Symptoms of Bipolar Disorder

Investigating the symptoms of bipolar disorder is an important first step towards understanding the causes of the disorder, and ultimately being able to effectively diagnose and treat bipolar patients. The main behavioural symptoms of bipolar disorder include alternating periods of depression for both types of the disorder, and mania or hypomania for bipolar I and bipolar II respectively.[1] Bipolar I patients can also experience mixed affective episodes, involving both depressive and manic symptoms, which lead to an increased risk for suicidal ideation and completion of suicide.[1] In addition to behavioural symptoms, patients with bipolar disorder also experience various cognitive and perceptual deficits, and structural irregularities in particular brain regions.[1] According to the latest estimate by the World Health Organization, the symptoms of bipolar disorder result in it being the 12th most prevalent cause of disability in the world.[2]

Mood and Behavioural symptoms

Figure 1 – Symptom Range [28]
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The range of symptoms exhibited in bipolar disorder.

Depression

Depressive episodes in bipolar disorder essentially consist of extended periods of sadness, which manifests as a wide variety of symptoms depending on the patient.[3] Bipolar patients may lose interest in and not experience pleasure from activities they previously enjoyed.[3] During depressive episodes different bipolar patients may experience symptoms on completely opposite ends of a spectrum, including: an abnormal increase or decrease in psychomotor activity; insomnia or hypersomnia; and an increase or decrease in weight and appetite.[3] These episodes also consist of feelings of low self esteem, guilt, and suicidal ideation.[3] All of these symptoms are highly variable from day to day during a depressive episode, and it seems that their progression is unpredictable.[4] It is important to note that between acute mood episodes, most people with bipolar disorder continuously experience subsyndromal depressive symptoms instead of euthymia (normal mood), which contributes to patients’ deficits in their ability to function normally.[3]

The depressive episodes experienced with bipolar disorder manifest in a similar way to the depressive episodes found in unipolar depression. It was long thought that the only differentia that set bipolar apart from unipolar depression was the additional presence of manic/hypomanic and mixed episodes.[3] However, recent evidence suggests that there are some differences between the disorders in their respective depressive episodes. On average, bipolar patients experience longer and more frequent depressive episodes.[5] In addition, during the depressive episodes bipolar patients experience relatively more psychomotor deficits, deficits in cognitive functioning, hypersomnia and trouble waking up in the morning, as well as hallucinations and delusions.[5]

Mania

Manic episodes occur in individuals with bipolar I. They consist of extended periods of extreme highs in mood, which can change between an extremely happy mood or a very irritable state.[3] The patient may become easily distracted, experience an increase in abnormal psychomotor activity, and experience ‘flights of ideas.’[3] These episodes also involve a shift towards extremes in personality, such as drastically increased frequency of speaking, increased social interaction, and an increase in risky behaviour such as drug use, gambling and sexual promiscuity.[3] These symptoms often become severe enough to cause disability in bipolar I patients, due to the increase in risky behaviour, impulsivity, and inability to focus.[11]

Differences in age contribute to variability of manic symptoms between patients. When making these comparisons between manic episodes, the most common method is comparing patients’ scores on the Young Mania Rating Scale (YMRS).[6] Scores on this scale are determined based on a series of eleven multiple choice questions relating to the severity of the symptoms of mania.[7] Younger patients’ mania tend to manifest as irritability and increased aggression.[6] Adult patients tend to have more of an increase in sexual appetite and grandiose ideation.[6]

The main feature that, if experienced, definitively distinguishes a full manic episode from hypomania is the presence of psychotic symptoms. Up to 68% of bipolar I patients will experience psychotic symptoms during manic episode.[8] Psychotic symptoms include delusions, grandiose ideation, being easily excitable, suspiciousness and hostility, low ability of judgment, and hallucinations.[8] An increased risk for experiencing these symptoms during a manic episode is associated with earlier onset of manic episodes in bipolar I patients.[8] Females are up to two times more likely than males to develop psychotic symptoms during a manic episode, and experience more severe symptoms overall, including more delusions per episode, more intense delusions and hallucinations, and higher YMRS scores.[9]

Hypomania

Hypomanic episodes occur in individuals with bipolar II, and are essentially less severe versions of manic episodes.[3] These episodes include the highs in mood, including irritability or increased happiness, but to a lesser degree.[10] During a hypomanic episode the patient may have increased energy, increased social, sexual, and physical activity, as well as some impulsive and risky behaviour.[10] However, because these symptoms do not become as severe as they do in manic episodes they normally do not cause dysfunction, and in many cases may improve functioning in bipolar II patients.[12]

Mixed affect

Mixed affective states can occur in up to 40% of bipolar I patients and are generally more severe than both depressive episodes and manic episodes.[13] In a mixed state the patient will experience symptoms of both depression and mania either at the same time or in relatively quick succession in the same day.[13] These states result in extreme instability of mood and behaviour, increased frequency of psychotic symptoms, extreme anxiety, and increased suicidality.[14] Females and those who have experienced mixed states in the past are at a greater risk of experiencing a mixed affective state.[14]

Prodromal symptoms

There has yet to be a robustly established set of prodromal symptoms that can accurately predict bipolar disorder because the currently identified symptoms only offer a low specificity.[15] A low ‘specificity’ indicates a high number of false positives, meaning that many of the symptoms identified as part of the prodrome of bipolar disorder also occur in individuals that do not go on to develop the disorder. However, there are a number of symptoms that have been identified as common in individuals who will go on to develop bipolar disorder, motivating further studies in identifying the specific prodrome.[15] The early prodrome appears to include anxiety, irritability and aggressiveness, insomnia or hypersomnia, and mood swings.[15] The prodrome appears to progress with subsyndromal manic and depressive symptoms gradually appearing, which sometimes takes years to develop into full bipolar disorder.[15]

Suicidality

Suicidal thoughts and behaviours are a major component of bipolar disorder, as 25% - 56% of bipolar individuals will attempt suicide at least once, and 8% - 20% of bipolar individuals will carry out suicide to completion.[16] These rates result in bipolar disorder placing seventh of all medical disorders for years of life lost.[16] Compared to individuals with unipolar depression, bipolar individuals engage in suicidal behaviours beginning at a similar age, and go on average attempt suicide the same number of times.[5] However, individuals with bipolar disorder seems to be much more aggressive in their suicidal behaviour than those with depression, as 26.7% of individuals with unipolar depression are admitted to the hospital for self injurious behaviour during their worst depressive episode, whereas bipolar individuals exhibit a rate of 46.3%.[5]

A variety of factors increase the risk of a bipolar individual committing suicide, however the length of time with bipolar and the intensity of depressive episodes do not contribute significantly.[16] Factors that contribute moderately include a high overall severity of symptoms, and if the individual does not comply properly with treatments prescribed by their psychiatrist.[16] Females are at a significantly higher risk than males, as well as individuals with histories of benzodiazepine use (such as those prescribed for panic and anxiety disorders), substance abuse, and alcohol abuse.[16]

A very wide variety of neurobiological factors have been found to be associated with suicidal behaviour in bipolar patients. Testosterone levels are known to be associated with aggressive and impulsive behaviour in general, and have been shown to be associated with an increase in the number of episodes of mania and attempted or completed suicide in bipolar individuals.[17] In suicidal bipolar individuals there appears to be abnormalities in related to several neurotransmitters, including a reduced level of serotonin reuptake, increased α2-adrenergic receptor density in the hypothalamus and frontal cortex, increased density of AMPA receptors in the caudate nucleus, and increased density of GABA neurons in the hippocampus.[16]

One current model of suicidality describes the progression towards suicidal behaviour as beginning with a stressor in the form of a ‘psychosocial crisis’ or a psychiatric disorder, which leading to suicidal ideation.[16] Suicidal ideation in combination with impulsivity and aggression or thoughts of hopelessness create a disposition for suicidal behaviour.[16] Bipolar patients experience both impulsivity and thoughts of hopelessness when they are in a mixed affective state, which may be an explanation as to why bipolar patients have such a high incidence of suicidality, especially when they are in a mixed state.[18] The administration of antidepressants to bipolar patients has been associated with an increase in mixed episodes, and there is some suggestion that antidepressants also correlate with suicidal behaviour in bipolar patients as a result.[18]

Comorbid disorders and symptoms

Up to 65% of bipolar patients also exhibit symptoms that qualify as an additional mental disorder least once in their lifetime.[19] The most common comorbid disorders seem to be anxiety disorders. A study found that the lifetime comorbidity of an anxiety disorder in individuals with bipolar disorder was 51.2%, and the rate of current morbidity in the subject was 30.5%.[20] Bipolar I patients had a 15.1% higher rate of current anxiety disorder comorbidity than bipolar II patients, and consistently exhibited higher rates of comorbidity throughout all types of anxiety disorders.[20] Substance abuse disorders also have a high rate of comorbidity, with 42% of bipolar individuals becoming dependent on a substance in their lifetime, most commonly alcohol.[19] The comorbidity of anxiety and substance abuse disorders has long been robustly established, but newer evidence suggests that eating disorders are a third category that sees high incidence of comorbidity.[19] Binge eating disorder has a particularly high rate of comorbidity with bipolar, motivating the possibility of a sub-phenotype classification of bipolar with binge eating disorder.[21]

Cognitive and perceptual deficits

Visual perception

Figure 2 – Perceptual Cognitive Tests [22]
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The four tests used to determine perceptual
cognitive deficits in bipolar patients:
A: identifying form on a noise background
B: identifying motion of a collection of dots
C: identifying the presence of a thin contrast grating
D: identifying movement of a wide contrast grating

It has been found that bipolar patients experience a variety of perceptual deficits relative to healthy individuals. The amount of deficit seems to be constant across both subtypes of bipolar disorder.[22] A test to measure motion discrimination ability involved measuring the ability of a participant to determine the motion of a collection of dots on a screen, in the presence of increasingly numerous randomly moving dots (see Figure 2: B).[22] The healthy controls were able to correctly determine the dot motion with approximately 10% more randomly moving dots present.[22] To determine sensitivity to contrast, participants were asked to determine if an image flashed on a screen contained a thin contrast grating, or to determine which direction a wide grating moved (see Figure 2: C and D).[22] Healthy controls were able to more accurately determine the presence and movement of contrast gratings than bipolar patients.[22] One task where healthy controls and bipolar patients did not exhibit any difference in performance was in the determining of shapes on a noise background (see Figure 2: A).[22] These tests’ findings were consistent across both bipolar I and bipolar II patients, as well as across current emotional states.[22]

A specific aspect of visual perception that appears to function abnormally in bipolar individuals is facial recognition. Bipolar patients were compared to healthy controls in their ability to determine which facial emotion was being exhibited in a photograph in the Facial Emotion Identification Test (see Figure 3), and their ability to discern if two faces are exhibiting the same emotion in the Facial Emotion Discrimination Test.[23] Bipolar patients scored significantly lower than the healthy controls on both tests.[23]

Figure 3 – Facial Emotion Identification Test [29]
Image Unavailable
An example of a set of images that may be
used in the Facial Emotion Identification Test.

Processing

Bipolar patients have been measured to exhibit lower scores relative to healthy controls in a wide variety of cognitive processing related tasks. It seems that, like with facial recognition, performance on these tasks do not differ between bipolar I and bipolar II patients.[24] Bipolar patients exhibited deficits in verbal fluency, as they were less fluent than normal controls when attempting to list words in a category.[24] Bipolar patients also scored lower on their ability to reproduce drawings they were shown, as well as on their ability to provide subsequent numbers in a given mathematical pattern.[24]

Structural irregularities

Figure 4 – Deep White Matter
Myelin Staining [27]
Image Unavailable
Examples of deep white matter myelin staining
intensities in samples taken from:
A & B: healthy control individuals
C: a schizophrenic patient
D: a bipolar patient
E: a patient with unipolar depression

A variety of structural irregularities in the brain have been found to correlate with bipolar disorder. One of the most significant irregularities is the increase in hippocampal volume. Bipolar patients have up to an 8.5% larger volume of the right hippocampus than healthy control individuals, regardless of whether the bipolar patient was being treated with lithium or had a family history of bipolar disorder.[25] In contrast to the right hippocampus, the left hippocampus was of similar size to the healthy controls, however there was a correlation between the decrease in left hippocampal size and how long the patient has had bipolar disorder.[25]

White matter abnormalities have had a long known association with bipolar disorder, schizophrenia, and unipolar depression.[27] This association is especially prominent in the dorsolateral prefrontal cortex, where all three disorders display decreased levels of staining intensity of the myelin of deep white matter when compared to healthy control individuals (see Figure 4).[27] However, the samples from schizophrenic samples only showed a tendency towards lower staining intensity, whereas the data from the bipolar and unipolar depression patients were statistically significant, further distinguishing the mood disorders from schizophrenia.[27]

Figure 5 – FA Comparison [26]
Image Unavailable
Visual representation of the difference between FA scores of healthy
control individuals and bipolar patients.
Green represents all areas of core white matter.
Red represents the areas where the FA score was
significantly lower in bipolar patients, which can be seen
in the AC (left) and the CC (right).

Bipolar individuals between the ages of 7 and 17 were found to exhibit lower fractional anisotropy (FA) scores when diffusion tensor imaging (DTI) measurements were done on their corpus callosum (CC) and anterior commissure (AC).[26] DTI essentially measures the direction of neurons in white matter by observing the direction of the flow of water through their myelin sheaths.[26] The lower FA score in the CC and AC of bipolar patients indicates a higher level of disorganization of neurons in the white matter of those areas (see Figure 5).[26] Interestingly, this increase in disorganization of the area that connects the two cerebral hemispheres is correlated with histories of aggression in bipolar patients.[26]

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