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What Causes Bipolar Disorder In The Brain

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Imaging Studies Of Bipolar Depression

The Brain Circuitry of Bipolar Disorder: A View from Brain Scanning Research

The limited number of imaging studies in bipolar depression have also highlighted changes in prefrontal and subcortical activity A resting state positron-emission tomography study in a notably large group of patients with bipolar depression reported decreases in prefrontal cortical metabolism, and increases in subcortical metabolism, compared with healthy controls. Both of these effects were correlated with depressive severity on the Hamilton scale. Using cognitive activation designs, decreased activation in the prefrontal cortex has also been reported, where attentional or executive tasks have been employed. In addition, resting state activation in the subgenual cingulate region was positively correlated with target detection performance on a CPT performed outside the scanner. Decreased blood flow in medial prefrontal cortex was also reported during a sad mood induction in remitted and depressed patients with type 1 bipolar disorder, although this study did not, include a healthy comparison group.

Do Antidepressants And Mood Stabilizers Have Neurotrophic Properties

‘Neuroplasticity’ subsumes diverse processes of vital importance by whichthe brain perceives, adapts and responds to a variety of internal and externalstimuli. The manifestations of neuroplasticity in the adult CNS have beencharacterized as including alterations of dendritic function, synaptic remodeling,long-term potentiation , axonal sprouting, neurite extension, synaptogenesis,and even neurogenesis .

There are several reports supporting the hypothesis that antidepressanttreatment produces neurotrophic-like effects .Chronic administration of an atypical antidepressant, tianeptine, was reportedto block the stress- induced atrophy of CA3 pyramidal neurons and to block other stress-induced changes in brain structureand neurochemistry . Male treeshrews subjected to a chronic psychosocial stress paradigm were found to havedecreased N-acetylaspartate , a putative marker of neuronal viability, measured in vivo by 1H-magneticresonance spectroscopy , decreased granule cell proliferation in thedentate gyrus of the hippocampus and a reduction in hippocampal volume ascompared to nonstressed animals. All these stress-induced effects were prevented/reversed in the animals treated concomitantly with tianeptine . However, the generalizability of these effects to otherclasses of antidepressants is unclear.

Bipolar Disorder Affects Brain Regions Controlling Inhibition Emotion

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Analysis of a large sample indicated widespread bilateral patterns of reduced cortical thickness in adolescents and adults with bipolar disorder.

is known to be highly heritable with individual risk depending partially on genetics. However, the underlying neurobiological mechanism of the disorder remains unclear. The prognosis for individuals with is mixed: currently approved medications are ineffective for many patients,Derrek Hibar, PhD, of the University of Southern California, Marina del Rey, and colleagues wrote.

To better understand pathophysiology of bipolar disorder, researchers assessed cortical gray matter thickness and surface area measures from brain MRI scans of 1,837 individuals with bipolar disorder and 2,582 healthy controls.

Participants with bipolar disorder exhibited thinner cortical gray matter in frontal, temporal and parietal regions of both brain hemispheres.

Bipolar disorder had the largest effect on left pars opercularis, left fusiform gyrus and left rostral middle frontal cortex.

When accounting for age at the time of MRI, longer illness duration was associated with reduced cortical thickness in frontal, medial parietal, and occipital regions.

A history of psychosis was associated with reduced cortical surface area, but mood state at time of scan was not.

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How Is Bipolar Disorder Diagnosed

Most people with bipolar disorder can be helped â but a psychiatrist or psychologist must first diagnose the disorder. Sadly, many people with the condition are never diagnosed or are not diagnosed properly. Without proper diagnosis and treatment, the disorder can become worse. Some teens with undiagnosed bipolar disorder can end up in a psychiatric hospital or residential treatment center, in the juvenile justice system, abusing drugs, or committing suicide.

Because children and teens with bipolar disorder do not usually show the same patterns of behavior as adults who have the condition, a mental health professional will observe a teen’s behavior carefully before making a diagnosis. This includes getting a complete history of the person’s past and present experiences. Family members and friends can also provide helpful insights into the person’s behavior. The doctor may also want a teen to have a medical exam to rule out other conditions.

Diagnosing bipolar disorder can be difficult. As yet, there aren’t any laboratory tests like a brain scan or blood test that will diagnose it. In teens, bipolar disorder can sometimes be mistaken for illnesses like schizophrenia and posttraumatic stress disorder, attention deficit hyperactivity disorder , and other depressive disorders. That’s why a complete, detailed history is so important.


What Does The Research Say


A 2017 found that people may experience changes in the working memory processes of update and recall both during and between episodes of bipolar disorder. This can make it hard for people to function in work or study.

A study published in 2007 found that some people who experience psychosis in bipolar disorder may have difficulty with executive functioning. This can affect their ability to plan or carry out tasks.

Other researchers have described impairment in executive functioning as a core dysfunction that some people may experience when they are between high and low phases.

People with bipolar disorder who experience psychosis are

The changes that occur with bipolar disorder may affect a persons memory, but some of the treatments for the condition can also have an impact.

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Imaging Differences Between Bipolar And Unipolar Depression

In addition to functional differences, there are also structural differences between unipolar and bipolar depression. Compared with bipolar depressed subjects, those with MDD had fewer deep white-matter hyperintensities, reflecting a lesser degree of white-matter impairment. Additionally, bipolar depressed subjects had increased corpus callosum cross-sectional area and decreased hippocampus and basal ganglia relative to unipolar patients. Both disorders manifested a larger lateral ventricular volume and increased rates of subcortical gray-matter hyperintensities compared with healthy controls .

Changes In Neuroplasticity And Neurotrophin Signaling

The role of BDNF in mood disorders has received more attention than other members of the neurotrophin family. It is involved in neuronal maturation, differentiation and survival, synaptic plasticity, and long-term memory consolidation . Furthermore, compelling preclinical evidence suggests that BDNF plays an important role in regulating the release of serotonin, glutamate, and gamma-aminobutyric acid , as well as in slow-wave sleep modulation . BDNF expression is particularly high in the cerebral cortex and hippocampus .

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How Does It Affect People

Bipolar disorder affects both men and women. For many people, the first symptoms show up in their early twenties. However, research has shown that the first episode of bipolar disorder is occurring earlier: It often shows up in adolescence, and even children can have the disorder.

Recent research suggests that kids and teens with bipolar disorder don’t always have the same behavioral patterns that adults with bipolar disorder do. For example, kids who have bipolar disorder may experience particularly rapid mood changes and may have some of the other mood-related symptoms listed below, such as irritability and high levels of anxiety. But they may not show other symptoms that are more commonly seen in adults.

Because brain function is involved, the ways people with bipolar disorder think, act, and feel are all affected. This can make it especially difficult for other people to understand their condition. It can be incredibly frustrating if other people act as though someone with bipolar disorder should just “snap out of it,” as if a person who is sick can become well simply by wanting to.

Bipolar disorder isn’t a sign of weakness or a character flaw it’s a serious medical condition that requires treatment, just like any other condition.


Can Lack Of Sleep Worsen The Symptoms Of Bipolar Disorder

What is Bipolar Disorder?

Some findings show that people with bipolar disorder have a genetic predisposition to sleep-wake cycle problems that may trigger symptoms of depression and mania.

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.

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Study Suggests Bipolar Disorder May Cause Progressive Brain Damage

    A study by researchers at the San Francisco VA Medical Center indicates that people with bipolar disorder may suffer progressive brain damage.

    For the first time, our study supports the idea that there may be on-going damage to certain regions of the brain as the illness progresses, said the studys lead author Raymond Deicken, MD. Deicken is the medical director of the Psychiatric Partial Hospital Program at the San Francisco VA Medical Center and UCSF associate professor of psychiatry.

    The study appears in the May issue of the American Journal of Psychiatry.

    More than 2 million Americans suffer from bipolar disorder, commonly known as manic depression. To date, there are no physiological markers used to diagnose the disease. Instead, it is identified by behavioral symptoms, including frequent mood swings between high-energy mania and severe depression.

    Deicken and his colleagues compared brain scans of 15 non-symptomatic male patients with familial bipolar I disorder to those of 20 healthy male comparison subjects. Male subjects were chosen to control for the effects of gender. In addition, test subjects were chosen based on several previous studies showing -that patients who have inherited the disorder have more prominent changes in brain structure and function.

    The hippocampus is also important from a therapeutic standpoint since it is one of two brain regions where new neuronal growth, or neurogenesis, can occur, offering hope for reversal of damage.

    Early Identification And Intervention Improve Outcomes

    Treatment interventions that improve PFC modulation might improve outcome

    Can we find the molecular basis of BPD1 to enable therapeutic intervention and improve the lives of people with BPD1, asked Professor Strakowski.

    Imaging and other measures can be used to identify those patients at high risk of BPD1, and treatment interventions that improve PFC modulation might be able to impact the course of the illness, Professor Strakowski said. Decreases in brain activation have been observed in patients being treated for BPD1, providing evidence for potential neuroanatomic treatment response markers in first-episode BPD1.2

    The natural course of the illness is shortening intervals between episodes of BPD1 over time. Lateral ventriculomegaly is greater in BPD1 patients, who have had repeated manic episodes and is associated with the number of previous manic episodes.5 This is probably part of the progressive course, said Professor Strakowski. A similar finding has been found in the cerebellum, but further work is needed to clarify the changes.

    The biggest predictor of treatment response is prior treatment response, concluded Professor Strakowski. Most importantly, patients who adhere to early treatment and who avoid recreational drugs and alcohol have much better outcomes, and most can lead normal lives with good management.

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    Neuroimaging In Patients With Bipolar Disorder

    Neuroimaging studies of bipolar disorder are frequently characterized by equivocal findings and, in some instances, a failure to replicate previous results. Furthermore, multiple factors confound any attempt to integrate neuroimaging findings into a single theoretical paradigm. Chief among these is the fact that many studies fail to unequivocally define the mood state of patients at the time of scanning or fail to provide information on subjects age or medication status, all of which can impact brain activity. Differentiating the effect of medication on the underlying pathophysiological processes in bipolar disorder imaging studies is a daunting task. The majority of subjects in the imaging studies are medicated, quite often with more than one class of medication. In an ideal scenario, one would conduct a comparison between medicated and unmedicated bipolar patients and healthy control subjects. Such a design would require that medications be gradually reduced and discontinued prior to randomization. Ethical and clinical concerns would prohibit researchers from discontinuing medications in stable bipolar patients with a history of severe symptomatology, prominent suicidality, difficult-to-treat psychosis, highly recurrent disease, or rapid and polyphasic cycling. If these patients were to be excluded, it would introduce a selection bias, since the studies would represent only patients with a milder form of disease who could better tolerate medication discontinuation .

    Brain Imaging In Bipolar Disorder

    An Overview of the Causes of Bipolar Disorder

    Structural and functional brain imaging studies in bipolar disorder lend direct, support to the indications of prefrontal cortical pathophysiology from studies of neurocognition. Classic studies of patients with secondary mood disturbance as a consequence of organic pathology like stroke or tumor reported increased prevalence of depressed mood following damage to the left, frontal cortex and the left, basal ganglia., Cases of secondary mania arc unsurprisingly less common than poststroke depression, but, are reported to show the reverse pattern of laterality, associated with right-lateralized damage to the frontal cortex and basal ganglia. These data highlight the connectivity between the frontal cortex and basal ganglia, and this frontostriatal circuitry is thought, to support, many aspects of attentional, executive and emotional function. Neurological patients with basal ganglia pathology also show elevated levels of depression, compared with other patient, groups with disorders matched for level of disability

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    What Are The Signs And Symptoms

    A person with bipolar disorder will go through episodes of mania and at other times experience episodes of depression . These aren’t the normal periods of happiness and sadness that everyone experiences from time to time. Instead, the episodes are intense or severe mood swings, like a pendulum that keeps arcing higher and higher.

    Symptoms of mania include:

    • anger, worry, and anxiety
    • thoughts of death or suicide

    In adults, episodes of mania or depression usually last for weeks or months, although they can be shorter in length. In children and adolescents, though, these episodes can be much shorter, and a kid or teen can even go back and forth between mania and depression throughout the day.

    Episodes of mania or depression may happen irregularly and follow an unpredictable pattern or they may be linked, with a manic episode always following a period of depression, or vice versa. Sometimes episodes have a seasonal pattern. Mania in the spring, for example, may be followed by depression in the winter.

    Between episodes, someone with bipolar disorder usually returns to normal functioning. For some people, though, there is little or no “break period” between their cycles. These mood swing cycles can change slowly or rapidly, with rapid cycling between mania and depression being much more common in women, children, and adolescents.


    How Can I Prevent Bipolar Disorder

    Nothing is known to prevent bipolar disorder. It is best to avoid drugs that may trigger the disease . Adopting a healthy lifestyle with regular sleep and exercise also may help.

    Relapses can be prevented or made less severe by following the treatment recommendations of your health care professionals. This includes taking medication as directed and attending counseling sessions.

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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 .

    Imaging Studies Of Euthymia/remission

    Causes of Bipolar Disease

    A number of studies have examined remitted patients with bipolar disorder in similar imaging protocols to those employed in mania. The Stroop test, where color words are presented in congruent or incongruent inks, has been widely validated for use in neuroimaging. This paradigm yields a robust signal in the anterior cingulate cortex during presentation of incongruent, stimuli, where the natural tendency to read the color word must, be overriden. Gruber et al reported reduced anterior cingulate activity in remitted bipolar patients compared with controls, which may indicate a failure to recruit prefrontal cortex during effortful executive control.- Remitted bipolar patients have also been reported to show deactivation in orbital and medial prefrontal cortex during the incongruent Stroop blocks,- an effect that was also seen in manic and depressed bipolar groups, suggesting a trait, marker of pathophysiology in the orbitofrontal cortex.

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    Bipolar Psychosis And The Brain

    It’s impossible to separate the physical brain from the neurochemicals in the brain, but there are actually structural differences in the brain of people who experience psychosis. There can be a chronic shut down of the frontal lobes and there is a particular part of the limbic system called the where the dopamine system is especially hyperactive. Antipsychotic medications work by blocking dopamine in this area. The limbic system, the emotional part of the brain, is also central to the causes and ultimately treatment of bipolar psychosis. Brain research into this area is vital as new medications and other treatments are based on new research. In other words, if we do find out exactly where psychosis resides in the brain and specifically what chemicals are affected, medications can be much more targeted.

    APA ReferenceFast, J. . What Causes Psychosis? Psychosis and the Brain, HealthyPlace. Retrieved on 2022, January 20 from

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