Download relationship between food, serotonin and affective

Food and mood: relationship between
food, serotonin and affective disorders
Wallin MS, Rissanen AM. Food and mood: relationship between food,
serotonin and affective disorders.
Acta Psychiatr Scand 1994: Suppl377: 36-40.
The relationship of food and eating with affective and other clinical
disorders is complex and intriguing. Serotoninergic dysfunction in
seasonal affective disorder, atypical depression, premenstrual syndrome,
anorexia and bulimia nervosa, and binge eating disorder is reviewed.
Patients exhibiting a relationship between food and behaviour are found
in various diagnostic categories. This points to a need to shift from
nosological to functional thinking in psychiatry. It also means application
of psychopharmacological treatments across diagnostic boundaries. The
use of phototherapy and psychotropic drugs ( M A 0 inhibitors and
selective serotonin reuptake inhibitors like fluoxetine) in these disorders
is discussed.
Der Mensch ist, was er ii3t (Man is what he eats)
- Ludwig Feuerbach (1804-1872)
Through the act of food intake, the biological and
cultural factors of the external world meet the biological and psychological factors of the individual's internal world. Eating is influenced by various
factors far beyond the mere nutritional value of the
food and the dietary needs of the individual. Such
factors include economic conditions, culturally-imposed ideals of body shape, life events, stress,
mood states, learned preferences and aversions,
attributes, beliefs and cognitions, and other psychological conditions, sensory/hedonistic aspects of
food, and brain chemistry (1).Eating is more than
just food intake: eating plays an important role in
our social interactions, and it can also be used to
alter emotional states, and even to influence brain
function.
Appetite and satiety
Appetite is essential for the maintenance of life. It
is also a biopsychosocial phenomenon that arises
as the end product of the intimate and complex interactions between the physiological processes of
the individual and the environment (1). The appetite control system regulates energy and nutrient
intake in order to maintain the homeostasis of the
biological processes, and to ensure the adaptation
of the individual to the environment. However, the
36
M. S. Wallinlx2, A. M. Rissaned
' Eating Disorders Unit, Outpatient
Department of Psychiatry, University of
Helsinki, Finland
National Public Health Institute,
Department of Mental Health, Helsinki,
Finland
Key words: Serotonin, eating disorders,
obesity, seasonal affective disorder,
depression, premenstrual syndrome,
fluoxetine, phototherapy
Matti Wallin, M.D., Eating Disorders
Unit, Outpatient Department of Psychiatry, University of Helsinki, Tukholmankatu 8 C , FIN-00290 Helsinki,
Finland
regulation of the balance between nutritional requirements and nutritional supply is not symmetrical. In the case of undersupply of food, the regulatory mechanisms generate the drive to eat, or
hunger. In contrast, in our affluent societies the
abundant supply of palatable food with a high density of energy (high fat and/or carbohydrate content) tends to promote overconsumption and to result in weight gain, especially in individuals with
genetic or other vulnerability to develop obesity.
Therefore, the appetite control system shows a
strong defence against undereating, but a rather
weak defence against overeating.
Several neurotransmitters participate in the regulation of appetite, including serotonin (2), noradrenalin, cholecystokinin (CCK), endogenous opioid peptides, neuropeptide Y, and peptide YY. The
paraventricular and ventromedial nuclei of the
medial hypothalamus are involved in controlling
energy balance, while the circadian pattern of eating is determined by the suprachiasmatic nucleus
(3). Serotoninergic stimulation of these nuclei results in satiety and leads to the termination of eating.
Dietary tryptophan and brain serotonin
Serotonin, or 5-hydroxytryptamine (5-HT), is a neurotransmitter that plays an important role in the
regulation of circadian and seasonal rhythms, the
control of food intake, sexual behaviour, pain, aggression, and the mediation of mood. Dysfunction
Food and mood: Relationship between food, serotonin and affective disorders
of the serotoninergic system has been found in a
wide array of psychiatric disorders: depression,
anxiety, disorders of the sleep-wake cycle, obsessive-compulsive disorder, panic disorder, phobias,
personality disorders, alcoholism, anorexia nervosa, bulimia nervosa, obesity, seasonal affective disorder, premenstrual syndrome, and even schizophrenia.
With respect to the relationship between nutrition and behaviour, 5-HT is interesting in many
ways. The synthesis of serotonin in the central
nervous system depends on the dietary supply of
the precursor amino acid tryptophan (TRP) (4). The
first step in the synthesis of 5-HT is the uptake of
TRP from the blood across the blood-brain barrier
into the brain. In the neuron, TRP is converted to
5-hydroxytryptophan catalyzed by the enzyme
tryptophan hydroxylase. Finally, 5-hydroxytryptophan is converted by the enzyme 5-hydroxytryptophan decarboxylase to serotonin. The rate-limiting step in the synthesis of 5-HT is the hydroxylation of tryptophan to 5-hydroxytryptophan. The
enzyme tryptophan hydroxylase has a poor affinity for its substrate TRP, i.e., the enzyme is relatively
unsaturated at the TRP concentrations normally
found in the brain. Therefore, variations in brain
TRP levels can change the substrate saturation of
tryptophan hydroxylase, and as a consequence,
rapidly alter the production rate of 5-HT (5).
The ingestion of TRP leads to rapid elevation in
brain TRP and 5-HT levels. However, TRP and other large neutral amino acids (LNAAs: valine, tyrosine, leucine, isoleucine and phenylalanine) share
a common competitive transport mechanism for
crossing the blood-brain barrier. Thus, the transport of TRP to the brain does not depend on the
absolute plasma level of TRP but on the plasma level of TRP in relation to the other large neutral amino acids. The plasma ratio of TRP to the other
LNAAs is significantly influenced by macronutrient intake. A protein-rich meal contains relatively
little TRP in contrast to the other amino acids,
which compete with TRP for entry into the brain,
and little TRP enters the brain. In contrast, highcarbohydrate (very low-protein) meals stimulate
insulin secretion, which increases the uptake of
LNAAs into muscle cells. As a result, the plasma
ratio of TRP to LNAAs is greatly increased, and
more TRP enters the brain with an increased 5-HT
synthesis as a result (6).
The importance of the role of TRP as the precursor of 5-HT is demonstrated by the fact that TRP
depletion has been shown to cause a rapid lowering of mood in normal males (7). TRP availability
is also crucial to the action of antidepressants (8).
Carbohydrate craving
Increased serotoninergic activity results in the reduction of energy intake. 5-HT has also been postulated to play a role in macronutrient choice, with
reduced serotoninergic activity leading to a preference for carbohydrates. According to the hypothesis of "carbohydrate craving", some individuals
have a strong need to consume carbohydrate-rich
food (9, 10). This might be explained by the increased brain 5-HT synthesis following carbohydrate intake. These patients seem to prefer carbohydrates as a "self-medication" attempt, because
they suffer from disorders in which deficient serotoninergic activity has been demonstrated, and because they typically report feeling better after ingestion of carbohydrates (11). However, the concept of carbohydrate craving has been criticized
(12, 13). Despite its limitations, the hypothesis may
be clinically helpful. The patient's eating behaviour,
especially dietary preference for carbohydrates,
gives the clinician some clues about the underlying pathophysiology. This in turn may help in
choosing the therapeutic approach.
Eating disorders
The prevalence of eating disorders has increased
strikingly in recent years. Anorexia nervosa is characterised by severe weight loss caused by deliberate selfstarvation, while bulimia nervosa is characterised by recurrent episodes of compulsive
overeating, followed by attempts to avoid the consequences of positive energy balance by self-induced vomiting or other drastic means. The nonpurging form of bulimia, also called the binge eating disorder (14,15), is often associated with obesity. A certain type of obesity, the so-called carbohydrate-craving obesity, is associated with excessive carbohydrate intake, which might be caused
by a defective feedback inhibition of carbohydrate
intake after its ingestion (3,9).
The background of eating disorders is complex,
and probably involves dysregulation of several
neurotransmitter systems. The involvement of impaired hypothalamic serotonin function in these
disorders is well documented (3,16). Such dysfunction could contribute to the onset, progression and
persistence of symptoms. In particular, there is
good evidence from experimental and clinical stu
ies to suggest that serotoninergic dysfunction creates vulnerability to recurrent episodes of large
binge meals in bulimic patients. Similarly, serotoninergic drugs like fluoxetine have been shown
to be effective in controlling bulimic episodes and
binge eating (17). Fluoxetine and other serotoninergic drugs, among them fenfluramine, are also
used in the treatment of obesity (18,19,20).
4-
37
Wallin and Rissanen
There is also evidence that bulimic behaviour has
a mood-regulating function, i.e., binging and purging are used by the patients to relieve psychic tension. However, bulimic behaviour seems to have
different functions for different subgroups (21).
Binging may be used to relieve anxiety, but it may
result in an increase in guilt and depression (22).
Seasonal affective disorder
A typical patient with seasonal affective disorder
(SAD) suffers from lack of energy, depressive
mood, social withdrawal, hypersomnia, and hyperphagia with resulting weight gain, during the dark
winter months (23). Often the patient is more disturbed by the lack of energy than by the low mood
itself. Women are more likely than men to develop SAD. Craving for carbohydrates has been observed in two-thirds of the patients, whose major
depression has a seasonal pattern, compared to
one-fourth of patients without seasonal periodicity (24).
However, only some SAD patients have seasonal changes of body weight, which is related to a difference between summer and winter in starch-rich
food intake (25).
These patients typically consume food with a
high glycemic index like pasta, bread, potatoes, rice
and corn during winter. They often report doing
this to elevate mood and alleviate fatigue. While
normal controls feel sedated following carbohydrate ingestion (26), SAD patients report activation
(27). Carbohydrate craving of SAD patients is suppressed by summer, bright light treatment (251,
tryptophan, fenfluramine, monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake
inhibitors like fluoxetine (23).
Serotonin is involved in the pathophysiology of
SAD. Hypothalamic 5-HT content falls in the winter even in normal individuals (3). The transmission of information about seasonal and circadian
rhythms is thought to proceed from the retina to
the circadian pacemaker in the suprachiasmatic
nucleus, and then to the paraventricular nucleus
in the medial hypothalamus (25). Photoperiod
can thus influence various metabolic processes.
Through retinal mechanisms, light therapy might
lead to decreased release of noradrenaline and/or
increased release of serotonin in the medial hypothalamus, which in turn would alleviate the atypical
symptoms of hyperphagia and hypersomnia in
SAD (25).The decrease of environmental light during winter may cause a greater drop of 5-HT in individuals susceptible to developing SAD. The role
of CNS 5-HT deficiency in SAD is also supported
by good treatment results with serotonin agonists.
However, bright light treatment is considered to be
the method of choice (23).
The SAD patients also show a high rate of major affective disorder, including SAD, and alcohol
abuse in their families, suggesting a genetic or familial origin of the disorders of the serotoninergic
system. According to our clinical experience, many
SAD patients also exhibit comorbidity with other
disorders linked to serotoninergic dysfunction, like
premenstrual syndrome, alcohol abuse, and overweight.
Premenstrual syndrome
Premenstrual syndrome (PMS) refers to emotional, behavioural and somatic symptoms experienced
during the late luteal phase of the menstrual cycle.
Many women have premenstrual symptoms, but
only 2 to 10 % of menstruating women are estimated to suffer from symptoms severe enough to interfere with normal functioning (28). ln the Diagnostic and Statistical Manual of Mental Disorders,
Third, Revised Edition (DSM-III-R) of the American Psychiatric Association the syndrome is called
late luteal phase dysphoric disorder. The typical
symptoms are depressive mood, mood swings, irritability, fatigue, concentration difficulties, hypersomnia, anxiety, and increased appetite.
Many women with PMS report carbohydrate
craving during the premenstrual week (291, but
some of them also show a preference for carbohydrates throughout the menstrual cycle. There is a
high rate of comorbidity with other psychiatric diagnoses, especially affective disorders (30).
The etiology of PMS is unknown, but theories
and treatments abound. These theories include dysfunction of the serotoninergic system, circadian
rhythm abnormalities, altered levels of estrogen
and progesterone, and disorder of the renin-angiotensin-aldosterone system.
PMS and major depression may be related. This
is suggested by the high rate of a history of depression, and an increased risk of developing depression later in PMS patients. These two disorders
may therefore have some abnormalities in common. According to the phase-advance hypothesis
of affective disorders, the central neural oscillator
in the hypothalamus regulating the circadian
rhythms of the body is phase-advanced (shifted
earlier) in relation to the sleep-wake cycle (31). A
similar phase-advance of circadian rhythms has
also been observed in PMS, and consequently,
bright light treatment in the evening (32) and sleep
deprivation (especially late-night partial sleep deprivation) (31) have been effective.
In view of the critical role of serotonin in the regulation of circadian rhythms and in the regulation
of appetite, carbohydrate craving in PMS can be
seen as an attempt at self-medication. In accordance
with this hypothesis, the selective serotonin re-
Food and mood: Relationship between food, serotonin and affective disorders
uptake inhibitor fluoxetine effectively suppresses
carbohydrate craving and other PMS symptoms
(28).
Atypical depression
Some depressive patients do not have classical
symptoms of depression (e.g. loss of appetite, decreased sleep, psychomotor agitation), but instead
show hyperphagia, hypersomnia, extreme fatigue,
chronic sensitivity to rejection, and mood reactivity (33, 34). The lifetime prevalence of this atypical
depression is estimated to be 0.7 O/o (35). Compared
to subjects with major depression without atypical
features, subjects with this disorder have a younger
age of onset, more psychomotor retardation, more
comorbidity with panic disorder, drug abuse or
dependence, and somatization disorder (35). Atypical depression might therefore be a distinct subtype of major depression that is responsive to treatment with MAOIs (33, 34). Antidepressants may
also be useful in mildly depressed patients with
atypical features (36).
Reversed neurovegetative signs of hypersomnia
and weight gain, in combination with motor retardation, fatigue and volitional inhibition, are often
seen in bipolar depression. This form of depression
is also called anergic depression (37, 38). MAOIs,
either alone or combined with lithium, are effective in treating this condition (37,38).
Another subtype of atypical depression is hysteroid dysphoria (33,34,39), which is characterized
by histrionic and narcissistic features. Individuals
with this disorder, who are usually but not exclusively women, show a romantic preoccupation,
seeking romantic attachment, approval and praise.
They exhibit rejection sensitivity and often develop episodes of atypical depression after the loss of
a romantic attachment. ”Self-medication” with
sweets or chocolate is reported in hysteroid dysphoria (39). It is not clear, however whether the
patients crave carbohydrates for their gratifying
aspects (sweetness, high fat content, palatability),
or whether this is an attempt to regulate brain serotonin and thereby to elevate mood (39).
Clinical implications
There is one subgroup of patients who exhibit characteristic symptoms compatible with the hypothesis of the relationship between food, mood and behaviour. In these ”food and mood” disorders, serotonin deficiency in the CNS seems to play a major role, and eating behaviour can be seen as a selfhealing attempt. However, this self-medication is
often not effective enough and may even lead to a
vicious circle, and pharmacological interventions
are called for.
The effects of food on mood and vice versa in
ordinary clinical populations often go unrecognized. These patients often report that their disorder has rarely been recognized by their doctor. The
patients can describe how, in contrast to their ”ordinary” psychological problems, their particular
symptoms of winter depression, lack of energy and
carbohydrate craving are “beyond their control”.
They may even spontaneously recognize the selfmedication aspect of their eating behaviour.
It is therefore important for the clinician to be
aware of these connections. When compiling the
patient’s history, the clinician should ask the crucial questions about the patient’s mood, eating behaviour, possible dietary preferences, weigh t
changes, seasonal patterns, family history of affective disorders, eating disorders, obesity, and alcoholism, and the effects of food on mood.
Because of the overlap between and coexistence
of the various syndromes (comorbidity), the prevalence rates of these “food and mood” disorders in
the general population are difficult to estimate. For
seasonal affective disorder, anorexia and bulimia
nervosa, binge-eating disorder, premenstrual syndrome and atypical depression, we can put forward
a very rough estimate that at least 2 to 5 per cent
of the population are suffering from these disorders. Most patients with a clear connection between
eating and their affective states also have signs of
the disorders discussed in this paper. A female patient with a family history of depression and alcoholism might, for instance, describe symptoms of
carbohydrate craving (preference for pasta, bread,
pastry, bananas, chocolate), overweight, PMS and
winter depression.
Knowledge of the symptom profile of the patient
allows the cIinician to plan a tailored treatment that
might consist of psychoeducation, cognitive-behavioural therapy or other form of psychotherapy, dietary therapy, bright light treatment, or pharmacotherapy with selective serotonin reuptake inhibitors or M A 0 inhibitors. Patients exhibiting a relationship between food and behaviour are found
in several diagnostic categories. This fact underscores the need for a shift from traditional nosological to modern functional thinking in psychiatry,
and consequently, the application of psychopharmacological treatments across present diagnostic
boundaries (40).
The relationships between food, eating apd
mood are complex and intriguing, and further
study is clearly needed.
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