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sufficient recovery, the term chronic stress-induced
exhaustion disorder or exhaustion disorder (SED) may
be used. SED is classified as an illness in the Swedish
version of ICD-10 since 2004. The term SED is used
in this paper when referring to studies that have used
diagnostic criteria for SED. The diagnostic criteria for
SED are described in Table I.
There are equivalents to SED in the international li-
terature, such as chronic burnout (10), clinical burnout
(9, 11), stress-related exhaustion (12), job stress-related
depression (13, 14) and, possibly, neurasthenia (15).
Clinically, the diagnosis SED is often subsumed under
depression or adjustment disorder. However, the main
symptom in SED is exhaustion, and not depressive
mood. In SED symptoms of depression and anxiety can
be present, but are rarely the major complaint. Typical
of SED are markedly reduced mental energy, lack of
endurance, and increased time needed for recovery
after mental effort. Somatic symptoms are common.
Many patients experience symptoms of the digestive
tract, nausea, gas and indigestion, headaches, and dizzi-
ness. These symptoms often decline with time (16).
Pathology of chronic stress-induced exhaustion
disorder
Cognitive impairment and structural differences in the
brain. Imaging studies comparing patients with SED
and controls have shown structural and functional
differences in the brain (5, 17–20). Patients with SED
demonstrate thinning of the prefrontal cortex (PFC),
the anterior cingulate cortex (ACC), left superior tem-
poral gyrus (STG), and reduced volumes of caudate
and putamen in the basal ganglia. Thinning of the PFC
and reduced volumes of caudate was correlated with
perceived stress, implying a possible causal link (5). In
addition, thickness of PFC as well as altered functional
couplings in the emotion- and stress-processing lim-
bic networks was correlated with an impaired ability
to down-modulate response to emotional stress (17).
Prolonged stress has been shown to cause morpholo-
gical changes in the hippocampus, including suppres-
sed production of new neurones in the dentate gyrus
regions of the hippocampus (21). These changes cor-
respond to deficits in spatial navigation and episodic
memory (22, 23).
The brain areas with altered volumes in patients
with SED are important for cognitive function, such
as attention, executive functions and memory. Similar
structural changes have been found in persons who
have experienced early life traumas and among persons
with PTSD (5).
Cognitive impairment may last for several months or
even years, in patients with SED (24). In a prospective
cohort study, patients with work-related stress per-
formed worse than controls when assessing memory,
mental speed and executive function in a neuropsy-
chological test at follow-up 1 year after inclusion (25).
Long-lasting cognitive impairment is also supported
by a magnetic resonance imaging (MRI) study de-
monstrating that thinning of PFC among patients with
SED normalized during a follow-up of 1–2 years (7).
Prolonged course and downregulation of the hypot-
halamic pituitary adrenal axis. During stress 2 main
systems are activated; the sympathetic system, and the
hypothalamus, pituitary and adrenal axis (HPA axis).
When the HPA axis is activated cortisol is released
from the adrenal gland. Patients with SED seem to
have decreased ability to mount a stress response
in the HPA axis. Testing the HPA axis by measuring
cortisol response to corticotrophin-releasing hormone
(CRH) after dexamethasone pre-treatment demon-
strated blunted cortisol response in women with SED
compared with controls, both at baseline and after 7
years’ follow-up (13, 14). This finding may support the
observed prolonged course that the patients experience
(13, 26). The finding is also in accordance with a meta-
Table I. Criteria for chronic stress-induced exhaustion disorder (SED) according to the Swedish National Board of Health and Welfare a
Criteria
A. Physical and mental symptoms of exhaustion during at least 2 weeks. The symptoms have developed in response to 1 or more identifiable stressors present
for at least 6 months.
B. The clinical picture is dominated by markedly reduced mental energy, as manifested by reduced initiative, lack of endurance, or increased time needed for
recovery after mental effort.
C. At least 4 of the following symptoms have been present, nearly every day, during the same 2-week period:
• Concentration difficulties or impaired memory
Markedly reduced capacity to tolerate demands or to work under time pressure
• Emotional instability or irritability
• Sleep disturbance
• Marked fatigability or physical weakness
• Physical symptoms, such as aches and pains, palpitations, gastrointestinal problems, vertigo or increased sensitivity to sound
D. The symptoms cause clinically significant distress or impairment in occupational, social or other important respects.
E. The symptoms are not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a physical illness/injury (e.g.
hypothyroidism, diabetes, infectious disease).
a
Criteria A–E must be fulfilled to diagnosis SED. Initially, there was a criterion F, which excluded cases of major depression. This criterion has since been removed,
since depressive symptoms are a common complication of exhaustion disorder. A concurrent depression could thus be seen as comorbid, rather than as an
exclusion criterion for SED.
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