Therefore, loss of myelin is thought to disrupt communication between neurons, leading to some of the thought disturbances observed in bipolar disorder and related illnesses. Brain imaging studies of persons with bipolar disorder also show abnormal myelination in several brain regions associated with this illness. In this case, structural neuroimaging studies also show abnormal myelination in several brain regions associated with bipolar disorder. Interestingly, gene expression and neuroimaging studies of persons with schizophrenia and major depression also demonstrate similar findings, indicating that mood disorders and schizophrenia may share some biologic underpinnings, possibly related to psychosis.
These types of data may also lead to the future revision of psychiatric diagnostic manuals based on a new understanding of the etiology of these disorders. Another approach to delineating the pathophysiology of bipolar disorder involves studying changes in gene expression induced in rodent brains after administration of pharmacologic agents used to treat bipolar disorder.
For example, investigators have demonstrated that 2 chemically unrelated drugs lithium and valproate used to treat bipolar disorder both upregulate the expression of the cytoprotective protein Bcl-2 in the frontal cortex and the hippocampus of rat brains. A postmortem study by Konradi et al of the hippocampus in both patients with bipolar disorder and healthy persons found that the 2 groups did not differ in the total number of hippocampal neurons.
Newly published study investigates seroquel as monotherapy. Between childhood maltreatment and the medical morbidity in. There is also some evidence to suggest that an evolution of mood symptoms may occur across the diagnostic categories of the bipolar spectrum disorders over time. Reduced amygdalar gray matter volume in familial pediatric bipolar disorder. Last fall, James started fifth grade at a school designed to accommodate emotional as well as learning issues. Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder. This is my parenting skills, my lack of discipline, my lack of structure.
These findings suggest alteration of hippocampal interneurons in patients with bipolar disorder that might lead to hippocampal dysfunction. Neuroimaging studies of individuals with bipolar disorder or other mood disorders also suggest evidence of cell loss or atrophy in these same brain regions. Thus, another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion. According to this hypothesis, mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency.
In , Mathew et al published a review of novel drugs and therapeutic targets for severe mood disorders that focus on increasing neuroplasticity and cellular resiliency. Post et al had previously proposed a mechanism involving electrophysiologic kindling and behavioral sensitization processes, which resonates with the neuronal injury hypothesis.
It also supports clinical observations that the more episodes a person experiences, the more he or she will have in the future, underscoring the need for long-term treatment. A number of factors contribute to bipolar disorder, or manic-depressive illness MDI , including genetic, biochemical, psychodynamic, and environmental factors. First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population.
One logitudinal study found that subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of subsequent manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder.
High-risk offspring, compared with offspring of parents without bipolar disorder, also had higher rates of ADHD, disruptive behavior disorders, anxiety disorders, and substance use disorders. Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur in families.
Children whose biologic parents have either BPI or a major depressive disorder remain at increased risk of developing an disorder, even if they are reared in a home with adopted parents who are not affected. Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that schizophrenic, schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability was the same for schizoaffective disorder as for the other 2 syndromes.
Gene expression studies also demonstrate that persons with bipolar disorder, major depression, and schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and abnormalities of white matter in various brain regions. Duffy et al. They assessed high-risk children and 87 control subjects and found the cumulative incidence of bipolar disorder was Depressive and manic symptoms predicted 2. Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular abnormality is difficult.
The blood pressure drug reserpine, which depletes catecholamines from nerve terminals, was noted incidentally to cause depression. This led to the catecholamine hypothesis, which holds that an increase in epinephrine and norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes depression. Drugs used to treat depression and drugs of abuse eg, cocaine that increase levels of monoamines, including serotonin, norepinephrine, or dopamine, can all potentially trigger mania, implicating all of these neurotransmitters in its etiology.
Other agents that exacerbate mania include L-dopa, which implicates dopamine and serotonin-reuptake inhibitors, which in turn implicate serotonin.
Researchers studied 6, patients who received a diagnosis of substance-induced psychosis over a year period and who did not have any previous record of treatment for schizophrenia spectrum disorders or bipolar disorder. Overall, Cannabis-induced psychosis carried the highest risk of conversion for patients at a rate of Evidence is mounting of the contribution of glutamate to both bipolar disorder and major depression. A postmortem study of the frontal lobes of individuals with these disorders revealed that the glutamate levels were increased.
Calcium channel blockers have been used to treat mania, which may also result from a disruption of intracellular calcium regulation in neurons as suggested by experimental and genetic data. The proposed disruption of calcium regulation may be caused by various neurologic insults, such as excessive glutaminergic transmission or ischemia. Interestingly, valproate specifically upregulates expression of a calcium chaperone protein, GRP 78, which may be one of its chief mechanisms of cellular protection.
Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder. In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of brain activity, functional neuroimaging studies are performed to find regions of the brain, or specific cortical networks, that are either hypoactive or hyperactive in a particular illness. For example a meta-analysis by Houenou et al found decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been associated with the regulation of emotions in patients with bipolar disorder.
This provides evidence for functional and anatomic alterations in bipolar disorder in brain networks associated with the experience and regulation of emotions. White matter hyperintensities WMH are more common in individuals with bipolar disorder than in those without, and one study found that WMH burden appears to be associated with familiality and type of BP.
In addition, researchers observed a positive linear trend by familiality and type of affectedness when comparing mean total WMH volume of all participants. Many practitioners see the dynamics of manic-depressive illness as being linked through a single common pathway. They see the depression as the manifestation of losses ie, the loss of self-esteem and the sense of worthlessness.
Therefore, the mania serves as a defense against the feelings of depression. Melanie Klein was one of the major proponents of this formulation. A study by Barnett et al found that personality disturbances in extraversion, neuroticism, and openness are often noted in patients with bipolar disorder and may be enduring characteristics. In some instances, the cycle may be directly linked to external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition. For example, pregnancy is a particular stress for women with a manic-depressive illness history and increases the possibility of postpartum psychosis.
Because of the nature of their work, certain individuals have periods of high demands followed by periods of few requirements. For example, a landscaper and gardener who was busy in the spring, summer, and fall became relatively inactive during the winter, except for plowing snow. Consequently, he appeared manic for a good part of the year, and then he would crash and hibernate during the cold months.
There have been a number of studies linking bipolar disorder and increased amount of sunlight during the day aka, springtime. In one study, researchers collected data from patients at 50 sites in 32 countries on six continents; onset of bipolar disorder occurred at locations in 57 countries. Results show a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset.
Futhermore, another study assessed psychiatric admission of patients and found the admission rate for patients with bipolar disorder was significantly higher during May, June, and July; months with maximum sunlight exposure. These findings suggest photoperiod is a key element in bipolar disorder. There is the risk that antidepressant treatment may propel the patient into a manic episode. These findings highlight the importance of considering risk factors for mania when treating people with depression. The lifelong prevalence of bipolar disorder, or manic-depressive illness MDI , including subsyndromal forms in the United States has been noted to range from 0.
Globally, the lifelong prevalence rate of bipolar disorder is 0. In cross-sectional, face-to-face household surveys of more than 61, adults across 11 countries, Merikangas et al, using the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3. The age of onset of bipolar disorder varies greatly.
This paper will review what is currently known and what still is left to learn about clinically salient topics that pertain to bipolar disorder in children and. The purpose of this paper is to examine the diagnostic challenges in identifying pediatric bipolar disorder and our contemporary understanding of the clinical.
Most cases of bipolar disorder commence when individuals are aged 15—19 years. The second most frequent age range of onset is 20—24 years. Some patients diagnosed with recurrent major depression may indeed have bipolar disorder and go on to develop their first manic episode when older than 50 years.
These individuals may have a family history of bipolar disorder. However, for most patients, the onset of mania in people older than 50 years should lead to an investigation for medical or neurologic disorders, such as cerebrovascular disease. The incidence of BPII is higher in females than in males. Bipolar disorder, or manic-depressive illness MDI , has significant morbidity and mortality rates.
Additionally, a study from the United Kingdom suggested that for patients with bipolar disorder, mortality 1 year after hospital discharge was also higher than that of the general population for natural causes, chiefly respiratory and circulatory disorders. Patients with BPI fare worse than patients with a major depression. Often, the cycling between depression and mania accelerates with age.
Treatment of patients with bipolar disorder, or manic-depressive illness MDI , involves initial and ongoing patient education. To this end, a strong therapeutic alliance is essential. Educational efforts must be directed not only toward the patient but also toward their family and support system.
Furthermore, evidence continues to mount that these educational efforts not only increase patient compliance and their knowledge of the disease, but also their quality of life. An explanation of the biology of the disease must be provided. This decreases feelings of guilt and promotes medication compliance. Information should be provided on how to monitor the illness in terms of an appreciation of the early warning signs, reemergence, and symptoms. Recognition of changes can serve as a powerful preventive step.
Education must also encompass the dangers of stressors.
Helping the individual identify and work with stressors provides a critical aspect of patient and family awareness. Efforts should be made to educate the patient about relapses within the total context of the disorder.