Subcortical And Medial Temporal Activation
In addition to studies of prefrontal cortex, functional abnormalities in striatum and other subcortical structures have been reported in bipolar disorder. Specifically, compared with healthy subjects, Baxter et al observed decreased caudate metabolism in depressed bipolar patients. However, after adjusting for hemispheric metabolism, which was also decreased in depression, the specific regional specificity in the striatum was less clear. OConnell et al reported increased blood flow in the basal ganglia, with right-sided flow greater than left, in bipolar patients during mania. Blumberg et al partially replicated this finding as they observed increased blood flow in the left head of the caudate in manic compared with healthy subjects. These latter investigators also compared a group of bipolar adolescents with healthy controls and found increased signal in the thalamus and putamen. However, the mood state of patients in this latter study was not described. Together, these findings suggested that state-dependent changes in activation occurred in striatum during the course of bipolar disorder that mirrored those in the prefrontal cortex.
The Brain And Bipolar Disorder
Three brain chemicals — norepinephrine , serotonin, and dopamine — are involved in both brain and bodily functions. Norepinephrine and serotonin have been consistently linked to psychiatric mood disorders such as depression and bipolar disorder. Nerve pathways within areas of the brain that regulate pleasure and emotional reward are regulated by dopamine. Disruption of circuits that communicate using dopamine in other brain areas appears connected to psychosis and schizophrenia, a severe mental disorder characterized by distortions in reality and illogical thought patterns and behaviors.
The brain chemical serotonin is connected to many body functions such as sleep, wakefulness, eating, sexual activity, impulsivity, learning, and memory. Researchers believe that abnormal functioning of brain circuits that involve serotonin as a chemical messenger contribute to mood disorders .
Mental Illness In Children And Adolescents
Mental illness is not uncommon among children and adolescents. Approximately 12million children under the age of 18 have mental disorders. TheNational Mental Health Association has compiled some statisticsabout mental illness in children and adolescents:
- Mental health problems affect one in every five young people at anygiven time.
- An estimated two-thirds of all young people with mental healthproblems are not receiving the help they need.
- Less than one-third of the children under age 18 who have a seriousmental health problem receive any mental health services.
- As many as 1 in every 33 children may be depressed. Depression inadolescents may be as high as 1 in 8.
- Suicide is the third leading cause of death for 15- to 24-years-oldsand the sixth leading cause of death for 5- to 15-year-olds.
- Schizophrenia is rare in children under age 12, but it occurs inabout 3 of every 1,000 adolescents.
- Between 118,700 and 186,600 youths in the juvenile justice systemhave at least one mental illness.
- Of the 100,000 teenagers in juvenile detention, an estimated 60percent have behavioral, cognitive, or emotional problems.
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What Happens In The Manic Phase Of Bipolar Disorder
Are you or someone you know affected by mood swings that seem extreme or out of the ordinary? Do those changes in mood affect your ability to stay focused or complete tasks? While occasional changes in mood are normal, when those changes occur often, or without obvious reason, they may be a reason for concern. For some, these could be signs of a mental health disorder known as bipolar disorder. Because not everyone who has bipolar disorder has been properly diagnosed or is receiving treatment, it is important to understand the symptoms and know when to seek help.
Classical Monoaminergic Neurotransmitter And Neuroendocrine Systems
The stimulus for the study of the biogenic amines in patients with BD wasprovided by the discovery of effective pharmacologic treatments for depressionand mania . In addition to thesecompelling pharmacological data, the biogenic amine neurotransmitter systemsare distributed extensively in the limbic system, which is implicated in theregulation of sleep, appetite, arousal, sexual function, endocrine function,and emotional states such as fear and rage. The clinical picture of BD involvesdisruption of behavior, circadian rhythms, neurophysiology of sleep, neuroendocrineand biochemical regulation within the brain . These complex illness manifestations areundoubtedly mediated by a network of interconnected neurotransmitter pathways the monoamine neurotransmitter systems are ideally placed to mediate suchcomplex behavioral effects, and thus represent attractive candidate systemsunderlying the pathophysiology of BD .
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Can Lack Of Sleep Worsen The Symptoms Of Bipolar Disorder
The problem for those with bipolar disorder, however, is that sleep loss may lead to a mood episode such as mania in some patients. Worrying about losing sleep can increase anxiety, thus worsening the bipolar mood disorder altogether. Once a sleep-deprived person with bipolar disorder goes into the manic state, the need for sleep decreases even more.
In one study, researchers interviewed 39 bipolar patients with primarily manic or depressed episodes to determine the presence of social rhythm disruptions during the two months prior to the onset of the mood.
When comparing the results with volunteers in the control group, researchers concluded that most people with bipolar disorder experience at least one social rhythm disruption prior to a major mood episode. In addition, the researchers found that social rhythm disruption affected more bipolar patients with mania than the patients with depression. Their findings concluded that 65% of the patients with bipolar disorder had at least one disruption in their daily rhythm in the eight weeks before the onset of a manic episode.
The Protein Kinase C Signaling Pathway
Protein kinase C exists as a family of closely related subspecies,has a heterogenous distribution in brain , and, together with other kinases, appears toplay a crucial role in the regulation of synaptic plasticity and various formsof learning and memory . PKC is one of the major intracellular mediators of signalsgenerated upon external stimulation of cells via a variety of neurotransmitterreceptors ,which induce the hydrolysis of various membrane phospholipids.
In view of the pivotal role of the PKC signaling pathway in the regulationof neuronal excitability, neurotransmitter release, and long-term synapticevents ,it was postulated that the attenuation of PKC activity may play a role inthe antimanic effects of lithium and VPA. In a pilot study it was found thattamoxifen ) may, indeed, possessantimanic efficacy . Clearly, theseresults have to be considered preliminary, due to the small sample size thusfar. In view of the preliminary data suggesting the involvement of the PKCsignaling system in the pathophysiology of BD, these results suggest thatPKC inhibitors may be very useful agents in the treatment of mania. Largerdouble-blind placebo-controlled studies of tamoxifen and of novel selectivePKC inhibitors in the treatment of mania are warranted.
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Bipolar Disorder And Neurochemistry
The brain uses a number of chemicals as messengers to communicate with other parts of the brain and nervous system. These chemical messengers, known as neurotransmitters, are essential to all of the brain’s functions. Since they are messengers, they typically come from one place and go to another to deliver their messages. Where one neuron or nerve cell ends, another one begins.
In between two linked neurons is a tiny space or gap called a synapse. In a simple scenario, one cell sends a neurotransmitter message across this gap and the next cell receives the signal by catching the messenger chemical as it floats across the gap. The receiving neuron’s capture of the neurotransmitter chemicals alerts it that a message has been sent, and this neuron in turn sends a new message off to additional neurons that it is connected to, and so on down the line.
Neurons cannot communicate with each other except by means of this synaptic chemical message. The brain would cease to function in an instant if chemical messengers were somehow removed. By providing a way for allowing neurons to communicate with one another, neurotransmitters literally allow the brain to function. There are millions and millions of individual synapses, or gaps, in the brain. The neurotransmitter traffic and activity happening inside those gaps is constant and complicated.
Does Bipolar Affect The Frontal Lobe
In a longitudinal structural MRI study of bipolar disorder, Abé et al. reveal a reduction in volume of frontal cortex in patients who experience manic episodes, but not in those who remain well. The results suggest that frontal grey matter loss in bipolar disorder can be attributed to the occurrence of mania.
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What Happens In The Brain With Bipolar Disorder
Bipolar Disorder May Change Your Brains Chemical Balance Scientists believe the main neurotransmitters affected by bipolar disorder include: Noradrenaline or norepinephrine, which increases alertness, arousal, and speeds up your reaction time. The neurotransmitter also plays a role in your ability to concentrate.
Integration Of Neurobiological Findings
As we noted at the beginning of this review, from a neurobiological perspective, there is no such thing as bipolar disorder. Rather, it is almost certainly the case that there are many somewhat similar, but subtly different, pathological conditions that produce a final common pathway disease state that we currently diagnose as bipolarity. This heterogeneity reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition puts a hard limit on all attempts to articulate an integrated perspective on bipolar disorder. Also posing a challenge to the integrative enterprise is the fact that nothing could be further from a static condition than bipolar disorder. Whereas, most psychiatric conditions vacillate within a single register between symptom exacerbation and various degrees of recovery, those attempting to fully understand bipolar disorder must contend with the fact that exacerbations come in two distinct flavors manias and depressions and that often these exacerbations can take any of a nearly infinite number of combinations of these two mood disturbances.
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Brain Chemistry And Biology
Bipolar disorder also has a neurological component.
Neurotransmitters are chemical messengers in the brain. They help relay messages between nerve cells throughout the body. These chemicals play an essential role in healthy brain function. Some of them even help regulate mood and behavior.
Older links three main neurotransmitters to bipolar disorder:
Imbalances of these brain chemicals may prompt manic, depressive, or hypomanic mood episodes. This is particularly the case when environmental triggers or other factors come into play.
Glutamatergic Interventions: Do They Represent A Neurotrophic Strategy
Another neurotransmitter system that has been implicated in regulatingneuronal plasticity and cellular resilience in a variety of neuropsychiatricdisorders is the highly complex glutamatergic system. In fact, glucocorticoidscan induce the release of glutamate in the hippocampal CA3 region, and veryhigh levels of type II corticosteroid receptor activation markedly increasecalcium currents and lead to increased expression of N-methyl-Daspartate receptor on hippocampal neurons,that could predispose to neurotoxicity and finally atrophy. Interest- ingly,NMDA blockade can prevent stress-induced atrophy in that region and it isthus noteworthy that recent preclinical studies have shown that the glutamatergicsystem represents a target for the actions of antidepressantsand mood stabilizers .
There are a number of glutamatergic ‘plasticity enhancing’ strategies whichmay be of considerable utility in the treatment of mood disorders. Presently,lamotrigine and ketamine, two anti-glutamatergic agents, have shown to haveantidepressant properties in bipolar and unipolar depression. Other agents- including NMDA antagonists, glutamate release reducing agents, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors potentiators -are under development or currently being clinically tested .
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Mental Illness And The Brain4
The term mental illness clearly indicates that there is a problem with the mind. Butis it just the mind in an abstract sense, or is there a physical basis to mentalillness? As scientists continue to investigate mental illnesses and their causes,they learn more and more about how the biological processes that make the brain workare changed when a person has a mental illness.
Researchers Create A Roadmap Of Bipolar Disorder And Its Effects On The Brain
A new study has found brain abnormalities in people with bipolar disorder.
In the largest MRI study to date on patients with bipolar disorder, a global consortium published new research showing that people with the condition have differences in the brain regions that control inhibition and emotion.
By revealing clear and consistent alterations in key brain regions, the findings published in Molecular Psychiatry on May 2 offer insight to the underlying mechanisms of bipolar disorder.
We created the first global map of bipolar disorder and how it affects the brain, resolving years of uncertainty on how peoples brains differ when they have this severe illness, said Ole A. Andreassen, MD, PhD, senior author of the study and a professor at the Norwegian Centre for Mental Disorders Research at the University of Oslo.
Bipolar disorder affects about 60 million people worldwide, according to the World Health Organization. It is a debilitating psychiatric disorder with serious implications for those affected and their families. However, scientists have struggled to pinpoint neurobiological mechanisms of the disorder, partly due to the lack of sufficient brain scans.
The study was part of an international consortium led by the USC Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC: ENIGMA spans 76 centers and includes 26 different research groups around the world.
Thousands of MRI scans
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Changes In The Intracellular Signaling Cascades
It is becoming increasingly evident that current mood-stabilizing agents have actions that extend beyond binding to neuronal membrane surface receptors. Therapeutic actions of psychotropics utilized in the treatment of bipolar disorder most likely rely on an interface with intracellular signaling cascades and eventual enduring changes in gene expression, accompanied by alterations in neurotransmission and neuroplasticity. Better understanding of intracellular signaling cascades may therefore provide valuable insights into the underlying causes of bipolar disorder and subsequently to more effective treatment strategies.
The phosphoinositide-3-kinase /AKT pathway is a general signal transduction pathway for growth factors, including BDNF and consequently for BCL-2. The GSK-3 signaling pathway modulates apoptosis and synaptic plasticity. Increased activity in the GSK-3 pathway supports apoptosis. Attenuation of GSK-3 activity leads to up-regulation of BCL-2 and beta-catenin and consequent enhancement of neuroplasticity and cellular resilience. This pathway is also involved in circadian regulation .
Interestingly, manipulation of the GSK-3 pathway produces both antimanic and antidepressant effects. Many agents with mood-stabilizing properties, such as lithium, valproate, and atypical antipsychotics, directly and indirectly modulate the PI3K, GSK-3, and Wnt signaling pathways, the very same ones implicated in genetic studies of bipolar disorder .
Any Other Factors That May Contribute To Developing Bipolar
As we described earlier, experts have good reason to believe that biology is mainly to blame for bipolar disorderin particular, specific areas in the brain that over- or under-produce particular brain chemicals.
However, its possible that certain environmental factors may trigger the disease in those who were already susceptible. Thats not to say that youd get the disease if you werent predisposed to it in the first place.
But its conceivable that bipolar could lie idle, only activating if certain factors arise. These may include:
Stressful events. Highly disturbing happenings like divorce, experiencing a death of a family member, or losing a job can set off a bipolar incident. Also, people whove experienced a traumatic event like sexual or physical abuse, neglect, or death of a parent early in life have an increased risk of bipolar later.
Sleep disturbances. Research found that 25% to 65% of people with bipolar had experienced a social rhythm disruptionscience speak for daily routines that can impact the sleep/wake cyclebefore an episode of mania.
Drugs and alcohol. More than 60% of people with bipolar disorder abuse alcohol or drugs. The classic chicken/egg questions arises here , and the answer is, its likely bidirectional. That is, people with bipolar take more risks, which allows for more alcohol and substance abuse, which may lead to brain and social stressors that increase the likelihood of the disorder.
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According To The National Alliance On Mental Illness 23 Million People In The United States Suffer From Bipolar Disorder
Every year, 2.9% of the U.S. population is diagnosed with bipolar disorder.1 But what is this condition? Bipolar disorder, or manic depression, is a serious brain disorder that causes extreme shifts in mood, energy, or functioning, and can range from episodes of mania to episodes of depression . These mood swings can range in severity and may last for hours, days, or months. But what causes these mood swings? How does bipolar disorder affect the brain?
Understanding Manic Episodes Of Bipolar Disorder
The way bipolar disorder symptoms manifest, the duration of symptoms, and the overall effect on a person may vary greatly from person to person. The manic symptoms of bipolar disorder may be especially difficult for some people to understand as people may react differently during these episodes. For example, when manic episodes occur, one person may experience mania or hypomania episodes with feelings of frustration or irritability while another may exhibit a decreased need for sleep, accelerated thinking, or hyperactivity.
When manic symptoms of bipolar disorder emerge, its not uncommon for one to experience feelings of creativity, heightened energy, or euphoria. Some people may feel they are destined for greatness or are invincible.
While the overall feeling of increased energy and euphoria may feel good at first, manic episodes can cause a spiral in emotions. For instance, during this phase, some people engage in dangerous or inappropriate behavior. They may become sexually promiscuous, gamble, or go on spending sprees. Some people are easily angered, may start fights or lash out at others, or blame those who criticize their behavior.
Some common symptoms of manic episodes include:
Warning Signs That Indicate Bipolar Mania Episodes
Treatment for Bipolar Disorder
Because bipolar disorder is a chronic, relapsing condition, it requires long-term treatment. This is true even when symptoms are not obvious.
Getting Help for Bipolar Disorder
You Are Not Alone
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