INFLAMMATION AND PSYCHOSIS

A report by Bloomfield et al. in the January 2016 issue of American Journal of Psychiatry showed further evidence that psychosis is associated with increased inflammatory activity in the brain.  What the researchers did was to use a marker, [11C]PBR28, which binds to activated white blood cells (microglia) in the brain.  None of the subjects had been treated with antipsychotic medications.  The researchers showed that in persons who are at high risk for the development of psychosis and in those in whom psychosis had emerged, there was a greater degree of binding of the marker indicating more activated microglia in the brain.  Moreover, they noted that degree of binding (degree of microglia activation) was correlated with the level of symptoms.

The Bloomfield et al. report fits in well with a larger literature pointing the finger at dysfunction in fast spiking GABA interneurons as the culprit in causing hallucinations and cognitive impairment. (This story is reviewed in chapter 6 in Neuroscience for Psychologists and Other Mental Health Professionals.) Inflammation negatively impacts fast spiking GABA interneurons.  Oxidative stress, a component of inflammation, also impairs the function of NMDA receptors which are the drive on the fast spiking GABA interneurons (Sorce, Schiavone, Tucci et al., 2010; Sullivan & O’Donnell, 2012).  Stressful life experiences can also increase oxidative stress and thus provides a mechanism for how trauma can increase the emergence of psychosis (Cabungcal, Steullet et al., 2013; Jing et al., 2013).  Many persons with psychosis relapse when they incur infections in other parts of the body which than can raise inflammatory factors in brain (see Brian Miller,  2016).

The Impact of Antipsychotic Drugs on Brain Inflammation: Bloomfield et al. (2016) cited two studies using microglia cells in a petri dish which showed that antipsychotics tamed activation of these cells (Bian et al., 2008; Kato et al., 2008).  They also cited a study by Zhu et al. (2014) in live rats which showed that when a molecule of the wall of a bacterium (lipopolysaccharide) is injected into the brain of a rat and subsequently the rat is given a 14 day administration of an antipsychotic the brain’s inflammatory response to the provocation is attenuated.  Bloomfield et al. did not cite the study by Cotel et al. The Cotel et al. study showed that antipsychotic treatment activates inflammation in the brain, the opposite of what the studies cited by Bloomfield et al. showed.  Arguably, the Cotel et al. study is more relevant to the question of how antipsychotic drugs influence inflammation in the brain.  Cotel et al. administered antipsychotics for 8 weeks, much longer than in the other studies.  Moreover, Cotel et al. did not use another activator of an inflammatory response (as was done in the other studies).  Cotel et al. only examined the impact of the antipsychotics in brains which were not exposed to another inflammatory provocation. The Cotel et al. study, which found that antipsychotics create brain inflammation, is important because it might offer an explanation/mechanism for how antipsychotics shrink cortex which was shown in the humans (see Ho et al., 2011) and in the primate studies (Dorph-Petersen et al., 2005). A study by Shao et al. (2013) further confirmed that blocking dopamine receptors, as antipsychotics do, will increase brain inflammation.

The Search for Alternatives to Antipsychotics:   There is a literature on using anti-inflammatories to treat psychosis.  In fact, in a study of children at high risk of converting to psychosis, omega-3s (which are anti-inflammatory) was the only treatment that prevented the emergence of frank psychosis with 27.5% becoming psychotic in the control group versus 4.9% in the omega-3 group at the 12 month follow-up (Amminger et al., 2010).  There is also a literature attesting to the beneficial effects of anti-inflammatories on psychosis.  The anti-inflammatories have included aspirin, minocycline, statins, N-acetylcysteine, and the COX-2 inhibitor, celecoxib (Keller et al., 2013; Sommer et al., 2014).  Sommer et al. concluded that aspirin, estrogen, and N-acetyl-cysteine showed the best effects.  Additionally, social support can also reduce systemic inflammation.  Hopefully, in the future, we’ll have drug trials of anti-inflammatories as the sole pharmacological treatment along with attention to an anti-inflammatory diet and Soteria Project support.  (There is little reason to believe that any chemical anti-inflammatory can eclipse the impact of an inflammatory diet.)  Perhaps the future will offer a better way.

Readers on this website may object to any notion that biology influences human behavior. At risk of offending this audience, I present the findings in these studies because they demonstrate the folly of antipsychotics even for those who believe in physiological explanations for hearing voices.  Since doctors probably won’t ever give up their prescription pads, perhaps they can be coaxed into gentler drugs to prescribe.  I think that for those who are involuntarily committed to the psychiatric hospital, telling the doctor to prescribe “this” instead of “that” and backing up the demand with a study published in a legitimate journal might hold some weight.  If asking for a legitimate alternative does not influence the doctor, it might influence a judge.  In fact, most states have informed consent laws which mandate that physicians discuss all the options available for treating a given condition so that the patient can choose which option they prefer.

Amminger, G. P., Schafer, M. R., Papageorgiou, K. et al. (2010). Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders:  a randomized, placebo-control trial. Archives of General Psychiatry, 67, 146-154.

Bian, Q., Kato, T., Monji, A. et al. (2008). The effect of atypical antipsychotics, perospirone, ziprasidone, and quetiapine on microglia activation induced by interferon-gamma. Progress in Neuropsychophamacology and Biological Psychiatry, 32, 42-48.

Bloomfield, P. S., Selvaraj, S., Veronese, M., Rizzo, G., Bertoldo, A., Owen, D. R., Bloomfield, M.A.P., Bonoldi, I., Kalk, N., Turkheimer, F., McGuire, P., de Paola, V., & Howes, O. D. (2016).  Microglia activity in people at ultra high risk of psychosis and in schizophrenia:  An [11C]PBR28 PET brain imaging study. American Journal of Psychiatry, 173 (1), 44-52.

Cabungcal, J-H., Steullet, P., Morishita, H., Kraftsik, R., Cuenod, M., Hensch, T. K., & Do, K. Q. (2013).  Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proceedings of the National Academy of Sciences, 110(22), 9130-9135.

Chaudhry, I. B. Hallak, J., Husain, N. (2012).  Minocycline benefits negative symptoms in early schizophrenia: a randomized double-blind placebo controlled clinical trial in patients on standard treatment. Journal of Psychopharmacology, 26, 1185-1193.

Cotel, M-C., Lenartowicz, E. M., Natesan, S., Modo, M. M., Cooper, J. D., Willaims, S. C. R., Kapur, S., & Vernon, A. C.  (2015).  Microglia activation in the rat brain following chronic antipsychotic treatment at clinically relevant doses. European Neuropsychopharmacology, http://dx.doi.org/10.1016/j.euroneuro.2015.08.004

Dorph-Petersen, K. A., Pierri, J. N., Perel, J. M., Sun, Z., Sampson, A. R., & Lewis, D. A. (2005).  The influence of chronic exposure to anti-psychotic medications on brain size before and after tissue fixation:  A comparison of haloperiodol and olanzapine in macaque monkeys. Neuropsychopharmacology, 30 (9), 1649-1661.

Ho, B. C., Andreasen, N. C., Ziebell, S., Pierson, R., & Magnotta, V. (2011).  Long-term antipsychotic treatment and brain volumes:  a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry, 68(2), 128-137.

Jiang, Z., Rompala, G. R., Zhang, S., Cowell, R. M., & Nakazawa, K. (2013).  Social isolation exacerbates schizophrenia-like phenotypes via oxidative stress in cortical interneurons. Biological Psychiatry, 73 (10), 1024-1034.

Kato, T., Mizoguchi, Y., Monji, A. et al. (2008).  Inhibitory effects of aripiprazole on interferonγ-induced microglia activation via intracellular Ca2+ regulation in vitro. Journal of Neurochemistry, 106, 815-825.

Keller, W. R., Kum, L. M., Wehring, H. J., Koola, M. M., Buchanan, R. W., & Kelly, D. L. (2013).  A review of anti-inflammatory agents for symptoms of schizophrenia. Journal of Psychopharmacology, 27 (4), 337-342.

Kirkpatrick, N., & Miller, B. J. (2013).  Inflammation and schizophrenia. Schizophrenia Bulletin, 39 (6), 1174-1179.

Miller, B. J. (2016, January 7).  Adjunctive monoclonal antibody immunotherapy in schizophrenia. Psychiatric Times

Miller, B. J., Graham, K. L., Bodenheimer, C. M., Culpepper, N. H., Waller, J. L., & Buckley, P. F. (2013).  A prevalence study of urinary tract infections in acute relapse of schizophrenia. Journal of Clinical Psychiatry, 74(3), 271-277.

Mṻller, N., Riedel, M., Scheppach, C. et al. (2002).  Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. American Journal of Psychiatry, 159, 1029-1034.

Shao, W., Zhang, S.Z., Tang, M., Zhang, X. H., Zhou, Z., Yin, Y.Q., Zhou, Q. B., Hang, Y. Y., Liu, Y. J., Wawrousek, E., Chen, T., Li. S. B., Xu, M., Zhou, J. N., Hu, G., & Zhou, J. W. (2013).  Suppression  of neuroinflammation by astrocytic dopamine D2 receptors via alphaB-crystallin.  Nature, 494, (7435), 90-94.

Sorce, S., Schiavone, S., Tucci, P., Colaianna, M., Jaquet, V., Cuomo, V., Dubois-Dauphin, M., Trabace, L., & Krause, K-H. (2010). The NADPH oxidase NOX2 controls glutamate release: a novel mechanism involved in psychosis like ketamine responses. Journal of Neuroscience, 30(34), 11317-11325.

Sommer, I. E., van Westrhenen, R., Begemann, M. J., de Witte, L. D., Leucht, S., & Kahn, R. S. (2014).  Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: an update. Schizophrenia Bulletin, 40 (1), 181-191.

Sommer, I. E., de Witte, L., Begemann, M., & Kahn, R. S. (2012). Nonsteroidal anti-inflammatory drugs in schizophrenia:  ready for practice or a good start? Journal of Clinical Psychiatry, 73(4), 414-419.

Sorce, S., Schiavone, S., Tucci, P., (2010). The NADPH oxidase NOX2 controls glutamate release:  a novel mechanism involved in psychosis-like ketamine response. Journal of Neuroscience, 30, 11317-11325.

Sullivan, E. M., & O’Donnell, P. (2012). Inhibitory interneurons, oxidative stress, and schizophrenia. Schizophrenia Bulletin, 38 (3), 373-376.

Zhou, F., Zheng, Y., Ding, Y.Q. et al. (2014). Minocycline and risperidone prevent microglia activation and rescue behavioral deficits induced by neonatal intrahippocampal injection of lipopolysaccharide in rats. PLoS One, 2014, 9:e93966

 

Serotonin Is Still Alive and Well in Psychiatry Land

In the September 2015 issue of JAMA Psychiatry, a team of Swedish researchers (see Frick et al.) published a study evaluating the serotonin system in persons with social anxiety.  They used Positron Emission Tomography an imaging technique wherein radio-active molecules that will bind in particular places in the brain and then allow for quantification of particular molecules in the brain are employed.  The researchers used two different molecules:  [11C]5-HTP, which is a precursor to the production of serotonin, and 5-hydoxytryptophan labeled with Carbon-11 that will bind to the serotonin transporter.  What the researchers found was an increase in both of these substances in brain areas that are known to be active during the experience of anxiety, viz., the amygdala and the dorsal Anterior Cingulate Gyrus.  The researchers concluded, “Collectively, these findings suggest that extracellular serotonin in the amygdala and dorsal ACC is positively related to severity of social anxiety symptoms” p. 789.  Translated into English, the researcher found that more serotonin release occurs during social anxiety.

Of course, the findings here are in direct contradiction to what the pharmaceutical companies would have us believe: anxiety and depression are caused by deficit levels of serotonin. There was an editorial by Stein and Andrews published in the same issue of JAMA Psychiatry in the “Clinical Review and Education” section which attempted to obfuscate the findings by referencing the heterogeneity in persons who exhibit social anxiety.

Unfortunately, neither Frick et al. article or the editorial referenced the work of neuroscientist Steven Maier on learned helplessness. Neuroscientists have been investigating what happens in the brains of animals that are subjected to uncontrollable shock for the last 30 years.  Given uncontrollable shock, the animals appear depressed and essentially “give-up” failing to make response that could turn off the shock when the opportunity is presented.  It turns out that one of the first areas to be activated by uncontrollable shock contains serotonin neurons in the caudal-dorsal raphe that project to the amygdala.  If these serotonergic neurons are destroyed, then no learned helplessness.  The Frick et al. findings are very consistent with the animal work: serotonin creates anxiety/depression.

While the Frick et al. findings are consistent with data on learned helplessness, Chris Lowry, a colleague of Steven Maier at University of Colorado, has identified multiple serotonin circuits in the raphe. While one of these circuits produces learned helplessness, another circuit turns it off.  Thus, serotonin is just another work-horse neurotransmitter capable of creating opposite effects.  It’s the connections among the neurons, not the particular chemical making the connections, that determines the outcome.  This is another “bad news” story for the pharmaceutical houses because ingesting a chemical such an SSRI, which presumably elevates serotonin in all circuits, will yield unpredictable effects.  There is no way given current technology to target the serotonin neurons you want.

What is clear from the two articles in JAMA Psychiatry is that psychiatrists are still focused on serotonin.  Whatever glib statements psychiatry-spokespersons utter for the general public (“we always knew it was more complicated”), in the psychiatric journals, where psychiatrists talk to each other, they acknowledge having bought the assumption that low serotonin creates anxiety.  Indeed, Stein and Andrews reflect “how do we understand the apparent paradox that potentiated serotonin signaling might underlie increased anxiety-related endophenotypes and the possible predisposition for developing anxiety disorders with the fact that some patients respond to SSRIs, which presumably further increases extracellular serotonin levels?”  As they went through tortured possibilities they could not resolve the paradox.  If they had read the animal literature, it’s far less confusing.

Frick, A., Åhs,F., Engman, J., Jonasson, M., Alaie, I., Bjöekstrand, J., Frans, O., Faria, V., Linnman, C., Appel, L., Wahlstedt, K., Lubberink, M., Fredrikson, M., & Furmark, T. (2015).  Serotonin synthesis and reuptake in social anxiety disorder:  A positron emission tomography study. JAMA Psychiatry, 77 (8), 794-802.

Stein, M. B., & Andrews, A. M. (2015).  Serotonin states and social anxiety. JAMA Psychiatry, 77 (8), 845-847.

 

Will the neurotransmitter of pleasure please stand up

Over the years a number of neurotransmitters have been described as the neurotransmitter of pleasure. The list includes serotonin, dopamine, endocannabinoids, and endogenous opiates such as endorphin.  In Chapter 2 of Neuroscience for psychologists and other mental health professionals, I discuss particular emotions (fear, sadness, anger) identifying those brain regions that are active when people report the subjective experience of various emotions.  Pleasure, because it comes in so many flavors (excitement, contentment, orgasms, eating delicious food, hugging friends, enjoying music), I speculated that various pleasures may be triggered by activity in several different circuits.  However, a recent wonderful review by Berridge and Kringelbach argues that all forms of pleasure are associated with activity in the pleasure centers of the ventral pallidum in the mid-brain, the subcortical forebrain regions of the Nucleus Accumbens and subregions of the Orbitofrontal cortex.  We’ll look at why serotonin and dopamine can be ruled out as neurotransmitters of pleasure.

Serotonin has been dubbed the neurotransmitter of pleasure by some. This notion may stem from the fact that the Selective Serotonin Reuptake Inhibitors, commonly prescribed antidepressants, selectively prevent serotonin’s uptake into the neuron that released the serotonin.  So, at least initially, the makers of antidepressants might have believed that serotonin is implicated in the experience of pleasure.  At present time, data have accumulated that SSRIs are not efficacious in treating depression.  (Lack of efficacy was the bottom line from the meta-analyses conducted by Irving Kirsch and others.)  Meanwhile, neuroscientists, who can actually selectively activate or destroy specific clusters of neurons, have conducted systematic investigations to identify the functions of various clusters of serotonergic neurons. Chris Lowry, a neuroscientist at the University of Colorado, has done definitive work clarifying the function of various neurons in the raphe, the area in the brain stem containing the neurons which produce serotonin.  Turns out there are multiple circuits that employ serotonin.  One circuit actually is the proximal cause of learned helplessness. (Learned helplessness results from subjecting an animal to uncontrollable shock.  Subsequently, the animal appears depressed and will not turn off the shock when the researcher makes it possible to do so.)  When the “learned-helplessness” serotonergic neurons are destroyed, then an animal will no longer give up after being subjected to uncontrollable shock.  So one major serotonin region causes anxiety and depression.  Another serotonin circuit is involved in taming the learned helplessness circuitry.  This latter circuit is activated by heat.  There are other circuits as well.  For example, a particular circuit induces movement of the projections on the cells lining the fluid-filled cavity in the brain, such that cerebrospinal fluid in the cavity is returned to the blood stream more rapidly.  (A good thing if there is an infection.)  The problem with raising serotonin levels with an antidepressant drug is that it is impossible to know where serotonin is being raised.  The effects of the antidepressants are unpredictable.  Indeed, antidepressants carry a black-box warning for suicidal ideation.

Dopamine is a second neurotransmitter that has enjoyed a reputation as the neurotransmitter of pleasure. Neuroscientists who study addiction noticed that dopamine is released when animals work for various drugs (cocaine, amphetamine, alcohol, opioids), as well as when animals lever press for food and opportunities for copulation.  This led to the initial idea that dopamine was the “pleasure” neurotransmitter.  Then the discrepancies began to emerge.  The idea that dopamine was about pleasure was reevaluated because of  the following observations: (1) dopamine is also released when an animal works to avoid shock as well as when the animal works for a pleasurable outcome; (2) if the dopamine neurons are selectively destroyed, the animal will still display signs of pleasure when force fed, but the animal will no longer work for the food, and (3) when the animal is actually copulating or eating, the time when pleasure should reach its highest point, then dopamine is no long being released; it’s when the animal is working for food that dopamine neurons fire.  The new view is that dopamine is the neurotransmitter of motivation (striving for), rather than pleasure.

Berridge has further explored the areas in the brain which are active when an animal experiences pleasure. The ventral pallidum, which is connected and very near the area where dopamine is released, is activated when the animal experiences pleasure.  Moreover, this area activates in response to a wide range of pleasurable experiences.  Thus, Berridge and Kringelbach argue that many types of pleasurable experiences converge here.  Berridge and Kringelbach also make a distinction between areas which enhance pleasure and areas which are necessary for pleasure.  While stimulation of areas in the Orbitofrontal cortex, the ventral pallidum, the parabrachial can enhance pleasurable responses, most of these areas if removed, don’t erase pleasure.  Only the ventral pallidum, when damaged, turns liking into disgust. The neurotransmitters released in the hedonic hot spots (rostral-dorsal medial shell of the Nucleus Accumbens and ventral pallidum) include opiate type neurotransmitters, orexin, and cannabinoid type neurotransmitters.

All of this parsing of activity in the brain does have implications for how behaviors are viewed.   Dopamine has been recognized as the neurotransmitter most relevant for addiction.  (All drugs that lead to compulsive use induce dopamine release.)  Addiction happens when the motivational system gets captured by a drug.  Although a drug might initially be taken for its impact on mood (the drug either relieves pain or produces pleasure), affective consequences of the drug cannot explain addiction.  Addicts use because they are compelled.  The affective consequences are irrelevant.  The story on how the dopamine system gets captured by a drug and how recovery can be achieved is also pretty interesting.  This story is told in Chapter 8 and will wait for another blog.

Major depression involves both a diminution of motivation and a decrease in pleasure. Being able to distinguish these two components of “depression” anatomically allows researchers to ask whether various environmental manipulations or chemical interventions will have differential effects on each dimension.  In fact, making an animal’s environment less formidable and more predictable enhances the activity of all the pleasure structures, although this manipulation does not affect motivated behavior.  Perhaps, in the future, the distinctions, which are obvious to neuroscientists, will penetrate the thinking of the lay public.

Berridge, K. C., & Kringelbach, M. L. (2015).  Pleasure systems in the brain. Neuron, 86, 646-664.

THE USE OF ANTIPSYCHOTIC MEDICATIONS IN CHILDREN

Increasing Use of Antipsychotic Medications. Mark Olfson and colleagues have been monitoring the use of antipsychotic medications for the treatment of children over many years. Since the mid-1990s antipsychotic medications have been increasingly prescribed for children, adolescents, and adults (Correll & Blader, 2015; Littrell, 2015). In the most recent report, Olfson, King, and Schoenbaum (2015) find a small reduction in the use of antipsychotics for younger children from 2006 to 2010, but an increase in use for older children from 2006 to 2010. According to the report, “The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults”, p.867.

Antipsychotics Are Primarily Used for Behavioral Control in Young Children. In an editorial discussing the Olfson et al. publication, Correll and Blader (2015) indicated that antipsychotic drugs have only received FDA approval for schizophrenia, bipolar mania, irritability associated with autism, and Tourette syndrome in children. Correll and Blader noted that most of the prescriptions of antipsychotics for children reported by Olfson et al. were for conditions which had not been approved by the FDA (called off-label use). Olfson et al. reported that for younger children those receiving antipsychotic medications most often carried a diagnosis of ADHD with aggression and/or disruptive behavior disorders. For adolescents, most carried a diagnosis of depression. Less than 25% of the children being treated with antipsychotics were receiving any type of talk therapy or family instructions on behavioral control.

Horrendous Side Effects of Antipsychotic Medications.   Antipsychotic drugs all share the property of blocking dopamine receptors. They have very significant side effects. Their use has been questioned for even the conditions for which they were initially designed to treat (see below).

  • Antipsychotic drugs, particularly the second generation antipsychotics such as risperidone, olanzapine, Seroquel cause weight gain that does not plateau. They induce diabetes and increase fats in the blood such that risk of heart disease is greatly increased. Children are much more sensitive to these effects (Correll & Blader, 2015)
  • Antipsychotics induce breast development in boys (references in Chapter 6 of Littrell)
  • Antipsychotics induce hormonal changes associated with osteoporosis (decreased bone strength) (references in Chapter 6 of Littrell)
  • Some second generation antipsychotics induce cardiac arrhythmias that are associated with risk of sudden death (references in Chapter 6 of Littrell)
  • Antipsychotics induce the expression of more dopamine receptors to which dopamine will bind more avidly such that after removal rebound psychosis might ensue (Grace, 2012; Seeman et al., 2005)
  • Antipsychotics induce dystonia or involuntary movement disorders which can make walking and locomotion almost impossible; dystonia occurs immediately upon antipsychotic initiation in about 15.7% of persons (Ballerini, Bellin, Niccolai, Pieroni, Ferrara, 2002); antipsychotics also can induce a second type of motor problem which is similar to the motor problems seen in those with Parkinson’s disease, although second generation antipsychotics are less likely to induce these effects (See Chapter 6 in Littrell, 2015)
  • Antipsychotics have been shown in primates to reduce the volume of the brain by significant amounts (Dorph-Petersen et al., 2005; Konopaske et al., 2007). Brain volume reduction has also been shown in people as well (Fusar-Poli et al., 2013; Ho, Andreasen, Ziebell, Pierson, & Magnotta, 2011). In terms of mechanism through which antipsychotics might reduce brain volume, recent research suggests that these drugs induce activation of white blood cells in the cortex (Cotel et al., 2015).

Concurrent Use of Antipsychotics with Other Medications. According to the Olfson et al. (2015) report, many children prescribed antipsychotic medications were concurrently prescribed other classes of medication in addition to their antipsychotics. For small children, 58.7% were also receiving stimulants; for older children 68.7% were receiving concurrent stimulants; for older adolescents, 59.1% were receiving concurrent antidepressants. Poly-pharmacy is alarming because drugs are evaluated for safety individually. Little information is available regarding the safety of various drug combinations.

Not only is poly-pharmacy an adventure into the land of the unknown with regard to safety, but knowledge regarding the mechanism of action of various drugs introduces wonderment over the rationale for the combinations being used in the treatment of children. Stimulants increase the release of dopamine, while antipsychotics block dopamine receptors that will receive the dopamine or serotonin message. The purported mechanism of action of antidepressants is increasing the availability of serotonin, which will be countered by the action of the atypical antipsychotic, which block serotonin receptor (Loy et al., 2012). It makes no sense to increase a neurotransmitter and then block its action.

Rather than having a theoretical basis for the use of antipsychotics, the current use of antipsychotics is based on the limited findings from 8 studies that they decrease aggressive behavior. The Cochrane Review (Loy et al., 2012) concluded that “there was some evidence of limited efficacy of risperidone in reducing aggression and conduct problems in children and youths (aged 5 to 18 years) with disruptive behavior disorders in the short term (four to 10 weeks) from a small number of studies in which there was some risk of bias of overestimating the true intervention effect” p. 19.

Irony that Antipsychotics Are Being Questioned for Use in Those Who Have Psychosis.  Antipsychotics are able to significantly reduce auditory hallucinations in those with psychosis. However, even for those with psychosis, antipsychotic use is being questioned. Long term studies find that those who are not medicated have better long term functional recovery (employment and social relationships) than those who are medicated (Harrow, Jobe, & Faull, 2012; Wunderink et al., 2013, see discussion in Chapter 6 of Littrell, 2015). It’s ironic that while antipsychotics are being questioned for the population for which they were initially named, they are being extended for use in new populations.

Alternatives to Antipsychotics for the Treatment of Aggression/Disruptive Behavior in Children. Physicians may feel compelled to prescribe antipsychotics for children because they are motivated to decrease the distress in families who are raising difficult children. However, alternatives to antipsychotics, without the horrendous side-effects, are available. Omega-3s have been shown to improve aggressive behavior in children (Raine, Portnoy, Liu, Mahoomed, & Hibbein, 2015). With regard to the older children treated for depression with antipsychotics, omega-3s, exercise, meditation all ameliorate depression (see Chapter 4 in Littrell, 2015). Perhaps, today’s physicians need to remember the admonition to “first, do no harm”?

Ballerini, M., Bellin, S., Niccolai, C., Pieroni, V., & Ferrara, M. (2002). Neuroleptic-induced dystonia: incidence and risk factors. European Psychiatry, 17 (6), 366-368.

Correll, C. U., & Blader, J. C. (2015). Antipsychotic use in youth without psychosis: a double-edged sword. JAMA Psychiatry, 72(9), 859-860.

Cotel, M-C., Lenartowicz, E. M., Natesan, S., Modo, M. M., Cooper, J. D., Williams, S. C. R., Kapur, S., & Vernon, A. C. (2015). Microglial activation in the rat brain following chronic antipsychotic treatment at clinically relevant doses. European Neuropsychopharmacology, http://dx.doi.org/10.1016/j.euroneuro.2015.08.004.

Dorph-Petersen, K. A., Pierri, J. N., Perel, J. M., Sun, Z., Sampson, A. R., & Lewis, D. A. (2005). The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: A comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychophramacology, 30(9), 1649=1661.

Fusar-Poli, P., Smieskova, R., Kempton, M. J., Ho, B. C., Andeasen, N. C. & Borgwardt, S. (2013). Progressive brain changes in schizophrenia related to antipsychotic treatment: A meta-analysis of longitudinal MRI studies. Neuroscience and Biobehavioral Reviews, 37(8), 1680-1691.

Grace, A. A. (2012). Dopamine dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. American Journal of Psychiatry, 161(9), 1750-1780.

Harrow, M., Jobe, T. H., Faull, R. N. (2012). Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychological Medicine, 42(10), 2145-2155.

Ho, B. C., Andreasen, N. C., Ziebell, S., Pierson, R., & Magnotta, V. (2011). Long-term antipsychotic treatment and brain volume: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry, 68 (2), 128-137.

Konopaske, G. T., Dorph-Petersen, K. A., Pierri, J. N., Wu, Q., Sampson, A. R., & Lewis, D. A. (2007). Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology, 32 (6), 1216-1223.

Littrell, J. (2015).  Neuroscience for psychologists and other mental health professionals: promoting well-being and treating mental illness.  New York:  Springer.

Loy, J. H., Merry, S. N., Hetrick, S. E., & Stasiak, K. (2012). Atypical antipsychotics for disruptive behavior disorders in children and youths. Cochrane Database System Review, doi: 10.1002/14651858.CD008559.pub.2.

Olfson, M., King, M., & Schoenbaum, M. (2015). Treatment of young people with antipsychotic medications in the United States. JAMA Psychiatry, 72 (9), 867-874.

Raine, A., Portnoy, J., Liu, J., Mahoomed, T., & Hibbeln, J. R. (2015). Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial. Journal of Child Psychology and Psychiatry, 56 (5), 509-520.

Seeman, P., Weinshenker, D., Quirion, R., Srivastava, L. K., Bhardwaj, S. K., Grandy, D. K., . .. Tallercio, T. (2005). Dopamine supersensitivity correlates with D2high states, implying many paths to psychosis. Proceedings of the National Academy of Sciences, 102(9), 3513-3518.

Wunderink, L., N., Nieboer, R. M., Wiersma, D., Sytema, S. & Nienhuis, F. J. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry, 70 (9), 913-920.

Does the System for Training Physicians Need to Change?

The lofty goal of evidence-based medicine: Evidence-based medicine became the mantra following the introduction of the term by David M. Eddy during the 1990s in publications in New England Journal of Medicine and Health Affairs. The idea is that research evidence rather than clinical hunch should guide the behavior of physicians. Guidelines for treating particular conditions have been developed based on the available findings from published studies. Medical schools base their training on guidelines and published studies.

Unfortunately, the term “evidence-based medicine” has become a mechanism for reassuring physicians that they are doing the right thing. The problem is that the edifice of the evidence is rigged to allow cheating. A variety of factors aggregate to create a system which ensures that the “evidence” should not be believed.

Believing the Positive Findings While Ignoring the Negative: In teaching research and statistics, an initial lesson includes a discussion of Type 1 Errors. In any test of statistical significance, researchers know how many times they will be wrong in concluding that a particular treatment was effective. The current standard is accepting wrong conclusions 5% of the time. (That is, in believing the results of your statistically significant test, you will be making a Type 1 error, 5% of the time.) The researcher knows that if a research study involves examining multiple measures, then that “willingness to be wrong 5% of the time” does not accurately describe the probabilities. One has to set a much tougher standard (a “p” value much smaller than 0.05) when making multiple tests of significance. We call this correcting for alpha-inflation. The problem with the current system for approving drugs is set up to make Type 1 errors. In approving drugs in psychiatry, the FDA does not aggregate across studies submitted by a drug company. The FDA bases approval on two positive trials. They ignore all the negative trials. When Irving Kirsch used the Freedom of Information Act to obtain all the trials on antidepressants from the FDA, he found that only for the very severely depressed do the drugs work better than a placebo. In the US, the bulk of antidepressants are prescribed for the less-severely depressed: the group for which the drugs are no better than placebo. Thus, in the US, we are spending a lot of money for placebos and more problematically, these placebos have plenty of very negative side effects (see Chapter 4 in Neuroscience for Psychologists and Other Mental Health Professionals for full details.)

The Medical Journals Are Also Set Up to Make Type 1 Errors: Erick Turner and Ben Goldacre, among others, have drawn attention to the fact that positive studies are much more likely to be published than negative studies. Indeed, the results of positive studies are often published multiple times, while the studies not supporting efficacy are buried. Thus, reading the literature, the source of information for most doctors, will yield a very biased perception of reality. Sometimes big meta-analyses reviewing all the published studies are conducted. But, again, when access to all the data is not available, including unpublished studies, there is little reason to believe aggregated findings. Unfortunately, pharmaceutical houses, which fund most of the trials of drugs in the US, are under no obligation to publish negative findings. There is no law against suppressing the truth.

The Ways to Put Lipstick on a Pig. Erick Turner, in the video “How publication bias corrupts the evidence base for psychiatric drugs” available through madinamerica.com, discusses the ways in which pharmaceutical trials can make negative trials of a drug look like support for drug efficacy. (Erick Turner knows where of he speaks. He was employed at the FDA but now teaches ethics at Oregon Health and Sciences University.) Basically, the ways of “putting lipstick on a pig” are variations on the theme of scan the data after the study to find the Type 1 errors, or, stated alternatively, see where you can capitalize on chance findings. The following strategies are popular favorites:

  • if the outcome is not supported at the planned study ending, scan for a point in time when the outcome supported drug efficacy and publish a study making it appear that the drug-favorable time point had been the planned time point for evaluating the outcome
  • If the planned outcome is not supportive, look for a minor measure that might be supportive and talk about this finding as if it were the planned major variable
  • slice the subjects into subgroups and see if there is some subgroup for which the drug worked
  • if four study sites were included in the study, see if things look better at a particular study site and only discuss the site which was positive
  • everyone knows that antidepressants and antipsychotics have rather severe withdrawal phenomenon, so in your study of drug efficacy, use subjects who had been medicated and then are pulled off the drug; when you resupply subjects with the drug, you will relieve withdrawal symptoms and the drug will appear efficacious
  • only count those subjects who have completed the trial and ignore all those subjects who left the trial because the drug wasn’t working

In the video “How publication bias corrupts the evidence base for psychiatric drugs” Erick Turner compares findings as reported to the FDA with the findings from the same studies published in journals. By using the clever strategies, the negative studies as reported to the FDA suddenly appear to support drug efficacy once the drug companies massage the data. In the publications, the source for educating physicians, it looks like the evidence in support of the drug is strong. 

Registration of Clinical Trials. As Erick Turner points out the proper way to evaluate the findings from a study is to know the specific hypothesis that is being tested. The outcome which is expected to be changed by the drug at a particular time point must be agreed upon before the study begins. Scanning the data after the fact for anything that might support the general hypothesis is capitalizing on chance. In 2007, the FDA began requiring drug companies to register their trials of various drugs for which approval applications had been made to the FDA. The International Committee of Medical Journal Editors pledged to only publish those studies that had been properly registered. The process of registration requires that the protocol for the study be provided. With specification of which measures will be evaluated at which points in time, a way to check whether a researcher is guilty of capitalizing on chance is available. It is possible for interested people to go to the FDA website to determine the design of the trial. Presumably the findings from the study are to be provided to the FDA within a year following completion and are to be publicly available. Any doctor can then go to the Clinicaltrials.gov website and access the information to do his/her own evaluation of the drug’s efficacy. (Turner has published directions for doctors on how to navigate the ClinicalTrials website.) However, the FDA is reluctant to provide the raw data making it difficult for interested persons to analyze the raw data themselves.

Compliance with Clinical Trials Registration: While the Clinical Trials web site is a very important step in the right direction, it won’t help everything. Post drug approval studies on a drug are not registered. The data from studies before the change in policy are not available. Moreover, Scott, Rucklidge, and Mulder (2015) evaluated the degree of compliance by journal editors with the new mandates. Only 33.1% of published studies were prospectively registered with clearly defined outcomes. Ben Goldacre in his book and Tedtalks also concludes that medical journal compliance with commitments to publish only the results of registered studies has not been good. While capitalizing on chance has been particularly widespread in psychiatry, McGauran et al. (2010) note that the lack of truth telling is not limited to psychiatry but occurs throughout various areas of medicine.

Questions Not Asked by the FDA. The FDA’s function is to evaluate drugs for safety and efficacy. When procedures and standards were promulgated at the FDA years ago, most of the available drugs were assumed to be taken like antibiotics: use them for a short period of time until the condition resolves and then stop. Times have changed. Many Americans take medications daily for years at a time. For psychotropic drugs, people take the drugs for decades. The FDA evaluates psychotropic medications for 8 weeks. They don’t collect data on efficacy after 8 weeks. While doctors are supposed to report adverse events (side effects), it is estimated that only 1-10% of adverse events are actually reported (See Chapter 3 of Neuroscience for Psychologist and Mental Health Professionals). Particularly for drugs that are taken daily for extended periods, the long term impact on the body is not known at the time of drug approval. Moreover, no evaluation of the difficulty of withdrawing from a drug is required by the FDA. (Withdrawal process from antidepressant medications is rather severe.) Certainly, information about long term efficacy, about the long-term impact on the body, and about the difficulty of drug discontinuation might be very important pieces of information to have for both physicians and patients when deciding whether to initiate drug use. This information is just not available when drugs are released onto the market. 

Effective System Change? Given the current system, I wonder how the broken system in medicine in the US will ever be fixed. Evidence-based medicine is a good thing, but that is not the system we have. Speilmans and Parry (2010) suggest that our current system is marketing-based medicine, not evidence- based medicine. Erick Turner suggests that individual doctors can go to the clinical trials web site to evaluate drugs for themselves. Perhaps some will. We can wait for someone like Irving Kirsch to evaluate all the FDA data to evaluate efficacy. But Kirsch is then fighting against all the “noise” in the literature on the published studies. I wonder whether America’s escalating medical costs and the fact that medical care consumes more of GDP in the US than in any other country in the world might be a force for demanding a more truthful system. Surely those who worry about the National Debt will want to ensure that their dollars are not being wasted. Perhaps it will be the states, which have to balance their budgets, whose Medicaid/medicare panels might demand honest evaluations of which treatments are safe and effective. I have faith that in the long run, the truth will win. However, as John Maynard Keynes said, “in the long run, we’re all dead.”

Ghaemi, S. N. (2009). The failure to know what isn’t known: negative publication bias with lamotrigine and a glimpse inside peer review. Evidence Based Mental Health, 12, (3), 65-68.

Goldacre, B. (2012). Bad pharma: how drug companies mislead doctors and harm patients. New York: Faber & Faber.

Kirsch, I. (2010). The emperor’s new drugs: exploding the antidepressant myth.   New York, NY: Basic Books.

McGauran, N., Wieseler, B., Kreis, J. Schuler, Y-B., Kolsch, H., & Kaiser, T. (2010). Reporting bias in medical research—a narrative review. Trials, 11, 37.

Melander, H., Ahlqvist-Rastad, J., Meijer, G., & Beermann, B. (2003). Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. British Medical Journal, 326, 1171.

Scott, A., Rucklidge, J. J., & Mulder, R. T. (2015). Is mandatory prospective trial registration working to prevent publication of unregistered trials and selective outcome reporting? An observational study of five psychiatry journals that mandate prospective clinical trial registration. PLoS One, DOI: 10.1371/journal.pone.0133718.

Spielmans, G. I., & Parry, P. I. (2010). From evidence-based medicine to marketing-based medicine: evidence from internal industry documents. Biomedical Inquiry, DOI 10.1007/s11673-010-9208-8

Turner, E. H. (2013). How to access and process FDA drug approval packages for use in research. British Medical Journal, 347, 15992.

Turner, E. H., Matthews, A. M., Lindardatos, E., Tell, R. A., & Rosenthal, R. (2008). Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine, 358 (3), 252-260.

 

STRESS INCREASES INFLAMMATION BUT ALSO DECREASES THE IMMUNE SYSTEM’S CAPACITY FOR FIGHTING VIRUSES AND CANCER

Stress does increase inflammation throughout the body. This conclusion is supported by correlational research and manipulated variable research. It is known that caregivers of patients with Alzheimer’s disease display elevations in markers of systemic inflammation.   Persons experiencing stress at work display elevations on inflammatory markers. When researchers induce stress in individuals by having them talk about embarrassing events in front of a scowling audience, inflammatory markers in the blood spike. (See the post on depression is inflammation for references.)

Systemic inflammation is a causal factor in the development of cardiovascular disease and type 2 diabetes.   Systematic inflammation is a marker of an activated immune system. However, the mystery is that stress impairs the body’s capacity for fighting cancer, fighting viruses, and mounting an immune response after vaccination. A new study sheds light on how the immune system can be both activated in some ways but depressed in other ways. The explanation focuses on a recently discovered class of white blood cells called Myeloid-Derived Suppressor Cells.

Myeloid-Derived Suppressor Cells have been the focus in research on tumors. Myeloid-Derived Suppressor Cells get recruited into cancerous tumors where they prevent the attack of the killer T cells, the cells which would otherwise kill cancerous cells.   Advancements have been made in the treatment of cancer. Antibodies to molecules expressed by tumors which turn off killer T cells can be blocked by antibody treatment.   Many cancers can be cured with these antibodies. However, solid tumors often fail to respond to the antibody treatment. The efficacy of the antibody treatment is impaired because of the second obstacle preventing the killer T cells from eliminating the tumor: Myeloid-Derived Suppressor Cells. The ways in which Myeloid-Derived Suppressor Cells prevent killer T cells from doing their job have been identified. In the future, ways to subvert the Myeloid-Derived Suppressor Cells will be forthcoming so that the immune system will be able to eradicate cancer.

Besides influencing the cancer outcomes, Myeloid-Derived Suppressor Cells can impair the immune system in other ways as well. They decrease the capacity of killer T cells to kill cells infected with virus. A recent study by Jin et al. showed that stressing animals by restricting their movement increased the number of Myeloid-Derived Suppressor Cells in circulation. This study demonstrated that psychological stress does increase the population of Myeloid-Derived Suppressor Cells.   Assuming this finding applies to many diverse types of psychological stressors it clears up the mystery of how stress can increase inflammation while weakening the immune system’s capacity for responding to cancer and viral infected cells.

As discussed in Neuroscience for Psychologist and Other Mental Health Professionals in Chapter 2, the arms of the immune system can be divided into the innate system and the adaptive immune system. The innate system responds non-specifically to any molecule that looks foreign. The adaptive immune system responds to a very specific foreign protein. The adaptive immune system is recruited by vaccination. Cells responding to the proteins in the vaccine are increased. These cells will only attack when they once again see the same protein that was in the vaccine. The Myeloid-Derived Suppressor Cells seem to primarily impair the function of the adaptive system, the system needed to fight cancer and viruses. Thus, Myeloid-Derived Suppressor Cells may be a critical link for how stress increases cancer risk and impairs the body’s capacity of eradicating viruses.

Jin, J., Wang, X., Wang, Q., Guo, X., Cao, J., Zhang, X., Zhu, T., Zhang, D., Wang, W., Wang, J., Shen, B., Gao, X., Shi, Y., & Zhang, J. (2013). Chronic psychological stress induces the accumulation of myeloid-derived suppressor cells in mice. PLoS One, 8 (9), e74497.

Thoughts on the Nature of Emotions

I recently finished reading Joseph LeDoux’s wonderful book Anxious: Using the Brain to Understand and Treat Fear and Anxiety. LeDoux has been working on fear for many decades now. LeDoux has written numerous books and articles. His style is very accessible and he makes neuroanatomy and neuroscience easy to understand. LeDoux does study the brain, but readers of this site should know that he is rather dubious about drugs being the answer to ameliorate anxiety or fear. He also raises questions regarding what domains of behavior belong to brain and which domains belong to mind. A little background on Joe LeDoux is appropriate for those who have not followed his work.

Split Brain Research. LeDoux’s doctoral mentor was Michael Gazzaniga. Under Gazzaniga, LeDoux worked with split brain patients. Persons with intractable epilepsy sometimes have the axons connecting the two sides of cortex severed so that seizure activity can no longer spread from one side of the brain to the other. For most functions of daily life these patients are fine. However, the fact that the right brain does not know what the left is doing leads to some interesting phenomena. In fact, language, that is the ability to comment on what one is doing, is housed in the left side of the brain, in most of us. Information from the right field of vision goes to the left brain where it can be commented on. Information from the left field of vision goes to the right side of the brain, where it can be acted upon but not commented on. (It is possible to set up screens so that visual information only goes to one side of the cortex.)  Numerous experiments have been conducted in which stimuli presented to the right brain induces some action and then the left side of the brain is asked “why did you do this?” LeDoux and Gazzaniga reflect that no one is ever puzzled by the question. Rather, the left brain just comes up with some plausible explanation for the motivation driving the behavior, which people apparently believe. (Of course, LeDoux knows that the left brains explanation is not correct because LeDoux knows what the right brain saw.) For Gazzaniga and LeDoux these findings raise the issue about whether anyone ever really knows why he/she did anything. People for Gazzaniga and LeDoux are effectively almost in the position of being observers of their own behavior just like another person observes our behavior and guesses at our motivation. In some cases, we can only guess about why we did what did in the same manner that others might guess about the motivation driving a behavior. It should be noted that Gazzaniga and LeDoux were not the first psychologists to discover this. Gazzaniga and LeDoux basically confirmed what social psychologists Nisbett and Wilson came up with years preceding their work: under particular circumstances, none of us can definitely know why we behave as we do. We can only piece together some plausible explanation based on observation of what we have done in the context of a particular environmental contingencies which we have consciously processed.

More About LeDoux and Fear Conditioning. After establishing an independent career in the 1980s, LeDoux embarked on the study of where in the brain fear conditioning occurs. (Fear conditioning means the organism comes to react to environmental stimuli associated with a harmful stimulus in the same manner as the actual harmful stimulus.)   LeDoux identified those neurons in the amygdala where information about the co-occurrence of a light (the conditioned stimulus) with shock (the unconditioned stimulus) enters the amygdala and then the parts of the brain to which the amygdala sends the output. Given a danger associated stimulus, the output from the amygdala increases cortisol levels in the blood (the stress hormone), induces an increase in heart rate and respiration, and the animal freezes (think: deer in headlights). (For the anatomical details, the reader should consult LeDoux’s book.)

Emotion Entails a Conceptual Narrative. What will interest visitors to this web site is that LeDoux argues that the animal’s freezing, the increase in blood pressure, and the rise in stress hormones is not anxiety. LeDoux characterizes freezing, an increase in stress hormones, and increased heart rates as hard-wired defensive programs. When under attack, we all have hard wired “defensive programs” which will be elicited. According to LeDoux, these defensive programs are not emotion. Emotions in general, and in particular here, anxiety, are defined by subjective, self-report.   Self-report of emotions (feelings) are concepts: stories that people tell themselves. To state it alternatively, when deciding how you feel you are constructing a narrative that integrates physical sensations and your concept of yourself responding to your environment. Thus, self-reports of emotion are, in part, a statement about one’s self-concept.

This of course returns us to the old debate between William James and Walter Cannon in the early 1900s. Walter Cannon argued that I’m scared so I run from the bear.   William James argued, I see myself running from the bear, so I decide I’m scared. In fact, a lot of data support William James’ position. Emotions are as much a product of self-observation as they are of awareness of internal events. If people are induced to behave consistent with a particular emotion or their facial expressions are manipulated by the experimenter to be consistent with a particular emotional expression, their self-report of emotion is greatly enhanced. When discussing these rather novel ideas with my students, I always ask the mothers in the class, “who did your two-year old look at after falling down to decide whether he/she should cry?”   Most little kids look to see whether mom is horrified before they decide if they’re hurt.

The idea that emotions are constructs raises issues about self-reports of depression. In an earlier post, I presented the data supporting the case that depression involves systemic inflammation and inflammatory hormones in the brain. Since a virus or bacteria will induce an equivalent physical state to one induced by stressful circumstances, it’s equally valid for persons with systemic inflammation to decide they are depressed as to decide they harbor a virus. The question is which explanation enables a faster recovery.

Caveats Regarding Trauma-Informed Psychotherapy. Assuming that self-report of emotion entails a conceptual narrative carries implications for talk therapy. Currently, trauma informed care and screening for trauma is in vogue. A problem with this approach is the implication is that if I have experienced a trauma, I should be traumatized. “Traumatized” is a concept. It’s a narrative incorporating the concept of who the person is in relationship to an event. Unfortunately, it’s not a narrative of resilience. Just as psychiatrists look at physical manifestations (e.g., low threshold for a startle reflex) and decide it’s evidence of a brain disease (PTSD), are those who screen for experience of traumatic events in the past making an analogous mistake of finding evidence of an unfortunate event in the past (my mother was very shaming) and deciding that the client is “traumatized”. Saying my diseased brain caused my current distress or my past caused my current distress leaves no room for personal choice. Could we instead be screening for evidence of strength in the client and helping them to find a narrative of resilience. (Yea, mom was shaming, but that was about her and not about me.   I’ll write my own narrative.)

With the emphasis on trauma-informed-care these days, I’m wondering if anyone remembers the last time we collectively went down that path. In the 1980s, everyone was searching for repressed memories of child sexual abuse. If a child was shy, many therapists asked who might have abused them. Therapists frequently defined themselves as doing a good job, when a client came up with another memory. Competent women who recalled their traumatic pasts would be hospitalized for extended periods of time with the diagnosis of borderline personality or multiple personality disorder. Treatment consisted of processing the memories. This all ended rather abruptly when a prominent psychiatrist lost his license and insurance companies began prosecuting for insurance fraud, a felony offense. The history of this trauma centered approach is recounted in Mistakes were made but not by me authored by Caroll Travis and Eliot Aronson. (Yea, talk therapy can do a lot of damage too.)

Are “How Questions” More Important Than “Why Questions” ? My social work students all want to explore why a client comes in with a particular problem. Perhaps it’s human nature to ask “why?” Those of us with a physiology bent ask about diagnosis and evidence of heredity. The social science people ask about “what happened to you?” These days some of us might ask about diet (see my last post). What I try to impress on my students is that in any particular case, we will actually never know “why”. There are just too many potential causes. In line with the late Jay Haley suggestion, “define the problem in such a way that you can solve it” perhaps the more important question is “how do we get from where we are now, to where we want to be?” Often times, how one got there has little to do with how one moves on.

Donovan, L. (December 8, 1999). Controversial psychiatrist suspended: recovered memory case spurs state move. Chicago Tribune