Bipolar Spectrum Disorder

Dr. Philip Grossi
Thursday, 27 January 2011

I thought I would devote this blog to bipolar spectrum disorder because its explanation and description occupies so much time in the office due to its commonality, complexity and extraordinary variety of presentation and life course.  It is in a sense a great masquerader because it can appear in the guise of a panic or anxiety disorder, a major depressive disorder or even as an acute paranoid psychosis or post traumatic stress disorder and/or coexists with other problems. This is then being posted mostly for patients to refer to and to reduce the time needed for my oral presentations. 

Bipolar I (BPI or the older term Manic Depressive) has a lifetime prevalence of 1.0%, Bipolar II (BPII) has a lifetime prevalence of 1.1%, Bipolar NOS (BPNOS) has a lifetime prevalence of 2.4%.  C. Moreno and colleagues and J.C. Blader and colleagues have found increased BP diagnosis in adult and pediatric populations.  Hirschfeld, Olfson, and McIntyre and their respective colleagueal groups have studied primary care groups and found that those patients manifesting and being treated for significant depressive symptomatology have an approximately 30% chance of falling in the bipolar spectrum.

What would account for the increased diagnosis of bipolar disorder?  Several explanations have been advanced.  A much wider conceptualization of bipolar disorder starting in earnest in the mid 1980s, overdiagnosis especially in young populations (possibly influenced by drug company marketing), much increased attention in the lay press, and finally some genetic explanation involving anticipation (younger age of onset) as well as assortative mating.

Prompt diagnosis of bipolar spectrum disorder is important because it reduces the risk of suicide, chronicity, and risk of relapse, to say nothing about the increased quality of life that is made possible.  Numerous studies have found that the average length of time between symptomatic presentation and diagnosis is between eight  to ten years.  Three years ago Patty Duke, the child movie star, spoke to a group of psychiatrists about her own experience.  She developed symptoms in the late teen years but was not diagnosed until she was 35 years old.  During those intervening sixteen or seventeen years she spent months at a time in bed arising only to go to the toilet and thinking repeatedly about suicide.   This delay in diagnosis is the rule rather than the exception.

illustration to bipolar spectrum disorder blog

I do not plan to review the diagnostic criteria for bipolar disorders because they are readily available at many sites including several links which can be accessed from the home page of this site.  However, I will review some of the clinical findings that help to differentiate BP spectrum from unipolar depression.  Any depressed person should be appraised for  bursts of increased energy and decreased need for sleep (hypomania).  BP spectrum disorders have an earlier age of onset, usually before 25 years of age.  An individual who meets criteria for a major depressive disorder who is not yet 20 years old has a much higher likelihood of developing into a bipolar patient than individuals who develop depression later in life. Cyclicality is the watchword for BP spectrum since mood swings is the major pathology rather than depression. This results in briefer periods that are symptom-free. The depression in BP spectrum tend to have some distinguishing characteristics, including a more abrupt onset that those with major depression.  BP spectrum patients tend to experience mood destabilization with sleep deprivation and transmeridian travel (this is common in Silicon Valley due to the amount of international travel).  Females in the BP spectrum tend to experience postpartum depressions with greater frequency and tend to have worse premenstral upset (dysphoria). While there is no absolutely diagnostic presentations of depression which dictate a specific diagnosis, atypical depressive presentations tend to be more common in BP spectrum.  Atypical depressive presentations include increased appetite and weight gain, hypersomnia (more time in bed, more time sleeping, naps) and overwhelming fatigue sometimes called leaden paralysis.  Typical depressions usually manifest insomnia, agitation, and weight loss. In arriving at a diagnosis, it is important to take into account the course of illness over time.  Central to BP spectrum is hypomanic states which include irritability, talkativeness, and racing thoughts, increased energy and decreased need for sleep.  Often these can only be elicited by talking to family member as the patient often seems to seal off these episodes from consciousness. Finally, we shouldn't forget that these are highly heritable disorders.  Therefore, looking at the family tree is important especially at the first degree relatives.  There are studies that show that the risk of having a BP spectrum disorder goes up 10 fold if one has a bipolar parent.

McIntyre and colleagues found that medical comorbities were prevalent in BP spectrum patients. Epilepsy, multiple sclerosis, migraine, circulatory disorders, and metabolic syndrome are much more common in BP spectrum than in the general population. Metabolic syndrome is an constellation of deviations from health that include insulin resistance, central adiposity, elevated lipid lab profile, elevated BMI, and hypertension.  In BP spectrum patients metabolic syndrome is supported by unfavorable lifestyle (smoking, poor diet, physical inactivity) and the effects of treatments used to treat BP spectrum including atypical anti-psychotics and some mood stabilizers. Substance abuse is also common in BP spectrum.  By some estimates, 60% of bipolar spectrum patients have an alcohol abuse problem at some time during their life.

When I make the diagnosis of BP spectrum disorder, I present this as a statistical or probabilistic statement.  There is no test for bipolar disorder, no gene or genes have been identified as causative, no brain image that is diagnostic and therefore the certainty of the diagnosis is somewhat less that 100%.  Still, prompt diagnosis and treatment is crucial to securing a positive outcome for a patient which should offer the chance for a "normal" life.

Creative Thinking

Dr. Philip Grossi
Tuesday, 28 December 2010

I have returned from my blog vacation. 

A few days ago I saw one of my college student patients who usually visit me during their break from school. This particular patient did not present a difficult treatment challenge as the first intervention worked well several years ago and continues to work well without complications, side effects or adjustments.  He originally wanted to go to medical school  but after some time at college and an experience with organic chemistry, he decided to change his field of concentration to mathematics.  He talked about the proposed aggressive reduction in the Math Department budget and its anticipated effects.  He shared his new view of mathematics, that is, he talked about real mathematics as distinct from applied or "school" mathematics.  Applied, school, or useful mathematics includes arithmetic, elementary algebra, elementary Euclidean geometry, elementary differential and integral calculus. Real mathematics do not appear to have any real application to the physical work but represent and underlying beauty and pattern. This includes such areas as modern algebra and geometry, number theory, theory of aggregates and functions, relativity, quantum mechanics, and the theory of matrices and groups.  Who could have predicted that matrices and groups would have application to physics? 

This brief story of my last visit with this patient contains many important strands to pull and fondle. First, I am reminded that the cultivation of a platform that supports and encourages creative new solutions to the problems that abound around us is hugely consequential for the future of the American economy.  Successful scientists, philosophers, and inventors have weighed in on this issue from the ancient Greeks to contemporaries like Richard Feynman.  Feynman's advice to be irreverent toward established ideas is mentioned on the home page of this site.  Probably the best advice for fostering creative thinking comes from G.H. Hardy, the Brittish mathematician, who worked in analytic number theory and developed the Hardy-Weinberg principle which states that both allele and genotype frequencies remain constant in a population.  This is an ideal state (not found in nature because of a variety of disturbing features such as mutations, non-random mating etc.) and can be used to compare actual observation to this ideal state.  In any event, he wrote a rather intriguing and provocative article in 1940 entitled  A Mathematicians Apology  in which he compared real mathematics to poetry and art.

illustration to creative thinking blogHardy talks about the mathematician as a creative artist, as a maker of patterns fashioned from ideas.  Painters use shapes and colors while poets use words.  Just as the painters colors and poet's words must be beautiful so must the mathematicians ideas be beautiful by fitting together harmoniously.  These mathematical ideas must also be serious, that is, it can be connected in a natural way with a large number of other complex mathematical ideas.  The seriousness lies in its content, not its consequences, just as Shakespeare enormously influenced the English language because of the superiority of his poetry and its deep content.  In order for the mathematical idea to be significant, it must have beauty, seriousness, and depth but also be general, that is, be a constituent in multiple mathematical constructs used to prove theorems in different areas of mathematics.  The final quality that Hardy discusses is that of unexpectedness combined with inevitability and economy.  The arguments are unusual, simple (often in the extreme) and produce far-reaching results.

What are the qualities of creative thinking?  Often in award ceremonies one hears the words creativity, importance, and impact to describe the winners scientific contribution.  One could just as well use Hardy's words significance, generalizability, and unexpectedness. 

In my opinion, the decision by administrators to cut the Mathematics Department budget was short-sighted and harmful to the American economy because it will likely reduce creative thinking in areas we need most.


Dr. Philip Grossi
Tuesday, 02 November 2010

The topic of marijuana is a  timely one considering  that California Proposition 19 (legalization of marijuana) is being voted on today.  People will undoubtedly vote their experience with marijuana or that of their friends or family  which makes the decision for the society at large irrational because one's response to it is determined by one's unique genetic makeup and the balance of various cannabinoids of which there are about 70 unique to the plant.  The balance between Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is especially important.  The social milieu is undoubtedly also important in producing specific behavioral responses. Therefore, any decision is based on an extraordinarily large number of factors which are unlikely to repeat in anything less than evolutionary time. 

illustration to marijuana blogCannabis is very popular the world over.  Its use has increased dramatically in the past dozen years.  Indeed, the European Monitoring Center for Drugs and Drug Abuse estimated that the number of people seeking treatment for abuse of marijuana has greatly increased since 1999 and represents one in seven referrals for drug abuse treatment.  In healthy individuals there are many studies that document the acute findings of cognitive impairment, anxiety, memory impairment, psychomotor control impairment, and psychotic or psychotic-like symptoms.  Longer term effects remain in question and very few develop dependence or psychosis. 

The main psychoactive ingredient is THC and it is this effect that  many people seek.  When THC is given intravenously to healthy people it produces anxiogenic effects and psychotic-like symptoms.  CBD however has anxiolytic effects, antipsychotic effects, and is thought to be neuroprotective.  In short,  CBD is thought to protect against the THC effects. (THC is a partial agonist at CB1 whereas CBD is an antagonist at CB1 and CB2.)

A recent naturalistic study by Morgan published in a recent issue of the British Journal of Psychiatry  compared compared 134 cannabis users on measures of memory (prose recall-- considered the best everyday predictor of everyday memory performance) and psychotomimetic symptoms as indexed by the PSI.  What they found was that those that smoked cannabis low in CBD had clear-cut memory impairment whereas those that smoked cannabis with high CBD had no memory impairment in immediate or delayed prose recall.  However, with regard to psychotomimetic effects, CBD did not effect the findings which were that both high and low CBD cannabis smokers showed similar symptoms when acutely intoxicated.  This last represents a null finding as the researchers had predicted that high CBD would reduce psychotomimetic symptoms.

There are several important implications to this study.  First, the current popularity of the skunk (low CBD to THC) type of marijuana will have more adverse cognitive and memory effects. Second, CBD may have a therapeutic role for memory problems especially from THC.  Third, CBD may well be a worthy research molecule for treatment of psychosis and anxiety. The marijuana sold in dispensaries should be labeled with THC and CBD content to allow the consumer to make a more informed decision.


November 3, 2010.  Proposition 19 did not pass.