is more common in individuals
who have low reproductive potential and who felt that they are a
burden to their kin (Brown et al., 1999; Decatanzaro, 1991;
deCatanzaro, 1995), despite the support structures that modern
societies have created to take care of their weakest members.
At the ultimate level of evolutionary analysis, natural selection
favours suicide in situations in which an individual contracts a ter-
minal disease that could infect their kin. For example, infected
worker bees (Apis mellifera) abandon their nest to prevent disease
transmission in their colony, resulting in an altruistic suicide
(Rueppell et al., 2010). At the proximate level of analysis, it has
in fact been found that sickness behaviour caused by the adminis-
tration of proinflammatory cytokines causes suicidal ideation in
some people (Capuron et al., 2002). Furthermore, depressed
patients who have high suicidal ideation have significantly higher
inflammatory index scores than controls and depressed individuals
with lower suicidal ideation (Holmes et al., 2017; O’Donovan et al.,
2013). It is possible that an elevated concentration of proinflam-
matory cytokines leads to suicidal ideation and increases the prob-
ability of suicide even in depression subtypes caused by other
events than a contagious disease. On the other hand, in some situ-
ations, the threat or attempt of suicide can be seen as a strategy to
extort those who benefit from their association with the afflicted
individual (Hagen, 1999).
5.3. Rumination
Rumination, the obsessive replaying of negative events, is often
seen as pathological by clinicians. This is because it typically pre-
vents the ability to concentrate on other things, it is difficult to
suppress, and it increases other depressive symptoms
(Nolenhoeksema, 1991). However, there are good reasons to
expect that rumination is a psychological adaptation (Andrews
and Thomson, 2009). Ruminating events that possibly triggered
depression is more frequent in situations in which there is an
increased likelihood of that event reoccurring (Keller and Nesse,
2006). Continued rumination helps the depressed person avoid
similar mistakes or situations in the future, and facilitates solving
complex social and psychological problems (Andrews and
Thomson, 2009). Reducing rumination with medication may there-
fore have harmful long-term effects for a patient’s well-being.
However, this does not mean that rumination is adaptive under
all circumstances. For example, if rumination is not associated with
the problem that triggered the depressive episode, the benefits it
provides for the individual are limited.
5.4. Change in appetite: Significant mass gain or loss
Obesity has been found to increase the risk for major depressive
disorder by 55% (Luppino et al., 2010). Obesity is an inflammatory
state and fat tissue is known to be a source of proinflammatory
cytokines (de Heredia et al., 2012; Shields et al., 2017), which
can increase the probability that an adaptive mood change turns
to a maladaptive chronic state with symptoms of sickness beha-
viour. On the other hand, depression has been found to increase
the risk of obesity by 58% (Luppino et al., 2010). Many depressed
individuals have increased cravings for sweet and fatty foods
because they enhance mood momentarily (see e.g. Macht and
Simons, 2000). This ‘‘comfort eating” seems to be a byproduct—
not an adaptation—and may propel a vicious cycle that leads to
obesity and even more depressed mood (cf. Luppino et al., 2010;
Shields et al., 2017).
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
9
In other cases, depression leads to a decreased appetite. There is
strong evidence supporting the hypothesis that loss of appetite is
caused by an increase in proinflammatory cytokine levels in
depressed patients with immune activation. This is because the
cytokines stimulate the release of leptin, a cytokine-like anorexi-
genic peptide (Andreasson et al., 2007). Although the loss of appe-
tite is often thought of as a deleterious side effect of disease, it
seems that it is in fact an active defence mechanism. It sounds mal-
adaptive because it occurs at the same time as the immune system
increases energy expenditure. However, since sickness-induced
anorexia redirects resources away from lipid transportation
towards immune function, it could be an adaptive response by
decreasing the trade-off between lipid transport and immune func-
tion (Adamo et al., 2010). In addition, sickness-induced anorexia
may reduce the availability of iron and other micronutrients that
are essential to pathogens (Exton, 1997). Sickness-induced anor-
exia may also reduce the likelihood that an individual will be
exposed to more parasites or pathogens with food while the
immune system is allocating its resources to combat infection.
The loss of appetite reduces activity by curtailing the need to
search for food and helps to save energy for the use of the immune
system.
5.5. Anhedonia
Pleasure and wanting are adaptations caused by natural selec-
tion—they motivate organisms to behave in fitness-enhancing
ways (Barron et al., 2010; Berridge and Kringelbach, 2013). The
absence of pleasure and wanting reduces an individual’s motiva-
tion to approach incentive targets (Martins et al., 2017). A typical
depressive symptom is anhedonia—the loss of interest in activities
that used to give pleasure to the individual. It has been suggested
that anhedonia may facilitate rumination: by preventing cognitive
distractions, anhedonia can help the depressed individual focus
their cognitive effort on the underlying problem (Watson and
Andrews, 2002).
Experimental evidence on humans and non-human animals
shows that injecting proinflammatory cytokines into the blood-
stream causes anhedonia (Chang et al., 2009; Dantzer, 2001;
Dantzer, 2006; De La Garza, 2005). Anhedonia is adaptive in sick-
ness behaviour caused by infection, since it makes the individual
decrease their activity, conserving energy to immune function
which facilitates healing (Anders et al., 2013). Thus, reducing anhe-
donia through pharmacological manipulation of central dopamine
signalling (Martins et al., 2017) may not always be in the patient’s
best interest.
5.6. Sleep disorder
Increased need to sleep is typical for SAD. It has been suggested
that it helps conserve energy when conserving energy yields
greater organismal benefit than activity does (Davis and Levitan,
2005; Eagles, 2004). Increased need to sleep is a common sickness
behaviour and it may also occur in other subtypes of depression in
which an organism benefits from conserving energy (Anders et al.,
2013).
The link between stress and depression is well established both
through early life adversity (Cirulli 2017) and through chronic
stress in adulthood (Miller and Raison, 2016). It is possible that
stress causes sleep disorders because people are in their most vul-
nerable and defenseless state when sleeping. A stressed person
typically has an overactive amygdala, which warns the organism
of danger and increases stress hormone levels (McEwen et al.,
2015). This is reflected in the quality of sleep: a stressed individual
sleeps lighter and may wake up due to even the slightest of sounds.
10 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
The rumination related to certain subtypes of depression may
itself cause a sleep disorder, since ruminating keeps neural activity
high and therefore prevents falling asleep (Watson and Andrews,
2002). The brain thus prioritizes a pivotal adaptive problem over
sleep.
5.7. Fatigue
Fatigue induced by infection helps an organism conserve energy
for the immune system (Anders et al., 2013). Fatigue can also be
caused by a chronic lack of sleep (Hur et al., 2012), which is caused
by the sleep disorders typical in certain subtypes of depression. Fati-
gue can therefore be a mere byproduct of other depressive symp-
toms. It can also be adaptive for example in depression induced by
hierarchy conflict, since it helps an individual conserve energy and
reduces the probability of challenging those higher up in hierarchy.
5.8. Anxiety
Anxiety disorders are commonly comorbid with depression epi-
sodes (Gong et al., 2017; Kaufman and Charney, 2000). Anxiety is
one way in which the body communicates an impending danger.
It keeps an individual alert, makes them avoid threatening situa-
tions and temporarily improves intellectual and physical perfor-
mance (Marks and Nesse, 1994). Anxiety can therefore be an
adaptive preparatory response to a threatening situation. If anxiety
becomes uncontrollable, however, it fails to prepare one optimally
for the future and can instead become a negative influence. In cir-
cumstances like this, anxiety loses its adaptive nature, justifying
the label anxiety disorder.
5.9. Psychomotor agitation or retardation
Some depressed individuals show psychomotor agitation.
When coupled with depression, psychomotor agitation seems to
be a byproduct of anxiety and is devoid of any adaptive compo-
nent. Other depressed individuals show psychomotor retardation,
which manifests as decelerated cognitive and psychomotor func-
tioning (Buyukdura et al., 2011). This may be a byproduct of
increased allocation of cognitive capacity to rumination. Psy-
chomotor retardation can also be a pathological outcome of low-
grade peripheral inflammation.
5.10. Pessimism
Pessimism is a common depressive symptom. Research sug-
gests that under normal circumstances, people are overly opti-
mistic about future and their abilities but that failure and
depression dissolve this optimism bias (Alloy and Ahrens, 1987).
This decreases lofty aspirations in situations in which failure is
more likely than success. Pessimism is adaptive in situations in
which previous failures predict future ones (Keller and Nesse,
2006). Pessimism can, however, be maladaptive if a person’s
understanding of their abilities and opportunities has become
excessively negative.
5.11. Self-accusations
An individual may feel strong guilt about the negative event that
triggered their depressive episode. Self-accusations and feelings of
guilt make an individual reflect how their own behaviour led to
the present outcome, helping them to steer clear of similar out-
comes in the future. The greater the role of the individual’s own
actions in the events, generally the greater are the resulting feelings
of guilt (Keller and Nesse, 2006). The symptoms become maladap-
tive if the self-accusations are unfounded or unreasonably strong.
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
5.12. Low self-esteem
Since self-esteem regulates an individual’s status in social hier-
archy and vice versa, the decreased self-esteem which results from
a defeat in hierarchy conflict temporarily prevents an individual
from challenging those higher up in the hierarchy, protecting the
individual from new problems. In contrast to popular belief, high
self-esteem per se is unlikely to translate to personal success.
Instead, it seems that high self-esteem is a result of success in
social hierarchy (Baumeister et al., 2003).
6. Discussion
The traditional way of diagnosing clinical depression is based
on the number and duration of symptoms (listed in Section 5) that
the patient has. This is nonsensical from an evolutionary point of
view (Rantala et al., 2017). The current diagnostic criteria for clin-
ical depression are completely arbitrary. When examined from an
evolutionary psychological point of view, depression’s short-term
harmfulness to an individual’s everyday life is an insufficient crite-
rion for classifying depression as a mental disorder.
The ultimate level of analysis shows how specific subtypes of
depression can constitute adaptive responses to certain instances
of life adversity. That is why the classification between clinical
depression that needs to be treated and an adaptive state of low-
ered mood which need not be treated should be based on whether
or not the symptoms help an individual cope with the adverse life
event which caused the lowered mood. Only when the symptoms
are excessive and fail to serve their adaptive purpose can a patient
be diagnosed with pathological depression that has to be treated.
Even low mood or emotional pain that is characteristic of major
depressive disorder may not always be a negative symptom that
should be treated—despite its potential to cause momentary dis-
tress for a patient. This is because low mood may be an adaptive
response to certain situations: for example, low mood after a fail-
ure to achieve certain goals in life makes an individual rethink
whether their goals match their actual abilities (Watson and
Andrews, 2002). Likewise, following the loss of status in hierarchy
conflict, low mood may be an adaptive signal of submissiveness
(Price et al., 1994), thus playing an important role in social commu-
nication (Watson and Andrews, 2002).
It is useful to bear in mind that although a certain behavioural
response was adaptive in the EEA, it may not be so in a modern
environment (Del Giudice and Ellis, 2016). Suicidal ideation, for
example, may have constituted an adaptive response under certain
circumstances in the EEA due to its potential to improve inclusive
fitness, but the benefit of this behavioural strategy is lower in mod-
ern Western societies which have organizational systems of insti-
tutional care for the elderly. Consequently, it is essential to
identify the adaptive component, if any, of a patient’s depressive
symptoms in their de facto environment, basing further treatment
evaluations on the fundamental question of ‘current utility’
(Bateson and Laland, 2013). The symptoms should not be treated
pharmacologically if they assist the patient in solving the adaptive
problem which triggered the depressive episode (Rantala et al.,
2017). Instead, the patient should be assisted in their attempts to
solve the problem, accompanied with advice that prevents the
reactive depressive state from exacerbating into a maladaptive
inflammatory state in the body. In cases where a depression epi-
sode is a functional response to adversity, suppressing it medically
could be harmful.
Additional complexity may follow when a depressed patient
faces several consecutive adverse life events. The resulting combi-
nation of symptoms may fail to serve their function of an adaptive
response to any single adverse life event. Due to an excess of
 M.J. Rantala et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
adverse life events, the symptoms may also become too severe as to
serve their original adaptive purpose. In situations like these, the
symptoms may cause a state that can be classified as a mental dis-
order. The reason why an evolutionarily shaped adaptive state of
lowered mood leads so often to pathological depression is likely
to be caused by the stark mismatch between the current environ-
ment and the ancestral environment in which these behavioural
features evolved. In addition, modern lifestyle has caused
increased inflammatory dysregulation and chronic stress, making
it more likely that low mood caused by adverse life events esca-
lates into an episode of major depressive disorder (Hidaka, 2012).
7. Conclusions
Depression treatment should be made more sophisticated by
identifying which subtype the depressive episode belongs to. If it
appears to be a response to an adverse life event, it should be eval-
uated whether the symptoms are adaptive or whether the depres-
sive episode has exacerbated into pathological depression, coupled
with features of sickness behaviour. In the future, it should also be
standard routine in psychiatry to take a blood test from patients to
measure hs-CRP (which reveals hidden inflammation) (Kohler-
Forsberg et al., 2017) and stress hormone levels to help identify
(1) what is the subtype of the depressive episode, (2) whether
the depressive episode has maladaptive features of sickness beha-
viour and (3) to track the effectiveness of treatment. These tests
would also help to examine the success of any therapeutic
interventions.
Evidence suggests that different adverse events lead to different
symptom profiles (Keller et al., 2007; Keller and Nesse, 2005; Keller
and Nesse, 2006). With future developments, depression treat-
ments should employ an analysis of symptom patterns together
with an in-depth interview and a blood test to verify the subtype
of depression and whether an adaptive mood change has changed
to a non-adaptive depressive episode. However, before we can
develop a reliable matrix of symptom profiles that helps identify
each depressive subtype, follow-up studies and studies replicated
in different populations are needed.
If an adaptive mood change after an adverse life event has exac-
erbated into a maladaptive episode which has symptoms of sick-
ness behaviour, and if inflammation has been the causal factor
behind this change, then the most effective treatment is to reduce
inflammation. Inflammation can be reduced effectively by lifestyle
interventions that mimic the life of hunter-gatherers (e.g.
inflammation-reducing diet and exercise) (Hidaka, 2012) and/or
pharmacologically by anti-cytokine therapy (Kohler et al., 2014).
Interestingly, even psychotherapy has been shown to reduce
inflammation (da Silva et al., 2016). In case the mood change is
adaptive, the most effective intervention would be to help the
patient resolve the adaptive problem that triggered the mood
change. For example, if rumination helps a depressed individual
avoid similar mistakes or situations that triggered the depressive
episode (while also facilitating social and psychological problem
solving: Andrews and Thomson, 2009), then interventions should
further help to find solutions to the social and/or lifestyle prob-
lem(s) that caused the depressive episode. Cognitive behavioural
therapy (CBT) based on evolutionary psychology can provide fur-
ther treatment options, as even traditional CBT has been also found
to reduce inflammation (Gazal et al., 2013; Keri et al., 2014).
Subtyping depression episodes based on the original trigger(s)
of the mood change would help to find the best customized inter-
ventions for each patient. For example, in the case of depression
induced by chronic stress, interventions should seek to reduce
stress levels either by using cognitive psychotherapy, exercise or
medication such as cannabis, which has been shown to reduce
Please cite this article in press as: Rantala, M.J., et al. Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate func-
tions. Brain Behav. Immun. (2017), https://doi.org/10.1016/j.bbi.2017.10.012
11
stress reactivity (Cuttler et al., 2017). As for depression induced
by loneliness (in which stress hormone levels are also elevated
(Cacioppo et al., 2011), the intervention should focus on reducing
loneliness (cf. Saeri et al., 2017), thus alleviating the stress.
Because of the novelty of the model presented in this article, it
is obvious that at this stage there are no studies systematically
testing whether depression subtypes based on evolutionary psy-
chiatry differ from each other in treatment responsiveness with
regard to commonly used interventions (antidepressant or psy-
chotherapy). It is expected that the 12 depression subtypes vary
in treatment responsiveness due to stress hormone and immune
function differences in each subtype. Differences in treatment
responses could also be expected when treating patients with an
adaptive mood change as opposed to patients with maladaptive
depression episodes that include symptoms of sickness behaviour.
Using an intervention to reduce symptoms for patients with an
adaptive mood change might not be beneficial if the symptoms
help the individual to cope with the adverse life event which
caused the lowered mood. In cases like these, the effectiveness of
the intervention should not be evaluated as a reduction of symp-
toms. Instead, the evaluation should be based on whether the
intervention helped the individual to cope with the adverse life
event which caused the lowered mood. Thus, the focus of a treat-
ment regime based on evolutionary psychiatry focuses on an indi-
vidual’s long-term mental and physical well-being instead of
myopically fixating on the short-term alleviation of symptoms.
We hope that the present subtyping based on an evolutionary
and immunological approach to depression will prove its practical
utility on a vast scale, helping to develop more effective therapeu-
tic treatments and drugs that are targeted to the specific subtypes
of depression identified here.
Acknowledgment
I.K. was supported by the Estonian Research Council (PUT-
1223).
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