Overactivity in Psychopathy

Individuals with psychopathic traits have deficits in their ability to experience remorse, and lack emotional empathy. Their interpersonal relationships are characterized by a pattern of manipulation of others for individual gain (Decety et al., 2013). Psychopaths make up approximately 1% of the general population, however these individuals comprise approximately 23% of prison populations (Decety et al., 2013). The discrepancy in the statistics between community and prison populations speaks to the inability of the mental health system and society in general to adequately manage, treat, and rehabilitate these individuals. Perhaps the difficulty with treatment is not only attributable to the treatment resistant nature of the disorder itself. It is possible that psychiatry and science has developed an understanding of these individuals that is incorrect. The conceptualization, description, and understanding of psychopathic individuals has long been rooted in what these individuals lack. Our understanding of these individuals has been colored by the fact that outwardly they seem to lack the very qualities that make us humans; connectedness, empathy, fear, and love.  The emphasis on what is lacking may be misguided. This may prevent a more accurate representation of these individual’s struggles, and impede successful treatment. Recent research has shed light on areas of the brain that are overactive in these individuals and ways in which this information can inform future treatment options.

Buckholtz et al. (2010) conducted a study that examined the role of the mesolimbic dopamine reward system, and how overactivity of this system in individuals with psychopathic characteristics may drive destructive behavior. Impairments in emotional empathy and social connectedness are concerning; however, impulsive, reward seeking and risky behaviors are what lead to violent crimes, recidivism, and substance abuse. In order to better understand what drives reward seeking behaviors Buckholtz et al. (2010) used positron emission tomography (PET) imaging to visualize participant’s brains and monitored dopamine release. The PET scan was done in conjunction with functional magnetic imaging (fMRI) to examine the brain’s reward system. The participants received a dose of amphetamine to induce a response from a physiologically rewarding experience. Following administration of amphetamine, brain scans were completed to measure dopamine release in response to the stimulant. Remarkably, people who had scored high on psychopathic trait tools had almost four times the amount of dopamine released in response to the pleasurable stimuli (Buckholtz et al., 2010). This finding is significant because it suggests that psychopathic behavior is not necessarily driven by a lack of empathy and a drive to harm others. This excessive dopamine response may suggest that behavior in these individuals is also driven by a need for pleasurable experience and reward response within the brain (Buckholtz et al., 2010).

Buckholtz et al. (2010) followed up by telling participants they would receive monetary rewards for completing a task. Participants’ brains were monitored with fMRI during task completion. The researchers found that the nucleus accumbens, the dopamine reward area of the brain, was more active in individuals with high psychopathic traits when anticipating the monetary reward. Again, this finding emphasizes the possibility that because of these exaggerated dopamine responses in reaction to rewards, psychopaths are not capable of considering the needs of others (Buckholtz et al., 2010). This drive for dopamine may then be translated outwardly to cold, callous affect and lack of regard for others that is seen in individuals with psychopathic traits.

In another study Decety et al. (2013) examined reactivity in response to imagined pain in the brains of their sample, which included individuals who scored high on a psychopathic trait inventory measure in addition to healthy controls. Participants who had scored high on psychopathic trait inventory imagined harm that would be severe enough to inflict physical pain being done to them. In response to this prompt, these individuals displayed an exaggerated response; regions involved in empathy including the anterior insula, the anterior midcingulate cortex, somatosensory cortex and the right amygdala all showed unusually pronounced neural activation. However, as expected, when these individuals imagined physical pain being inflicted upon others, these neural networks failed to become activated (Decety et al., 2013). This study reveals a potential possibility of using the response individuals with psychopathic traits are capable of experiencing in response to their own imagined pain to “kick start” the process of empathy for others. Further research is required to better understand how the process could be generalized however the concept of kick starting empathy with one’s own imagined pain is interesting nonetheless.

These studies by do not provide specific treatment options to implement with individuals with psychopathic traits, nor do they imply that these tendencies can be easily treated or reformed. What can be taken from these studies is that the inner workings and processes that drive psychopathic behaviors are complex in nature. These studies suggest the possibly that the symptoms that characterize antisocial personality disorder are as deeply rooted within the neurobiology as the processes of love, compassion, and need for social connectedness are in you and me. With additional research, and a better understanding of the neurobiology behind antisocial personality disorder, there is the possibility that we can be successful in reducing the rates of incarceration and improving outcomes within community settings.


Buckholtz, J. W., Treadway, M. T., Cowan, R. L., Woodward, N. D., Benning, S. D., Li, R., . . . Zald, D. H. (2010). Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nature Neuroscience Nat Neurosci, 13(4), 419-421. doi:10.1038/nn.2510

Decety, J., Chen, C., Harenski, C., & Kiehl, K. A. (2013). An fMRI study of affective perspective taking in individuals with psychopathy: imagining another in pain does not evoke empathy. Frontiers in human neuroscience, 7, 489.

Gregory, S., Blair, R. J., Ffytche, D., Simmons, A., Kumari, V., Hodgins, S., & Blackwood, N. (2015). Punishment and psychopathy: A case-control functional MRI investigation of    reinforcement learning in violent antisocial personality disordered men. The Lancet Psychiatry, 2(2), 153-160. doi:10.1016/s2215-0366(14)00071-6

Humphreys, K. L., Mcgoron, L., Sheridan, M. A., Mclaughlin, K. A., Fox, N. A., Nelson, C. A., & Zeanah, C. H. (2015). High-Quality Foster Care Mitigates Callous-Unemotional Traits Following Early Deprivation in Boys: A Randomized Controlled Trial. Journal of the American Academy of Child & Adolescent Psychiatry, 54(12), 977-983. doi:10.1016/j.jaac.2015.09.010


Putting the Brakes on Emotional Reactions: Dialectical Behavior Therapy in the Treatment of Borderline Personality Disorder

Dialectical Behavior Therapy was developed in the 1980s by Dr. Marsha Linehan, a psychologist who used her own insights from living successfully with borderline personality disorder to develop this therapy. DBT is a modified form of cognitive behavioral therapy and has been used to treat individuals with chronic suicidality and self-injurious behavior. In the first randomized control trial of DBT for borderline personality disorder, individuals who received DBT treatment versus treatment as usual had fewer suicidal episodes, fewer psychiatric hospitalizations, less treatment drop-out, and improved scores on global as well as social adjustment (Linehan et al., 1991). DBT was groundbreaking in its ability to target otherwise treatment resistant behaviors that could lead to adverse outcomes as fatal as suicide.

Since its inception, DBT has been more broadly applied to treat individuals struggling with substance use (Beckstead et al., 2015), treatment-resistant depression (Harley et al., 2008), eating disorders (Safer et al., 2010), and emotion regulation in general (Neacsiu et al., 2014). DBT is a multi-modal approach, and it involves individual psychotherapy, group skills training, and even phone consultations, with consistent coaching as part of treatment (Freedman & Duckworth, 2013). The Dialectics module of treatment refers to an approach of validation, where individuals are trained to accept their identified thoughts, emotions, and behavior rather than struggle with them. This validation facilitates a process of change (Dimeff & Linehan, 2001). The behavioral module focuses on specific behavioral coping skills that allow individuals to live with the symptoms of mental illness. Mindfulness practice is utilized in DBT to become conscious of one’s thoughts and feelings by paying attention to associated bodily sensations with an attitude of non-judgment and acceptance. Mindfulness practice is part of the process of validation, where one becomes tolerant of distressing thoughts and emotions without self-criticism. Mindfulness techniques such as progressive muscle relaxation and deep breathing are also utilized in the behavioral skills training module of DBT (Freedman & Duckworth, 2013).

DBT is a well-validated empirical approach to the treatment of borderline personality disorder as well as a range of other pathologies involving emotion dysregulation. To better appreciate the value of DBT, this blog will examine a less emphasized aspect of the treatment: its neurobiological effects on the brain and how the components of DBT may actually alter the brain’s capacity to respond to difficult emotions in a more adaptive way.

In their psychobiological framework of borderline personality disorder, Siever and Davis (1991) identify affective instability (AI) as a core dimension of the illness. Affective instability involves an inability to regulate intense and prolonged emotional intensity (Marwaha et al., 2014). This emotional intensity can manifest as rapid and dramatic oscillations of mood or affect in response to even small triggers in the environment, with these triggers usually being interpersonal in nature (Koenigsberg et al., 2010).

Neuroimaging data has linked the inefficient control of emotions in BPD to impaired regulatory control of the amygdala by the prefrontal cortex (Lis et al., 2007). The amygdala, part of the limbic system, is involved in emotional responses to stimuli (Davidson et al., 1999) and the frontal cortex is responsible for putting the breaks on these emotions. Dysfunctional coupling of fronto-limbic structures is thought to result in ineffective emotion regulation, the hallmark trait of BPD (New et al. 2007).

Growing evidence from fMRI studies shows increased amygdala activity in individuals with BPD in response to emotional faces (Donegan et al., 2003) and emotionally-triggering scripts (Beblo et al., 2006). In a recent meta-analysis, Schulze et al. (2016) found hyperactivity in the left amygdala, along with blunted activity in the bilateral dorso-lateral prefrontal cortex (DLPFC), during the processing of negative emotions in BPD. This pattern of an overactive amygdala and underactive PFC is consistent with the emotional instability that manifests in the presentation of the disorder. Structural abnormalities, including decreased gray matter in the left amygdala and hippocampus, as well as increased gray matter in subregions of the DLPFC may also be implicated in ineffective frontal inhibition of limbic hyperactivity (Shulze et al., 2016).

In a related line of research, Hazlett et al. (2012) showed that compared with healthy controls, individuals with BPD failed to show amygdala habituation to emotional stimuli (pleasant and unpleasant pictures). This means that no matter how many times individuals with BPD saw the same disturbing image, their amygdala reacted with the same intensity. This inability for the brain to adjust to a repeated emotional trigger in these individuals seems to reflect an overactive amygdala that is slow to return to baseline.

While limited research has explored the role of BPD treatment on activity in the prefrontal cortex, there is significant research suggesting a role of this treatment in tempering the emotional hypersensitivity associated with responsiveness in the amygdala. In a study looking at a 12-month course of DBT, treatment was found to normalize amygdala hyperactivity and lack of habituation to repeated stimuli in BPD (Goodman et al., 2014). These effects are similar to the absence of amygdala hyper-responsitivity found in individuals with BPD on psychotropic medications compared to individuals with a BPD diagnosis alone (Shulze et al., 2016). These findings suggest a neurobiological basis for the empirical support for DBT in managing affect instability in BPD and point toward the usefulness of further study in this field. To more fully understand the impact of DBT on the emotionally labile brain, future studies should target the neurobiological underpinnings of DBT in other clinical populations and should also explore the neurobiological correlates associated with specific sub-modules of DBT, such as mindfulness practice and acceptance or skills group training.

For example, mindfulness practice, a component of DBT training, has been shown to improve prefrontal regulation of emotionally sensitive brain regions. Even short-term mindfulness interventions have been associated with increased prefrontal activity and reduced amygdala activity when people were expecting to see negative or emotionally triggering images (Lutz et al., 2010). Expanding this type of research to explore each of the sub-modules of DBT may contribute to our understanding of how exactly this treatment affects the brain and the impact of these neural changes on treatment outcomes.

The emotional instability characteristic of borderline personality disorder has been associated with specific neurobiological patterns that lead to overactive emotions. Dialectical behavior therapy has been shown, not only to lead to clinical results, but also to produce changes in the brain that affect this neurobiological pattern and help put the brakes on emotional hypersensitivity. As we learn more about how treatments such as DBT target individual brain patterns, we can hope for more refined treatment recommendations that not only help individuals cope with emotional sensitivity, but actually improve resilience by boosting the brain’s capacity to hold responses to emotional triggers in check.



Beblo, T., Driessen, M., Mertens, M., Wingenfeld, K., Piefke, M., & Rullkoetter, N. (2006). Functional MRI correlates of the recall of unresolved life events in borderline personality disorder. Psychological Medicine, 36(6), 845-856. doi:S0033291706007227.

Beckstead, D. J., Lambert, M. J., DuBose, A. P., & Linehan, M. (2015). Dialectical behavior therapy with American Indian/Alaska native adolescents diagnosed with substance use disorders: Combining an evidence based treatment with cultural, traditional, and spiritual beliefs. Addictive Behaviors, 51, 84-87. doi: http://dx.doi.org/10.1016/j.addbeh.2015.07.018

Davidson, R. J., Abercrombie, H., Nitschke, J. B., & Putnam, K. (1999). Regional brain function, emotion and disorders of emotion. Current Opinion in Neurobiology, 9(2), 228-234. doi:http://dx.doi.org/10.1016/S0959-4388(99)80032-4

Dimeff, L., & Linehan, M. M. (2001). Dialetical behavior therapy in a nutshell. The California Psychologist, 34, 10-13.

Donegan, N. H., Sanislow, C. A., Blumberg, H. P., Fulbright, R. K., Lacadie, C., & Skudlarski, P. (2003). Amygdala hyperreactivity in borderline personality disorder: Implications for emotional dysregulation. Biological Psychiatry, 54(11), 1284-1293. doi:http://dx.doi.org/10.1016/S0006-3223(03)00636-X

Freedman, J. L., & Duckworth, K. (2013). Dialectical behavioral therapy fact sheet. Retrieved April 17, 2016, from https://www2.nami.org/factsheets/DBT_factsheet.pdf

Goodman, M., Carpenter, D., Tang, C. Y., Goldstein, K. E., Avedon, J., & Fernandez, N. (2014). Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder. Journal of Psychiatric Research, 57, 108-116. doi:http://dx.doi.org/10.1016/j.jpsychires.2014.06.020

Harley, R., Sprich, S., Safren, S., Jacobo, M., & Fava, M. (2008). Adaptation of dialectical behavior therapy skills training group for treatment-resistant depression. The Journal of Nervous and Mental Disease, 196(2) Retrieved from http://journals.lww.com/jonmd/Fulltext/2008/02000/Adaptation_of_Dialectical_Behavior_Therapy_Skills.8.aspx

Hazlett, E. A. (2016). Neural substrates of emotion-processing abnormalities in borderline personality disorder. Biological Psychiatry, 79(2), 74-75. doi:10.1016/j.biopsych.2015.10.008 [doi]

Hazlett, E. A., Zhang, J., New, A. S., Zelmanova, Y., Goldstein, K. E., & Haznedar, M. M. (2012). Potentiated amygdala response to repeated emotional pictures in borderline personality disorder. Biological Psychiatry, 72(6), 448-456. doi:http://dx.doi.org/10.1016/j.biopsych.2012.03.027

Koenigsberg, H. W. (2010). Affective instability: Toward an integration of neuroscience and psychological perspectives. Journal of Personality Disorders, 24(1), 60-82. doi:10.1521/pedi.2010.24.1.60 [doi]

Linehan M.M., Armstrong H.E., Suarez A., Allmon D., & Heard H.L. (1991). Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Archives of General Psychiatry, 48(12), 1060-1064. doi:10.1001/archpsyc.1991.01810360024003

Lis, E., Greenfield, B., Henry, M., Guilé, J. M., & Dougherty, G. (2007). Neuroimaging and genetics of borderline personality disorder: A review. Journal of Psychiatry & Neuroscience, 32(3), 162-173. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1863557/

Lutz, J., Herwig, U., Opialla, S., Hittmeyer, A., Jancke, L., & Rufer, M. (2014). Mindfulness and emotion regulation–an fMRI study. Social Cognitive and Affective Neuroscience, 9(6), 776-785. Retrieved from http://europepmc.org/abstract/MED/23563850

Marwaha, S., He, Z., Broome, M., Singh, S. P., Scott, J., & Eyden, J. (2014). How is affective instability defined and measured? A systematic review. Psychological Medicine, 44(09), 1793-1808. doi:10.1017/S0033291713002407

Neacsiu, A. D., Eberle, J. W., Kramer, R., Wiesmann, T., & Linehan, M. M. (2014). Dialectical behavior therapy skills for transdiagnostic emotion dysregulation: A pilot randomized controlled trial. Behaviour Research and Therapy, 59, 40-51. doi:http://dx.doi.org/10.1016/j.brat.2014.05.005

New, A. S., Hazlett, E. A., Buchsbaum, M. S., Goodman, M., Mitelman, S. A., & Newmark, R. (2007). Amygdala-prefrontal disconnection in borderline personality disorder. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 32(7), 1629-1640. Retrieved from http://dx.doi.org/10.1038/sj.npp.1301283

Safer, D. L., & Jo, B. (2010). Outcome from a randomized controlled trial of group therapy for binge eating disorder: Comparing dialectical behavior therapy adapted for binge eating to an active comparison group therapy. Behavior Therapy, 41(1), 106-120. doi:http://dx.doi.org/10.1016/j.beth.2009.01.006

Schulze, L., Schmahl, C., & Niedtfeld, I. (2016). Neural correlates of disturbed emotion processing in borderline personality disorder: A multimodal meta-analysis. Biological Psychiatry, 79(2), 97-106. doi:http://dx.doi.org/10.1016/j.biopsych.2015.03.027

Siever, L. J., & Davis, K. L. (1991). A psychobiological perspective on the personality disorders. American Journal of Psychiatry, 148(12), 1647-1658.

van Zutphen, L., Siep, N., Jacob, G. A., Goebel, R., & Arntz, A. (2015). Emotional sensitivity, emotion regulation and impulsivity in borderline personality disorder: A critical review of fMRI studies. Neuroscience & Biobehavioral Reviews, 51, 64-76. doi:http://dx.doi.org/10.1016/j.neubiorev.2015.01.001

Deep Brain Stimulation: Tourette Syndrome

Much of Tourette Syndrome is unknown and there lies an aura of mystery around the predispositions and treatment approach to this disorder. Tourette syndrome is a chronic neurological disorder typically diagnosed through motor or vocal tics. Tics are repetitive movements, either in movement or speech, which are uncontrollable and involuntary (McNaught, 2011). It is typically seen with an onset around 5-8 years old although it currently impacts those of all ages (Jankovic, 2011). Those with milder cases of Tourette syndrome may be able to suppress the tics but it will still cause detrimental impairments in various aspects of their lives. Many of those who have a Tourette Syndrome often exhibit other symptoms other than tics such as hyperactivity, impulsivity, obsessions and compulsions, anxiety, and depression as well (Jankovic, 2011). These often lead to comorbid diagnoses, the two most common ones being Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD) (Jankovic, 2011)

The mystery around Tourette syndrome is that so much of the etiology of the disorder is unknown. There is current research to show that the abnormalities are targeting specific regions of the brain such as basal ganglia, frontal lobe, and prefrontal cortex (Cannon, 2012). The evidence points to an impact on the dopamine, serotonin, and norepinephrine neurotransmitters with the main abnormal metabolism of dopamine. A significant twin study shows that a large component of Tourette syndrome is genetic and that there are implications that Tourette syndrome can be inherited as though it were an autosomal dominant condition (Müller-Vahl, 2011). Other non-genetic factors such as gestational stress, severe trauma, drug/alcohol abuse, or gestational infections may play a big factor in causing Tourette syndrome (McNaught, 2011). Similar to the cause of Tourette syndrome being unknown, there is currently no evidence to show that there is a cure for this psychiatric condition. Treatment modalities are focused on behavioral therapy with occupational therapy, psychological counseling therapy, and pharmacological therapy to aid in managing the symptoms (McNaught, 2011).

Diverging away from the more conventional approaches to treatment, research shows that there has been one mode of treatment that has shown promising efficacy in improving symptoms of Tourette syndrome. Deep brain stimulation is a neurosurgical procedure involving a plantation of electrodes to parts of the brain that will be stimulated by electrical pulses (Ackermans, 2006). Essentially, the procedure induces neuromodulation so that the abnormal nerve activity for those with Tourette syndrome will be altered to mimic normal impulses (Bajwa, 2007). Deep brain stimulation still has yet to be FDA-approved for Tourette syndrome but is currently FDA-approved for Parkinson’s disease, tremors and dystonia (Cannon, 2012). Because of its efficacy and safety in Parkinson’s disease, deep brain stimulation has been applied to other movement disorders, such as Tourette syndrome (Black, 2009). This method of treatment is reserved for patients who have undergone significant behavioral and pharmacologic treatments without seeing significant improvements for their involuntary tics (Cannon, 2012). Those considered for this mode of treatment would also show that their impairments are detrimental and cannot be alleviated.

As Tourette syndrome is believed to have loop dysfunction in the basal ganglia-thalamocortical circuits, deep brain stimulation attempts to regulate the abnormal communication that causes the involuntary tics (Priori, 2013). The surgical procedure for deep brain stimulation would involve implanting two different components: electrodes, implanted into specific regions in the brain, to deliver electrical pulses and an impulse generator, implanted under the collarbone, to stimulate the pulses (Houeto, 2005). The delivery of the electricity would generate impulses to the affected parts of the brain to alter the abnormal circuitry seen in those with Tourette syndrome (Hariz, 2010). These affected parts have been many and include the frontal lobe, the limbic system, the thalamus, and the cerebellum (Shahed, 2007). The two sites that seem to prove best are “the internal globus pallidus (GPi) and the centromedian-parafascicular nuclei of the thalamus, near the middle of the brain (CM-Pf)” (Black, 2009). Side effects are concurrent with any other neurosurgical procedures (Hariz, 2010). However, with regulation of abnormal impulses that cause these severe tics, clients may show noteworthy improvements for their symptoms.

The research behind deep brain stimulation for the use of Tourette syndrome and tic disorders is still emerging (Krack, 2010). However, there is enough evidence to show that this treatment modality has proven efficacy in clients with a debilitating tic disorder and severe impairments in the major aspects of their lives (Piedad, 2012). In cases where medication and behavioral therapy has proven ineffective, deep brain stimulation can serve as an option to improve severely disruptive motor and vocal tics (Lyons, 2011). This will be an interesting mode of treatment to follow and continued research on the neurobiological process of Tourette syndrome and the neuromodulation of deep brain stimulation will only further psychiatric understanding of this disorder (Servello, 2010).





Ackermans, L., Y. Temel, et al. (2006). “Deep brain stimulation in Tourette’s syndrome: two targets?” Mov Disord 21(5): 709-13.

Bajwa, R. J., A. J. de Lotbiniere, et al. (2007). “Deep brain stimulation in Tourette’s syndrome.”Mov Disord22(9): 1346-50.

Cannon, E., Silburn, P., Coyne, T., O’Maley, K., Crawford, J. D., & Sachdev, P. S. (2012). Deep brain stimulation of anteromedial globus pallidus interna for severe Tourette’s syndrome. American Journal of Psychiatry.

Hariz, M. I., & Robertson, M. M. (2010). Gilles de la Tourette syndrome and deep brain stimulation. European Journal of Neuroscience, 32(7), 1128-1134.

Houeto, J. L., C. Karachi, et al. (2005). “Tourette’s syndrome and deep brain stimulation.” J Neurol Neurosurg Psychiatry 76(7): 992-5.

Jankovic, J., & Kurlan, R. (2011). Tourette syndrome: evolving concepts. Movement disorders, 26(6), 1149-1156.

Krack, P., Hariz, M. I., Baunez, C., Guridi, J., & Obeso, J. A. (2010). Deep brain stimulation: from neurology to psychiatry?. Trends in neurosciences, 33(10), 474-484.

Lyons, M. K. (2011, July). Deep brain stimulation: current and future clinical applications. In Mayo Clinic Proceedings (Vol. 86, No. 7, pp. 662-672). Elsevier.

McNaught, K. S. P., & Mink, J. W. (2011). Advances in understanding and treatment of Tourette syndrome. Nature Reviews Neurology, 7(12), 667-676.

Müller-Vahl, K. R., Cath, D. C., Cavanna, A. E., Dehning, S., Porta, M., Robertson, M. M., … & ESSTS Guidelines Group. (2011). European clinical guidelines for Tourette syndrome and other tic disorders. Part IV: deep brain stimulation. European child & adolescent psychiatry, 20(4), 209-217.

Piedad, J. C. P., Rickards, H. E., & Cavanna, A. E. (2012). What patients with gilles de la tourette syndrome should be treated with deep brain stimulation and what is the best target?. Neurosurgery, 71(1), 173-192.

Servello, D., Sassi, M., Brambilla, A., Defendi, S., & Porta, M. (2010). Long‐Term, Post‐Deep Brain Stimulation Management of a Series of 36 Patients Affected With Refractory Gilles de la Tourette Syndrome. Neuromodulation: Technology at the Neural Interface, 13(3), 187-194.

Shahed, J., J. Poysky, et al. (2007). “GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities.” Neurology 68(2): 159-60.


A Double Whammy: Curbing Addiction and Enhancing Attention

How many times have you been told to “pay attention?” From those early days in the classroom to meetings on the job, paying attention is something we are often expected to do. In fact, we are commanded to do it as if we know what specific action we must take when in reality, few of us know how exactly to turn our brains toward something in a truly attentive way. Fascinatingly, even though we don’t quite know what it means to pay attention, we respond to these commands readily, as if “paying attention” is something we know exactly how to do. From a neurobiological perspective, paying attention involves a complex set of neuronal pathways that selectively ignore distractions and amplify the important stimuli in our environment that we are motivated to process (Higgins & George, 2013).

Some of us are much better at this task of “paying attention” than others. People who find it extremely difficult to pay attention may also be more prone to drug addiction. That’s because just like we have to inhibit our impulses in order to ignore appealing activities and pay attention to longer tasks, we must inhibit our impulses in order to ignore the appeal of addictive substances.   People who are better at paying attention also seem to find longer tasks more gratifying, while people prone to addiction may only get that same gratification when they pursue short-term rewards (Kober et al., 2010).

Now if attention and addiction are closely related, then wouldn’t you think that there might be something to learn about paying attention from all the research on treatments that help curb drug addiction? In fact, the research on addiction is packed with lessons on improving attention, even in individuals without a substance use problem. Many of the interventions that enhance impulse inhibition in substance users also improve impulse inhibition more generally. Improving impulse control is bound to improve attention because attention demands controlling distracting impulses and instead focusing on the task at hand.

Mindfulness-based training is an example of an intervention that has been used to target alcohol use disorder, but that also seems to improve attention. Mindfulness is a practice of attending to one’s immediate surroundings with acceptance. Interestingly, one of the ways that mindfulness seems to help people avoid alcohol is by reducing their attentional bias to alcohol-related stimuli (Garland et al., 2010). Meaning, they become less likely to selectively pay attention to objects that have to do with drinking. Mindfulness not only helps drinkers ignore alcohol cues, but it also improves their attentional control more generally. Mindfulness improves performance on the Stroop task (Chan & Woollacott, 2007), which measures an individual’s ability to ignore distracting stimuli in order to pay attention to important information. More directly, mindfulness has been shown the brain’s neuronal response (P3a event-related brain potential) to distracting stimuli among experienced meditators (Cahn & Polich, 2009). Overall, meditation seems to help control alcohol use because enhances the brain’s capacity to ignore distractions and focus on what’s important.

Medications used to treat substance abuse disorders also seem to improve impulse inhibition. Opioid antagonists, like Naltrexone, are first line drugs for treating addiction.   Simply, these drugs block the rewarding effects of drugs. But interestingly, these medications seem to dampen the rewarding effects of impulsive acts, even when these acts don’t involve drugs. For example, opioid antagonists have been shown to reduce impulsive stealing (kleptomania) and gambling, behaviors that don’t even involve substance use directly (Grant et al., 2006; Grant & Odlaug, 2009)! In rats, naltrexone also reduced their likelihood of choosing smaller immediate rewards over larger, delayed rewards (Kieres et al., 2004). Aside from blocking the actions of opioids, opioid antagonists seem to tamper the brain’s response toward impulsive choices and short-term gratification more broadly.

Cognitive Behavioral Therapy for individuals with cocaine use disorder also seems to enhance impulse control more broadly.   During the Stroop task, CBT reduced the fMRI BOLD signal associated with cognitive interference from distracting stimuli (DeVito et al., 2012).   In a related study, using CBT-based strategies increased activity in frontal brain regions compared to subcortical regions (Kober et al., 2010). These results suggest that in helping individuals resist substance use, CBT actually enhances the brain’s ability to self-regulate and ignore distracting stimuli, the key characteristics of maintaining attention.

In a number of meta-analyses, substance use rates were found to be higher among individuals with ADHD than the general population (Charach et al., 2011). Treatment of ADHD has also been associated with reduced rates of drug use in adulthood (van Emmerik–van Oortmerssen et al., 2013).   The clinical link between ADHD and drug use reinforces the theoretical connection between attention and impulse control. When the brain is better able to inhibit ignore distracting stimuli and inhibit impulsive responses, it is then capable of attending to important cues.

The good news is that the brain’s capacity to pay attention seems somewhat malleable. Many treatments that were developed to treat addiction only also seem to be enhancing the brain’s general capacity to self-regulate and sustain attention. Improved performance on the Stroop task during treatment for addiction is a fascinating example of how managing addiction can have relevant implications for the many of us who want to attend successfully to the many challenging tasks we face every day.

There isn’t a single person who wouldn’t benefit from better attentional control. Every day, we are faced with millions of distractions that vie for our attention and offer us immediate thrills. Surprisingly, the research on drug addiction has some important lessons to teach us about improving our attention. Medications that reduce impulsivity, meditative practices that involve attending to one’s immediate experience, and CBT strategies that involve coping with one’s thoughts and feelings, all seem to directly affect our ability to pay attention to what’s important in our lives. Like exercising, practicing attention seems to strengthen our brain’s ability to filter out distractions. And for some of us, paying attention may be as difficult as shelving the bottle. But across the board, strategic interventions hold promise in providing us with some equipment to exercise those attentional biceps.



Cahn, B. R., & Polich, J. (2009). Meditation (Vipassana) and the P3a event-related brain potential. International Journal of Psychophysiology, 72(1), 51-60.

Chan, D., & Woollacott, M. (2007). Effects of level of meditation experience on attentional focus: is the efficiency of executive or orientation networks improved? The Journal of Alternative and Complementary Medicine, 13(6), 651-658.

Charach, A., Yeung, E., Climans, T., & Lillie, E. (2011). Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. Journal of the American Academy of Child & Adolescent Psychiatry, 50(1), 9-21.

DeVito, E. E., Worhunsky, P. D., Carroll, K. M., Rounsaville, B. J., Kober, H., & Potenza, M. N. (2012). A preliminary study of the neural effects of behavioral therapy for substance use disorders. Drug and Alcohol Dependence, 122(3), 228-235.

Garland, E. L., Gaylord, S. A., Boettiger, C. A., & Howard, M. O. (2010). Mindfulness training modifies cognitive, affective, and physiological mechanisms implicated in alcohol dependence: results of a randomized controlled pilot trial. Journal of psychoactive drugs, 42(2), 177-192.

Grant, J. E., Potenza, M. N., Hollander, E., Cunningham-Williams, R., Nurminen, T., Smits, G., & Kallio, A. (2006). Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. American Journal of Psychiatry. Robbins, T. W. (2002). ADHD and addiction. Nature Medicine, 8(1), 24-25.

Grant, J. E., Kim, S. W., & Odlaug, B. L. (2009). A double-blind, placebo-controlled study of the opiate antagonist, naltrexone, in the treatment of kleptomania. Biological Psychiatry, 65(7), 600-606.

Higgins, E. S., & George, M. S. (2013). Neuroscience of Clinical Psychiatry: the pathophysiology of behavior and mental illness. Lippincott Williams & Wilkins.

Kober, H., Mende-Siedlecki, P., Kross, E. F., Weber, J., Mischel, W., Hart, C. L., & Ochsner, K. N. (2010). Prefrontal–striatal pathway underlies cognitive regulation of craving. Proceedings of the National Academy of Sciences, 107(33), 14811-14816.

Kieres, A. K., Hausknecht, K. A., Farrar, A. M., Acheson, A., de Wit, H., & Richards, J. B. (2004). Effects of morphine and naltrexone on impulsive decision making in rats. Psychopharmacology, 173(1-2), 167-174.

van Emmerik–van Oortmerssen, K., Vedel, E., Koeter, M. W., de Bruijn, K., Dekker, J. J., van den Brink, W., & Schoevers, R. A. (2013). Investigating the efficacy of integrated cognitive behavioral therapy for adult treatment seeking substance use disorder patients with comorbid ADHD: study protocol of a randomized controlled trial. BMC psychiatry, 13(1), 132.

Inflammation and Mood

There has been a growing body of research around the idea that inflammation could be contributing to and/or causing mood disorders. Depression is commonly found in people who are also suffering from autoimmune diseases, gastrointestinal inflammation, cardiovascular diseases, type 2-diabetes, and cancer, all of which have chronic low-grade inflammation as a substantial contributing factor (Balacco, et al., 2011). Research suggests that dysfunction of the “gut-brain axis” may be the primary cause of inflammation, and that treating gastrointestinal inflammation with Vitamin B, Vitamin D, probiotics, and Omega-3 fats may improve depressive symptoms by lessening inflammation in the brain (Balacco, et al., 2011). Essentially, when you are experiencing chronic inflammation, it wreaks havoc on your body and can affect your brain as well.

Other sources suggest that not only does inflammation play a role in depression, but it may be its primary cause (Kendall-Tackett, 2007). Cytokines found in the blood, and inflammatory messengers such as IL-1, IL-6, CRP, and TNF-alpha have been shown to be linearly correlative (Howren, 2009) and predictive for depression (Cauley, 2012). It has been validated that in depression and bipolar, white blood cells called monocytes express genes that are pro-inflammatory leading to the release of cytokines. This simultaneously leads to decreased cortisol sensitivity, which is the body’s stress hormone and inflammatory buffer creating a harmful cycle (Bergink, et al., 2014). Once these inflammatory agents are triggered they transfer information to the nervous system, usually through stimulation of major nerves mainly the vagus, which connects the gut and the brain. Microglia are the specializes cells in the brain related to immunity and they are activated in inflammatory states (Cohen, 2002).

A number of trials have looked at the role of anti-inflammatory agents in reducing depressive symptoms. In a recent trial, patients who had been identified as resistant to antidepressant treatment and had serum levels of CRP >3mg/L were responsive to treatment with infliximab (Remicade), which is a TNF-alpha antagonist (anti-inflammatory) (Drake, 2013).

There was a recent case in 2015, where a patient who had recently received a gastrectomy developed their first manic episode. The researchers thought that this could be related to intestinal barrier dysfunction and altered gut microbiota. The patient was given activated charcoal, which absorbs inflammatory cytokines. It acts by neutralizing the effect of inflammatory mediators in the gut, and was thought to improve both manic symptoms and systemic inflammation. After the treatment began, 15 days later, the patient was asymptomatic for mania, and remained so at 8 months follow up. No psychiatric drugs were used (Boukouaci, 2015).

Given this information, what in our diet and lifestyles causes inflammation? Wouldn’t it make sense to identify and reduce these things in an attempt to alleviate psychiatric symptoms? One of the main contributors to inflammation is gluten intolerance, which has been shown to cause seizures, headaches, multiple sclerosis/demyelination, depression, anxiety, and ADHD. This is not just a concern with those who have celiac disease, as inflammation has been shown to occur in those who have gluten sensitivities and may not even be aware of it (Eaton, 2012; Ford, 2009).

Herbicides, such as the commonly used RoundUp, have been shown to kill beneficial bateria and promote inflammation in our gut. This has an affect on our micribiome every time we consume food that has been sprayed with this product (Samsel, 2013). NSAID’s have been shown to damage the gut lining and cause inflammation (Bjarnason, 1998). Insufficient sleep has also been shown to increase inflammation and cognitive impairment (Archer, 2013). Gluten, herbicides, NSAID’s, and lack of sleep could all be contributing to the amount of inflammation in a person’s body, and therefore their mood as well.

There are also many things that we can do to reduce inflammation in our bodies. Consuming probiotics have been shown to improve brain function by altering the intestinal microbiota (Ebrat, 2013). Consuming sufficient Omega-3 fats has also been shown to reduce inflammation, decrease anxiety (Andridge, 2011), and reduce depressive symptoms (Carlezon, 2005). Meditation has been shown to reduce inflammation (Davidson, 2013). The spice tumeric was shown in a study to improve depression more than Prozac (Goel, 2014), perhaps this is due in part to its powerful anti-inflammatory effects (Aggarwal, 2004).

Implementing anti-inflammatory measures into our lives can not only help to prevent future psychiatric disturbances, but it can also help in relieving current symptoms as well. Mental health professionals could help prevent and reduce psychiatric symptoms in their patients by informing them of things to avoid as well as things to bring into their lives to reduce inflammation. Clearly more research should be pursued in this, but reducing inflammation is a proven way to help relieve mood disturbances.


Works Cited:

Aggarwal, B. B., et al., (2004), Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation, Oncogene, 23(57):9247-58, doi: 10.1038/sj.onc.1208169

Andridge, R., et al., (2011), Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial, Brain, Behavior, and Immunity, 25(8):1725-34, doi: 10.1016/j.bbi.2011.07.229

Archer, S. N., et al., (2013), Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome, PNAS, 110 (12): 1132-1141, doi: 10.1073/pnas.1217154110

Balacco, G., et al., (2011), Role of gastrointestinal inflammations in the development and treatment of depression, Orvost Hetilap, 152(37): 1477-85, doi: 10.1556/OH

Bergink, V. et al., (2014), Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder, Translational Psychiatry, 4, e344, doi: 10.1038/tp

Bjarnason, I, et al., (1998), Intestinal permeability and inflammation in patients on NSAIDs, Gut, 43(4):506-11, doi: 10.1136/gut.43.4.506

Boukouaci, W., et al., (2015), Resolution of a manic episode treated with activated charcoal: Evidence for a brain–gut axis in bipolar disorder, Australian and New Zealand Journal of Psychiatry, 1-3, doi: 10.1177/0004867415595873

Carlezon Jr., W.A., et al., (2005), Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats, Biological Psychiatry, 57(4): 343–350, doi: http://dx.doi.org/10.1016/j.biopsych.2004.11.038

Cauley, J. A., et al., (2012), How predictive of dementia are peripheral inflammatory markers in the elderly?, Neurodegenerative Disease Management, 2(6): 609–622, doi: 10.2217/NMT.12.68

Cohen, H. J., (2002), Cytokines and Cognition—The Case for A Head-to-Toe Inflammatory Paradigm, Geriatric Bioscience, 50:2041–2056, Retrieved January 30, 2016, from http://www.usc.edu/projects/nexus/faculty/dept-ldsg/finchcaleb/388%20Finch%20Cytokines%20and%20Cognition.pdf

Davidson, R. J., et al., (2013), A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation, Brain Behavior and Immunity, 27(1):174-84, doi: 10.1016/j.bbi.2012.10.013

Drake, D. F., et al., (2013), A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers, JAMA Psychiatry, 70(1):31-41, doi: 10.1001/2013

Eaton, W.W., et al., (2012), Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity, Psychiatric Quarterly, 83(1): 91–102, doi: 10.1007/s11126-011-9186-y

Ebrat, B., (2013), Consumption of fermented milk product with probiotic modulates brain activity, Gastroenterology, 144(7):1394-401, doi: 10.1053/j.gastro.2013.02.043

Ford, R. P., (2009), The gluten syndrome: a neurological disease, Medical Hypotheses, 73(3):438-40, doi: 10.1016/j.mehy.2009.03.037

Goel, A., et al., (2014), Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial, Phytotherapy Research, 28(4):579-85, doi: 10.1002/ptr.5025

Howren, M. B., (2009), Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis, Psychosomatic Medicine, 71(2):171-86, doi: 10.1097/PSY

Kendall-Tackett, K., (2007), A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health, International Breastfeeding Journal, 2: 6, doi: 10.1186/1746-4358-2-6

Samsel, A., (2013), Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases, Entropy, 15(4), 1416-1463, doi: 10.3390/e15041416




Moving toward a more accurate characterization of Anhedonia

Over the last several decades the concept of anhedonia has been subject to interesting developments in the field of behavioral neuroscience. Research into the neurobiological processes involved in reward behavior has succeeded in convincing us to reconsider the dimensions of a term that has become commonplace in the mental health field. Anhedonia is generally understood to mean the inability, or diminished capacity, to experience pleasure. It is also refers to a deficit in motivation to engage in typically rewarding behaviors. Exploration of the absence of pleasure dates back to Epicurus (Der-Avakian & Markou, 2012). The term became included in the DSM in 1980 and the International Classification of Diseases in 1992 (Berrios and Olivares, 1995). Despite the widespread use of the concept, it has been inconsistently defined in the literature (Ho & Sommers, 2013).

The concept of anhedonia warrants important consideration and scientific inquiry for several reasons. Well-documented in depression, schizophrenia and other psychiatric and neurologic conditions, anhedonia has the potential to impair quality of life and produce considerable suffering. In an epidemiological study (N=7076) anhedonia was found to be a poor prognostic indicator in treatment outcomes for people with MDD (Spijker, Bijl & DeGraaf, 2001). Multiple studies have found that first-line pharmacologic agents for MDD (SSRIs) do not adequately treat anhedonic symptoms (Treadway & Zald, 2011). Given the evidence for the limited efficacy of SSRIs and poor response to treatment in depressed patients with diminished pleasure and motivation it makes both economic and ethical sense to pursue research that increases our understanding of the pathological processes involved.

In its process of inquiry, behavioral neuroscience has facilitated the need to reconsider our conceptualization of anhedonia. The dopamine (DA) deficiency hypothesis of anhedonia, first posited in 1980, gained traction in its suggestion that DA was a key mediator in the experience of pleasure (Treadway & Zald, 2011; Wise, 2008). Subsequent research has demonstrated that mesolimbic DA is not implicated in the experience of pleasure involved in reward behaviors (Berridge & Robinson, 2003). Rather, it has been demonstrated that the primary neurotransmitters involved in the experience of pleasure are endogenous opioids (Thomsen, Whybrow & Kringlebach, 2015). Significant expression of (mu) opioid receptors exists in the ventral striatum, on the shell of the nucleus accumbens, as well as the ventral pallidum, a structure of the basal ganglia (Penciña, Smith & Berridge, 2006). Endocannabinoids and orexin have also been found to stimulate these areas and result in increased sensory pleasure (Thomsen, Whybrow & Kringlebach, 2015).

Research has demonstrated that DA does play a central role in the motivational aspects of engagement in reward behaviors (Treadway & Zald, 2011). Much of this is attributable to the integral role of DA in the development of behaviors, habits and preferences through motivation, learning and reward anticipation (Wise, 2008). Motivational anhedonia has been associated with the mesolimbic systems of the brain, notably those involving DA transmission, as well as structures of the cortex (Thomsen, Whybrow & Kringlebach, 2015).

The research presented above is a small window into the neurbiological processes involved in the experience of anhedonic symptoms. This research demonstrates the need for a more nuanced approach to conceptualizing the various components of anhedonia, reward behavior and their neurobiological substrates. There have been several recently proposed frameworks that offer a more dynamic understanding of anhedonia. Treadway and Zald (2011) differentiate between three different elements of anhedonia: motivational, consummatory (pleasure experienced) and decisional anhedonia. Berridge and Kringlebach (2008) suggest the importance of neural networks involved in “wanting” (motivation), “liking” (pleasure) and “learning.” These processes correspond to the cycle through which we engage in rewarding behaviors, experience pleasure from them and learn to sustain them. These components of anhedonia and reward are dynamic and integrated. More precise definition of the aspects of reward behavior will allow researchers to more effectively study the treatment-refractory symptoms of anhedonia.

Anhedonia is a unit of analysis in both the “negative valence” and “social processes” domains of the Research Domain Criteria Initiative (RDoC) (RDoC Constructs). The RDoC is an in initiative spearheaded by the National Institute of Mental Health (NIMH) that sets forth a framework for researching the symptoms involved in mental disorders. This research agenda brings together information from different lines of inquiry. These range from genomics and neural circuits to behavior and self-report. The purpose of the RDoC is to facilitate understanding of the multi-dimensional and interwoven processes that occur to produce all forms of human behavior. The recent developments in our understanding of the neurobiological correlates of anhedonia and reward behavior, combined with a more nuanced characterization of these processes, offers an opportunity to research interventions that target these functionally impairing, disruptive symptoms.


Berridge, K. C., & Kringelbach, M. L. (2008). Affective neuroscience of pleasure: Reward in humans and animals. Psychopharmacology, 199, 457-480. doi:10.1007/s00213-008-1099-6

Berridge, K. C., & Robinson, T. E. (2003). Parsing reward. Trends in Neurosciences, 26, 507-513. doi:http://dx.doi.org/10.1016/S0166-2236(03)00233-9

Berrios, G. E., & Olivares, J. M. (1995). The anhedonias: A conceptual history. History of Psychiatry, 6, 453-470. doi:10.1177/0957154X9500602403

Der-Avakian, A., & Markou, A. (2012). The neurobiology of anhedonia and other reward-related deficits. Trends in Neurosciences, 35, 68-77. doi:http://dx.doi.org/10.1016/j.tins.2011.11.005

Ho, N., & Sommers, M. (2013). Anhedonia: A concept analysis. Archives of Psychiatric Nursing, 27, 121-129. doi:10.1016/j.apnu.2013.02.001

Peciña, S., Smith, K. S., & Berridge, K. C. (2006). Hedonic hot spots in the brain. The Neuroscientist, 12, 500-511. doi:10.1177/1073858406293154

RDoC consutrcts. Retrieved February/8, 2016 from http://www.nimh.nih.gov/research-priorities/rdoc/rdoc-constructs.shtml

Salamone, J. D., Correa, M., Farrar, A., & Mingote, S. M. (2007). Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology, 191, 461-482. doi:10.1007/s00213-006-0668-9

Spijker, J., Bijl, R. V., De Graaf, R., & Nolen, W. A. (2001). Determinants of poor 1-year outcome of DSM-III-R major depression in the general population: Results of the netherlands mental health survey and incidence study (NEMESIS). Acta Psychiatrica Scandinavica, 103, 122-130. doi:10.1034/j.1600-0447.2001.103002122.x

Thomsen, K., Whybrow, P. C., & Kringelbach, M. L. (2015). Reconceptualizing anhedonia: Novel perspectives on balancing the pleasure networks in the human brain. Frontiers in Behavioral Neuroscience, 9, 49. doi:10.3389/fnbeh.2015.00049

Treadway, M. T., & Zald, D. H. (2010). Reconsidering anhedonia in depression: Lessons from translational neuroscience. Neuroscience and Biobehavioral Reviews, 35, 537-555. doi:10.1016/j.neubiorev.2010.06.006

Wise, R. A. (2008). Dopamine and reward: The anhedonia hypothesis 30 years on. Neurotoxicity Research, 14, 169-183. doi:10.1007/BF03033808

Lead Exposure Exposes Environmental Racism

by Alli Van Leer

Environmental Justice affirms the need for urban and rural ecological policies to clean up and rebuild our cities and rural areas in balance with nature, honoring the cultural integrity of all our communities, and provided fair access for all to the full range of resources. – 12th Principle of Environmental Justice, 1991

For over sixty years scientists, business leaders and government officials have been aware of the detrimental impact of childhood exposure to lead. In the 1970’s research by Herbert Needleman, MD and his team in exposed the effect of even a low dose of lead exposure during childhood. Needleman et al.’s paper, “Deficits in psychologic and classroom performance of children with elevated dentine lead levels” also shifted the focus from the somatic based health effects of lead to the physiological and cognitive effects.

Lead has historically been used in a wide array of industrial products, most importantly gasoline, paint and water piping. The process of removing lead from gasoline began in 1965 and was officially banned from on road vehicles in 1996. Lead was banned from the use of paint in 1978, though remains on the wall of buildings and houses painted prior to 1978. While lead is rarely used today in water piping it remains in many homes and city water lines (Gilbert, 2006).

No level of lead is good for our health (Gilbert, 2006). There has been a slow and gradual trend in lower and lower acceptable blood levels from 600 mcg/L in the 1960’s to todays 50 mcg/L (CDC set the level from 100 mcg/L to 50 mcg/L in 2012). As long as 2000 years ago there is record of human’s knowledge of the negative effect of lead on human health with the unknown quote, “lead makes the mind give way.” Research has shown that lead accumulates in the body over time is most detrimental to the nervous system (Hou 2013). Infants and children are at most risk due to a more permeable blood brain barrier and more gut absorption of lead compared to adults (Heath 2003).

The term lead poisoning is misleading since any amount of lead is toxic to varying degrees but is uses to refer to lead levels found higher than the CDC recommends.  Lead exposure has been widely shown to be associated with lower IQ scores (Needham, 1990, Chen, 2003). Recent studies in China by Hou et al. has shown additional negative association between lead exposure to children ages 1-5 and gross motor performance, fine motor performance, language development, aggression, and destruction. (Hou, 2013).  A study by Miranda et al. showed that even low levels of lead levels (20-50 mcg/l) in children negatively impacts later life reading and math levels. A study by Mendola et al found that children with previous lead exposure to be correlated with decreased attention. In a society where intellectual and cognitive ability greatly defines one’s ability to access economic and social capital we can draw clear positive correlation between lead exposure and forced poverty and decreased social mobility.

While epidemiologists have been able to provide significant data on the relationship between lead exposure and its inverse relationship to learning, attention and IQ, molecular and neuro biologists are just beginning to uncover lead’s mechanism of action on the nervous system. Researchers in the late 80’s and 90’s found that lead primarily acts on glutamate receptors (Guilarte, 1997, Regunathan and Sundaresan, 1985 and Savolainen et al., 1995). The glutamate receptors are classified into both ionotropic and metabolic subtypes depending on whether they are ion channel or G-protein coupled receptors. Two primary glutamate receptors found to be involved in lead based neurotoxicity thus far are the NMDAR ionotropic receptor found primary in the hippocampus and the metabolic glutamate receptor 5 (mGluR5) found post-synoptically primarily also in the hippocampus. Both receptors seem to play a role in hippocampal based learning and memory (Xu, 2009). The mechanism of action of lead on these receptors is still unclear and further research is needed to delineate whether these are truly they key elements involved in lead based neuro toxicity

You cannot change any society unless you take responsibility for it, unless you see yourself as belonging to it, and responsible for changing it.

– The late Grace Lee Boggs, a long time Detroit based organizer

Lead exposure is in the spot light as the people of Flint Michigan deal with a year plus of high levels of lead exposure from their tap water. Residents of Flint- a majority black and working class community- have pointed out that their exposure to lead is clear example of environmental racism. Environmental racism is a term coming out of the civil rights movement and became popularized in the 1980’s and 90’s as a way to define institutional racial discrimination that exposes black and brown people to disproportionately higher rates of toxic and hazardous environments and materials. This frame work helped inspire the First National People of Color Environmental Leadership Summit in 1991 where a global framework of Environmental Justice was laid out.

In 2013 the CDC put out a study that showed that between the years 2007 to 2010 black children (1-5 years old) had twice the rate of lead poisoning than white children nationally. Here in Connecticut the CT Department of Health put out a report on lead exposure in 2012 (Hung, 2014). This report, like the CDC report showed that black children were more than twice as likely as white children to experience lead levels higher than the CDC recommended level of 50 mcg/L. The study also shows lead exposure by town across Connecticut. When comparing the map of highest lead exposure to the map of demographics it is evident that all of the locations with the highest rate of lead exposure are the locations with the highest density of people of color- primarily communities of African Americans (Hung, 2012).

(Hung, 2014)

“A map showing the majority racial or ethnic group in Connecticut by census block” by Pgalag87 – Using ArcGIS and census data. Licensed under CC BY-SA 3.0 via Commons https://commons.wikimedia.org/wiki/File:A_map_showing_the_majority_racial_or_ethnic_group_in_Connecticut_by_census_block.png#/media/File:A_map_showing_the_majority_racial_or_ethnic_group_in_Connecticut_by_census_block.png

Lead exposure and subsequent poisoning demands that mental health workers be engaged in ongoing environmental justice work. Mental health practitioners occupy and important role in advocating for communities that are most impacted by lead exposure, informing the public of the serious life-span based impacts of lead, and develop programs to support children already impacted by lead exposure.

There are many ways to incorporate an environmental justice framework into our mental health practices. It begins with being aware of the environment our clients live in. If we are not from the same community as the people we work with than it takes concerted effort to educate ourselves about the water quality, air quality, sound levels, and where these toxins are coming from. It means recognizing that experience trumps outside opinions. With an awareness of the impacts we can develop a practice that incorporates this knowledge. We can work to get our clinics to provided water filters, we can lobby local Politian’s to make changes to public policy demanding those responsible for the toxins clean them up, we can get behind local organizing efforts to bring attention and change the polluted environment. We can better document the effects environmental racism has on our patients by being sure to accurately diagnose our patients, IE attributing certain disorders to toxic exposure as opposed to an individual biological process. In the case of lead it is important that we get lead levels from our patients who are exhibiting ADHD, aggression and/or intellectual disability behaviors at a young age.

Engaging in environmental justice work offers a pathway for mental health workers to become more directly engaged in partnering with our patients and their communities to better the mental health for all. It is a daunting task but the data is unforgiving and we cannot deny the serious detrimental impacts of toxins like lead on our communities.

Resources on lead and environmental justice:




Frostenson, Sarah. America’s lead poisoning problem isn’t just in flint. It’s everywhere. – vox. January 21, 2016. Retrieved from http://www.vox.com/2016/1/21/10811004/lead-poisoning-cities-us

Centers for Disease Control and Prevention. Blood lead levels in children aged 1–5 years — united states, 1999–2010. Morbidity and Mortality Weekly Report (MMWR): April 5, 2013 / 62(13);245-248 Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6213a3.htm

Chen A, Dietrich KN, Ware JH, Radcliffe J, Roqan WJ: IQ and blood Lead from 2 to 7 years of age: are the effects in older children the residual of high blood Lead concentrations in 2-year-olds?. Environ Health Perspect. 2005, 113 (5): 597-601. 10.1289/ehp.7625.

Even A bit of lead is bad for kids’ psychological development. American Psychological Association, February 2014. Retrieved from http://www.apa.org/action/resources/research-in-action/lead.aspx

Gilbert, S. G., & Weiss, B. (2006). A rationale for lowering the blood lead action level from 10 to 2 μg/dL. Neurotoxicology, 27(5), 693-701. doi:http://dx.doi.org/10.1016/j.neuro.2006.06.008

Heath LM, Soole KL, McLaughlin ML, McEwan GT, Edwards JW: Toxicity of environmental Lead and the influence of intestinal absorption in children. Rev Environ Health. 2003, 18 (4): 231-50.

Hung, T 2014. CT Department of Public Health Annual Disease Surveillance Report on Childhood Lead Poisoning, based on 2012 data. Hartford, CT: Connecticut Department of Public Health.


K.M. Savolainen, J. Loikkanen, J. Naarala Amplification of glutamate-induced oxidative stress Toxicol. Lett., 82–83 (1995), pp. 399–405

Miranda, M. L., Kim, D., Galeano, M. A. O., Paul, C. J., Hull, A. P., & Morgan, S. P. (2007). The Relationship between Early Childhood Blood Lead Levels and Performance on End-of-Grade Tests. Environmental Health Perspectives,115(8), 1242–1247. http://doi.org/10.1289/ehp.9994

Needleman HL, Gatsonis CA. Low-Level Lead Exposure and the IQ of Children: A Meta-analysis of Modern Studies. JAMA.1990;263(5):673-678. doi:10.1001/jama.1990.03440050067035.

Needleman, H. L., Gunnoe, C., Leviton, A., Reed, R., Peresie, H., Maher, C., & Barrett, P. (1979). Deficits in psychologic and classroom performance of children with elevated dentine lead levels.  The New England Journal of Medicine, 300,  689-695.

  1. Regunathan, R. Sundaresan Effects of organic and inorganic lead on synaptosomal uptake, release, and receptor binding of glutamate in young rats J. Neurochem., 44 (1985), pp. 1642–1646


T.R. Guilarte. Glutamatergic system and developmental lead neurotoxicity neurotoxicology, 18 (1997), pp. 665–672

Xu, J., Yan, C., Yang, B., Xie, H., Zou, X., Zhong, L., Shen, X. (2009). The role of metabotropic glutamate receptor 5 in developmental lead neurotoxicity. Toxicology Letters, 191(2–3), 223-230. doi:http://dx.doi.org/10.1016/j.toxlet.2009.09.001

Food for thought: topiramate use in patients with psychotropic associated weight gain

One of the largest challenges in modern psychopharmacology is the difficult nature of side effects. These side effects are usually predictable and non-life threatening in patients (Hodgson and Kizior, 2013). However, the side effects of some psychotropic medications contribute importantly to the development of obesity, and obesity may be a risk factor for the development of some mental disorders (American Psychiatric Association, 2013). One of the most often associated side effects from pharmacological treatment in psychiatric patients is weight gain; and many of the psychotropic medications used to treat bipolar disorder cause weight gain (Sachs and Guille 1999). Although atypical antipsychotic medications have significantly fewer side effects and should be used as a first line treatment (Albers, Hahn, Reist, 2011), the concern for weight gain has led to the exploration of medications such as topiramate, lorcaserin, and buproprion. Limited information is available on the effectiveness of these medications but it is important to review the data to better determine the future of addressing weight gain as it relates to symptomology and side effects of psychotropic medications from a psychopharmacological perspective.

While there are several theories examining the cause of weight gain as a side effect from psychotropic medications, there are insufficient bodies of research that are able to pin down definitive causes of the mechanism of action of weight gain. In addition to psychiatric medications having side effects of weight gain, many psychiatric symptoms and conditions can cause dysregulation with eating habitus and subsequently cause weight gain. The American Psychiatric Association (2013) writes “there are robust associations between obesity and a number of mental disorders (e.g. binge-eating disorder, depressive and bipolar disorders, schizophrenia). Vogelzangs, Kritchevsky, and Beekman (2008) found that depression and other psychiatric symptoms increase with body mass index. There are currently only two medications that are FDA approved for weight management: lorcaserin and phentermine-topiramate (Stahl, 2011). Though the mechanism of action for weight loss is unknown, one focus for future research may be topiramate’s unique pharmacological profile which includes negative modulatory effects on the AMPA/kainate subtype of glutamate receptors, Na+ channels and some types of high-voltage-activated Ca2+ channels, and a positive modulatory effect on gamma-aminobutyric acid type A (GABAA) receptors (Shank et al. 2000). Though an FDA-approved anti-epileptic medication, topiramate has several off-label uses that has been of interest to clinicians in recent years. A few off-label uses of topiramate that clinicians have been treating patients with include binge eating disorder, bulimia nervosa, and weight loss (antipsychotic induced weight gain) (Stahl 2011). Hedges, Reimherr, Hoopes, et al.  (2003) write “topiramate is not an effective mood stabilizer but may be potentially useful for bulimia nervosa and binge eating disorder.” Future exploration and investigation into the effectiveness of off-label uses of topiramate may generate more FDA approved medications for the potentially beneficial psychotropic.

In clinical studies, though minimal in amount, the use of topiramate was associated with weight loss. In a meta-analysis of topiramate use in six trials, the average six-month weight loss was 6.51% with a placebo effect of about 2% (Li 2004). In Shapira, Goldsmith, and McElroy (2000), they found that the 13 female outpatients with binge-eating disorder mean topiramate dose was higher in patients who lost > or = 5 kg than in patients who lost < 5 kg; topiramate dose correlated significantly with weight loss (p < .01). According to McElroy, Shapira, Arnold, et al. (2004 and 2005), topiramate appears to be effective in reducing binge eating and promoting weight loss in the short and long term. When considering the implication of short term and long term weight loss for psychiatric patients who may have developed weight gain as a side effect of medications, there are many factors to consider. The weight loss associated with topiramate for both short term and long term offers potential for treatment, especially if other interventions have been unsuccessful. The lack of weight gain as demonstrated from these clinical trials may improve both patient compliance and self-esteem, especially since patients who gain weight from medications are at high risk for becoming treatment noncompliant (Sachs and Guille, 1999).

Bray, G. G. (2003-06). A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obesity research, 11(6), 722-733

Bray, G. G. (2003-06). A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obesity research, 11(6), 722-733

Though these clinical studies have produced hopeful results, clinicians need to also consider the side effects from patients trialed on topiramate. Hedges, Reimherr, Hoopes, et al. (2003) noted that practitioners observed several patients exhibiting adverse effects during a trial on topirmate, such as word-finding difficulties and paresthesias in a sizable minority of patients. These adverse effects suggest that they may have been related to excessively rapid rates of dosage increases (Hedges, Reimherr, Hoopes, et al.,2003). McElroy, Shapira, Arnold, et al. (2004 and 2005) also found that in the short term and long term, topiramate had side effects such as cognitive problems, paresthesias, and somnolence, which may limit its clinical utility for some individuals. In the APA’s Practice Guideline for treatment of patients with eating disorders, Yager, Devlin, Halmi, et al. (2012) write “because adverse reactions to this medication are common, it should be used only when other medications have proven ineffective.”

Topiramate could be potentially beneficial as an adjunct medication option for clinicians when considering the side effect profiles of various antipsychotic, antidepressants, and mood stabilizers but continued clinical case studies, open-label studies, and randomized controlled trials will be essential to determine efficacy and future use.  Additional data and research would need to work to identify a use of topiramate in augmentation to other psychotropic medications. Future clinical trials, long-term studies, and research will be necessary to assess the effectiveness of topiramate in its use of various psychiatric disorders and as an essential tool for clinicians to utilize.



Albers, L.J., Hahn, R.K., Reist, C. (2011). Handbook of psychiatric drugs. Blue Jay: Current Clinical Strategies, 6.

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM 5, 5th edition, DSM 5. Washington, D.C., APA Press.

Bray, G. G. (2003-06). A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obesity research, 11(6), 722-733.

Hedges DW, Reimherr FW, Hoopes SP, Rosenthal NR, Kamin M, Karim R, Capece JA: Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebocontrolled trial, part 2: improvement in psychiatric measures. J Clin Psychiatry 2003; 64:1449–1454

Hodgson, B., & Kizior, R. (2013). Saunders nursing drug handbook 2013. St. Louis: Elsevier/Mosby. x-xi.

Hoopes SP, Reimherr FW, Hedges DW, Rosenthal NR, Kamin M, Karim R, Capece JA, Karvois D: Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures. J Clin Psychiatry 2003; 64:1335–1341.

Li, Z. Z. (2005-04). Meta-analysis: pharmacologic treatment of obesity. Annals of internal medicine, 142(7), 532-546.

McElroy SL, Arnold LM, Shapira NA, Keck PE Jr, Rosenthal NR, Karim MR, Kamin M, Hudson JI (2003): Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry. 160:255–261.

McElroy SL, Shapira NA, Arnold LM, Keck PE, Rosenthal NR, Wu SC, Capece JA, Fazzio L, Hudson JI (2004) Topiramate in the long-term treatment of binge-eating disorder associated with obesity. J Clin Psychiatry. 65:1463–1469.

McElroy SL, Suppes T, Keck PE et al. (2000), Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 47:1025–1033.

Sachs GS, Guille C. Weight gain associated with use of psychotropic medications. J Clin Psychiatry.1999;60:16–9.

Shank, R. P., Gardocki, J. F., Streeter, A. J. and Maryanoff, B. E. (2000). An Overview of the Preclinical Aspects of Topiramate: Pharmacology, Pharmacokinetics, and Mechanism of Action. Epilepsia, 41: 3–9.

Shapira NA, Goldsmith TD, McElroy SL (2000). Treatment of binge-eating disorder with topiramate: a clinical case series. J Clin Psychiatry. 61:368–372.

Stahl, S. M. (2011). Essential psychopharmacology: The prescriber’s guide, 4th Ed.  New York: Cambridge University Press.

Vogelzangs N, Kritchevsky SB, Beekman AF, et al. (2008). Depressive Symptoms and Change in Abdominal Obesity in Older Persons. Arch Gen Psychiatry. 65(12):1386-1393.

Yager J, Devlin MJ, Halmi KA, et al. Guideline watch (August 2012): practice guideline for the treatment of patients with eating disorders, 3rd edition. APA Practice Guidelines.


What is CTE?

You may have heard a lot about the neurological condition known as chronic traumatic encephalopathy (CTE) lately. There seems to have been an increase in news stories and public awareness of the condition during the past several months. Adding to the increased awareness, Concussion, a major motion picture, was recently released. The movie portrays the story of Dr. Bennet Omalu, the neuropathologist who first identified CTE in a deceased professional football player (Keilman, 2015). But what exactly is CTE? What causes it? What changes in the brain are found in the condition? This post will explore the etiology, neuropathology, and symptoms of CTE.

Much of the discussion surrounding CTE involves the National Football League (NFL) and current and former football players in the NFL.  Professional football players endure frequent hard hits which can include hits to the head, possibly resulting in multiple head injuries known as concussions or mild traumatic brain injuries. These repetitive blows to the head are thought to be related to the development of CTE (Blennow, Hardy, & Zetterberg, 2012). Research suggests that head trauma does not have to result concussion to contribute to the development of CTE but that the risk of CTE is compounded by the repeated occurrence of any blows to the head, both concussive and sub-concussive (Montenigro, Bernick, & Cantu, 2015). However, it is important to note that not all individuals exposed to repetitive brain trauma develop CTE. There are likely other factors that contribute to the risk of CTE development including age, gender, and genetic predisposition (Stern et al., 2011).

With all of the attention that the NFL gets in relation to CTE, it may seem like only NFL players develop the condition. This is not the case. Any situation in which repetitive head trauma occurs can lead to the development of CTE. Cases of the condition have been identified in athletes, victims of domestic violence, and war veterans exposed to blast injuries (Gandy et al., 2014; McKee, Daneshvar, Alvarez, & Stein, 2014).

It is difficult to determine the true prevalence of CTE among professional athletes and the general public because CTE can only be definitively diagnosed by post-mortem autopsies (Montenigro, Bernick, & Cantu, 2015). Characteristic post-mortem neurobiological findings include an overall reduction in brain mass, along with atrophy of multiple specific brain structures including the medial temporal lobe, thalamus, mammillary bodies, and brain stem. More advanced cases of CTE may include atrophy of the hippocampus, entorhinal cortex, and amygdala (McKee et al., 2009). Other structural abnormalities include enlarged lateral and third ventricles, thinning of the corpus callosum, and cerebellar scarring. In the most advanced cases of CTE, there is significant depletion of the neurons in the substantia nigra and a significant loss of myelin in the white matter of the cerebral (McKee, Daneshvar, Alvarez, & Stein, 2014).

CTE is also marked by the presence of hyperphosphorylated tau proteins and neurofibriallary tangles (NFTs). These are the same kind of tangles that are found in the brains of individuals with Alzheimer’s disease and some other forms of dementia (Gandy et al., 2014). In contrast to the NFTs found in Alzheimer’s disease, the NFTs present in CTE brains are larger and more predominately found in the depths of the cortical sulci (McKee, Daneshvar, Alvarez, & Stein, 2014).

Amyloid beta deposits, which form the plaques characteristically found in Alzheimer’s disease, can be found in some brains in the most advanced stages of CTE. However, these deposits have not been found in the early stages of CTE. It is uncertain if they play a significant role in the development of CTE (McKee, Daneshvar, Alvarez, & Stein, 2014).

The symptoms of CTE typically present years or even decades following exposure to brain injuries (Baugh, Robbins, Stern, & McKee, 2014).  According to Montenigro et al. (2015), there are generally two distinct clinical presentations of CTE according to age of onset. Individuals with an earlier onset of the condition (mean age of 34.5) generally present with more predominant behavioral and mood symptoms. The most defining behavioral symptoms of CTE include physical and verbal violence, explosivity, loss of control, having a ‘short fuse,’ impulsivity, and paranoid delusions. The most defining behavioral symptoms include depression, hopelessness, suicidality, anxiety, fearfulness, irritability, and apathy.

Individuals with a later onset of CTE (mean age of 58.5) generally present with more predominant symptoms of cognitive impairment. The most defining cognitive symptoms include memory impairment, executive dysfunction, impaired attention, and impaired ability to write (Montenigro et al., 2015).

Although some psychotropic medications and other therapeutic interventions may be helpful in the treatment of some of the specific presenting symptoms of CTE, there is no comprehensive cure (Lakhan & Kirchgessner, 2012). Because there is no cure, an important question to ask is: What can be done to prevent the development of CTE? Taking steps to limit exposure to brain trauma is likely the most important practice in the prevention of CTE. Individuals should be aware of the risks of CTE when making choices to participate in activities that may place them at risk for repetitive brain trauma. More research is needed to better quantify the risks of certain activities in relation to the development of CTE to allow individuals to make better informed decisions.


Baugh, C. M., Robbins, C. A., Stern, R. A., & McKee, A. C. (2014). Current understanding of chronic traumatic encephalopathy. Current Treatment Options in Neurology16(9), 1-13.

Baugh, C. M., Stamm, J. M., Riley, D. O., Gavett, B. E., Shenton, M. E., Lin, A., … & Stern, R. A. (2012). Chronic traumatic encephalopathy:  Neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging and Behavior6(2), 244-254.

Blennow, K., Hardy, J., & Zetterberg, H. (2012). The neuropathology and neurobiology of traumatic brain injury. Neuron, 76(5), 886-899.

Gandy, S., Ikonomovic, M. D., Mitsis, E., Elder, G., Ahlers, S. T., Barth, J., … & DeKosky, S. T. (2014). Chronic traumatic encephalopathy: Clinical‐biomarker correlations and current concepts in pathogenesis. Molecular Neurodegeneration9(1), 1-22.

Jordan, B. D. (2014). Chronic traumatic encephalopathy and other long-term sequelae. CONTINUUM: Lifelong Learning in Neurology20(6, Sports Neurology), 1588-1604.

Keilman, J. (2015). Real life ‘Concussion’ doctor says film captures struggle to expose CTE risks. Chicago Tribune. Retrieved from http://www.chicagotribune.com/news/ct-concussion-movie-chicago-doctor-met-20151223-story.html

Lakhan, S. E., & Kirchgessner, A. (2012). Chronic traumatic encephalopathy: the dangers of getting “dinged”. SpringerPlus1(1186), 2193-1801.

McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., … & Stern, R. A. (2009). Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury. Journal of Neuropathology & Experimental Neurology68(7), 709-735.

McKee, A. C., Daneshvar, D. H., Alvarez, V. E., & Stein, T. D. (2014). The neuropathology of sport. Acta Neuropathologica127(1), 29-51.

Montenigro, P. H., Bernick, C., & Cantu, R. C. (2015). Clinical features of repetitive traumatic brain injury and chronic traumatic encephalopathy. Brain Pathology25(3), 304-317.

Stern, R. A., Riley, D. O., Daneshvar, D. H., Nowinski, C. J., Cantu, R. C., & McKee, A. C. (2011). Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. PM&R3(10), S460-S467.


Fibromyalgia as a Lens for Exploring the Effects of Depression on the Subjective Experience of Pain

In 1990, the American College of Rheumatology released a report outlining and updating the main symptoms of fibromyalgia, which had first been suggested as a clinical syndrome in 1977 and is estimated to affect 2% of the population (Bennett, 2009, Ang et al., 2011). The core symptom of fibromyalgia was defined as chronic widespread pain (WSP). In addition to this core symptom, the report noted that fibromyalgia sufferers may experience joint stiffness, trouble sleeping, fatigue, low energy, forgetfulness, and anxiety and depression. Depression in particular has been explored as a very common key co-morbidity in fibromyalgia syndrome. In fact, fibromyalgia was once considered to be a psychiatric illness prior to its classification as a musculoskeletal/rheumatologic syndrome. Early studies showed that fibromyalgia sufferers consistently scored high on hypochondriasis, hysteria and depression scales within the Minnesota Multiphasic Personality Inventory. In general, it is accepted within the field of psychiatry that there is a high rate of overlap in fibromyalgia not just with depression but also with generalized anxiety disorders and PTSD (Bennett, 2009). This correlation appears to be unique to fibromyalgia versus other clinical syndromes or illnesses characterized by WSP such as rheumatoid arthritis (Hassett et al., 2000). For our purposes, it is important to explore this link not to question the etiology or legitimacy of fibromyalgia which can be quite debilitating and distressing to those who suffer from it, but to use it as a lens for better understanding how mental illness (depression in particular) might distort our subjective experiences of pain.

Although it has long been thought that depression can impact the experience of pain, and that chronic pain is often associated with depression, the dynamics between this correlation have been hotly debated. It has been posited that patients with a predisposition to depression (whether currently suffering from depression or simply having a past history of depressive episodes) are more likely to experience higher levels of pain than individuals with no history of depression. It has also been suggested that the experience of chronic pain can cause depression or make it more likely to develop. Some researchers have stated the association is “likely a reciprocal influence process” where a multitude of factors interrelate (Tennen, Affleck & Zautra, 2006). Proposed explanations vary from cognitive in nature, to personality factors to neurobiological underpinnings.

A commonly referenced personality trait in fibromyalgia sufferers is neuroticism which can be defined as “a normal personality characteristic associated with vulnerability to distressing emotions” (Tennen, Affleck & Zautra, 2006). Neuroticism may contribute to cognitive distortions in “pain appraisals” via “catastrophizing” the pain by assuming a more dangerous underpinning or unrelenting course and “less perceived control over pain coping,” as well as increasing the tendency for “negative self-statements” in the context of pain. Coping skills may in fact be impaired, with depressed patients being less likely to “take action” to decrease pain, instead tending to vent emotions, use more passive coping strategies such as praying and hoping, and getting caught in a cycle of inactivity (Tennen, Affleck & Zautra, 2006, Hassett et al., 2000). Depressed patients are also less likely to be able to ignore the pain (Hassett et al., 2000). Negative mood alone would likely have an impact on how patients with fibromyalgia feel, think about/perceive, and respond to their pain (Tennen, Affleck & Zautra, 2006).

Neuroimaging studies of fibromyalgia sufferers have produced mixed and modest results suggesting the neurological underpinnings of the disorder. Early studies with single-photon emission computed tomography (SPECT) showed that regional cerebral blood flow (rCBF) was decreased in the thalamus (particularly the right side of the thalamus) and caudate nucleus areas in patients with fibromyalgia versus control subjects. Decreased rCBF in the thalamus has been seen in other pain-related conditions such as metastatic breast cancer and traumatic peripheral neuropathy as well. Inhibited activity in the thalamus is associated with “persistent prolonged excitatory nociceptive input.” Nociceptors are our pain receptors, so this means pain signals being sent out from the thalamus last longer and are less likely to be turned off in patients with reduced thalamic blood flow versus controls (Nebel & Gracely, 2009). Additional studies have replicated the findings related to nociceptive receptors, with one summarizing that “increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input” is a key pathophysiologic concept in fibromyalgia (Ang et al., 2011).

Building on these findings, researchers have used fMRI to explore the brains of patients with both fibromyalgia and depression, looking at what is happening in the thalamus. An association has been found between greater activity in the contralateral anterior insula and bilateral amygdala during pain stimulation in patients with fibromyalgia and major depressive disorder where increased activity in these areas is not seen in patients with fibromyalgia and normative mood. As the amygdala can be thought of as the center for affect and emotion, it is possible this is how depression influences the processing and emotional interpretation of pain signals in patients with fibromyalgia (and perhaps those without fibromyalgia as well, which future studies should assess). This same study did find significant activation in brain regions associated with the anticipation of and attention to pain as well, demonstrating that a wide net of neurobiological underpinnings is likely implicated in this relationship (Nebel & Gracely, 2009).

A variety of other research exists which explores how the role of SSRIs in treating fibromyalgia, the presence of inflammatory cytokines and biomarkers, psychodynamic factors such as sexual abuse history, and other clinical correlates might explain the etiology of co-morbid depression with fibromyalgia (Mazza et al., 2009, Ribeiro & Proietti, 2004, Ross, Jones & Bennett, 2007, Wang et al., 2009, De Civita, Bernatsky & Dobkin, 2004). While the complex development and perpetuation of this syndrome remains unclear, and while not every fibromyalgia sufferer demonstrates depressive symptoms, it is clear that depression has the ability to play a central role in its course. The direction of the relationship between depression and pain perception is likely an interactive one, as previously noted. Fibromyalgia patients with and without a history or present diagnosis of depression present us with a unique and rich opportunity for evaluating this complex feedback loop. This particular research niche has the potential to unearth valuable insights into the pathophysiology of depression, particularly as we begin to look more at how inflammatory processes and other neurobiological aspects might be at least partially to blame. There is certainly reason to hope that this research might contribute to more effective treatment options for either or both of these debilitating illnesses!


Ang, D., Chakr, F., France, C., Mazzuca, S., Stump, T., Hilligoss, J., & Lengerich, A. (2011). Association of nociceptive responsivity with clinical pain and the moderating effect of depression. American Pain Society, 12(3), 384-389. doi: 10.1016/j.jpain.2010.09.004.

Bennett, R. (2009). Clinical manifestations and diagnosis of fibromyalgia.Rheum Dis Clin N Am, 35, 215-232. doi: 10.1016/j.rdc.2009.05.009.

De Civita, M., Bernatsky, S., & Dobkin, P. (2004). The role of depression in mediating the association between sexual abuse history and pain in women with fibromyalgia. Psychology, Health & Medicine9(4), 450-455. Retrieved February 6, 2016 from http://web.b.ebscohost.com/ ehost/detail/detail?sid=2af29bb2-0b6f-46d2-9e52-831b298ca636%40sessionmgr111&vid=0&hid=116&bdata=JkF1dGhUeXBlPWlwJnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#AN=106517221&db=c8h.

Hassett, A. L., Cone, J. D., Patella, S. J., & Sigal, L. H. (2000). The role of catastrophizing in the pain and depression of women with fibromyalgia syndrome. Arthritis & Rheumatism, 43(11), 2493-2500. doi: 10.1002/1529-0131(200011)43:11<2493::aid-anr17>3.0.co;2-w.

Mazza, M., Mazza, O., Pomponi, M., Nicola, M., Padua, L., Vicini, M., . . . Mazza, S. (2009). What is the effect of selective serotonin reuptake inhibitors on temperament and character in patients with fibromyalgia? Comprehensive Psychiatry, 50, 240-244. doi: 10.1016/j.comppsych.2008.08.004.

Nebel, M., & Gracely, R. (2009). Neuroimaging of fibromyalgia. Rheum Dis Clin North Am., 35(2), 313-327. doi: 10.1016/j.rdc.2009.06.004.

Ribeiro, L., & Proietti, F. (2004). Interrelations between fibromyalgia, thyroid autoantibodies, and depression. Journal Of Rheumatology31(10), 2036-2040. Retrieved February 6, 2016 from http://web.b.ebscohost.com/ehost/detail/detail?sid=3bbf7f10-866f-498d-8845-0bef0d2d4d88%40sessionmgr113&vid=0&hid=116&bdata= JkF1dGhUeXBl PWlwJnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#AN=106561747&db=c8h.

Ross, R., Jones, K., & Bennett, R. (2007). Biochemical markers of major depressive disorder subtypes in fibromyalgia. Communicating Nursing Research40, 40323-40323. Retrieved February 6, 2016 from http://web.b.ebscohost.com/ehost/detail/detail?sid= d8b6c2e8-e854-40da-8eef-2aaf995bdec9%40sessionmgr102&vid=0&hid =116&b data=JkF1d GhUeXBlPWlwJnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#AN=105 763423&db=c8h.

Tennen, H., Affleck, G., & Zautra, A. (2006). Depression history and coping with chronic pain: A daily process analysis. Health Psychology, 25(3), 370-379. doi: 10.1037/0278-6133.25.3.370.

Wang, H., Buchner, M., Moser, M., Daniel, V., & Schiltenwolf, M. (2009). The role of IL-8 in patients with fibromyalgia: A prospective longitudinal study of 6 months. Clinical Journal Of Pain25(1), 1-4. doi:10.1097/AJP.0b0 13e31817e13a3.