[Frontiers in Bioscience E4, 2722-2730, June 1, 2012]

Emotional dysfunction as a marker of bipolar disorders

Chantal Henry1,2,3,4, Mary Phillips5,6,7, Ellen Leibenluft8, Katia M’Bailara9,10, Josselin Houenou1,2, Marion Leboyer1,2,3,4
1
INSERM, U955, IMRB, departement de Genetique, Creteil, F-94000, France, 2Universite Paris-Est, Faculte de Medecine,
IFR10, Creteil, F-94000, France, 3AP-HP, Hopital Henri Mondor-Albert Chenevier, Pole de Psychiatrie, Creteil, F-94000,
France, 4Fondation FondaMental, Fondation de cooperation scientifique, France, 5Department of Psychiatry, Western
Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 6Department of Psychological
Medicine, Cardiff University School of Medicine, Cardiff, UK, 7Institute of Psychiatry, King's College London, UK, 8Emotion
and Development Branch, Intramural Research Program, National Institute of Mental Health, Department of Health and Human
Services, Bethesda, MD, USA, 9Laboratoire de psychologie, Universite Victor Segalen, Bordeaux 2, France, 10Departement de
Psychiatrie Adulte, CHS Charles Perrens, Bordeaux, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Clinical data regarding emotional reactivity in bipolar and major depressive disorders
3.1. Emotional reactivity in euthymic bipolar patients
3.1.1. Self-report studies
3.1.2. Experimental studies
3.2. Emotional reactivity during manic and mixed episodes
3.2.1. Self-report studies
3.2.2. Experimental studies
3.3. Evaluation of emotional reactivity during depression
3.3.1. Identification of two subtypes of bipolar depression: Self-report studies
3.3.2. Emotional reactivity in major depressive disorder: Self report and experimental studies
4. Summary of clinical data on emotional reactivity during mood disorders
5. Brain imaging and abnormal emotional reactivity in mood disorders
6. Neurochemical systems, genes and emotional reactivity
7. Conclusion
8. References

1. ABSTRACT 2. INTRODUCTION

Background assessment of emotional reactivity, Little is known about the interaction between
defined as rapid emotional responses to salient mood and emotional reactivity in people who suffer from
environmental events, has been neglected in mood major affective disorders (major depressive disorder or
disorders. This article reviews data showing the relevance bipolar disorder). Mood is a diffuse feeling state that lasts
of using emotional reactivity to better characterize bipolar hours, days, or longer, while emotions are short-lived
mood episodes. Method We reviewed clinical data on responses to stimuli that elicit adaptive responses (1).
emotional reactivity during all phases of bipolar disorders Emotional reactivity refers to the threshold for, and
(euthymic, manic, mixed and depressive states) and brain- magnitude of, emotional responses to these salient stimuli.
imaging, neurochemical, genetic studies related to These emotional responses typically involve changes in
emotional reactivity disturbances. Result Euthymic bipolar several response systems, including perception, feelings,
patients show mild abnormalities (hypersensitivity to expressive behavior, and peripheral and central physiology.
emotional stimuli and higher arousability) in comparison to Emotional regulation may be part of an individual's coping
controls. Both manic and mixed states are characterized by style, while emotional dysregulation may impair
a significant increase in emotional reactivity. Furthermore, functioning and be associated with a psychiatric disorder.
emotional reactivity may discriminate between two types of However, the diagnostic criteria for mood disorders only
bipolar depression, the first being characterized by center on sustained mood disturbances i.e., sadness in
emotional hypo-reactivity and global behavioral inhibition, depressive episodes and elevated, expansive, or irritable
the second by emotional hyper-reactivity. Brain-imaging mood in manic episodes (2).
studies can help to identify the underlying mechanisms
involved in disturbances of emotional reactivity. Historically, most studies of affective disorders
Conclusion Emotional reactivity can be used to refine more focused on mood characteristics; the study of emotion is
homogeneous pathophysiological subtypes of mood only a recent development in this area, fostered by
episodes. Future research should explore possible tremendous advances in understanding the basic science of
correlations between biomarkers, response to treatments emotion (3). Moreover, the advent of neuroimaging
and these clinical phenotypes. techniques has made it possible to examine the neural

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circuitry mediating emotional responses and emotion To test the sensitivity of euthymic bipolar
regulation. An increasing number of studies show that patients to daily life-events, we evaluated euthymic bipolar
mood disorders are associated with specific structural and patients (type I and II) and control subjects using two self-
functional abnormalities in the neural systems regulating rating scales, the Affective Lability Scale (ALS) (11) and
emotion (4). Ironically, then, researchers use fMRI to study the Affect Intensity Measure (AIM) (12). ALS items assess
the pathophysiology of mood disorders, but to do so they the subject’s perception of their ability to shift from what
use paradigms that rely on evoking emotional responses, they consider to be their normal (euthymic) mood to
rather than moods, because the time frame of emotions is affective states such as anger, depression, elation and
particularly well-suited for study within the fMRI anxiety over a short time frame (a day, a few hours or even
environment. Therefore, when interpreting the results of a few minutes). It measures the rapid instability of mood.
functional brain-imaging studies in mood disorders, it is AIM, more focused on the intensity of emotional responses,
important to understand the links between mood episodes assesses individual differences in emotional reactivity
and emotional reactivity. As a corollary, more research is regardless of the hedonic tone of the stimuli. Items include
needed on the nature of emotional reactivity in patients statements such as, “When I solve a small personal
with mood disorders. problem, I feel euphoric” and “When I do feel anxiety, it is
normally very strong”. The two scales were built to assess
Moods and emotions appear to be interconnected affective dimensions as traits independent of clinical status.
in that moods may potentiate emotions of a similar type Although they assess different aspects of emotional
(e.g. sad mood exacerbates emotional reactivity to negative responses, these two scales are highly correlated since the
stimuli). However, some data do not support this higher the reactivity, the higher the lability (13).
hypothesis (5), and the relationship between mood and
emotional reactivity in bipolar disorder is complex since We found that affective intensity and lability of
some episodes are associated with both depressed and emotions in response to daily life events were markedly
elevated mood (mixed states, dysphoric mania). higher in euthymic bipolar subjects (n=179) than controls
(n=86) (respectively p=0.006; and p<0.0001) (13).
The purpose of this review is to better understand Compared to controls, bipolar patients report being more
interactions between mood episodes and emotional reactive in daily life to both pleasant and unpleasant
reactivity. First, we review the clinical data on emotional emotional stimuli.
reactivity in all phases of bipolar disorder (euthymic,
manic, mixed and depressive states) and in major Using an experience sampling method, Myin-
depressive disorder. We have classified data as those Germeys et al. (14) found that bipolar patients differ from
obtained using clinical tools (mostly self-reports) and those those with major depression in their emotional reactivity to
obtained from mood induction experiments or tasks daily life stress. Specifically, they found that, compared to
exploring the interference of emotional information with controls, patients with history of major depressive episodes
cognitive processes. Second, we review results from brain- had increased negative emotional reactivity and,
imaging, neurochemical, and genetic studies that can help surprisingly, patients with bipolar disorder had decreased
to elucidate the pathophysiology of the disturbed emotional positive affect (14). However, in this study bipolar patients
reactivity in bipolar disorder. Finally, using emotional in partial remission were included, meaning that sub-
reactivity as a key dimension, we propose a new model to syndromal depressed symptomatology might have
better define bipolar disorders that could be useful in influenced the results.
guiding both pathophysiological and pharmacological
studies by providing more homogeneous sub-groups. Several studies have assessed the relationship
between personality and bipolar disorder. Two personality
3. CLINICAL DATA REGARDING EMOTIONAL dimensions, neuroticism and extraversion, have received
REACTIVITY IN BIPOLAR AND MAJOR particular attention. Neuroticism is characterized by
DEPRESSIVE DISORDERS proneness to anxiety, emotional instability, and self-
consciousness, whereas extraversion involves positive
3.1. Emotional reactivity in euthymic bipolar patients emotionality, energy, and dominance (15). Thus, these two
Many studies indicate that, even during personality traits encompass emotional reactivity, focused
remission, most bipolar patients continue to display on the negative side for neuroticism and on the positive
symptoms, including sleep disturbance (6), impulsivity (7), side for extraversion. Taken together, these studies have
or cognitive impairment (8). Here we review studies reported inconsistent findings with bipolar patients having
demonstrating that emotional dysregulation may also be higher, equal or lower neuroticism or extraversion scores
characteristic of this inter-episodic period. than control subjects (16). When compared to unipolar
patients, patients with bipolar disorder have had higher,
3.1.1. Self-report studies lower, or equal neuroticism scores, and equal or higher
In a review, Johnson (9) reported that extraversion scores (16). These mixed results might be
sensitivity to incentive stimuli measured with the BAS explained in part by the fact that subsyndromal symptoms,
(10) in euthymic bipolar patients is greater than that of which are very common in patients with bipolar disorder,
healthy controls. He also suggests that emotional can influence self-reports of personality dimensions. It is
reactivity and instability are robust predictors of relapse possible that examinations of more focused traits, such as
after life stressor. emotional reactivity, might yield more consistent results.

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3.1.2. Experimental studies bipolar disorders to clarify whether a mild emotional

In addition to self-report, emotional responses hyperreactivity can be considered as a marker of
can be measured with standardized behavioral paradigms. In vulnerability.
the experimental setting, emotions may be triggered by
emotional induction tasks e.g., those including exposure to 3.2. Emotional reactivity during manic and mixed
images or films with different valences (positive, negative or episodes
neutral). Patients’ responses to stimuli can be assessed through Manic episodes are characterized by euphoric or
their self-reported perception of the stimuli (typically, valence irritable mood, accompanied by symptoms such as
and arousal) and through the measurement of autonomic distractibility, increased impulsivity and a decreased need
nervous system (ANS) responses. Measures of ANS responses for sleep (1). Patients in this acute mood state often engage
include variations in skin conductance or cardiac vagal tone, in behaviors with such an intensity that the potential for
and startle eyeblink modulation. harmful consequences is high. These disturbed behaviors
can be in part linked to increased emotional reactivity.
Other tasks, such as the affective go/no go or the
emotional Stroop, assess the impact of emotion on cognitive 3.2.1. Self-report studies
function. During the affective go/no go, an adaptation of As there was no clinical tool in use for the
classic go/no go paradigms, subjects have to respond as assessment of emotional reactivity in mood states, we
quickly as possible to target stimuli and withhold responses to developed and validated the dimensional MATHYS
distracter stimuli. In affective go/no go paradigms, some of the (Multidimensional Assessment of Thymic States) self-rated
distracter stimuli have emotional content. The emotional scale. This scale was built a priori, with five clinically relevant
Stroop task requires subjects to name, as fast as possible, the quantitative dimensions (emotional reactivity, cognition,
printed colors of both neutral and emotional words. In both motivation, psychomotor agitation or retardation and sensory
tasks, differences in response time between trials with neutral perception), which vary from inhibition to activation. Using
vs. emotional stimuli can be used to measure the degree of this scale, all bipolar mood states (manic, hypomanic, mixed
interference from the emotional stimuli. and depressive episodes) can be evaluated as a function of a
total score measuring global levels of behavioral
Using an emotional induction task, we have shown activation/inhibition and a sub-score assessing emotional
that euthymic bipolar patients assigned the same valence and reactivity (hyper/hyporeactivity) (19). The scale is a visual
arousal to positive and negative pictures as did control analog scale including 20 items related to how the individual
subjects. However, bipolar patients perceived neutral images felt during the previous week. The English version of the scale
as more pleasant and arousing than did controls. The startle can be found at this link:
reflex was concordant with self-assessment, as neutral pictures (http://www.biomedcentral.com/content/supplementary/1471-
triggered a stronger startle reflex in euthymic bipolar patients 244X-8-82-S1.doc) .
than in controls (17). The same responses between bipolar and
control subjects, in the case of positive and negative pictures, Using the MATHYS, we have observed that manic
might represent a ceiling effect. and mixed episodes are characterized by a high global level of
behavioral activation and high emotional hyperreactivity.
Using both a classical and an emotional Stroop Patients reported experiencing all emotions with a greater
tasks, attentional deficits and emotional bias were reported in intensity than usual (20). Although no differences in the level
manic, depressed and euthymic bipolar patients when of emotional reactivity are reported by manic vs. mixed
compared to healthy subjects since all patients were slower on patients on the MATHYS scale, mixed patients complain more
neutral, positive and negative conditions (18). These findings about negative affect (20).
suggest that bipolar patients demonstrate impaired
performance on emotionally salient attentionally demanding 3.2.2. Experimental studies
tasks. In an emotion induction study, we compared 33
manic patients with 33 matched euthymic patients and 33
These data, though admittedly limited, suggest that, healthy control subjects. Subjects rated the arousal and valence
relative to controls, euthymic bipolar patients may exhibit of pictures extracted from the International Affective Picture
increased reactivity to emotional stimuli, when reactivity is System. The level of arousal in response to positive, negative,
measured by self-report, response to emotion induction, or the and neutral pictures was higher in manic patients than in
impact of emotional stimuli on cognition. More studies are euthymic patients and healthy subjects (21). These data
needed, and one challenge for such studies is that, even during suggest that manic episodes may be characterized by
euthymic periods, many patients with bipolar disorder emotional hyper-reactivity to variables of all valences, rather
experience mild depressive or manic symptoms that may than simply as over sensitivity to positive stimuli.
impact on the dependent variables being measured. Moreover,
the cross-sectional design of these studies does not allow Elliot and al. (22) used an affective go/no go task
investigators to test the stability of these measures, and no during a brain-imaging study to assess how affective valence
studies have examined the impact of pharmacological of words can modulate cognitive processing in patients with
treatment. Studies in unaffected relatives could help to rule mania. Manic patients compared with controls showed
out the impact of treatment while also identifying possible differential neuronal responses associated with emotional
risk markers. However, there is a major lack of studies targets relative to neutral targets. This effect was present for
including first-degree relatives or subjects at risk for both happy and sad stimuli. Second, using a recall task with

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emotional words, Lyon et al (23) also reported slower associated with antidepressant treatment-emergent mania or
responses for both positive and negative words in manic hypomania (26,27). These findings highlight the clinical need
patients, compared to controls. Finally, Besnier et al (2010), for improved assessment of the differences between pure
using an emotional Stroop task, found that manic patients bipolar depression and that associated with manic symptoms,
showed more interferences with both negative, as well as which may help in predicting short-term prognosis and in
positive, valence words (24). selecting appropriate medications. To compare our results with
those of the STEP-BD, we categorized bipolar depression
All together, these data support the conclusion according to the presence or absence of manic symptoms and
that manic patients are hyperresponsive to negative as well assessed these two sub-groups with the MATHYS (28).
as positive stimuli. Depressive episodes with manic symptoms had higher levels
of activation and showed emotional hyper reactivity, whereas
3.3. Evaluation of emotional reactivity during depression major depressive episodes without manic symptoms showed
Currently, the same criteria are used to diagnose emotional hypo-reactivity (28). Thus, both our dimensional
unipolar and bipolar depressions (1). However, depression is approach and the categorical model of STP-BD find that
not a homogeneous condition and it is important to distinguish bipolar depressions are not homogeneous.
sub-groups in order to choose the most appropriate treatment.
In this section, we review studies on emotional reactivity in 3.3.2. Emotional reactivity in major depressive disorder:
bipolar and unipolar depression to explore whether this self report and experimental studies
criterion might usefully discriminate them. Rottenberg’s Emotion Context Insensitivity (ECI)
model states that depressed individuals show reduced
3.3.1. Identification of two subtypes of bipolar depression: reactivity to all emotional cues, regardless of valence (5). The
self-report studies ECI model is derived from the evolutionary hypothesis that
We used the MATHYS scale to characterize bipolar describes depression as a defensive motivational state which
depression on the basis of global levels of behavioral fosters environmental disengagement (29). According to this
activation/inhibition and emotional reactivity (19). All patients hypothesis, depressed mood states evolved as internal signals
met DSM-IV criteria for bipolar disorder in an acute to bias organisms against action in adverse situations where
depressive phase and did not meet criteria for a mixed episode. continued activity was potentially dangerous.
Using all the MATHYS items, we performed a cluster
analysis, which discriminated two types of bipolar depression. In a meta-analysis of 19 studies, Byslma et al. (30),
Using as a comparison the mean for euthymia, one type is evaluated the emotional reactivity of healthy individuals and
characterized by behavioral inhibition and emotional hypo- individuals with major depressive disorder. This meta-analysis
reactivity (n=38/60). The second type of bipolar depression is only included studies that used DSM criteria for major
characterized by mild behavioral over-activity and high depressive disorder (MDD) and elicited emotion in a well-
emotional reactivity (n=22/60). This dimensional analysis controlled manner. The meta-analysis included studies that
indicates that bipolar depression is not a homogeneous group. assessed positive and negative emotional reactivity using self-
reported experience, expressive behavior, and/or peripheral
Using a Likert scale (never to constantly), the physiology. The authors found that MDD was characterized by
MATHYS scale can also be used to assess the frequency of the reduced emotional reactivity to both positively and negatively
emotions reported by the patient (sadness, joy, irritability, valenced stimuli, although this reduction was larger for
panic, anxiety, anger, exaltation) during the last week (25). positive stimuli. The authors concluded that the findings of the
Compared to depression with emotional hypo-reactivity, meta-analysis did not support the concept of mood-congruent
depression with emotional hyper-reactivity was associated processing bias, in which depression would tend to bias
with higher irritability (p<0.0001), panic (p<0.0001), anxiety stimulus processing towards negative information (31).
(p<0.0001), anger (p<0.001), and exaltation (p<0.0001).
Globally, these patients are more sensitive to their environment 4. SUMMARY OF CLINICAL DATA ON EMOTIONAL
and have more affective lability than those with depression REACTIVITY DURING MOOD DISORDERS
with an emotional hyporeactivity. Thus one subtype of bipolar
depression is associated with emotional hyporeactivity Mild emotional hyperactivity may be
(patients are less sensitive, whatever the valence of stimuli), characteristic of bipolar patients during euthymia and could
and the other with emotional hyper reactivity (patients be considered as a marker of vulnerability, although data
frequently report negative affects but are still able to react to regarding the latter are limited. During manic and mixed states,
positive stimuli). there is consistent emotional hyper-reactivity and patients
experience all emotions with a greater intensity than in the
Data from the Systematic Treatment Enhancement euthymic state. Intuitively, it makes sense that emotional
Program for Bipolar Disorder (STEP-BD) indicates that: i) reactions are stronger when they are congruent with a pre-
two-thirds of bipolar depressed patients had concomitant existing mood. However, contrary to this intuitive idea, even
manic symptoms; ii) compared to patients who did not during euphoric mania, patients can become irritable and even
experience concomitant manic symptoms during depression, violently aggressive. This is contrary to the idea of mood-
those who did had more severe illness with onset at an early congruent processing bias and instead supports the notion of
age, more bipolar I subtype, more rapid cycling in the past global emotional dysregulation during mania. In bipolar
year, and a more frequent history of suicide attempts;, and iii) depression, the characterization of patients according to
bipolar depression with concomitant manic symptoms is emotional reactivity allows the identification of two subtypes:

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one associated with emotional hyporeactivity and the other activity to emotional stimuli. Chen et al. (36) report that
with emotional hyper reactivity, the latter probably belonging depressed and manic patients overactivate brain regions in
to a broad spectrum of mixed states. response to facial expressions of happiness and sadness, and
both groups showed increased neural responses to facial
5. BRAIN IMAGING AND ABNORMAL EMOTIONAL expressions of fear. The pattern of increased subcortical limbic
REACTIVITY IN MOOD DISORDERS activity to positive emotional stimuli may distinguish bipolar
from unipolar depressed patients. Indeed, abnormal amydala-
Most functional imaging studies in bipolar disorder prefrontal effective connectivity to happy faces may
have used behavioral paradigms that study emotional distinguish bipolar depression from MDD (37). However,
processing. In particular, the most frequently used designs in since, as noted above, bipolar depression is unlikely to be a
brain-imaging studies involve either facial affect recognition homogenous group, there is a need to better characterize which
tasks (32) or response to emotional stimuli. Neuroanatomic kind of bipolar depressed patients were included in the study in
investigations implicate a network of both cortical and order to be able to properly compare them.
subcortical anterior limbic structures in emotion processing.
These include the amygdala, ventral striatum, subgenual Future studies should subtype individuals with
(ventral) cingulate, ventromedial prefrontal cortex, anterior bipolar depression, as described above, in an effort to ascertain
hippocampus, and anterior insula (33). The prefrontal cortex whether these two subtypes of bipolar depression are
and amygdala, are two major components of emotion associated with different neural activation patterns in response
regulatory networks; the former negatively modulates the to emotional stimuli.
amygdala response when subjects identify emotional facial
expression. 6. NEUROCHEMICAL SYSTEMS, GENES AND
EMOTIONAL REACTIVITY
Functional brain-imaging studies in euthymic
bipolar disorder patients demonstrate abnormal responses to A number of abnormalities within the amine
emotional stimuli and dysfunction in emotional processing neurotransmitter systems have been identified in bipolar
circuitry, especially the anterior limbic regions (32). However, disorder. However, little is known about relationships
neural responses to emotional challenges in euthymic bipolar between these abnormalities and emotional reactivity, since
patients as a function of stimulus valence have been examined this feature has not typically been characterized.
in only a few studies. Lawrence et al (34) investigated neural Nonetheless, potential clues may be derived from data
activation in response to emotionally salient stimuli in bipolar concerning anhedonia and the dopaminergic system.
and MDD patients, and healthy control subjects. Euthymic Anhedonia is defined as loss of interest and pleasure, with
bipolar patients had elevated subcortical (ventral striatal, lack of reactivity to positively valenced emotional stimuli.
thalamic, hippocampal) and ventral prefrontal cortical Anhedonia might be considered to be a component of
responses, particularly in response to mild and intense fear, emotional hypo reactivity, in that the latter involves
mild happy, and mild sad expressions. Thus, compared with globally blunted responsiveness. Studies show associations
healthy controls and MDD patients, euthymic bipolar patients between anhedonia and dysfunction in the brain reward
had increased subcortical and ventral prefrontal cortical system, which is mediated primarily by dopaminergic
responses to both positive and negative emotional expressions. mechanisms (38). Thus, reduced ventral striatum activity
The authors concluded that these results might indicate an during performance of a reward task is associated with
enhanced salience of both positive and negative emotional anhedonia in depression (39,40).
stimuli in euthymic bipolar patients, which may be associated
with the increased mood lability observed in these patients. Conversely, the post-partum blues may be a
However, there is no study that explores directly the link potential model to explore transient emotional hyper-
between emotional reactivity and brain imaging patterns. reactivity. This specific period is characterized by minor
mood disturbances affecting many women a few days after
To examine the interference of emotional delivery (41). The pattern of symptoms and their time course,
information with cognitive processes, euthymic bipolar peaking between the third and fifth post-partum days, suggest
patients and healthy comparison subjects underwent functional that the underlying causes include biological determinants.
magnetic resonance imaging (MRI) while performing an Although the post-partum blues have often been considered to
emotional go/nogo task. Bipolar disorder patients, compared to be a mild depressive state, it is better defined as a transient
healthy controls, exhibited an over activation in ventral-limbic, period characterized by emotional hyper-reactivity and
temporal and dorsal brain structures when they have to affective lability (42). We performed a study designed to
inhibited responses to emotional stimuli compared with neutral evaluate the possible role of the serotonin system during this
stimuli (35) However, there was no behavioral difference period by assessing brain tryptophan availability. Post-partum
between groups. blues were associated with a decrease in brain tryptophan
availability, and the intensity of symptoms correlated
All these results are consistent with the conclusion significantly (p<0.05) with tryptophan availability (43).
that increased emotional reactivity is characteristic of euthymia
patients with bipolar disorder. Turning to genetic data, the association of the
serotonin transporter (5-HTT) gene with bipolar disorder has
Studies during mood states in bipolar disorder been investigated in a series of studies because the initial
patients have also demonstrated increased subcortical limbic studies showed a positive association between the short allele

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and the disorder. However, recent meta-analyses have shown depression. To go further, we need to assess if different clinical
no or only a small association between bipolar disorder and phenotypes respond differently to specific treatments.
this polymorphism (44,45,46). However, three recent Currently, there is no study using clinical characteristics as
independent meta-analyses have demonstrated a significant potential predictor of response to the various pharmacological
association between the short allele of the gene and treatments. One can hypothesized that pure depression, close to
neuroticism or harm avoidance (47,48,49). The 5-HTT gene the characteristics of unipolar depression might respond to an
therefore may be more strongly linked to affective instability association of a mood stabilizer plus an antidepressant.
rather than to a specific disorder. Conversely, hyperreactive depressions might be worsened by
antidepressant because they belong to a broad spectrum of
Many others genes can be involved in emotional mixed states and have a better response to atypical
regulation and the purpose of this section is not to be antipsychotics. This point is purely speculative and need to be
exhaustive. The findings on 5-HTT illustrate the possible explored.
evolution in genetic studies, showing first an association
between a gene and a disease that turn out to be likelihood an Finally, there is also a need to study the impact of
association with a trait. medicine on the level of emotional reactivity. Patients under
mood stabilizer often complain to become less sensitive. Is it
7. CONCLUSION the price they should pay to avoid relapses? Conversely, what
are the links between long prescription of antidepressant in
In this review, we have highlighted the importance bipolar patients, emotional reactivity and rapid cycling or
of emotional reactivity in the characterization of all phases of chronic major emotional instability?
bipolar disorder. Self-report and brain imaging studies suggest
that euthymia may be characterized by hypersensitivity to As suggested by the research agenda for DSM-V,
emotional stimuli. Major increases of emotional reactivity are a there is a clear need to translate basic and clinical research
key component of manic and mixed mood states, as patients findings into a new classification system for psychiatric
are more likely than controls to respond with exaggerated disorders based upon etiological processes (53). For this
intensity to emotional stimuli of all valences. reason, we need to: a) define clinically relevant homogeneous
groups; b) have appropriate clinical tools to assess these
Hasler et al. (50) have tried to explain the limited groups; c) establish correlations between biomarkers and the
success of studies on mechanisms underlying major depression clinical measures for reclassifying the current DSM-IV
and have raised questions concerning the definition of relevant categories of mood disorders across a continuous spectrum of
phenotypes. They propose a dissection of the depressive affective pathology; and d) use these biomarkers and their
phenotype into key components to allow the more precise clinical correlates to guide personalized treatments for
definitions of putative psychopathological intermediate individuals across the spectrum of affective disorders.
phenotypes. They also suggest the development of a new
classification system to reduce the heterogeneity of depression, Our dimensional model for defining mood episodes
as this has been a major barrier to understanding the based on the assessment of emotional reactivity and
mechanisms of the disease. Our model of assessing emotional behavioural activation/inhibition level can help improving
reactivity together with a global level of behavioural activation characterization of bipolar mood states. We now need to
is a step in this direction. When developing a new further explore the mechanisms involved in such
classification system, it is important to avoid including criteria disturbances using this model.
with opposing states (e.g. insomnia and hypersomnia,
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