The thought of developing bipolar disorder seemingly out of nowhere can be scary. Also known as manic-depressive illness, the disease can be severe and life-changing. Drastic changes in mood, including lows that leave you unable to function and highs that remove you from reality, can make it nearly impossible to make it through a daily job or routine.

Scientists have known for some time that certain genes are likely to cause bipolar disorder, and some of these genes are also linked to an increased risk of schizophrenia and alcoholism. But the things behind the development of bipolar disorder are likely a mix of different factors, ranging from gene mutations to a person’s upbringing, as well as that person’s penchant for anxiety and other mental health issues.

Genetics

The first thing that comes to mind when scientists discuss bipolar disorder is its tie to certain genes that may cause it. These genes tend to run in families, increasing the risk for a bipolar person’s relatives to also eventually get the disease.

But all the genes that might go into bipolar disorder still aren’t fully known. According to a new study published in Proceedings of the National Academy of Sciences, the accumulation of certain rare versions of genes might have something to do with the disease. The researchers sequenced the genomes of 200 people from 41 different families that had a history of bipolar disorder, and identified 164 rare forms of genes that were more likely to appear in people with the disease. Bipolar people had six of these rare forms on average, while their healthy counterparts averaged about one. These genes in question are involved in the monitoring of ions to enter or leave neurons in the brain, which in turn affects how neurons pass information through the brain.

“There are many different variants in many different genes that contribute to the genetic risk,” Jared Roach, a geneticist at the Institute for Systems Biology in Seattle and an author of the study, said. “We think that most people with bipolar disorder will have inherited several of these… risk variants.”

But genes are certainly not the only factor behind the disease. “Studies of identical twins have shown that the twin of a person with bipolar illness does not always develop the disorder, despite the fact that identical twins share all of the same genes,” the National Institutes of Health (NIH) writes on its website. “Research suggests that factors besides genes are also at work,” such as environmental factors.

Brain Structure

Through functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), scientists have discovered over time that people with bipolar disorder have different brain structures than people without the disorder. A 2005 study found that people with bipolar disorder may lose more brain gray matter while aging, and there was less gray matter in the prefrontal brain regions in general. Another study published in the Journal of Neuroscience concluded that indeed, “genetic and phenotype-related influences on brain structure” in bipolar patients was definitely different from healthy people.

Anxiety, Depression, And Mental Disorders

If a person already suffers from anxiety, or other mental illnesses like post-traumatic stress disorder (PTSD) or social phobia, they may have a higher risk of developing bipolar disorder, according to the NIH. In addition, simply going through stressful experiences, or moments of grief, can increase a person’s risk for bipolar disorder.

This may perhaps explain why 11 to 39 percent of bipolar patients also meet criteria for PTSD. Whether PTSD is a direct cause of bipolar disorder or vice versa, however, isn’t completely understood. It’s possible that traumatic experiences in childhood, such as physical or sexual abuse, can lead to bipolar disorder; but it’s also possible that someone with bipolar disorder might be more likely to be exposed to traumatic experiences during a manic episode and thus develop PTSD later as a result of bipolar disorder.

In addition, studies have shown that children with attention-deficit disorder (ADD) or attention-deficit hyperactivity disorder (ADHD) are more likely to develop bipolar later on. But it’s important to recognize that ADHD and bipolar disorder are not the same; people often confuse the symptoms of one for the other.

Substance Abuse

Many people going through a traumatic experience or depressive episode often turn to alcohol or drugs to cope. Developing a substance abuse problem can only lead to worsened depression and moodiness, thus potentially being a player in some cases of bipolar disorder. Since alcohol and other drugs may intensify emotions, they can make people’s sadness deeper, or manic moments even more intense. If substance abuse isn’t a direct cause of bipolar disorder, it can still often exacerbate symptoms among people with the disease.