I went to the Lab today and had a good discussion about the project I’ll be working on. We have neural progenitor cells (essentially neuronal stem cells) from the olfactory neuroepithelium of individuals with bipolar illness and matched controls (ONP cells). The cells from bipolar individuals have the genetic heritage of Bipolar d/o.These cells have been treated with MSG at a concentration of 1mM. The cells from Bipolar individuals apoptose (undergo programmed cell death) much more than from healthy controls. Now we are going to grow these cells in a 3 dimensional cell culture and determine epigenetic alterations specific to the illness. Epigenetic alterations are changes in a gene that do not involve changes in its sequence. These alterations are additions to the DNA sequence of the gene, such as:

1) Methylation (addition of a methyl = CH3 group),

2) Acetylation (addition of an Acetyl = O=C–CH3
3) As well as changes in Histones, which are proteins that bind the DNA tightly into chromosomes.

The theory is that Bipolar d/o is caused by epigenetic changes.

Also, I found out today about an article that came out on Oct. 14, by Dr. E. I. Ginns et al (http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp2014118a.html) that says a gene, funnily enough named Sonic hedgehog (Shh) is protective against getting Bipolar d/o.

In her research among the Old Order Amish, which extends back more than 40 years, Janice A. Egeland, PhD, professor emerita of Psychiatry and Behavioral Sciences at UMMSM and co-author of the current study, found that both EvC (a form of dwarfism) and bipolar were prevalent in an extended family descended from the same progenitor. Both conditions clearly travelled together over the generations in a few families extending from this same pioneer. Yet no person with EvC was ever reported with bipolar disorder despite decades of research across multiple generations.

EvC dwarfism results from genetic mutations that disrupt the signaling pathway known as sonic hedgehog (Shh). Statistical analyses confirmed the significant negative association between EvC and bipolar disorder. This further suggested that the Shh pathway plays a role in bipolar disorder. The great thing about this is that drugs already in clinical trials for other medical conditions that target Shh protein signaling may have the potential to be better treatments for bipolar disorder.

Ginns cautioned that although “we have a good idea of potential novel drug target(s) that could stop symptoms, it’s still unclear what changes along the Shh pathway lead to bipolar disorder. The Shh pathway involves more than a dozen other molecules, and interacts with over 100 other genes. It’s likely that other genes or proteins in this pathway may participate in determining the various symptoms and sometimes catastrophic outcomes seen in patients with affective disorders, including suicide.”

Ginns and his collaborators are already working to unravel more details of the puzzle and identify changes in the Shh signaling and related pathways that correlate with disease symptoms. “Even though the symptoms of bipolar affective disorder can be quite varied and complicated, the underlying genetics might actually have a more simple cause than we could have imagined,” said Ginns.

All in all a very exciting day for people interested in Bipolar d/o and especially meaningful for me.

Early detection of schizophrenia may lead to not developing the disease or mitigation of symptoms.   See: http://www.npr.org/blogs/health/2014/10/20/356640026/halting-schizophrenia-before-it-starts?utm_source=facebook.com&utm_medium=social&utm_campaign=npr&utm_term=nprnews&utm_content=2044

What an intriguing thought! If an illness, that is much more severe than bipolar d/o, may be prevented by not letting the first psychotic break happen, then can bipolar disorder be attenuated or obliterated by early detection? There are no studies of this sort, and anyway, how can you say what would have happened if… or what wouldn’t have happened if… But if this can be done, it would be amazing for people with bipolar d/o genes. Bipolar is incompletely penetrant, this means that not all people who carry the genes that have been associated with bipolar disorder, actually get the disease. See: http://hmg.oxfordjournals.org/content/early/2014/07/15/hmg.ddu335.full

Perhaps, the incomplete penetrance of bipolar disorder is due to it having been caught early and stopped from developing fully into a disease. Just a thought.

Thank goodness! The migraines are gone, mood is fine, now this might be too much to ask, but can the muscle weakness and muscle pain please go away?

Gosh, I was looking at a bunch of bipolar blogs, and it’s scary how alike we sound sometimes… of course moods, of course. Moods are what our lives are about. But also the ultra sensitivity. Sometimes, the anger (I haven’t been angry lately, but I have in the past), poetry, so many poems! Also how we all kind of make the bipolar d/o a separate entity. Not within us, but outside of us. How it is “hijacking our brain”, how it exists outside of us! God are we the Borg? How can people raised by different parents, in different cultures, with different values, and different outlooks, be so alike? Is this one disease such a unifying factor that genes as in nature, and culture as in nurture, are null and void? Oh except the bipolar genes of course. Wow, how powerful are these bipolar genes, that they can make people so alike in the face of pretty huge differences?

Some one should study this in a lab. It can be a collaboration between biologists and social scientists. An interesting experiment, though probably quite difficult to do. I’ll talk to the person whose whose lab I am starting in tomorrow or Tuesday, about this. Yes the day is finally here and I am extremely excited to be starting work in this lab. I think my project will be looking at the molecular biology of the action of Lithium! So incredibly excited. I wonder if all my bipolar friends would be this excited as well… just a thought.

The purpose, the reason, the aim. What is it? Why am I here? I find myself asking these questions, mostly when I am veering toward the depressive side. Not the manic side, not the mixed side and not the anxious side, only the depressive side. Existential questions come up. Existential answers do not. Anyway, who asks these questions when they are busy and happy and well occupied? No one, that’s who. Who has time to ruminate when one is happy, productive, involved. The only time, besides some rollicking discussions with philosophers I know, I get too thoughtful is when my mind can’t stop nitpicking and over thinking everything. I am sure this happens to many people, but it probably happens more often to people with bipolar disorder.

Then what do you do? You can partake of some physical activity, such as walking in the woods, one of my favorites, or listen to some uplifting music, Beethoven’s 9th Symphony is one of mine, or read some poetry, perhaps Shakespeare, or even have a rousing conversation with a friend. Meditation may help. Just shake yourself out of the rumination, get back to the now and live your life.

That is really one of the saddest parts of having bipolar, it totally has the ability to stop you from living your life, from enjoying it, from savoring it, appreciating it. This disease is a robber, of happiness, of health, peace of mind, of life. But we have to be stealthier, more powerful than it, and live our lives happily, successfully, and contentedly.

Now if only the migraines would go away so I could have one whole, productive, normal day, that would be wonderful. I’m getting migraines from increasing the dose of Seroquel. This increased dose has definitely brought me out of whatever phase was trying to hijack my life again. But now I wake up with a blinding migraine everyday. For the love of God, I can’t win for losing. Hopefully my body will get used to this increase in Seroquel and the migraines will go away. I have an appointment with my psychiatrist. Let’s see what he says. Wish me luck.

Both sides of my family, although wealthy beyond belief at one point, have so much mental illness that it is indeed a miracle that I am as normal as I am. My father’s family members were suspected to have had bipolar disorder. I say suspected because in the early 1900’s in India, it was difficult to diagnose or treat mental illness. He had relatives who had to be shut in rooms at certain times and they were perfectly normal at other times. Sounds like bipolar d/o. On my mother’s side, one of my grandmother’s brothers had committed suicide. I would say pretty much all my aunts and uncles from my mom’s side have some kind of mental illness. One of them has schizophrenia, another is cyclothymic. One was a savant in languages, also had epilepsy but was so innocent that ALL the shopkeepers in Pakistan knew him and loved him because they could cheat him out of oodles of money. One aunt has depressive episodes and possibly because of anoxia to the brain while being birthed, has cerebellar ataxia, an awful disease in which the cerebellum suffers mini strokes so the patient loses control of their voluntary muscles. She lives with my cousin, her nephew, along with her niece, who are amazingly loving and kind to take care of her. I mean how many nieces and nephews do you know who take care of their aunts and uncles? My other aunt, I am convinced, suffers from bipolar 2 and my mother had major depressive d/o. The only person who was normal was my Khalid Mamoon, and he, tragically, died when he was 21 years old, in a motorcycle accident. Oh the irony of it all, my grandmother had to suffer through a lot of tragedy in her life. So that about covers it all. Such a bag of mental illness genes we all are! Really quite unbelievable! We should have been studied as a family of individuals with so many mental/neurological illnesses. Amazing, I say it again, that I am as normal as I am considering my genealogy..
Incidentally, Baba Farid, our Sufi saint ancestor, well I am convinced that he suffered from bipolar disorder as well. I mean he is supposed to have hung upside down in a well for seven years with no food or water. I mean, really, who even thinks of doing that?
Anyway, he was a talented poet, and did preach love and nonviolence, can’t really argue with that.
More later.

A few days ago, I had started feeling bad! Depression? Mania? Mixed? Who knows! Just extremely bad… And I was off the Zoloft, have been for about a month to stop “mini” cycles. So now what do I do? Can’t take Zoloft if it is a depression. I was still on 900 mg of Lithium and 50 mg of Seroquel, which is another mood stabilizer.
I started taking 100 mg of Seroquel and in TWO days, I feel almost normal. My normal singing, talking, thinking, SMILING, interested in things me!!! Do you have any idea how big this is! In two days!
I absolutely worship my doctor, he was right. Let’s see if I continue to stay on 900 mg Lithium and 100 mg of Seroquel, will my mood continue to be controlled? Oh my goodness, I hope so. This is amazing. I am so thankful for this that I could jump up and down with joy. Just thought I’d share the good news. :))

My mother.                                My father.

It wasn’t that my grandmother didn’t love her children. She did, most certainly and fiercely. It was that she became a mother at the age of 13/14, she had no mother as hers had passed away when she was a very small girl, and I am sure she suffered from intermittent explosive disorder. This is when a person becomes so angry that they black out and without even realizing it, they do violence to other people. Unfortunately and really heartbreakingly, my grandmother’s victims were her own children. By the time I came along, she was mild and loved me more than life itself. It is her love and my Ammi Khala’s, Fatto Khala’s, and my Ahmed Mamoon’s love and care that has made me as strong and as normal as I am. Truly it is. Without their love and care and adoration, I think I would have been a total basket case. Why you ask? Because even though my mother was never beaten, she must have internalized all the violence. She was not allowed to be beaten because my grandfather forbade it, because she was beautiful, intelligent and my grandfather’s favorite. So, she was never beaten. My mother was in Medical school in Bhopal, India, where my father, Shahid Kamal Pasha, (his real last name was Khan, but because his oldest sister loved Mustafa Kemal Pasha, she named him that) saw her. He was also from a princely family, the youngest of his siblings. They were from the family of the Nawab of Bhopal. He fell madly in love with my mother, and being the handsome, spoilt, young, entitled man that he was, he pursued my mother. In those days, as even now, there was no dating allowed, but my mother was far away from UP (United Provinces), where her home was, and they did sort of date. And against my mother’s family’s strong wishes, my mother and my father got married. Then I came along. I was born in Bhopal on June 30th, 1960. Apparently one of my lungs collapsed when I was just a few days old and I had to be hospitalized in those days’ version of the NICU. My mother’s Pediatric professor was my doctor and told her best friend, Saroj, that he didn’t think I was going to pull through. But pull through I did. I have had an enormous amount of strength since the day I was born! My mother had not graduated from Medical school yet, she was in 2nd year. So my grandmother took me to Karachi, Pakistan, where my whole family  was moving. I lived with my grandmother, My aunt Liaquat, whom I called Ammi Khala, my Farhat Khala (khala means maternal aunt) and Ahmed Mamoon (mamoon means maternal uncle) for two blissful years. I was perfectly taken care of, I was adored, every need of mine was met. I don’t think they ever let me cry. Ammi Khala cared for me and loved me like I was her own daughter and I loved her as if she was my mother. They took pictures of me and sent them to my mother. In the meantime, my mother’s young marriage was not doing too well, and she and my father moved to Karachi after she graduated from Medical school. Of course she reclaimed me and life in paradise was over. My parents’ marriage deteriorated steadily. And by the time I was four years old, my mother started beating me mercilessly. She finally stopped when I was fourteen years old, when I lifted my hand as if to strike her, to protect myself. Finally, it took me TEN years to say “Enough, you can’t hit me anymore!” Oh I had black eyes, bloody lips, a bloody nose, black and blue marks all over from being hit with anything that came into her hands. Yes I did. And I know why she was doing it. She was spoilt, her husband was probably cheating on her, he didn’t have a job, she was angry that she had to work all the time to support us. She probably suffered from the aforementioned disorder (IED) and she had no one to take it out on except a defenseless young child. I hated her for a long time, I was extremely angry for a long time, but around the time I was in my early thirties, I forgave her. I decided to let it all go. With the help of one of my best friends, Deb, I truly forgave my mother and started loving her as a daughter should. I forgave my father as well. He had never stayed in touch with us since their divorce in 1965, I looked him up in 1999, and stayed in touch with him until he passed away a few years ago. They were people and people make mistakes. And anyway, they were not the same people in the 1980’s or 1990’s or the 2000’s as they were when I was a child, so how could I keep holding grudges against them? I couldn’t. After forgiveness comes love. Comes lightness, airiness, comes Grace. And all the mistakes I’ve made involving anyone, my beloved son and husband, my beloved friends, my beloved family members, I hope they will forgive me too, not only for my sake, but for their own sake as well.

Should I feel guilty about writing this down? I do. Even though it is my story, I feel like I am blackening my mother’s name and I really did love her very much. She was an extraordinary woman, an MD in India, when girls weren’t allowed to have any education, she sang well, she was a self taught gourmet cook. She loved Art, Music, Fashion, Architecture, Urdu Poetry, she was a remarkable woman and I did and do love her immensely. My story is my story and I think it needs to be told. Maybe the truth shall set you free…

Rest of the story, soon.

My grandfather’s card.

My Uncles, Wahid and Waris.               Uncle Waris

So my grandmother, Begum Mushtaq Fatima, was married to my grandfather, Ahsan Mohammad, when she was 13 and he was 20. He was handsome, 6 ft tall, and educated in the Western style. She was diminutive, not even 5 ft. tall, but she had a formidable personality, was a crack shot with a rifle, and if you knew what was good for you, you did not cross her! They started having children immediately of course, as no birth control was available at the time (India 1920’s.) They had two strapping baby boys, Waris, which means the inheritor or successor, and Wahid, which means singular or unequalled. My paternal great grandfather said they shouldn’t have named the second child Wahid, that was the bad luck that caused it. Their first child, Waris, being a rambunctious, spirited boy, ran out into the street when he was five years old and was hit by a car. He didn’t survive. That was the bad luck. A few years after that my great grandfather decided to ship my uncle Wahid off to boarding school, in order to save him from a similar fate. More about that later. In the meantime, my grandmother had my aunt Wajahat, my aunt Liaquat, my uncle Ahmed, My mother Sabahat, my aunt Farhat, and finally my uncle Khalid.

From the stories I have heard, I am convinced my grandmother suffered from Intermittent Explosive Disorder. She apparently got so enraged and angry at her little children, and about minor things, that she lost total control of her self and beat them mercilessly. When my uncle Waris was four years old and my uncle Wahid was three, they decided to rum away from home because of these heartless beatings. They walked to the train station and boarded a train to leave! However my grandparents were well known in the area (they owned most of it, and because of our central asiatic roots, we are all recognizable) the little children were recognized and taken back home. I don’t know what happened to them when they got home, whether they were embraced with loving tears, or beaten, I don’t know…

Here’s a story I was writing last year, and quite accidentally came upon again. I will finish it in the near future.

A long time ago, and very far away… isn’t that how stories start out? My nanny, in the hot afternoons in Lahore, used to start her stories like that. She would tell us stories about adventures, about boys who put salt in the cuts on their fingers so they wouldn’t fall asleep and miss the ship that was taking them to their fabulous adventures Then she would forbid us to ever do what these boys had done, no salt in our cuts, she warned, because it stings and hurts.

She didn’t know the sting and the hurt that had already been in my life and none of us knew what stings and hurts and tragedies life held in store for us.

I start and then I don’t want to go on. I don’t want to write about the sad things and relive the devastating emotions. So I start and start and leave it unfinished. Anxiety makes me stop. But I will conquer this anxiety and go on.

She was my grandmother. She was only 13 when she got married. She was raised like a princess, the only daughter of a very wealthy adoring land owner father, who owned 1000’s of acres of land, in fact whole villages and was a Nawab, the Indian equivalent of a Duke. Her mother had died when she was a baby so she was brought up by her wet nurse, who adored her and was adored in return. However, the wet nurse really still being a servant, had no authority over my grandmother and so my grandmother grew up imperious, spoilt and used to getting her way. When she inevitably started having children soon after she was married, she did not know how to be a mother. She was 14 at the most when she had her first son. A child herself and spoilt and imperious and impatient and used to being waited upon, not waiting on a new born.

More to come, soon.