Behavioral Training Improves Connectivity and Function in the Brain

Children with poor reading skills who underwent an intensive, six-month training program to improve their reading ability showed increased connectivity in a particular brain region, in addition to making significant gains in reading, according to a study funded in part by the National Institute of Mental Health (NIMH). The study was published in the Dec. 10, 2009, issue of Neuron. LPCC Continuing Education
"We have known that behavioral training can enhance brain function." said NIMH Director Thomas R. Insel, M.D. "The exciting breakthrough here is detecting changes in brain connectivity with behavioral treatment. This finding with reading deficits suggests an exciting new approach to be tested in the treatment of mental disorders, which increasingly appear to be due to problems in specific brain circuits."

For the study, Timothy Keller, Ph.D., and Marcel Just, Ph.D., both of Carnegie Mellon University, randomly assigned 35 poor readers ages 8-12, to an intensive, remedial reading program, and 12 to a control group that received normal classroom instruction. For comparison, the researchers also included 25 children of similar age who were rated as average or above-average readers by their teachers. The average readers also received only normal classroom instruction.

Four remedial reading programs were offered, but few differences in reading improvements were seen among them. As such, results for participants in these programs were evaluated as a group. All of the programs were given over a six month schooling period, for five days a week in 50-minute sessions (100 hours total), with three students per teacher. The focus of these programs was improving readers' ability to decode unfamiliar words.

Using a technology called diffusion tensor imaging (DTI), the researchers were able to measure structural properties of the children's white matter, the insulation-clad fibers that provide efficient communication in the central nervous system. Specifically, DTI shows the movement of water molecules through white matter, reflecting the quality of white matter connections. The better the connection, the more the water molecules move in the same direction, providing a higher "bandwidth" for information transfer between brain regions.

At the outset of the study, poor readers showed lower quality white matter than average readers in a brain region called the anterior left centrum semiovale. Six months later, at the completion of the intensive training, the poor readers showed significant increases in the quality of this region. Children who did not receive the training did not show this increase, suggesting that the changes seen in the remedial training group were not due to natural maturation of the brain.

In an effort to further pinpoint the mechanism underlying this change, the researchers deduced that a process called myelination may be key. Myelin is akin to electrical insulation, allowing for more rapid and efficient communication between nerve cells in the brain. However, the directional association between brain changes and reading improvements remains unclear—whether intensive training brings about increased myelination that results in improved word decoding skills, or whether improved word decoding skills leads to changes in reading habits that result in greater myelination.

"Our findings support not only the positive effects of remediation and rehabilitation for reading disabilities, but may also lead to improved treatments for a range of developmental conditions related to brain connectivity, such as autism," noted Just.


Source: Timothy Keller, Ph.D.; Marcel Just, Ph.D.

Left brain image shows the area of lower quality white matter (blue area) among poor readers relative to good readers at the beginning of the study.

Center brain image shows the area where the white matter quality increased (red/yellow area) among poor readers who received the remedial reading instruction.

Right brain image shows that following the instruction, there were no differences between the poor and average readers with respect to the quality of their white matter.

Reference
Keller TA, Just MA. Altering cortical connectivity: Remediation-induced changes in the white matter of poor readers.

New Approach to Reducing Suicide Attempts Among Depressed Teens

A novel treatment approach that includes medication plus a newly developed type of psychotherapy that targets suicidal thinking and behavior shows promise in treating depressed adolescents who had recently attempted suicide, according to a treatment development and pilot study funded by the National Institute of Mental Health (NIMH). The study, described in three articles, was published in the October 2009 issue of the Journal of the American Academy of Child and Adolescent Psychiatry. Continuing Education for Counselors
Background
Youth who attempt suicide are particularly difficult to treat because they often leave treatment prematurely, and no specific interventions exist that reliably reduce suicidal thinking and behavior (suicidality). In addition, these teens often are excluded from clinical trials testing depression treatments. The Treatment of Adolescent Suicide Attempters Study (TASA) was developed to address this need and identify factors that may predict and mediate suicide reattempts among this vulnerable population. A novel psychotherapy used in the study—cognitive behavioral therapy for suicide prevention (CBT-SP—was developed to address the need for a specific psychotherapy that would prevent or reduce the risk for suicide reattempts among teens. CBT-SP consisted of a 12-week acute treatment phase focusing on safety planning, understanding the circumstances and vulnerabilities that lead to suicidal behavior, and building life skills to prevent a reattempt. A maintenance continuation phase followed the acute phase.

In the six-month, multisite pilot study, 124 adolescents who had recently attempted suicide were either randomized to or given the option of choosing one of three interventions—antidepressant medication only, CBT-SP only, or a combination of the two. Most participants preferred to choose their intervention, and most (93) chose combination therapy. Participants were assessed for suicidality at weeks six, 12, 18 and 24.

Results of the Study
During the six-month treatment, 24 participants experienced a new suicidal event, defined as new onset or worsening of suicidal thinking or a suicide attempt. This rate of recurrence is lower than what previous studies among suicidal patients have found, suggesting that this treatment approach may be a promising intervention. In addition, more than 70 percent of these teens—a population that is typically difficult to keep in treatment—completed the acute phase of the therapy. However, many participants discontinued the treatment during the continuation phase, suggesting that treatment may need to include more frequent sessions during the acute phase, and limited sessions during the continuation phase.

The study revealed some characteristics that could predict recurrent suicidality, including high levels of self-reported suicidal thinking and depression, a history of abuse, two or more previous suicide attempts, and a strong sense of hopelessness. In addition, a high degree of family conflict predicted suicidality, while family support and cohesion acted as a protective factor against suicide reattempts. Other studies have found similar results, according to the researchers.

Significance
Although the study cannot address effectiveness of the treatment because it was not randomized, it sheds light on characteristics that identify who is most at risk for suicide reattempts, and what circumstances may help protect teens from attempting suicide again. In addition, the study found that 10 of the 24 suicide events occurred within four weeks of the beginning of the study—before they could receive adequate treatment. This suggests that a "front-loaded" intervention in which the most intense treatment is given early on, would likely reduce the risk of suicide reattempt even more.

What's Next
The effectiveness of CBT-SP—alone or in conjunction with antidepressant medication—will need to be tested in randomized clinical trials. In the meantime, because many suicide events occurred shortly after the beginning of the trial, the researchers suggest that clinicians emphasize safety planning and provide more intense therapy in the beginning of treatment. In addition, they note that therapy should focus on helping teens develop a tolerance for distress; work to improve the teen's home, school and social environment; and rigorously pursue coping strategies for teens who experienced childhood trauma such as abuse.

References
Vitiello B, Brent D, Greenhill L, Emslie G, Wells K, Walkup J, et al.. Depressive symptoms and clinical status during the treatment of adolescent suicide attempters. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(10):997-1004.

Brent D, Greenhill L, Compton S,Emslie G, Wells K, Walkup J, et al. The treatment of adolescent suicide attempters (TASA): predictors of suicidal events in an open treatment trial. Journal of the American Academy of Child and Adolescent Psychiatry. 2009;48(10):987-996.

Stanley B, Brown G, Brent D, Wells K, Poling K, Curry J, et al. Cognitive behavior therapy for suicide prevention (CBT-SP): treatment model, feasibility and acceptability. Journal of the American Academy of Child and Adolescent Psychiatry. 2009;48(10):1005-1013.

Runaway Vigilance Hormone Linked to Panic Attacks

Translational Experiments in Rats, Humans Suggest New Medication Target
A study has linked panic disorder to a wayward hormone in a brain circuit that regulates vigilance. While too little of the hormone, called orexin, is known to underlie narcolepsy, the new study suggests that too much of it may lead to panic attacks that afflict 6 million American adults. LPC Continuing Education
"Targeting the brain's orexin system may hold promise for a new generation of anti-anxiety treatments," said Thomas R. Insel, M.D., Director of the National Institute of Mental Health (NIMH), part of the National Institutes of Health. "This is a good example of how translational experiments in rats and humans can potentially yield clinical benefits."

NIMH grantee Anantha Shekhar, M.B., Ph.D., and colleagues at Indiana University and Lund University, report on their findings online Dec. 27, 2009 in the journal Nature Medicine. They showed that blocking orexin gene expression or its receptor prevented panic attack-like responses in rats. The study also revealed that panic disorder patients have excess levels of the hormone.

Background
Orexin, also called hypocretin, is secreted exclusively in a circuit emanating from the brain's hypothalamus, known to regulate arousal, wakefulness and reward.

Panic attacks can be experimentally-induced by infusing susceptible humans with a normally innocuous salt called sodium lactate. The salt similarly triggers panic-like anxiety behaviors in susceptible rat strains, suggesting that something is altered in their arousal circuit. Since sodium lactate activated orexin-secreting neurons in panic-prone rats but not in control rats, the researchers hypothesized that something might be orexin.

Results of This Study
The investigators first discovered that increased gene expression in orexin-secreting neurons correlated with increases in anxiety-like behavior in panic-prone rats following sodium lactate infusions. Using a technique called RNA interference, they then protected the panic-prone rats from developing anxiety behaviors following the infusions by first injecting them with a genetically-engineered agent that prevented orexin genes from turning on. Blocking orexin receptors with a drug that specifically binds to it also blocked the anxiety like behavior following the infusions. This mirrored effects, seen in both rats and humans, of benzodiazepine medications used to treat panic disorder.

The excess sleepiness of narcolepsy, traced a decade ago to loss of orexin-secreting neurons in the arousal circuit, might seem to be an opposite state of a panic attack. However, the researchers demonstrated in rats that such sedation could not account for orexin's effects on anxiety. Also in rats, they traced orexin neurons to their end target to pinpoint the specific brain site that accounts for the anxiety effects, disentangled from cardio-respiratory components of the panic response.

Finally, by measuring orexin in cerebrospinal fluid of 53 patients, the researchers showed that those with just panic disorder had higher levels of orexin than those with both panic disorder and depression.

Significance
Taken together, these results and other evidence suggest a critical role for an overactive orexin system in producing panic attacks, say the researchers.

What's Next?
Medications that block the orexin receptor may provide a new therapeutic approach for the treatment of panic disorder, they add.

The research was also supported, in part, by NIH's National Center for Research Resources.

Reference
A key role for orexin in panic anxiety. Johnson PL, Truitt W, Fitz SD, Kelley PE, Dietrich A, Sanghani S, Traskman-Bendz L, Goddard AW, Brundin, L, Shekhar A. Nature Medicine. Epub 2009 Dec 27.

Just Over Half of Americans Diagnosed with Major Depression Receive Care

More Receive Psychotherapy than Medication; Study Provides New Detail on Disparities
Overall, only about half of Americans diagnosed with major depression in a given year receive treatment for it, and even fewer—about one fifth—receive treatment consistent with current practice guidelines, according to data from nationally representative surveys supported by NIMH. Among the ethnic/racial groups surveyed, African Americans and Mexican Americans had the lowest rates of use of depression care; all groups reported higher use of past-year psychotherapy vs. medication for depression. MFT Continuing Education
Background
Depression is a leading cause of disability in the United States. Past research has found that many people with depression never received treatment, and that the percentage of those receiving treatment varies with ethnicity and race. In order to provide comprehensive and up-to-date information on depression care, with a particular emphasis on minority groups, NIMH's Collaborative Psychiatric Epidemiology Surveys initiative (CPES) has combined data from three nationally representative studies: the National Survey of American Life, the National Comorbidity Survey-Replication, and the National Latino and Asian American Study.

This Study
Scientists at Wayne State University, Detroit, MI; the University of Michigan, Ann Arbor; the University of California, Los Angeles; and the Harvard School of Public Health, Boston, MA, carried out the current study, which reports on data from CPES collected between February 2001 and November 2003 from 15,762 residents 18 years and older. The size of the sample makes it possible to examine health care use in ethnic/racial groups with a new level of detail, distinguishing between groups often surveyed as one population. The investigators were able to break out types of care used, and to assess to what extent the care used was consistent with the American Psychiatric Association (APA) Practice Guidelines for the Treatment of Patients with Major Depressive Disorder. Finally, they examined how factors enabling healthcare access—insurance, education, and household income—influenced rates of care.

A central finding was that overall, 51 percent of all those in the study who met criteria for major depression during the prior year received some kind of treatment for it, with only 21 percent receiving care that was consistent with the APA Guidelines.

Other key study findings addressed disparities, types and quality of care received, and factors that enable access to healthcare.

Prevalence and severity of major depression was similar among the five studied ethnic/racial groups—Mexican Americans, Puerto Ricans, Caribbean Blacks, African Americans, and non-Latino Whites. However, African Americans and Mexican Americans were least likely to receive any care or care consistent with practice guidelines. Compared with non-Latino Whites for example, of whom 54 percent with depression received care, 40 percent of African Americans and 34 percent of Mexican Americans did. The rate of care for Puerto Ricans was close to that of Whites, 50 percent.
Across these population groups, psychotherapy was used more frequently than medications (pharmacotherapy). Overall, 34 percent received pharmacotherapy; 45 percent psychotherapy. Psychotherapy was more likely to be consistent with APA guidelines than pharmacotherapy, suggesting that adherence—the extent to which patients completed the recommended therapy—was greater for psychotherapy than pharmacotherapy. The contrast between the rates of Guideline-consistent psychotherapy and pharmacotherapy use was greatest among Caribbean Blacks, African Americans, and Mexican Americans.
Puerto Ricans had rates of treatment use, and treatment that was consistent with care guidelines, that were similar to, or higher than, non-Latino Whites.
Differences in factors enabling healthcare access appeared to contribute substantially to disparities in mental healthcare use, particularly for Mexican Americans. When differences in these enabling factors were controlled for statistically—so in effect, the population groups being compared had the same rates of enabling factors—the degree of disparities in use of care by Mexican Americans was reduced. For Caribbean Blacks and African Americans, statistical control of enabling factors reduced disparities in psychotherapy use, but not use of pharmacotherapy.
Health insurance coverage was associated with a greater likelihood of depression care, but not guideline consistent care. The pattern with education was reversed: education was associated with a greater likelihood of care that was consistent with the APA Guidelines, but not with greater use of care in general.
Significance
This study, with its large sample size and emphasis on minority groups, provides a more nuanced and detailed picture of the care received for major depression among different ethnic/racial groups and of factors that contribute to disparities. Lead author Hector González at Wayne State University said that Mexican-Americans make up over two-thirds of Latinos in the U.S.: "We found in our study that there are some really distinctive differences in mental healthcare use between Mexican Americans and other Latino subgroups that have not been previously reported." Estimates suggest that Latinos will make up close to one-third of the U.S. population by mid-century; the study findings suggest that Mexican Americans should be a focus of efforts to reduce health disparities to ensure the nation's health in coming decades.

All groups were more likely to have received psychotherapy than pharmacotherapy. Caribbean Blacks and African Americans were particularly unlikely to receive pharmacotherapy consistent with APA guidelines; enabling factors such as education, health insurance, and income did not explain the lower rates of medication use. The authors note possible reasons for this, including research indicating that perceived discrimination can shape health care seeking. They speculate that the non-immigrant status of Puerto Ricans—and with that, greater predominance of English language use within this group—may be factors in their relatively high rates of health care use.

Findings from this study will inform future research on adherence to various depression therapies, and the factors that shape differences in care among racial/ethnic groups. "Future studies," say the authors, "should explore the extent to which patients' subjective experiences of racial bias may affect their access and utilization of mental healthcare."

Reference
González, H.M., Vega, W.A., Williams, D.R., Tarraf, W., West, B.T., and Neighbors, H.W. Archives of General Psychiatry 2010;67(1):37-46.

Novel Model of Depression from Social Defeat Shows Restorative Power of Exercise

In a study in a mouse model that mimics the contribution of social stress to human depression, an environment that promotes exercise and exploration alleviated depressive behavior in the mice. The beneficial effect of activity depended on the growth of new neurons in the adult brain. Continuing education for counselors
Background
In the 1990s scientists established that new neurons grow in the adult as well as the immature brain. The functions of neurogenesis, or new neuronal growth, are still being explored, but it is known that stress slows this growth in the hippocampus―a brain center involved in the formation of new memories―and that antidepressant treatment promotes it.

Previous research in animal models has also demonstrated that environmental enrichment―the addition of features in an animal's cage that provide opportunities for exercise and investigation―fosters resilience to stress and can alleviate the depression-like behavior that results from uncontrollable stress. Environmental enrichment has also been shown to promote hippocampal neurogenesis in animals.

This Study
This work, by Michael Lehmann and Robert Schloesser and colleagues in NIMH's intramural research program, focused on the ability of environmental enrichment to reverse depressive behaviors caused by social defeat, a situation paralleling the social stresses that can trigger human depression. Past work in animal models has often used physical stressors such as electric shock, restraint, or forced exercise to create depressive behaviors. In addition, the scientists inserted a gene in mice that made it possible to selectively interrupt the growth of new neurons at a specific time and in a specific population of cells in the hippocampus, avoiding any spillover effects to other tissues.

More on Mouse Behavior
Although "dominant and aggressive" may not sound like descriptors that apply to mice, male mice in the wild live apart from other males and they are intensely aggressive if housed together. In this study, male mice were allowed to interact directly for no more than five minutes at a time and were supervised to make sure one mouse did not injure or kill the other.

Mice naturally cover territory in the wild; if furnished with running wheels in a cage, they will, on their own, run the equivalent of as much as 6 to 10 kilometers in one day.
Stress―in this case social defeat stress―has unmistakable effects on the behavior of mice. Researchers use a variety of tests to describe changes in behavioral tendencies, including observing how boldly the mice explore an unfamiliar cage; how much time they will choose to spend in a dark (safe) vs. light (risky) compartment; and the extent to which they'll indulge their taste for something pleasant like sweetened water. Mice who have been the losers of repeated social defeats are visibly cautious and subdued, even in the judgment of observers who do not know whether they were winners or losers in a conflict.

Test mice in this study were housed across a partition in the home cage of a dominant, aggressor mouse. For 5 minutes per day, the partition was removed, allowing the "intruder" and dominant mouse to interact directly. After 2 weeks, the test mice consistently behaved submissively. The test mice were then divided and placed in either a spare environment, or one enriched with running wheels, and tubes of various shapes and sizes. Some of the mice assigned to either environment were a standard laboratory strain. Others had an inserted gene targeted to a population of hippocampal cells that give rise to new neurons; in mice with this transgene, the antibiotic valganciclovir is toxic to dividing cells so neurogenesis is prevented when the drug was added to the animals' feed.

The nontransgenic test mice in the enriched environment, but not those in the more spartan cages, recovered from the submissive behavior seen after social defeat. The transgenic mice, in which neurogenesis was stopped, remained submissive, resembling the mice housed in the impoverished environment.

In tests to probe affect, or mood, the transgenic mice housed in the enriched environment also resembled mice housed in the impoverished environment in that they showed the same reduced inclination to explore, greater anxiety, and a less than normal interest in sweet solutions which mice usually prefer. Interruption of neurogenesis had no effects on the baseline health and behavior of the animals, so the lack of new neurons did not cause depression, but interfered with recovery.

Significance
This study demonstrates that psychosocial stress in mice can cause behavior resembling human depression, which environmental enrichment can ameliorate as long as neurogenesis is intact.

Key elements of this study included its use of a social stressor, more analogous to the social experiences that can contribute to human depression than the physical stressors often used in research. In addition, the use of the transgene in test animals enabled the scientists to control the interruption of neurogenesis with precision with respect to both timing and location and with no effects on neighboring cells.

According to author Michael Lehmann, "There are multiple avenues through which environmental enrichment can have a positive impact on depression. In this model we use a natural psychosocial stressor with relevance to social stress in humans, to induce depressive-like behaviors. We show that environmental enrichment can facilitate the recovery from social stress, and that adult neurogenesis is a requirement for the rehabilitating effects of enrichment."

The authors suggest that neurogenesis may be central to the ability of an animal to update emotional information upon exposure to a novel environment. With neurogenesis impaired, they may be unable to integrate information on the features of a new, changed environment. The resulting cognitive distortions may trigger symptoms of major depression.

Research suggests that one important consequence of environmental enrichment is its impact on the function of the body's stress response system. Animals in these enriched environments show positive effects on the physiology of stress resilience. In humans, successful antidepressant treatment is reflected in similar beneficial changes. Prior research has also linked neurogenesis with positive changes in the stress response system.

The authors also point out that in humans, physical exercise and positive psychosocial activity have beneficial effects on depression and stress resilience. Forms of entertainment that encourage mental activity, according to Lehmann, such as reading, video games, exercise and outdoor recreation could have longer lasting changes for many suffering from mild depressive symptoms than pharmacologic treatment, without the accompanying side effects.

Reference
Schloesser, R.J., Lehmann, M., Martinowich, K., Manji, H.K., and Herkenham, M. Environmental enrichment requires adult neurogenesis to facilitate recovery from psychosocial stress. Molecular Psychiatry 2010 Dec;15(12):1152-1163. Epub 2010 March 23.

From Neurons to Thought: Coherent Electrical Patterns Observed Across the Brain

Amidst the background hum of electrical signaling generated by neurons in the brain, scientists have found that local groups of neurons, firing in coordination, sometimes create a signal that is mirrored instantaneously and precisely by other groups of neurons across the brain. These transient episodes of coherence across different parts of the brain may be an electrical signature of thought and actions. MFT CEUs
Background
One of the goals of neuroscience research is to identify how thoughts and actions are encoded in the activity of neurons. A challenge has been to extract meaningful patterns from the ongoing tumult of electrical activity in the brain. This global electrical activity is built from the firing of individual neurons. A single neuron responds to a stimulus in an all or nothing manner—if the stimulus reaches a certain threshold, the neuron “fires” an electrical signal. Groups of neurons firing in a coordinated way create a local electrical field that is in itself a signal that can vary in pattern. These local field potentials (LFPs) have been a target of research.

This Study
In this research, Dietmar Plenz and colleagues at NIMH and Duke University pinpointed LFPs in the cortex that surpassed a minimal size threshold, and then searched the rest of the cortex to see what was occurring at the same time. In each case, they found other answering LFPs across the brain that mimicked each other with high precision: there was no degradation or loss of power (amplitude) in the signal. Unlike what is observed after dropping a stone in a pond—with wavelets getting smaller farther from the stone—the intensity of the LFPs was the same across the brain. The investigators call these LFPs coherence potentials. Although LFPs that occur during these transient episodes of coherence are identical to each other, they are also multidimensional and potentially infinitely diverse, providing a means to encode information. Most LFPs do not reach the threshold that characterizes a coherence potential but with those that do, propagation of the LFPs across the brain is extraordinarily rapid. The authors note that the rapid dispersion of such a signal mimics the spread of ideas and behaviors in social networks; a sufficiently provocative idea can spread very swiftly through a population.

Significance
Coherence potentials simultaneously engage groups of neurons in different parts of the brain with diverse functions. This is consistent with the multi-faceted nature of mental associations and memories—a memory focused on a person or object might conjure various kinds of sensations and thoughts—visual, tactile, auditory, and emotional, for example.

These findings emerged from recent work that demonstrated that, like other systems in nature, the cortex exists at a critical state between stability and instability. A characteristic of this state in the brain is the presence of neuronal avalanches—if a stimulus reaches a certain threshold, it will set off cascades of neuronal firing. This dynamic is analogous to when the slope of a sandpile reaches a point at which adding one more grain will trigger an avalanche. The adherence of the cortex to this critical state ensures that the brain can respond to a wide range of stimuli, but not lapse into a chaos of excess activity (such as the too-synchronous firing during epilepsy). Coherence potentials emerge predominantly when the cortex is critical, that is, when it displays neuronal avalanches. Nudging the cortex away from this point, by inhibiting neuronal signaling with medications for example, disrupts these dynamical patterns.

What’s Next
Coherence potentials were present in cells in culture as well as awake monkeys, a robust demonstration that they occur in the functioning cortex. Future studies will be aimed at monitoring coherence potentials in the context of behavioral function with the ultimate aim of making a connection between specific coherence potentials and behaviors.

Reference
Thiagarajan, T.C., Lebedev, M.A., Nicolelis, M.A., and Plenz, D. Coherence potentials: loss-less, all-or-none network events in the cortex. PLoS Biology 2010, doi:10.1371/journal.pbio.1000278.

Effects on Personality May Be Mechanism of Antidepressant Effectiveness

Results of a study of antidepressant treatment for major depression suggest that changes in personality traits seen in patients taking the drug paroxetine (Paxil) may not be the result of the medication’s lifting of mood but may instead be a direct effect of this class of drugs and part of the mechanism by which they relieve depression. MFT Continuing Education
Background
People with a high level of the personality trait neuroticism—characterized by a tendency to experience negative emotions and moodiness—are more likely than others to develop depression. Neuroticism is one of five personality traits that psychologists use as an organizing scheme for understanding personality: the other four traits are extraversion, openness, conscientiousness, and agreeableness. People who take anti-depressants report lower levels of neuroticism and increased extroversion, in addition to a lifting of depression. The assumption has been that these changes in personality measures were the result, not the cause, of a lifting of depression.

Studies in twins suggest that to a large degree the same genetic factors underlie both neuroticism and depression risk. Research also suggests that the neurotransmitter serotonin plays a role in the expression of both neuroticism and extraversion. The class of anti-depressant drugs to which paroxetine belongs—the selective serotonin reuptake inhibitors (SSRIs)—increase the neurotransmitter’s availability in the brain.

This Study
To test the relationship between SSRIs and personality, investigator Tony Tang and colleagues at Northwestern University, Evanston, IL, the University of Pennsylvania in Philadelphia, and Vanderbilt University in Nashville, TN, randomly assigned patients with major depressive disorder (MDD) to receive paroxetine (120 patients), placebo (60 patients), or cognitive therapy (60 patients).

After 8 weeks, medication and cognitive therapy (CT) each proved more effective than placebo in reducing depression. In addition, measures of neuroticism (based on standard surveys) in the groups receiving medication or cognitive therapy dropped, while extraversion scores rose. The changes were striking; while patients receiving placebo also reported small changes in both traits, the changes in patients on paroxetine were four to eight times as large. Patients receiving paroxetine had much greater changes in personality traits than patients receiving placebo even when the degree of improvement in depression was the same. This suggested that the effects on personality traits were not the result of the drug’s lifting of depression. After accounting for decreases in depression in patients receiving CT, the improvement in extraversion, but not neuroticism, remained significant.

In further comparison of paroxetine with placebo, patients who had initially taken placebo were given the option after 8 weeks to take paroxetine. During the placebo phase, there were small changes in neuroticism and extraversion; much greater changes occurred after 8 weeks on paroxetine. Finally, those patients on paroxetine with the greatest degree of change in neuroticism (but not extraversion) were least likely to relapse to depression; the degree of changes in personality in those receiving CT did not affect the chances of relapse.

Significance
While the neurochemical effects of SSRIs are known, how those changes act to reduce depression is not clear. These results contradict the prevailing assumption that changes seen in personality traits in patients taking SSRIs are a result of the drugs’ effects on depression. SSRIs may alter personality directly—and thus lift depression—or may act on a third factor that underlies both. CT may alter personality by a different path. Continued research on how these treatments work can provide a clearer understanding of the mechanism of action of SSRIs and how treatment can be best used to reduce depression and minimize relapse.

Reference
Tang, T.Z., DeRubeis, R.J., Hollon, S.D., Amsterdam, J., Shelton, R., and Schalet, B. Personality change during depression treatment. Archives of General Psychiatry 2009 Dec;66(12):1322-30.