Thursday, August 11, 2022

Can Bipolar Disorder Be Genetic

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Early Models Of Disease Transmission And Heritability In Bipolar Disorder

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In some families, bipolar disorder has been transmitted over several generations, closely resembling a Mendelian disorder . This observation had originally inspired researchers to study rare, large multi-generational pedigrees under the assumption of a single gene with large effect size and autosomal dominant, recessive, or X-linked inheritance . After initial enthusiasm supported by strong genetic linkage signals, it was quickly discovered that these results could not be replicated . Incomplete penetrance, etiological heterogeneity, and recombination events might have contributed to the replication failure. However, it was also likely that the underlying disease model was not supported by the data. After all, not all segregation studies had supported a disease model built on a single major disease locus . The high frequency in the population of bipolar disorder also clearly distinguished the disease from rare Mendelian disorders. As a consequence, the idea of a single major risk locus was quickly rejected .

Subtypes Of Bipolar Disorder

One of the principles that can be used to increase the power to detect genes involved in complex diseases is to focus investigation on specific phenotypic subtypes known or thought to represent more genetically homogeneous forms of the disorder. A number of such potentially useful subtypes are known in bipolar disorder and researchers are beginning to take an interest in these.

How Common Is Bipolar Disorder

Bipolar disorder, also referred to as manic-depressive disorder, causes dramatic fluctuations in the individuals mood and energy levels. While everyone experiences ups and downs due to causes such as hormones, the weather, and stress, those with bipolar experience strong mood swings that can make it very difficult to carry out day-to-day tasks.

Based on the most recent data from the National Institute of Mental Health, about three percent of U.S. adults were diagnosed with bipolar in the past year, and a little over four percent of adults are diagnosed with this condition at some point in their lives. Its equally prevalent in males and females, with 2.9 percent of males and 2.8 percent of females having this disorder.

While this disease affects a relatively small portion of the population, especially compared to conditions such as depression and anxiety, its symptoms are often very disruptive. An estimated 83 percent of adults with bipolar disorder experience serious impairment, which is the highest percentage of serious impairment across all mood disorders. About 17 percent of individuals have moderate impairment.

Adolescents are diagnosed with bipolar disorder at a similar rate as adults. Information gathered in the National Comorbidity Survey Adolescent Supplement shows that among those aged 13-18, 2.9 percent have bipolar and 2.6 percent experience serious impairment. Among this age group, bipolar is a little more common in females versus males .

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What Is The Relationship Between Depression And Genetics

Many of us experience depression occasionally. But for some of us, the emotion is ongoing. It can come about for seemingly no reason and last for days, weeks, months, or years. It can get in the way of a person being able to perform the most basic tasks. For years, researchers have been trying to uncover the causes of depression, and the relationship between depression and genetics. Once they get to its underlying roots, they are better prepared to come up with a solution. It has been proven that people who have a close family member who is dealing with depression will be more likely to develop it themselves. This article will look at the relationship between depression and genetics so you can see how the two relate.

Does Knowing My Family History Help

An Overview of the Causes of Bipolar Disorder

If members of your family have been treated for bipolar disorder, it can be useful to know which treatments have or have not worked for them. Just remember that you are still an individual, and theres no substitute for finding the treatment that works best for you.

At the end of the day, theres nothing you can do about your genesbut you can do something about your other risk factors. You can remove yourself from toxic environments, practice healthier habits, and seek treatment and support.

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Bipolar Disorder Genetics: From My Grandmother To Me

There’s a strong genetic component to bipolar disorder. Researchers have already shown that bipolar disorder can be passed from generation to generation.

When diagnosed with bipolar 2 disorder, my doctor was curious as to who could have passed the bipolar gene down to me. In my immediate family, no one showed symptoms of bipolar disorder. Looking deeper into my family history, it became apparent that my grandmother had bipolar disorder. Her story made me think about the differences between what our lives are like living with bipolar.

Causes Of The Condition

With bipolar disorder, extreme mood changes occur. The shifts can influence a persons energy, mood, behavior, and level of functioning.

An individual can experience mania , hypomania , or major depressive episodes.

While the exact cause of bipolar disorder is unclear, research indicates genetic and environmental factors as possible contributors.

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Genetic Contributions To Bipolar Disorder: Current Status And Future Directions

Published online by Cambridge University Press: 21 April 2021

Kevin S. O’Connell*
Affiliation:Division of Mental Health and Addiction, NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo University Hospital, 0407Oslo, Norway
Brandon J. Coombes
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
*

What Are The Symptoms

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The symptoms of each of these disorders are highly variable. They depend on the persons psychological makeup, as well as where a person is in their bipolar cycle.

Possible manic symptoms include:

  • Taking risks such as drinking, taking drugs, or having reckless sex

On the other hand, depressive episodes may come with:

  • Feelings of sadness, hopelessness, or worthlessness
  • Difficulty concentrating
  • Insomnia or sleeping all the time
  • Increased appetite and weight gain
  • Forgetfulness

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What The Genetic Factor Means

What does this mean for you? If you have BPD, it means that it is not your fault. You probably have a genetic predisposition to develop the disorder. Perhaps you have also experienced a few of the environmental events that seem to be linked to BPD in some cases, such as being abused as a child or losing a loved one.

You do not have BPD because you are weak or cant handle things. There is a reason why you experience the symptoms you do.

If you have a first-degree relative with BPD, it means that you may have an increased chance of developing the disorder yourself. However, this by no means guarantees that you will develop BPD. In fact, chances are likely that you will not.

Copy Number Variant And Rare Allele Studies

Autism spectrum disorders such as autism, Asperger’s syndrome and Rett’s syndrome, are developmental psychiatric disorders with high heritability . Over the past few years, genetic studies of ASDs have consistently identified rare and de novo point mutations and large structural variants present in genes encoding interacting synaptic proteins . Such studies have reported co-segregation of putative high-risk alleles with ASDs or performed so-called ‘burden analysis’, in which different alleles of a particular gene are aggregated and the frequency in cases compared with that in controls. Initial studies of ASDs using small samples found rare missense point and structural mutations in the X-linked Neuroligin-3 and Neuroligin-4 genes . Neuroligins are a family of post-synaptic proteins that bind trans-synaptically to a family of pre-synaptic proteins called neurexins. Although these findings were interesting, incomplete penetrance of the mutations and lack of power made the results equivocal. However, missense mutations were subsequently identified in the Neurexin-1 gene at a high frequency in individuals with autism . These suggestive findings have been augmented by the results of recent genomic studies discussed below.

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Why Is Bipolar Disorder So Common In The Population

The question of why and how severe and debilitating disorders, such as bipolar disorder, could have persisted in the population at a relatively high rate of about 24% is among the leading questions of evolutionary epidemiology . According to Darwinian Theory, common, positively selected traits provided an evolutionary advantage, but in the case of some traits, left almost all members of a population vulnerable to the disease . Supporting evidence has come from comparisons of the human genome to the genome of the chimpanzee, which revealed evidence for positive selection in the opioid receptor genes and immune response genes . These studies provided support for a link between entire genes or even gene families and common human traits, such as creativity and novelty seeking, which might have not only provided an evolutionary advantage but also made all humankind susceptible to addiction and other psychiatric disorders .

Figure 1. Evolution-based hypothesis about traits and diseases.

Symptoms Of Mania And Hypomania

Is Bipolar Genetic And Do I Have It?

During manic episodes, which can cause extreme highs in mood, people may experience:

  • a lower need for sleep
  • a desire to engage in reckless behaviors such as using drugs or consuming alcohol
  • anger
  • difficulty concentrating or making decisions
  • irritability
  • high energy levels and restlessness
  • high self-esteem

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How Is Bipolar Disorder Diagnosed

In order for a doctor to diagnose bipolar disorder, a person needs to experience at least one episode of mania or hypomania. Your doctor will conduct tests to make sure that there are no underlying physical conditions that may be causing your symptoms.

Your therapist will discuss your symptoms with you to find out how frequently episodes occur and how severe the episodes of mania or hypomania are. This will help them to determine the type of bipolar disorder you are experiencing.

Summary And Future Directions In Genetic Studies Of Bipolar Disorder

Scientists and clinicians who may have hoped that one or a few genes would eventually be identified that, would explain the majority of risk for bipolar disorder must, face the reality that there are likely to be many genes of relatively small effect, involved in bipolar disorder, and the genetic dissection of this disorder will be a subtle and complex process. Genetic testing for bipolar disorder will likely ultimately require careful weighing of the presence or absence of many gene variants, when counseling is being done at the population level. As specific genes are clearly identified to play a role in bipolar disorder, it remains quite possible that, within specific families or clusters, genes of moderate effect will be discovered, but, we must face the fact that, thus far, no clear bipolar disease causing variant, has been discovered in any family studied. In the next, decade, a feasible goal might, be to clearly implicate at, least a handful of genes , from which the biochemical pathways underlying the disease can be more thoroughly studied at the level of cell biology and physiology. Such approaches may yield clear pharmacologic targets which can intervene in disease processes that have their origin in genetic risk variants, at. times by acting on an enzyme or protein that is part, of the biochemical pathway rather than on the gene or gene product, itself.

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Who Is At Risk Of Bipolar Disorder

More than 10 million Americans have bipolar disorder. Bipolar disorder affects men and women equally, as well as all races, ethnic groups, and socioeconomic classes.

Although men and women appear to be equally affected by bipolar disorder, rapid cycling is seen more often in women. Women also tend to experience more depressive and mixed state episodes than do men. A man’s first experience with bipolar disorder may be in a manic state women tend to first experience a depressive state.

Bipolar disorder can present itself at any age, but typically, onset occurs around age 25.

Chromosome 10q26 Deletion Syndrome

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The chromosome 10q26 deletion syndrome is characterized by mild to moderate intellectual disability, short stature, small head, and characteristic facial features. Cardiac, renal, and genital abnormalities have been described in some individuals.87 Rapid mood swings are common: eg, very affectionate behavior could unpredictably turn into aggressive and provocative actions.88 Hyperactivity and attention deficits are also common.89,90 Poor speech and language development, as well as autistic traits, have been described. Cognitive impairment is highly variable and can range from mild learning disabilities to severe mental handicap and absent speech. Familial transmission has been described,91 and in these instances the risk could be as high as 50%.

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Are You Born With Bipolar Disorder

Babies arent born with symptoms of bipolar disorder. But someone with a genetic risk is born carrying the genes that may increase their chances of developing the condition later in life.

However, many other factors besides heredity and genes play a role in whether these genes will be triggered, causing the disorder to develop.

Its rare for symptoms of bipolar disorder to begin in childhood. For most people with bipolar disorder, symptoms start to appear in late adolescence or early adulthood.

A Biological Process Disrupted Across Traditional Diagnostic Boundaries

The evidence for involvement of neurexins , neuroligins and related proteins such as shanks , MINT2 and CASPR2 in ASDs is substantial and growing. There is also strong evidence implicating some of these genes in schizophrenia, although not all of them have been examined. Given this overlap, it is possible that the genes may be exerting their effects through a biological pathway common to both disorders.

The neurexins are a family of transmembrane proteins that have extracellular, membranous and intracellular domains . Neurexins can be divided into two groups, and neurexins both are encoded by three genes. The neurexins are primarily expressed in neurons, where they are known as pre-synaptic heterophilic adhesion molecules, and they typically bind across the synapse to neuroligins. The neuroligins represent a similar class of proteins to neurexins and the binding of the two types of molecule to each other is controlled by alternative splicing. The intracellular domains of neurexins bind scaffolding proteins and assemble large molecular complexes that are known to link to synaptic systems such as receptors, ion channels and vesicle release machinery .

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So Is Bipolar Disorder Genetic

Its long been thought that bipolar disorder has a genetic component. Family members with a bipolar parent or sibling are more likely to develop bipolar disorder themselves. However, there have also been instances wherein bipolar disorder skips one or more generations. This suggests that both genetic and environmental factors may play a part.

Studies on the Inheritability of Bipolar Disorder

While the research around whether bipolar is genetic or environmental is still in its infancy, preliminary results have been somewhat mixed.

One 2009 review in the peer-reviewed journal Neuroscience examined the results of twin, linkage, and association studies. This review found that twin studies suggest bipolar disorder is genetic, and that having a relative with bipolar increases your risk of developing bipolar tenfold.

Another review from the peer-reviewed journal Dialogues in Clinical Neuroscience looked at the results of family studies. These include twin studies, adoption studies, and segregation analysis. The authors found that family-based studies suggest bipolar I in particular is most likely polygenetic, which means several genes contribute to an increased likelihood of developing bipolar disorder.

Is Bipolar Disorder Caused By A Single Gene

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Bipolar disorder is not caused by a single gene. Rather, many gene variants and factors are involved in the development of bipolar disorder for someone who has a family history.

Other environmental factors also play a role in triggering the onset of bipolar disorder in people with a genetic risk, but appear to contribute to a lesser degree.

study , researchers evaluated the family histories of people with bipolar I disorder to see how often the disorder appeared.

In total, they looked at 156 participants with bipolar disorder and their family members:

  • Among 57 participants, bipolar disorder was detected in a first degree relative: parents, siblings, and children.
  • Among 22 people, the condition was detected in a second degree relative: grandparents, aunts and uncles, or neices and nephews.
  • In 14 participants, it was detected in third degree relatives and beyond: cousins, great grandparents, and great uncles and aunts.

Similar results appeared regardless of whether the genetic risk came from the mothers or fathers side of the family.

suggests that people with a family history of bipolar disorder may be more likely to experience:

  • earlier onset of symptoms

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Relationship Between Schizophrenia And Bipolar Disorder

Traditional clinically ascertained family studies during the 20th century, employing main-lifetime diagnoses, generally did not find a significant excess of bipolar disorder among the relatives of individuals with schizophrenia, or vice versa,,,, supporting the concept of an etiological dichotomy between the 2 disorders. However, these studies could not exclude a degree of familial coaggregation due to sample size limitations.

Consistent with this, a twin study, based on the Maudsley twin register in London, found no co-occurrence of schizophrenia and bipolar disorder in MZ twin pairs when a hierarchical main-lifetime diagnosis was employed, again with the caveat of sample size limitations. However, when a nonhierarchical lifetime-ever approach was taken, significant coaggregation was seen between schizophrenic and manic episodes in twin pairs, and model-fitting showed a significant genetic correlation of 0.68 between lifetime-ever schizophrenia and mania.

Additionally, a meta-analysis of family studies published between 1980 and 2006 found evidence of familial overlap, with the first-degree relatives of probands who had schizophrenia showing a significantly elevated risk of bipolar disorder compared with relatives of controls .

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