1 Boring Old Man

The place of antipsychotics in the treatment of Psychosis remains clouded in controversy in spite of more than a half century of study, experience, and debate. Neither Kraepelin’s Dementia Praecox, a progressive deteriorating illness leading to an early death, nor Bleuler’s Schizophrenia, a defined syndrome with multiple types, survives as the dominant model for predicting the course of illness. We now tend to see episodes of psychosis punctuating a variable level of functional impairment over time. While traditional guidelines call for maintenance medication based on relapse prevention, long term studies document that many patients regularly discontinue the treatment. And others feel strongly that maintenance medication itself interferes with recovery. Both of these opposing recommendations are backed by studies, anecdotal case reports, passionate ideologies, and interpretations of the bias of the opposing view. Since these medication have now been around now for a lifespan we’re seeing large population surveys that bear on this controversy. This one’s from Scandanavia, a traditional resource for this big population studies:

Antipsychotic treatment and mortality in schizophrenia.

by Torniainen M, Mittendorfer-Rutz E, Tanskanen A, Björkenstam C, Suvisaari J, Alexanderson K, and Tiihonen J.

Schizophrenia Bulletin. 2015 41[3]:656-663.

BACKGROUND: It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view.

METHODS: We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 [N = 21 492], aged 17-65 years, and persons with first-episode schizophrenia during the follow-up 2006-2010 [N = 1230]. Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010.

RESULTS: Compared with age- and gender-matched controls from the general population [N = 214920], the highest overall mortality was observed among patients with no antipsychotic exposure [hazard ratio [HR] = 6.3, 95% CI: 5.5-7.3], ie, 0.0 defined daily dose [DDD]/day, followed by high exposure [>1.5 DDD/day] group [HR = 5.7, 5.2-6.2], low exposure [<0.5 DDD/day] group [HR = 4.1, 3.6-4.6], and moderate exposure [0.5-1.5 DDD/day] group [HR = 4.0, 3.7-4.4]. High exposure [HR = 8.5, 7.3-9.8] and no exposure [HR = 7.6, 5.8-9.9] were associated with higher cardiovascular mortality than either low exposure [HR = 4.7, 3.7-6.0] or moderate exposure [HR = 5.6, 4.8-6.6]. The highest excess overall mortality was observed among first-episode patients with no antipsychotic use [HR = 9.9, 5.9-16.6].

CONCLUSIONS: Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.

While the implications of this study may seem to conflict with other oft·quoted papers [eg Wunderink, Harrow, etc] the outcome parameters are different – functional improvement there vs overall mortality here. Further, all of these reports can’t possibly factor in the most confounding variable of all – the unique clinical field that the patient, the clinician, and the family face at any given moment in time. So reading the blogs, the individual case reports, and the various commentaries on this topic can be confusing as they often discuss these decisons as if they fall into the domain of morality – using maintenance medication is good as opposed to using maintenance medication is bad.

South Carolina House votes to remove Confederate flag from statehouse grounds

Washington Post

By Elahe Izadi and Abby Phillip

July 9, 2015

South Carolina Gov. Nikki Haley is set to sign a bill that will bring down the Confederate flag on the statehouse grounds, less than a day after lawmakers in the state House of Representatives voted to remove it. Haley, a Republican, called for the flag’s removal last month in the wake of the shooting massacre inside a Charleston church. The bill cleared its final legislative hurdle early Thursday morning when the House voted 94 to 20 in favor of the proposal.

After more than 13 hours of debate — which became increasingly contentious as the night wore on — House Republicans and Democrats agreed not to amend the legislation with a proposal that threatened to make final passage more difficult. Just before 1 a.m., the lawmakers voted 93 to 27 to move it forward in a critical second-reading vote. Minutes later, the bill easily cleared the two-thirds threshold needed for it to officially pass the chamber, a hurdle the state Senate cleared earlier this week.

If you didn’t grow up in the South in the 1940s and 1950s, you couldn’t possible imagine how big this is. That license plate on the right was on the front of many cars [in some places "most cars"] and "The South shall rise again!" was a stock phrase. Even those of us who were dedicated to racial equality and were marching in the streets saw that flag and those slogans, as having some misty-eyed meaning. That was wrong. And many of us figured that out along the way. But for the Legislature of the State of South Carolina to actually do something about it is truly a something I thought I’d never see. There will come a time when this something will be the history that South Carolinians are proud of…

^{[click image for the full version]}

Some time back, I began to hear a new term – "New Vigil." I thought it was a street drug – slang – because the people where I live were traveling some 50 miles away during the recession to work in the numerous chicken processing plants there [shift work]. So I thought "New Vigil" was a nickname for some new version pep pill they were taking to stay up all night plucking chickens.

Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.

by Ketter TA, Yang R, and Frye MA.

Journal of Affective Disorders. 2015 181:87-91.

BACKGROUND: In a previous study, adjunctive armodafinil 150mg/day significantly improved depressive symptoms associated with bipolar I disorder.

METHODS: Multicenter, double-blind study of patients with a major depressive episode despite bipolar I disorder maintenance therapy randomized to adjunctive placebo or adjunctive armodafinil 150 or 200mg/day for 8 weeks; for logistical reasons, assignment to armodafinil 200mg/day was discontinued early. Primary efficacy was measured by change from baseline to week 8 in 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score.

RESULTS: Patients were randomized to adjunctive placebo (n=230), adjunctive armodafinil 150mg/day (n=232), or adjunctive armodafinil 200mg/day (n=30; analyzed for safety only). Least-square mean change in IDS-C30 total score was numerically superior for adjunctive armodafinil 150mg/day vs adjunctive placebo, but was not statistically significant (p=0.13). Armodafinil was well-tolerated. Adverse events (AEs) observed in >5% with adjunctive armodafinil 150mg/day and more frequently than with adjunctive placebo were headache (16% [38/231] vs 13% [30/229]) and nausea (7% [17/231] vs 2% [5/229]). The most common AEs with adjunctive armodafinil 200mg/day were diarrhea and dry mouth (17% [5/30] each vs 6% [13/229] and 1% [3/229], respectively, with adjunctive placebo).

LIMITATIONS: Early study discontinuation for logistical reasons by the sponsor limited adjunctive armodafinil 200-mg/day assessment.

CONCLUSIONS: FDA-approved bipolar I depression treatments are limited. Adjunctive armodafinil 150mg/day reduced depressive symptoms associated with bipolar I disorder to a greater extent than adjunctive placebo, although the difference failed to reach statistical significance. Safety data indicate treatment with adjunctive armodafinil was well-tolerated.

Pharma Make The Most of A Negative Result

Discover Magazine Blogs

By Neuroskeptic

June 28, 2015

A misleading piece of statistical rhetoric has appeared in a paper about an experimental antidepressant treatment. The study is published in the Journal of Affective Disorders. JAD is a respectable mid-ranked psychiatry journal – yet on this occasion they seem to have dropped the ball badly. The study examined whether the drug armodafinil [Nuvigil] improved mood in people with bipolar disorder who were in a depressive episode. In a double-blind trial, 462 patients were randomized to treatment with either armodafinil 150 mg/day, or placebo, in addition to their regular medication, for 8 weeks.

The results showed no statistically significant difference between the two groups in change on the depression rating scale, the IDS-C30. [p = 0.24 LOCF, p = 0.13 at week 8]. So this means that there was no evidence that armodafinil helped treat depression. Oh dear. It’s a textbook example of a negative, or null, result. Despite this, however, the paper’s abstract concludes on a remarkably upbeat note…

FDA-approved bipolar I depression treatments are limited. Adjunctive armodafinil 150mg/day reduced depressive symptoms associated with bipolar I disorder to a greater extent than adjunctive placebo, although the difference failed to reach statistical significance.

The second sentence is quite misleading. The mean reduction in symptoms was indeed slightly higher in the armodafinil group than in the placebo group, but in the absence of statistical significance, the difference of means is meaningless [no pun intended]. Even assuming that the drug has no effect, there would be a 50% chance of the drug group having the greater improvement – and a 50% chance of the placebo being greater. One of the values has to be greater, after all. There will always be some mean difference. Which is why we need statistical significance testing.

So we simply can’t say that the drug “reduced depressive symptoms to a greater extent”, not even if we qualify this with the caveat that the effect was not statistically significant. The caveat is so big that it negates the entire statement. Other statements about how the drug group showed “numerically greater” improvement appear in the main text…

There’s some other weirdness – like "Received  30 March 2015, Accepted  2 April 2015."  When did they even do peer review? And there’s something else worthy of note. There are four studies of in Bipolar Depression, and three of them share something peculiar:

The CROs spread their studies over multiple sites to make recruitment easier and and speed up the trial. But I’ve never seen anything that approximated this number of sites. There’s a statistical method to partition variance to separate out the effect of the sites from the effect of the drug, and testing the drug x site interaction checks for particular sites skewing the results [though I couldn’t see that they availed themselves of that test]. But even if they had, this pushes the practice of using multiple sites well beyond any credibility.

Psychotic experiences and risk of death in the general population: 24-27 year follow-up of the Epidemiologic Catchment Area study.

by Sharifi V, Eaton WW, Wu LT, Roth KB, Burchett BM, and Mojtabai R.

British Journal of Psychiatry. 2015 May 7 [Epub ahead of print].

[full text on-line]

[First received 10 Dec 2013, final revision 24 Nov 2014, accepted 24 Nov 2014, Published online 1 July 2015.]

Background: Psychotic experiences are common in the general population and are associated with adverse psychiatric and social outcomes, even in the absence of a psychotic disorder.

Aims: To examine the association between psychotic experiences and mortality over a 24-27 year period.

Method: We used data on 15,049 adult participants from four sites of the Epidemiologic Catchment Area baseline survey in the USA in the early 1980s, linked to the National Death Index and other sources of vital status up until 2007. Psychotic experiences were assessed by the Diagnostic Interview Schedule.

Results: Lifetime psychotic experiences at baseline [n = 855; weighted prevalence, 5.5%] were significantly associated with all-cause mortality at follow-up after adjustment for sociodemographic characteristics and psychiatric diagnoses, including schizophrenia spectrum disorders [P<0.05]. Baseline psychotic experiences were associated with over 5 years’ shorter median survival time. Among the underlying causes of death, suicide had a particularly high hazard ratio [9.16, 95% CI 3.19-26.29].

Conclusions: Future research needs to explore the association of psychotic experiences with physical health and lifestyle factors that may mediate the relationship of psychotic experiences with mortality.

 

Earlier this year when the British Psychological Society released their Understanding Psychosis and Schizophrenia, Dr. Jeffrey Lieberman unleashed an ad hominem attack that a lot of us felt was way out of bounds [even for him] [see which side of the street?…] similar to another a bit later against Robert Whitaker [just stop…]. But calling out Dr. Lieberman for conduct unbecoming didn’t necessarily signal support for the BPS Report. It really was a hard report to even discuss because it was presented more as an emotional polemic than a scientific report. If you haven’t read it, please do. It isn’t something that can be easily summarized. But there are only two possible responses: Psychiatry pathologizes normality or The BPS normalizes pathology. Here were some of my reactions at the time it came out : <to be continued>…, back to the drawing board…, impossibility…, jettison schizophrenia?…, and jettison schizophrenia? no thanks…. In this study, beside the loss of 6+ years from the lifespan [survival curve above], the other data of note in this paper is in Table 2 [abbreviated below]:

^{[truncated for simplicity]}

In both the Cox and the Generalized Gamma Models, the shortened lifespan was significant for the overall group reporting psychotic experiences [p<0.001]. And when the analysis was repeated with the covariates separated out [formal psychotic disorders like Schizophrenia, Bipolar Disorder, etc], the significance remained [p<0.05]. In the overall group with psychotic experiences, suicide was a particularly prominent cause of death [Cox Model 9.16(3.19–26.29) p<0.001], but not in the psychotic experience without psychotic disorder group [Cox Model 2.28 (0.36–14.41) p>0.05].

This was a population study with information limited to the recorded parameters without specific subject narratives. But the difference, over a six year shortening of lifespan, is impressive. The contrast between the pictures painted by the British Psychological Society’s Understanding Psychosis and Schizophrenia and an article like this one is dramatic. The BPS Report would characterize the psychotic experience without psychotic disorder group as a benign variant of normal, not something that would be expected to be associated with morbidity or shortened life.

I find the controversies that swirl around these differences difficult. In their recent book, Psychiatry Under the Influence, Whitaker and Cosgrove make much of the guild interests that have driven a lot of the psychiatric literature in the recent decades, and they are justified – as am I when I make similar complaints. But I can’t read that BPS Report or many of the like-minded blog posts without seeing the guild interests of those authors front and center as an equally prominent force. I expect there will come a time when all of this is will be clear, but I’m not sure this is it. It feels like it’s a yes/no argument that needs a large [non-binary] study that reframes the issue into one with many answers done by impartial people, and there aren’t many in sight. Guild wars appear to be the currency of the day.

Internet hit by lightning.

see you next week…

Gilead could have had Pharmasset cheap: founder

Reuters

By Bill Berkrot

November 22, 2011

Investors in Gilead Sciences may believe the company is paying too much to buy Pharmasset Inc VRUS.O at $11 billion. Emory University researcher Raymond Schinazi, who founded Pharmasset, knows by just how much. "They could have had the company for $300 million or less in 2004. Somebody made a huge mistake," Schinazi said in a telephone interview a day after the big deal was announced.

Schinazi, 61, is the largest individual shareholder of Pharmasset and saw the value of his own 4 percent stake leap to more than $440 million. The biotech is developing a hepatitis C treatment considered so promising that Gilead agreed to an 89 percent premium over Pharmasset’s already soaring stock price. Schinazi said he was surprised that Gilead, the world’s largest maker of HIV drugs and a company well-versed in antiviral treatments, did not recognize what Pharmasset was offering when it solicited offers back in 2004. "Now they paid the premium. Of course, now the risk has been reduced significantly," he said of the drug that has demonstrated impressive results in clinical trials…

Something of a one-man bridge between the worlds of academic and commercial science, Schinazi is director of the Emory University Center for AIDS Research and a star in the world of HIV research and treatment. He has also founded five companies developing treatments for viral diseases such as AIDS, hepatitis and herpes…

He has not been involved in running Pharmasset since 2006 and had no part in the Gilead deal announced on Monday. But he was chairman of the board and led its chemistry group when the molecule that led to the hepatitis treatment was discovered…

FDA is Sued by Advocacy Groups That Want Gilead Hepatitis C Trial Data

Pharmalot: WSJ

by Ed Silverman

06/29/2015

A pair of public health advocacy organizations has filed a lawsuit against the FDA, claiming the agency failed to release clinical trial data for Gilead Sciences  hepatitis C treatments on a timely basis. And the move is only the latest installment in an ongoing drama in which researchers and patient advocates have tussled with drug makers and regulators over access to such information.

Here’s what happened: Late last year, Treatment Action Group and the Global Health Justice Partnership asked Gilead for patient-level trial data for the Sovaldi and Harvoni drugs. They sought the data because the drugs are widely prescribed, thanks to very high cure rates, and because the FDA approved the drugs as part of a regulatory process known as a breakthrough designation, which accelerated review…

In their lawsuit, the groups maintain doctors “lack the benefit of any independent assessment of the data.” And given the high cost of the drugs, the groups argue in their lawsuit that it is “crucial that policymakers be able to evaluate the cost-effectiveness… based on the underlying clinical data…” Sovaldi and Harvoni cost $84,000 and $94,500, respectively, for 12-week regimens, before discounts. But Gilead never replied to their requests last November for trial data, according to the lawsuit.

So last December, the groups turned to the FDA and submitted a Freedom of Information request for the data, since the drug maker had submitted the information to the agency as part of the drug approval process. However, the groups say the FDA denied their request for “expedited processing” and maintained it would take from 18 to 24 months to fork over the data, according to the lawsuit…

"When I tried to look at more recent drugs, things were less smooth. For one of the last requests I submitted, I got a call from the FDA and the FDA lady tried to talk me out of making the request in the first place. When I refused and asked her how long it would take, she said about two years [that was three years ago] and I never heard from them again."

The irony here is obvious. We give Gilead an FDA break for the R&D work they didn’t do, fast track them to patent protection, so they can charge an outrageous fee to patients with Hepatitis C [most of whom can’t afford it so governments end up paying] so they can pay their head honcho $192+ M as a yearly salary, but we can’t expedite the NDA report from the FDA to allow some attempt at vetting the drug. I reckon Gilead has cut its business teeth on squeezing people with AIDS, and really knows how to play the system…

The EMA revolution gathers pace

BMJ Blogs

by Tom Jefferson

30 Jun, 15

[full text on-line]

Are we ready for the EMA revolution?

BMJ Blogs

by Tom Jefferson

30 Jun, 15

[full text on-line]

But be careful what you ask for. You might just get it. There are literally thousands of pages with each RCT. I’ve spent the last year and a half working on just one trial and it’s a maddening exercise, bouncing around in these documents looking for elusive needles among the hay. So how this data is presented and cataloged is as important as its availability. Tom’s blogs are about how the EMA is going to implement Phase I of their roll-out [the operative saying being, "the devil’s in the details"]. Here’s my monotonous graphic, updated to fit the new EMA proposals:

a pri·o·ri  [ä′ prë-ôr′ë]
adj.

1. from a general law to a particular instance;
   valid independently of observation.
2. existing in the mind independent of experience.
3. conceived beforehand.

Phase 1 covers the release of clinical overviews [Module 2.5 in regulatory speak], clinical summaries [Module 2.7], and the all important clinical study reports [CSRs]. CSRs will include the main body [a sort of IMRAD style document], the trial protocol with its dated amendments, blank (or sample) case report forms [CRFs], and the statistical analysis plan or SAP [appendices]. See this exploratory review for a description of each cited document.

The value of these documents available at the click of a button to a researcher is difficult to overplay. For example, Module 2.5 contains a complete description of the manufacturer’s trial programme. For those of us who laboured for six months to reconstruct trial programmes, cross-referencing fragments of information from disparate sources, this is the honey pot served on a plate. CSRs are the most detailed accounts of the setting up, conduct, and analyses of trials on pharmaceuticals by their sponsors.

The radical nature of the EMA’s policy lies in its offer of routine access to full clinical study reports [CSRs] with [hopefully] minimal redactions just a few days after drug approval [or rejection]. CSRs offer us the possibility of delving into and cross checking all aspects of trials: from protocol to informed consent forms, from intended analysis methods to those which were actually used, to templates for participant data collection. Some other aspects of the policy and its implementation are revolutionary, such as access to CSRs of drugs that did not make it to the European market. The thousands of pages provide a hitherto rarely tapped bonanza of detail and the possibility to address reporting bias — the biggest threat to contemporary, ethical research synthesis.

Regulators will also be in a difficult position, with the Food and Drug Administration [FDA] left looking like a stranded whale wrapped in a sort of pre-New Deal commercial secrecy isolationism. The FDA does not release CSRs and the public can only access FDA reviews of the market authorisation application [which it calls NDAs or new drug applications]. These, like all reviews, do not tell you everything about all the trials in the programme, but represent the FDA’s take on the one or two pivotal trials that regulators looked at in depth with sponsors’ agreement. We tried to reconstruct a CSR narrative with sufficient detail to allow full appraisal from FDA medical officers reviews [MORs] in our neuraminidase inhibitors review. We failed completely because of a lack of sufficient information in the MOR and other documents available from Drugs@FDA. Use of FDA MORs instead of full CSRs risks swapping one incomplete source [journal articles] for another [FDA reviewers’ comments].

Gregor Mendel was an Augustinian Monk in Moravia whose studies of plant inheritance brought such things into the realm of science. My sister’s blue eyes meant that both of our brown-eyed parents carried recessive blue-eye genes. The postman was out of the picture. Mendel’s schemes of inheritance were like that – very precise statistical predictions based on dominant genes. Things stayed pretty clean through Watson and Crick’s images of the double helix DNA structure, even Nirenberg’s nucleotide code sequences. But then things got out of hand – the Genome…

That’s something I said this time last year in a post criticizing Dr. Insel’s NIMH and his funding priorities. It was after the Psychiatric Genomics Consortium report: Biological insights from 108 schizophrenia-associated genetic loci. I’m not competent to judge these "big data" studies coming from genomic research, but I am competent to complain that the NIMH isn’t looking into the plight of our psychotic patients living in prison – and that’s what I was addressing in those posts. I was looking for balance from the NIMH [in vain, I might add].

This week, psychologist Jay Joseph who writes on Mad in America, adds [Are DSM Psychiatric Disorders “Heritable”?] to his series of posts [the list] and books [The Gene Illusion: Genetic Research in Psychiatry and Psychology under the Microscope,  The Missing Gene: Psychiatry, Heredity, and the Fruitless Search for Genes, The Trouble with Twin Studies: A Reassessment of Twin Research in the Social and Behavioral Sciences] challenging the psychiatric research and perspective on the genetics of mental illness. While looking over his posts, I came across one in particular that I’ve wanted to say something about for a while – DSM-5’s “Speculative” 2002 Diagnostic System Based On Expected Gene Findings.  He’s referring to a book [A Research Agenda for DSM-V] that I think has been too quickly forgotten. The book was published in 2002 edited by David Kupfer, Darrel Regier, and Michael First but had multiple contributers. Kupfer and Regier later became the co-chairmen of the DSM-5 Task Force. The premise of the book was that the previous DSMs had been based on descriptive criteria [atheoretical], and that it needed to be revised to include the biological bases for the various disorders. Jay’s post is pointing to a scheme in that book speculating about classifying mental disorders based on their genotypes:

At the time this was written, we didn’t know that any major mental condition was either biologic or genetic – though there was suggestive indirect evidence for some. We certainly had no clue about any genotypes. This book introduced a series of [extensive and expensive] symposiums funded by the APA and the NIMH to pursue the outlined agenda [see DSM-5 retrospective I…]. This enterprise – the book and  the symposiums – was quite a reach beyond the DSM-III and DSM-IV. It aimed to move away from Spitzer’s reliability to the elusive dream of validity. And it made a broad assumption of biologic causality, not as a hypothesis, but as an as-yet-unconfirmed fact – at least that’s how it sounded to me.

I didn’t read that book until a few years after it was published and the symposiums had been completed, but all I could think about while reading it was why they ever thought they could make a leap of that magnitude between 2002 and 2010, or even come close. Why climb out on that limb? The only thing I could think of was that it was conceived around the time that the Human Genome Project was nearing completion, and they genuinely thought that locating the genotype of psychiatric syndromes would a snap. Further, looking at that Table 2-5, they were laying out a path of discovery and the discoveries to follow that was pretty specific – what kind of genes they were going to find and where they were going to be headed with this cascade of future findings – particularly in relationship to "targeted pharmacotherapy." As we now know, this enterprise was a definitive and very public flop. They had to admit defeat in March 2011 [Neuroscience, Clinical Evidence, and the Future of Psychiatric Classification in DSM-5] and abandon the grand plan.

"In A Research Agenda for DSM-V, we anticipated that these emerging diagnostic and treatment advances would impact the diagnosis and classification of mental disorders faster than what has actually occurred."

DSM-V promises to be the state of the art in terms of psychiatric diagnoses, and when it was initiated we anticipated that this iteration of the DSM would incorporate biological markers and laboratory-based test results to augment the historical and phenomenologic criteria that traditionally are used to establish psychiatric diagnoses. Sadly, this has proved to be beyond the reach of the current level of evidence for incorporating into this version of the DSM, and it appears that psychiatric diagnoses, which may be rearranged, consolidated, and modified in some ways, will still be based predominantly on symptomatic and historical criteria. However, I am here to tell you that the time is not far off in the future when psychiatric diagnoses of mental disorders and behavioral disturbances will be aided by laboratory-based tests, and this will mark a milestone in the evolution of psychiatric medicine and will occasion an enormous transformation in the accuracy and the reliability of psychiatric diagnoses…

Finally, genetic testing will also come into play. As you probably know, commercial companies already are marketing DNA testing. They provide a "readout" of your genotypes for all of the known coded human genes along with associations with specific diseases in the different organ systems that these correspond to, to the best level of evidence that currently exists. These are not accepted as medically validated and are not used routinely in clinical practice but there is no reason psychiatry cannot begin to use these as other fields of medicine have done. Because all mental disorders will almost certainly prove to be polygenic or multigenic, we will need a gene profile to utilize in term of diagnostic information….

I’m not competent to vet Joseph Jay’s science. He seems to be aiming towards the conclusion that there is no genetic loading in Mental Illness which feels to me like an overstated polemic, though I’m not knowledgeable enough to judge with conviction. But I have absolutely no trouble at all thinking that Dr. Lieberman’s alternative, "all mental disorders will almost certainly prove to be polygenic or multigenic" is currently indefensible at face value – particularly after the decade long attempt that followed A Research Agenda for DSM-V. I don’t know of any findings since that book was released that justifies the not-quite-yet just-around-the-corner attitudes still prevalent in the ranks of the NIMH and much of academic psychiatry. They talk as if these now aging hypotheses from that book are still elusive truths in need of confirmation, rather than wishful thinking that has become increasingly unlikely with each passing study. The certainty implied by Dr. Lieberman here [there and everywhere], or Dr. Insel’s certainty with his RDoC or his sponsorship of the Clinical Neuroscience meme [and curriculum project – see the talk that matters…] has outlived credibility.

I was excited by the Genome Project too. I think I was as naive as the next guy, thinking it would be a cornucopia of answers. It has turned out to be a first step in a new ballgame we don’t even know how to play – more Sputnik than Star Trek. But it is what it is. It’s a long way around this corner, and we have no clue what we’ll find there. If I had some sermons to preach about all of this, one would be that it’s high time to get all of this out of the guild wars. We’re spending a lot of money and brain power fighting the battle of the guilds, psychology vs psychiatry vs other, and that’s not going to lead us anywhere worth going. This isn’t about guild legitimacy, it’s about Mental Health. But my loudest sermon would be about research funding, particularly by the NIMH. This whole business of special areas that get high priority in funding hasn’t panned out. "Translational Science" didn’t work for mental health as evidenced by how little there has been to "translate." Tom Insel and his staff have no special knowing about what directions we need to move in, and that’s been proven to everyone’s satisfaction. We need to open up the NIMH to our investigators and see what they can come up with on their own, rather than asking them to follow directions set from above.

At the beginning of the week, I worked in the clinic. One of the patients I saw was a woman in her early thirties with increasing depression over the last year. She’d been seen several weeks earlier by a Nurse Practitioner and started on Citalopram which had helped "some." Her story: In spite of being a good student, she had quit school as soon as she turned sixteen and married. By her mid-twenties, she had four children [now ages 9 through 16]. The part of her history that caught my attention was that she also had "two babies" age 1½ and 2½. Doing the math, 9-2½=6½. So she’d started this second family when her youngest had entered school. Exploring the why? of that, I hit pay dirt.

She and her sister had been raised by parents who were little more than children themselves, lifelong substance abusers who provided the amenities, but did little parenting ["we ran wild" "we raised ourselves"]. Her mother was given to "going off" for varying periods of time. The net result from this un-parented childhood was a lifelong intense fear of abandonment that literally organized her experience. Her husband had "rescued" her from her "crazy family." Then her children became her life, and she had to struggle not to be overprotective. She had a crisis when her youngest went to school, and actively chose to fill her "empty nest," but then realized that she felt "trapped" by six children and having no life outside of her family. Her oldest, a sixteen year old daughter had gotten her "first boyfriend," and for my patient, that was a double-edged sword. On the one hand, it meant that her daughter was going to leave [at some future point], tapping into her preoccupation with abandonment. On the other hand, it confronted her with how she had prematurely ended her own childhood when her own "first boyfriend" came along.

There was a lot more to this story, but that’s enough to get at what I’ve been thinking about ever since. She reminded me of lots of patients I saw when I was an Internist, cases where I knew there was something that needed to be understood, but I didn’t know how to figure out what it was. Back then, I doubt I wouldn’t have ever gotten to her fears of abandonment, much less seen how her childhood related to this adult depression. But nowadays, I doubt I could miss it. But that’s because an army of teachers, supervisors, case conferences, book authors, patients, etc. taught me how to conduct an interview, how to always have a life timeline running, how and where to listen, what kind of things can happen in a childhood, what being a mother is about, and the million other things that automatically run in the background when I’m listening to a patient. It’s an acquired intuition, but I can’t take credit for anything other than sticking to the task of learning.

So the thing I’ve been thinking about since my last clinic day is still Collaborative Care. I’ve been thinking about why I have such a visceral negative reaction when I read about it, yet it’s something I already do every time I’m in the clinic. Almost any psychiatrist that works in a clinic does it all the time. I did it Tuesday, with the LPC, a Doctor or two, a Nurse. Hallway consults. The difference between what I already do and what I read about is that I always have the option to see the patient in my version. And when I look at the diagrams, in this one, talking to the patient doesn’t even seem like an option [it says "(medication) recommendations"]:

and in this one, they go out of their way to say "infrequent" for contact with either the primary care physician or the patient:

In either case, this model strips me of the only real value I bring to the table – my acquired intuition. And it implies that the first [or perhaps only] treatment for mental illness is medications. If that’s true, they don’t need a psychiatrist. They need some algorithms. Little wonder that my reaction to Collaborative Care is so negative. And little wonder so many patients are over-medicated. My guess is that the main reason for the firewall between patient and psychiatrist is some kind of cost containment maneuver.

As for the case I mentioned above. Once her abandonment fears were on the table, any number of solutions were immediately apparent. One reason she was never away from her kids was she never wanted them to feel "abandoned" – an idea easily dispelled. And there were other resources available to help her get some freedom and "have a life." She wanted to finish school and perhaps train for work outside the home. Both of those things are easy to arrange. Her husband was with her in the clinic, and hearing her fears, he came up with all kinds of ways he could [and would] help her. He seemed relieved to know how she felt.

I suppose most Southerners have something to say about  the goings on after the Charleston shooting and all the media attention about the battle flag. As a boy growing up in Chattanooga Tennessee literally in an area peppered with cannons and Civil War Monuments, I had no idea that the Civil War was even about slavery. That seems as outrageous to my to say as it must be to read. When I hear other people say things like that, I hear it as possibly reconstructing history, but for me to say otherwise would be a lie. My Dad was from an Italian immigrant family; grew up in a Northern coal mining town on the wrong side of prejudice; and came South on a football scholarship. My mother was from rural Georgia – a vaudeville family – and a soft spoken do-gooder somewhere to the left of anyone else in Tennessee I ever met. We were raised to sit in the back of the bus and go out of our way to be respectful to black people. It was odd, because I never met anyone else that said that, But for that matter, I can’t recall anyone actually talking about segregation much in those times. It was just part of the fabric of life. And it was disconnected from the stories of chivalry and honor – and that flag.

Back in the summer of 66, my young wife and I took a camping trip down the Mississippi Delta from Memphis where I was finishing Medical School. We wanted to take some Jim Crow pictures to preserve what it had been like there – thinking that we were finally on the downhill leg of the Civil Rights Movement, and people might try to forget. In the course of our travels, we saw a sign to Ruleville Mississippi – a place we’d heard of from watching the Democratic Convention when the Mississippi Freedom Democrat Party tried to be seated. Their most eloquent spokesperson was Fannie Lou Hamer from Ruleville, a tiny town in the heart of the cotton fields that covered the Delta in those days. [Notice that President Johnson cut her off of national television during her speech]:

As we drove into town, we knew we were in the right place for our photographs. There was a Dairy Queen on the way into town with a strange addition built onto the front of it with a large picture window. On the back wall was a huge Confederate Battle Flag tacked up on the wall. The sign outside said, White Citizens Council Annex, Private Club. So we drove through town, photographing the "white" and "colored" signs that had defined the segregated South of our childhood. My wife was driving as I clicked away. She circled back, determined to get a picture of the White Citizens Council Dairy Queen. We parked nearby, but I noticed that the same two-tone blue 1956 Ford that had been following us earlier pulled up right behind. I also notice that there was a shotgun mounted vertically between the two guys in the front seat.

So we drove on, forgoing our photo-op, followed by the two-tone blue Ford. When we reached the Sunflower County Line, it mercifully turned around. When we finally stopped for gas and gathered some composure, we started wondering how they knew we were "foreigners." There, on the rear bumper of my car was the answer – a black and white A.C.L.U. bumper sticker that simply said, "JUSTICE." Our pictures didn’t survive the 50 years in between, but the memories did.

In the mid-1980s, my teenaged daughter and a friend announced that they were going to "a march." They’d heard us and our friends tell our epic tales of our marching days, and decided they wanted to get in on the action. There was a poor rural county north of Atlanta, all white, that was "racist." A school teacher had organized a small MLK day parade, that had been broken up by "the Klan." The next week, Hosea Williams, a local Civil Rights leader took a bus filled with students from the Black Atlanta colleges, and the same thing happened. So he got serious, and mobilized a big march. Meet at the King Center and ride buses up to this town. So the four of us showed up along with 20,000+ other Atlantans. They finally got all the City buses there and every church bus in town, and off we went. There were more marchers than people in that whole county. The comic relief was this armada of buses stopping on the Interstate for a 20,000 person strong pee break. Men on the port side at the fence, women in the woods on the starboard side. The county was overwhelmed by the invading horde [now a bustling suburb with McMansions in what used to be those empty fields].

But the point is that back then, the sides of the highway were lined with people, mouths agape, some of whom had denim jackets with Klan logos, waving those battle flags and throwing snowballs from what was left of a rare Georgia snowstorm. When we got back to the buses, we were among a few hundred people that didn’t get on a bus. By then, it was night, and we were gathered on an overpass. And here came the pickup trucks with battle flags mounted on the beds and people leaning out the windows twirling chains and hurling epithets. They had been soundly defeated and they were plenty mad. After about 45 very long minutes [during which I questioned my parental judgement], the State Troopers discovered us and herded us into a parking lot, calling for more buses. As fate would have it, our bus broke down as we got off  the Interstate in Atlanta, and we had to walk the full length of "Sweet Auburn Avenue" – the heart of the black Atlanta "club scene" with two very cute blond teens who were quite the objects of interest on this particular Saturday night. A memorable day – snowballs early and cat-calls late. But if I had any remaining romantic attachments to that flag, 45 minutes on that overpass put an end to them for good.

In 2001, then Georgia Governor Roy Barnes changed the Georgia flag, a leftover from segregationist days. It actually probably cost him being re-elected [now I read our "new flag" was a confederate flag too. Who knew?]. But whatever, I feel kind of proud that the Southern States are moving towards finally removing those anachronistic symbols. Whatever they meant, or now mean, we can do without them: