by L M Williams, C Debattista, A-M Duchemin, A F Schatzberg and C B NemeroffTranslational Psychiatry. (2016) 6, e799. Published online 3 May 2016Discussion
Overall, the higher rate of trauma observed in the present MDD sample is in line with registry and observational studies.Thus, childhood trauma and especially abuse may contribute to the development of depression observed in routine practice in multiple outpatient settings spanning primary and specialist care settings. Our findings suggest that abuse in particular, and not overall exposure to traumatic events, predicts a lower rate of acute response and remission after antidepressant therapy. Sexual, physical and emotional abuse compared with other types of trauma psuch as death of a parent/sibling, personal life-threatening illness/injury, or disaster], may have a specific impact on the neurobiological mechanisms of non-response to treatment. Neuroimaging studies suggest that there may be a differential effect of childhood sexual abuse on the subsequent functioning of emotional brain circuits in adulthood depression. Childhood abuse has also been associated with a greater sensitivity to stress, cognitive impairment, alterations in brain morphometry and immune and metabolic abnormalities that may impact the course of depression and capacity to respond to antidepressants. It is also possible that abuse may recur and that it is the recurrence of the trauma that produces poor treatment outcomes.In addition to the type of stressor, our results suggest that there is a critical period [4 to 7 years] in which childhood trauma occurs and has the most significant impact on subsequent poor response to antidepressants in adulthood. There is a rapidly growing body of work to suggest that gene polymorphisms and epigenetic modifications interact with childhood trauma to exert their effect on risk for depression, and that this effect is greatest at critical neurodevelopmental periods. This evidence is consistent with the view that the extent of brain plasticity varies during development, such that trauma occurring during critical neurodevelopmental periods may alter brain morphometry, circuit function, endocrine regulation, immune function and subsequent physiologic reactions to stress in an enduring way.
Abuse occurring at age 4 to 7 years was associated with significantly poorer outcomes following the treatment with sertraline compared with the other selective serotonin-reuptake inhibitor escitalopram and the SNRI venlafaxine-XR. The participants who were abused at this age showed significantly less improvement in both clinician and self-rated symptoms following 8 weeks treatment with sertraline. Sertraline, in contrast to other serotonin-reuptake antidepressants, has an additional relatively specific effect on inhibiting dopamine. There is some evidence that subgroups of patients are also characterized by dopamine circuit dysfunction and number of traumatic events has been associated with higher ventral striatal dopamine response to amphetamine. Although speculative, these lines of evidence suggest that a possible dopamine-related mechanism might contribute to our specific observation of especially poor outcomes following sertraline in those exposed to early abuse.
Clinical translational significance
Here, we provide evidence from a well-powered study that outpatients with MDD have a fourfold higher incidence of childhood abuse than their healthy peers, and a twofold higher incidence of early exposure to other traumatic events. The greater the exposure to trauma, the less likely these depressed patients were to remit following antidepressant response. Thus, the translational significance of these findings is that in routine clinical management of depression it may be important to screen for childhood trauma to identify those patients that may not benefit from standard first-line antidepressants and may require additional therapy to more directly address the impact of trauma.
This is one of my slides from the late 70s/early 80s showing a few lines of development plotted by age. The pictures are typical self portraits from various ages [some from my daughter] paralleling the formation of the self representation. The bottom line shows attachment/separation schema [Mahler] and the stages of cognitive development [Piaget].
The four year old sees himself "out of his eyes" with the arms and legs coming out of the head [Mr. Potato-head]. It’s not until around age seven that the child will see herself as we see her, a whole person. In-between, Mr. Potato-head gets some hair, and has some "felt" body parts [here, a heart or genitals]. It’s a vulnerable work-in-progress period, and abuse can disrupt multiple vital developmental processes. Logical constructs aren’t available in the preoperational cognitive set so the child has no tools to understand abuse. It can and does have a profound impact on the developing self image, the templates for relating to others, and the general experience and understanding of the world. Whether these unfolding developmental sequences and the toll of abuse are the result of or cause actual changes in the brain itself or take place in a psychological domain is as unknown now as it was forty years ago. But the particular vulnerabilities of the preschool child and the enduring consequences remain a paramount concern whether hardware or software. And by the way, their finding highlights the inadequacy of the Major Depressive Disorder categorical diagnosis.
Yes, it does seem like they are rediscovering the wheel. Because of the weak design, there is not much we can conclude from this study, and their trenchant inferences aren’t really justified. For all we know, the abused cases may simply be unresponsive to the placebo effect of receiving antidepressant medication. But we will never know because there was no placebo control group.
My reaction on reading the full paper yesterday was that they go to great lengths to hide the primary data behind multivariate analyses. There is not even a simple declarative statement of how many patients in the abused/nonabused groups responded/remitted to any of the 3 drugs. That is a rookie mistake – senior authors Nemeroff and Schatzberg should have known better. Why should we trust their multivariate analyses when these authors are on record for a previous retraction of analyses they misrepresented? Oops… they glossed over that here. Check out references 9 and 10 in the article and see my discussion of it here.
As for their claim of translational significance: that is an empty conceit. The entire article is heavy on woo-woo speculation but light on real information about translational mechanisms.
And one can only agree with your closing point: “And by the way, their finding highlights the inadequacy of the Major Depressive Disorder categorical diagnosis.” Remember, in trials conducted by the company associated with authors Schatzberg and DeBattista, placebo response rates as high as 85% were claimed in patients with psychotic depression! And they said it with a straight face! So much for the ecological validity of MDD diagnoses in some of the clinical trials that get cranked out nowadays. Do we really need more trials like this one that enroll persons who respond to advertisements? Not that they disclosed how many such cases were enrolled.
If there is an 85% placebo response in psychotic depression then Thomas Szasz was right and we shouldn’t exist as a profession because nothing we do is better than 85%.
Where are the editors? Rhetorical question, the answer is having dinner at Elaine’s with the authors.
“If there is an 85% placebo response in psychotic depression then Thomas Szasz was right and we shouldn’t exist as a profession because nothing we do is better than 85%”
Is there anything you recommend people read to get information about the latest and most accurate research about treating psychotic depression? .Is there a placebo response rate associated with psychotic depression?
Sally, this short article in BMJ might get you started.
PubMed ID: 23097553
actually there is one treatment that might beat this fictional placebo response rate…ECT
which is of course, rarely used anymore
my theory…the ads are bringing in drug users in search of money who report depression and psychotic symptoms but deny drug use…why be honest from their standpoint?
this goes back to my old point about the need for psychometrics and drug screening in research…
Let’s be so brutally honest here, it’s the ultimate purge from a figurative feeling enema that should exhaust anyone who really is both concerned and invested in the well being of what psychiatry should be providing to heal, not harm.
What is this utter and shameful idea of 15 med checks to just shill for pills? These patients come in and expect us to give them direction and hope for restoration of health and function, and we just cut them off within at best, what, a minute of dialogue and start selling chemicals to fix these psychosocioeconomic struggles? And let me tell you, this pathetic election coming up pitting a destructive narcissist versus a hell bent antisocial liar of an opportunist, the anxiety and depression is beyond palpable!
I’ve been doing temp work in the Mid Atlantic these past 6 years now, and the flagrant push for just making us assembly line pushers if not just well dressed janitors, it is just beyond disgusting to participate in day in and out. If I didn’t have a family to provide for, I’d be on a southern beach in a shack, like the Cliff Robertson character in the first “Gidget” movie. Live day to day, enjoy a free meal, and just surf some waves, now there is a life pursuit circa 2016!
And maybe some sand and surf reflection could be therapeutic?!?!
Some of you want to make sense of the senseless, good luck! We have allowed the alleged hierarchy of this profession to not only sell us out, but shackle those of us who don’t have the luxury of concierge private practices, who come here and note how there is still a market for psychotherapy.
Really? How many true and sincere patients are invested in at best q week 1 hour psychotherapy visits for at least 20 consecutive times and honestly and effectively are doing the work to problem solve issues above legitimately being on meds for real Axis 1 disorders that have a genuine likelihood of responding to chemical intervention?
Burn out? Outlandish cynicism?? Brutal Pessimism? Or, just pervasive realism, with a dash of legitimate outrage?! I am embarrassed and shamed by too many colleagues out there who are just slowly killing people with med regimens out of a horror movie.
Yeah yeah yeah, another rant by Joel, what a long, hot, and dark summer awaits us, eh, colleagues…
“How many true and sincere patients are invested in at best q week 1 hour psychotherapy visits for at least 20 consecutive times and honestly and effectively are doing the work to problem solve issues…”
Let’s see, I’ve got about four at, near, or well over 20 sessions, six others coming up on 10 sessions, two new ones with only a couple of sessions.
Total caseload is now 14 and relatively stable– I expect a few new ones and a few dropouts.
Of course, I’m not a psychiatrist, and I think that is part of your point. And most of these folks are coming in well south of $100 per hour. Their copays might be as low as $10, or they might be full fee at $80 or $100, it’s all over the map.
But I do have the feeling that out here in LA, there are plenty of patients who do feel psychotherapy works, and very much prefer it to drugs. And they are not afraid to say so.
And I do find that I have fewer clients that are on complex polypharmacy regimes, despite the fact that my referrals are coming from HMOs, and many of them present with relatively severe psychopathology. As I’ve mentioned before, that’s very different from what I was seeing in community mental health as an intern 5 years ago.
One thing I’ve learned from reading this blog is that many different, seemingly contradictory things seem to be happening all over the country, so I’m trying not to make assumptions about what patients do or don’t want or are asking for elsewhere. For all I know, in Cincinnati, they’re all screaming for Prozac or benzos or whatever. Not in my corner of tinseltown, and that surprised me.
As for your notes on the recent political cycle? Oh, hell, yeah– I stopped listening to the news in January, I consume so little media that II wouldn’t know if my own house was on fire, and the entire spectacle fills me with dread, horror and shame.
As for the shack on the beach? Go for it. If the surf’s up, you can borrow my board. Borrow my car. I wish some of you guys were local, and in private practice, I’d probably refer you clients– you could borrow them, too. (Actually, it seems like there is EAP and testing work out here for psychiatrists.)
LA is definitely two tiered, much lick the demographics of LA itself. Seems there is one high end group that does like psychotherapy, yoga, hates overmedication but then goes overboard on anti-vax and gluten and bad plastic surgery, new-new age etc. The successful but not happy group has always tended to be a good pure psychotherapy demographic. I know, I used to be one of them.
Then there is another low-middle Wily Loman group sliding from U-1 to U-6 on those unemployment charts with chronic health issues often complicated by metabolic syndrome sliding into polypharmacy.
As a passionate and (as much as I can) empirical moderate I find myself pushing my case in both directions.