Demystifying Tourette Syndrome

What is Tourette Sydnrome?

Tourette Syndrome (TS), also refereed to as Tourette Disorder, is a neurological disorder that causes people to do things – like make involuntary movements and noises, or sometimes even say words or phrases – that they cannot control.  These involuntary actions are called “tics”, and are present, in varying degrees, throughout the entire course of the disorder.  Individuals with TS typically have their first symptoms in childhood, and while it is thought of as a life-long disorder, symptoms severity and frequency decrease over time for most people.  However, periods of stress or excitement almost always cause an increase in symptoms, just as periods of calm and intent focus (say while deeply involved in a project, hobby, or game) may cause a brief decrease in symptoms.

What is a motor tic?

A motor tic is an involuntary movement that is not goal-oriented and does not serve a functional purpose for the individual.  Motor tics most commonly occur in clusters, called “bouts”, throughout the day.  Common motor tics include: eye blinking, shoulder shrugging, jerking the head back, hopping, or quick, sudden flexing of the arms, wrists, or other joints.  Some motor tics may be painful and/or cause physical injury.  For example, eye rolling tics in which one’s eyes roll back extremely far may cause eye pain, or rapid, forceful tics of the extremities can contribute to joint and muscle pain (Pain and Tourette Syndrome, n.d.)

In the diagram below, each tick mark (tic-mark!) indicates one isolated tic.  Just as the frequency of tics changes throughout the day, the frequency and patterns of bouts of tics change over longer periods of time such as months and years.


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What is a phonic tic?

A phonic tic is a type of tic that creates an audible sound.  Like motor tics, phonic tics are involuntary and occur in bouts throughout the day.  Phonic tics are sometimes called “verbal tics”, however this is a really misnomer, as not all phonic tics are verbal in nature.  Common phonic tics include: sniffing, throat clearing, grunting, blowing, or making more intentional-seeming sounds such as humming or saying words.  It is important to remember though, that while phonic tics may seem intentional – based on complexity of the word(s) said or context in which they occur – they are not.

What about swearing?

In the media, people with TS are often portrayed as having swearing tics or tics that cause them to say socially taboo words or phrases.  In reality, however, these types of symptoms are quite rare.  Phonic tics of this socially inappropriate nature are called coprolalia, and occur in less than 10% of people with diagnosed TS (Tag Archives, n.d.).

Copropraxia, the motor tic equivalent of coprolalia, involves making socially inappropriate gestures such as pointing a middle finger or momentarily touching of ones own genitals (over their clothing, often observably similar to someone scratching or motioning “below the belt”).  Copropraxia occurs even less frequently than coprolalia. (Smith, 2008)

Like other tics, the symptoms of coprolalia and copropraxia are thought to result from abnormalities in the basal ganglia and prefrontal cortex, and from alternations in the neurotransmitters dopamine, serotonin, glutamate, and GABA (discussed below), though the exact neurobiology is not known with certainty.

For both coprolalia and copropraxia, it is important remember that person who has these types of tics often experiences very high levels of distress as a result, and is not doing these behavior to offend, draw attention, or otherwise solicit a reaction from others.

Can’t they just control it?

This may seem like a valid question – tics sometimes appear to be willful acts.  If they are distressing or socially inappropriate, why don’t people just stop?  Is it just a problem of discipline or motivation for self-control?  While the exact pathophysiology of TS is yet unknown, the answer is most definitely no.  It is very clear to scientists and clinicians that TS is the result of brain wiring or function that is different from the norm.

The basal ganglia (an area of the brain involved in emotional and cognitive functioning, as well as coordinating movements) and the prefrontal cortex (the brain’s “brakes” in terms of planning and executing voluntary movement) are thought to play a major role in the symptoms of TS (Chudler, n.d.).

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As well, chemicals in the brain called neurotransmitters — in particular: dopamine (often involved in reward-motivated behaviors and bonding), serotonin (involved in mood), glutamate (the brain’s “power horse” in terms of keeping it up and running), and GABA (which has an inhibitory effect in the brain, often balancing out glutamate) — might further contribute to symptoms (Chudler, n.d.).  Fellow Exploring Mental Health blogger, Angela Julian, has provided a wonderful, up-to-date overview of current hypotheses about the neurobiology of tics and pathophysiology of TS.

If I can control it to some degree, then does that mean I don’t have TS?

So, now that I have tried hard to express that the symptoms of TS really are beyond one’s control, I want to tell you that this may not always be the case.  While tics are involuntary, some people may actually be able to be delay their occurrence.  The best analogy for this is typical blinking of the eyes that we all do every day, all day long.

Eye blinking is an involuntary act, that is, everyone does it, no one thinks much about it, and we really can’t not do it.  We don’t need to keep a schedule or reminders, or even any conscious thought at all.  From deep in our brain, our globus pallidus structure tells our eye muscles to blink, and we do.  However, exactly when and how frequently we blink our eyes can, to some degree, be up to us.  We can put our blinking on hold for a bit (staring contest anyone?), or we may unconsciously decrease its frequency (such as when we are playing a video game or perusing the internet).  But we can only do this for so long before we absolutely must blink.

Sometimes, when we lose this staring contest – either with our friend or our computer – we find we must blink many times in a row.  We have to sort of “make up” for the lost blinks.  Tics can be this way too.  Some people may control the timing or frequency of their tics for a short while, but ultimately individuals with TS find they must release their tics.  Sometimes this means an exacerbation of severe tics after a long day of school or work, while others may create small, subtle outlets throughout the day to release some of the pent up tic energy.  Many adults with TS find it possible to disguise some of their tics as a cough, a scratching of their face, or a bathroom break during which they can tic behind closed doors. (Tourette Syndrome Fact Sheet, n.d.)

Is there a cure?

Currently, there is no cure for TS.  Mediations such as antihypertensives, antipsychotics, and those used to treat ADHD or OCD are often effective in managing both motor and phonic tics.  This may be confusing.  If you are wondering why a blood pressure medication or an antipsychotic would help control tics, then you have some of the same questions as the most expert researchers in the field!  Again, we have a lot to learn and discover about the brain chemistry of TS.

For severe and debilitating cases of TS, more invasive treatments such as Deep Brain Stimulation (DBS) may be helpful.  In DBS, a neurosurgeon places a small electrode into the areas of the brain called the thalamus (which relays sensory and motor information) and the globus pallidus (which is involved in regulating voluntary movement, and was mentioned above with regard to blinking).  (DBS, n.d.)

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Recent research in behavioral therapy for tics has also shown promising outcomes, and patients who undergo a TS-focused type of behavior therapy called Comprehensive Behavior Intervention for Tics have demonstrated reproducible success in managing their symptoms.  This type of therapy is becoming a widely respected treatment option.  However, the exact neurochemistry of the changes it causes in people’s brains is still being researched. (CBIT, n.d.)

The good news is that TS not life-threatening, it is not degenerative, and generally symptoms improve over time and into adulthood.

Involuntary movements, neurosurgery…. are there any good parts about having TS?

A life-long, commonly misunderstood neurological disorder of largely unknown pathophysiology that causes involuntary movements and behaviors may sound a bit daunting – or at the very least, exhausting!  But there might be some good from it too.  A 2011 study (Jackson et al) suggests that reason some people develop control over when and where they express their tics, is because their brains builds compensatory mechanisms.  These mechanisms are not only allow them to gain control over their tics, but are actual give them better motor control overall — better, even, than people without TS.  Perhaps it is this overcoming of slightly-off brain wiring or function that helped Tim Howard (soccer goalie, Everton and the US National Team), Jim Eisenreich (former MLB player), and David Beckham (former soccer goalie, Manchester United), become some of the most well-known individuals with TS (Famous, n.d.).

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CBIT TSA Brochure. (n.d.). CBIT TSA Brochure. Retrieved February 23, 2014, from

Chudler, Eric. (n.d.) Tourette Syndrome. University of Washington Faculty Homepage. Retrieved February 23, 2014, from

DBS for Tourette Syndrome Common Questions and Answers for Patients and Families. (n.d.). DBS for Tourette Syndrome Common Questions and Answers for Patients and Families. Retrieved February 24, 2014, from

Famous People With TS or OCD. (n.d.). Tourette Syndrome “Plus”. Retrieved February 25, 2014, from’s-syndrome/some-famous-people-with-ts-or-ocd/

Jackson, S., Parkinson, A., Jung, J., Ryan, S., Morgan, P., Hollis, C., et al. (2011). Compensatory Neural Reorganization in Tourette Syndrome. Current Biology, 21(7), 580-585.

Pain and Tourette Syndrome. (n.d.). Tourettes Action. Retrieved February 24, 2014, from—pain-and-TS.pdf

Smith, Christopher. (2008). A Tourette Syndrome Primer for Therapists (Doctoral dissertation). Retrieved from ProQuest. (304395565)

Tag Archives: Copropraxia. (n.d.). TSParentsOnline. Retrieved February 24, 2014, from

Tourette Syndrome Fact Sheet. (n.d.). : National Institute of Neurological Disorders and Stroke (NINDS). Retrieved February 22, 2014, from

Zinner, S. (2004). Tourette Syndrome – Much more than tics. Contemporary Pediatrics, 21(8), 22-36.

Image Credits:

1 – Zinner, S. (2004). Tourette Syndrome – Much more than tics. Contemporary Pediatrics21(8), 22-36.  Retrieved February 24, 2014 from:

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Tourette’s Disorder

According to the DSM5, Tourette’s disorder (TD) (307.23) is diagnosed when both motor and vocal tics are present prior to the age of 18 years, and have persisted for over one year. These tics may not be attributable to physiological effects of a substance or another medical condition (American Psychiatric Association, 2013, p. 81). The prevalence rates of TD has been estimated from 3-8/1,000 in school age children, with males more commonly affected than females (American Psychiatric Association, 2013, p. 83). The neurobiology of TD remains one of the undefined neurobiologic abnormalities within psychiatry. In this week’s post I will be walking you through some of the proposed hypotheses of Tourette’s syndrome, and inviting you to consider how current pharmaceutical treatments might function in the brain. The pathophysiology has been difficult for researchers to discern, as many individuals with Tourette’s syndrome also have comorbid illnesses of ADHD, OCD, mood disorders, and executive function deficits (Leckman, Bloch, Smith, Larabi, & Hampson, 2010; Singer & Minzer, 2003). As you read on about the proposed neurobiology involved, I invite you to consider where the overlap may lie between TD and comorbid conditions.


The major concepts driving the neurobiology of Tourette’s syndrome can be broken down into neuroanatomical localization and synaptic neurotransmission. In other words, where in the brain do the symptoms lie? And how are those parts of the brain functioning and communicating?


Post-mortem studies of individuals with acquired Tourette’s or Tourette’s like symptoms have demonstrated lesions in the central grey matter of the midbrain tegmentum (Singer & Minzer, 2003). Studies involving both live subjects and humans, however, point to the involvement of the cortico-striato-thalmo-cortico circuit in the pathogenesis (Leckman et al., 2010; Hoekstra et al., 2004; Singer & Minzer, 2003). Single photon emission computed tomography suggests hypoperfusion of the basal ganglia in TD (Singer & Minzer, 2003).  Further studies demonstrate that there is decreased perfusion in the left caudate, cingulate, right cerebellum, and right and left dorsolateral prefrontal regions in those affected by TD (Singer & Minzer, 2003). But what can this mean? The caudate plays a large role in voluntary movement, the cingulate in motivation and learning, the cerebellum in learned sequential movement, and the dorsolateral prefrontal regions in executive functioning and inhibition. A disruption in each of these areas might contribute to the motor and vocal tics of TD. Volumetric MRI studies also indicate that there are caudate or lentricular nuclei abnormalities in both volume and symmetry (Leckman et al., 2010; Leckman, 2002; Singer & Minzer, 2003). Might there be impaired cortical inhibition or disinhibited afferent thalamo-cortical signals?


So, if these parts of the brain are involved in the pathogenesis of Tourette’s, what is happening on the level of the neurotransmitter? Studies suggest that there may be a disinhibition of excitatory neurons in the thalamus, which is contributing to hyperexcitability of cortical motor areas, which permits the release of tics (Hoekstra et al., 2004; Singer & Minzer, 2003).  They also suggest that over-activity in the matrosome contributes to tics by inhibiting the neurons that suppress unwanted movement (Singer & Minzer, 2003). There are four main neurotransmitter imbalances that are proposed to play a role. First we will discuss dopamine. D1 receptors are excitatory to the movement pathway, which D2 is inhibitory to the movement pathway (Singer & Minzer, 2003).  An imbalance in either of these areas is proposed to contribute to tics, while fluctuating levels of DA is hypothesized to influence the waxing and waning nature of tics (Leckman et al., 2010; Singer & Minzer, 2003).  Glutamate is the second neurotransmitter that possible plays a role. Researchers propose that a decrease in glutamate in the subthalamic nucleus would cause a decrease in the inhibition and thus an increase in thalamo-cortical excitation (Leckman et al., 2010; Singer & Minzer, 2003). Similarly, a decrease in a third neurotransmitter, GABA, within the striatum can lead to decreased inhibition of the thalamo-cortical excitation (Leckman et al., 2010; Singer & Minzer, 2003).  The fourth neurotransmitter which we will discuss in serotonin (5HT). While the exact role of 5HT is unknown, studies have demonstrated decreased levels of plasma tryptophan and decreased whole blood 5HT in TD (Singer & Minzer, 2003).  Perhaps it plays a role as a modifying factor in tic pathogenesis.


Now let’s take a closer look at some of the pharmacological treatments for TD. How do they relate to these brain areas and neurotransmitters we discussed above? Both antihypertensives and antipsychotics have been indicated for use in Tourette’s, as means to decrease tics (Leckman, 2002).


Clonidine and Guanfancine are two antihypertensives often used in the treatment of Tourettes’s (Leckman, 2002; Stahl, 2011). It is a centrally acting alpha 2 agonist in the prefrontal cortex (Stahl, 2011). As the prefrontal cortex is responsible for modulating working memory, attention, impulse, control, and planning, it is thought that these drugs function in the prefrontal cortex to enhance regulation of attention and behavior (Stahl, 2011). Although the exact mechanism is unknown, trials have demonstrated that Clonidine may suppress tics (Stahl, 2011). Guanfacine is another antihypertensive that similarly is a centrally acting alpha 2 agonist in the prefrontal cortex. It is similarly indicated in Tourette’s though less research has been performed on its effectiveness (Stahl, 2011).


Risperidone and Ziprasidone are examples of two atypical antipsychotics used in Tourette’s (Leckman, 2002). Risperidone is a serotonin-dopamine antagonist that causes an enhancement of dopamine release (Stahl, 2011). It is indicated for use in behavioral disturbances (Stahl, 2011). Ziprasidone is similarly a serotonin-dopamine antagonist used to control behavioral disturbances (Stahl, 2011). It is believed that their effect of blocking D2 receptors can suppress tic behaviors (Leckman, 2002).


While much is still unknown about the psychopathology of Tourette’s disorder, research has come a long in way in identifying both pathways of the brain and specific neurotransmitters that contribute the overall presentation of individuals with TD. With this knowledge, and the knowledge of effective pharmaceutical agents, I am hopeful that we will continue to learn more about the neurobiology of this disease.




American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.


Hoekstra, P. J., Anderson, G. M., Limburg, P. C., Korf, J., Kallenberg, C. G. M., & Minderaa, R. B. (2004). Neurobiology and neuroimmunology of Tourette’s syndrome: An update. Cellular and Molecular Life Sciences, 61, 886-898


Leckman, J. F., Bloch, M. H., Smith, M. E., Larabi, D., Hampson, M. (2010). Neurobiological substrates of Tourette’s disorder. Journal of Child and Adolescent Psychopharmacology, 20 (4), 237-247


Leckman, J. F. (2002). Tourette’s syndrome. Lancet, 360, 1577-1586.


Singer, H. S. & Minzer, K. (2003). Neurobiology of Tourette’s syndrome: Concepts of neuroanatomic localization and neurochemical imbalances. Brain & Development, 25(suppl 1), S70-S84


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


Additional Resource: National Tourette’s Syndrome Association


Borderline Personality Disorder

What is Borderline Personality Disorder?

Individuals suffering from Borderline Personality Disorder (BPD) experience a highly chaotic and intensely emotional world. Persistent patterns of unstable relationships, irritability, and self-destructive behaviors characterize this disorder. Those with BPD also have a deep fear of being abandoned and experience a feeling of immense emptiness on a recurring basis (Varcolis & Halter, 2009, p. 182). It is also common for those with BPD to have other mental health issues, such as depression, eating disorders, anxiety, and substance abuse (“Borderline personality disorder,” 2012).

In terms of prevalence, 1 in 20 or 25 people live with BPD (“Borderline personality disorder,” 2012). Onset of this disorder is around the time of adolescence, and the average age of onset of recognizable clinical symptoms is age 18 (Perese, 2012, p. 619). There is no one cause of BPD, but there are certain experiences that those with BPD often share, such as childhood chronic illness or traumatic events (“Borderline personality disorder,” 2012). Like other forms of mental illness, both genetics and environment are involved in the development of BPD.

(“The biopsychosocial model of borderline personality disorder.” Retrieved from
What parts of the brain are affected by BPD?

While there is a lot we don’t know about BPD, we do know that certain areas of the brain involved in the regulation of emotions, called subcortical structures, have reduced volume in patients with BPD and are therefore less active. In addition, a system that controls the regulation of hormones involved in the stress response, called the HPA axis, is actually hyperactive. We also know that those with BPD have a higher rate of birth-related complications as well as brain injuries attained in childhood (Perese, 2012, p. 620). Certain hormones, like oxytocin, and neurotransmitters, like serotonin, also may play a role in BPD (“Borderline personality disorder,” 2012).

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(Retrieved from

How is BPD diagnosed and how is it treated?

BPD is diagnosed by thorough psychiatric interview. There are specific criteria outlined in the DSM-5, a manual published by the American Psychiatric Association, providing parameters for diagnosing mental disorders, including BPD.

In terms of treatment, there is no one-way to treat BPD. Various therapy modalities, as well as medications, can be utilized. Dr. Marsha Linehan, a psychologist who has also suffered from BPD, created an innovative therapeutic technique called Dialectical Behavior Therapy (DBT). DBT was adapted from Cognitive Behavioral Therapy (CBT) to be a suitable treatment for those with BPD suffering from recurring self-harm and suicidal behaviors. This therapy incorporates elements of “mindfulness,” deep breathing and relaxation techniques, and encourages “accepting” thoughts and behaviors, instead of wrestling with them. Homework, such as keeping a diary, is also part of DBT (“Dialectical behavior therapy,” 2013).

No medications have been approved by the FDA for the treatment of BPD, however several can be used to treat some of the associated symptoms. Such medications include mood stabilizers or antipsychotics and antidepressants. Mood stabilizers and antipsychotics are often the better choice, as they have more of an impact on a wider range of symptoms of BPD (Silk, Skodol, and Hermann, 2013). Medications are prescribed to help those with BPD cope with mood instability, out of control and impulsive behaviors, and perceptual and thinking disturbances (“What is borderline personality disorder?”, 2001). With psychotherapy and, in some circumstances, adjunctive medication therapy, individuals with BPD can manage their symptoms.

Helpful Resources:

Documentary on BPD:



“Borderline personality disorder.” (2012). Retrieved February 3, 2014, from

“Dialectical behavior therapy.” (2013). Retrieved February 3, 2014, from

Perese, E.F. (2012). Psychiatric advanced practice nursing: A biopsychosocial foundation for practice. Philadelphia, PA: F.A. Davis Company.

Silk, K.R., Skodol, A., Hermann, R. (2013). “Borderline personality disorder: Treatment and prognosis.” Retrieved on February 3, 2014, from

“What is borderline personality disorder?” (2001). Psychiatric Services, 52(12). Retrieved February 3, 2014, from

Varcolis, E.M. & Halter, M.J. (2009). Essentials of psychiatric mental health nursing: A   communication approach to evidence-based care. St. Louis, MO: Saunders Elsevier.

Is glutamate the answer to OCD?

Obsessive Compulsive Disorder (OCD) is an often debilitating neuropsychiatric condition that effects 1-2% of the nation’s population (APA, 2013). The disorder is characterized by persistent intrusive thoughts, repetitive intrusive behavior, and excessive anxiety (APA, 2013). Currently, a combination of medication and Cognitive Behavioral Therapy (CBT) are recommended as first line treatment for the disorder (Pittenger, Krystal, & Coric, 2006).  Current first line medications for OCD are selective serotonin reuptake inhibitors (SSRIs) and clomipramine, a tricyclic antidepressant. These medications work by increasing the levels of neurotransmitter serotonin available in the synaptic cleft. However, only 50-60% of patients respond to these medications (Wu, Hanna, Rosenberg, & Arnold, 2012). Also, higher doses of these medications are often required before clinical improvement is seen in OCD than when used for depression, exposing patients to a greater risk of experiencing dangerous or intolerable side effects. Unfortunately, even those that are considered responsive to treatment still experience significant OCD symptoms and impairment to their quality of life. There is thus a significant need for new approaches to OCD treatment. Fortunately, recent improvements in the understanding of neurobiology and etiology of OCD provide opportunities for the development of these strategies.

Currently, dysfunction involving the basal ganglia has been implicated in the pathophysiology of OCD. The basal ganglia, including the caudate and putamen (together known as the striatum) and the globus pallidus, are structures typically associated with motor control and the coordination of higher level functions, such as motivation, with body movements. Functional imaging studies of OCD have repeatedly shown hyperactivity in a neuronal circuit running from the orbital frontal cortex, to the striatum, thalamus, and back to the cortex (CSTC circuit) (Higgins & George, 2013). Insult to these regions can produce OCD symptoms, and surgical interruption of the loop provides improvement of these symptoms (Higgins & George, 2011).

Glutamate, an excitatory neurotransmitter in the brain, is a primary neurotransmitter in the CTSC circuit. When glutamate is released from a pre-synaptic neuron following an action potential it can bind to postsynaptic receptors (NMDA and AMPA) to elicit an excitatory response, or to presynaptic receptors, providing negative feedback to limit further glutamate release. Glutamate can also diffuse out of the synaptic cleft, which causes an activation of extrasynaptic NMDA receptors and can lead to neuronal damage and death. Glutamate concentration is therefore tightly controlled in the brain by various reuptake transporters (Stahl, 2011).

Increasing evidence has shown that the neurotransmission of glutamate within CTSC circuits is disrupted in OCD (Pittenger, Bloch, & Williams, 2011; Wu et al., 2012). Magnetic Resonance Spectroscopy (MRS) imaging is able to detect levels of glutamatergic (Glx) compounds in the brain. Several studies have demonstrated abnormal glutamate levels in several regions of the brain, although specific findings are inconsistent. In several MRS studies, Glx has been increased in the striatum of adults with OCD, and decreased in the Anterior Cingulate Cortex (SCC) in both adults and children with OCD. One study found increased Glx levels in the orbitofrontal cortex of those with OCD, but a more recent study has demonstrated contradictory results (Pettinger et al., 2011). Two studies have found increased levels of glutamate in cerebral spinal fluid (CSF) in unmediated adults with OCD, which is presumed to be a reflection of a general abnormality of glutamate balance in the brain (Wu et al., 2012).

The heritability of OCD has been well supported for decades and several recent studies have been able to link the presence of OCD to glutamate related genes. There has been promising research surrounding the association of the glutamate transporter gene Slc1A1 with OCD.  Gene studies have linked polymorphisms in Slc1A1, a gene that encodes for the EEAT3 protein, with OCD (Wu et al., 2012). The EEAT3 protein plays a role in the reuptake of this extrasynaptic glutamate. It has been suggested that polymorphisms in this gene that lead to reduced expression of the transporter may be associated with increased expression of OCD. The Sapap3 gene, which encodes a protein critical to glutamate receptors, has been consistently associated with OCD spectrum disorders, including Trichotillomania. Finally, recent studies have examined the association between OCD and Grin2 and Grik3 genes, both encoding for subunits of NMDA receptors, with promising early results (Wu, et al., 2012). Additional evidence supporting genetic etiology of glutamate dysfunction in OCD would be especially important to treatment as it would implicate that glutamate dysfunction as a cause to OCD rather than a result of OCD pathology.

This evidence from clinical research supports the glutamatergic system as a potential target for pharmacological therapy for OCD. Fortunately, medications that affect glutamate levels are already FDA approved for other medical conditions, although research with the OCD population has been limited.  Riluzole, a drug indicated for ALS has been studied most extensively with the OCD population. Riluzole is thought to reduce glutamatergic neurotransmission through the inhibition of voltage-dependent sodium channels and stimulation of glutamate reuptake by transporters (including EEAT3). Slightly more than half of patients with OCD treated in in several open label trials have reported significant OCD symptoms improvement (Wu, et al. 2012).

Memantine and other NMDA antagonists have also shown preliminary success in decreasing OCD symptoms using the rationale that it reduces the activation of a glutamate receptor whose excessive activation can lead to neurotoxic sequelae. Two recent open-label case series suggest that the addition of memantine to standard medication therapy can benefit both children and adults with OCD (Pettinger, et al., 2011).

In contrast, N-acetylcysteine, an OTC antioxidant, is expected to increase extrasynaptic glutamate. While this seems counter-intuitive to the proposed mechanisms of OCD, animal studies and one published case study have demonstrated its effectiveness in attenuating OCD symptoms (Wu, et al., 2012).  Other drugs under investigation include D-cycloserine and antiepileptic agents including Lamotigrine and Topirimate (Pettinger, et al., 2006).

Although research examining the etiology of OCD remains in preliminary stages, results consistently indicates that glutamatergic dysregulation is involved at some level. These findings provide new opportunities to better understand the neurobiology and to develop more effective treatments (both pharmacological and other) for OCD and potentially other psychiatric disorders. It also seems to raise more questions than it has answered. Where and how is glutamate deregulated? Is glutamate dysfunction the cause of OCD or a consequence of its pathology? What role does epigenetics, if any, have in its development?  Glutamate is used extensively in the brain, what potential effect will glutamate antagonists have on other brain structures? What kind of OCD patient would benefit most from these medications? Do CBT and other behavioral therapies exert their effect through the same mechanism? Hopefully, as the exact mechanisms of glutamate dysfunction become better understood and more clinical medication trials are preformed, some of these questions will be answered and an effective treatment for this impairing neuropsychiatric disorder can be developed.


American Psychiatric Association. (2013). Obsessive-Compulsive Related Disorders.            In Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.

Higgins, E.S. & George, M.S. (2013). The Neuroscience of Clinical Psychiatry: The                   Pathophysiology of Behavior and Mental Illness, Second Edition  Publisher: Lippincott        Williams & Wilkins.

Pittenger, C., Michael H. Bloch M.H., & Williams, K. (2011). Glutamate abnormalities in             obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment.                  Pharmacology & Therapeutics, 132(3), 314-332. Retrieved from Ovid database.

Pittenger C., Krystal J.H., & Coric, V. (2006). Glutamate-Modulating Drugs as Novel                   Pharmacotherapeutic Agents in the Treatment of Obsessive-Compulsive Disorder.            NeuroRX, 3(1), 69-81. Retrieved from Ovid database.

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

Wu, K., Hanna, G.L., Rosenberg, D.R., & Arnold, P.D. (2012). The role of glutamate                   signaling in the pathogenesis and treatment of obsessive–compulsive disorder.                  Pharmacology Biochemistry and Behavior, 100(4), 726-735. Retrieved from OVID             database.


Understanding PTSD

What is it?

Posttraumatic stress disorder (PTSD) is the condition a person may experience after personally living through or witnessing another endure a particularly traumatic event.  In the moment, you may have feared for your safety or another’s, or felt helpless without any sense of control over the situation.  And now, after this traumatic occurrence, you find yourself feeling a lot different than you had before.

What does it feel like?

Sufferers of PTSD report a number of similar changes and symptoms that surface after enduring trauma.  These changes can be extremely distressing, and sometimes are just as horrifying as the actual event.  Usually, symptoms begin to arise within 3 months of exposure; however, this is not always true as some cases of PTSD develop after 6 months (APA, 2013).

Some side effects as outlined by The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM–5; American Psychiatric Association, 2013) are listed below:

  • Re-experiencing the trauma
    • Intrusive “flashbacks” or dreams
    • Hyperarousal/hypervigilance
      • Increased tension/anxiety
      • Easily startled
      • Impulsivity
      • Increased heart rate, blood pressure, etc.
      • Avoidance of trauma triggers

Often, individuals will begin abusing substances like alcohol, marijuana, opiates and benzodiazepines in an effort to cope with the unwanted changes brought on by their trauma (Bremner et al., 1996; Jacobsen et al., 2001; Logrip, Zorrilla, & Koob, 2012).  You may also find that after being exposed to trauma, personal relationships with loved ones suffer or your performance in school or at work drops off (APA, 2013).  If any of the symptoms or similar situations noted above have been going on in your life recently, seek out your healthcare provider or someone that knows how to as soon as possible to get help.

Who does it happen to?

Unfortunately, PTSD can happen to anyone affected by trauma.  In the United States, nearly 1 in 10 people will develop PTSD symptoms so though it may feel like it, you are not alone (APA, 2013; Shalev, 2009).  The disorder is twice as likely to affect women as men and symptom development can begin at any age (APA, 2013; Ditlevsen & Elklit, 2010; Sherin & Nemeroff, 2011).  A considerable amount of research suggests that lesbian, bisexual and gender nonconforming individuals are at greater risk for trauma exposure leading to PTSD (Lehavot, Molina & Simoni, 2012; Roberts et al., 2012).  PTSD affects people from all different backgrounds, though combat veterans, survivors of sexual assault and victims of terrorism and genocide are among the groups with the highest rates of the disorder (APA, 2013; Karstoft et al., 2013; Kessler et al., 1995; Shalev, 2009).  Individuals exposed to repeated instances of abuse and neglect during childhood are also at an increased risk to develop PTSD (Petrakis et al., 2011).

Why do only some people develop PTSD?

Researchers have focused mainly on genetic and environmental factors that make a person susceptible to PTSD by looking at the brain and through conducting patient interviews.  Heritability of PTSD has been suggested in studies of families and twins (Lyons et al., 1993; Sack, Clarke & Seeley, 1995; Yahuda, Halligan & Bierer; 2001); however, pinning down the responsible genetic culprits has proven difficult.  Alterations in dopamine (Comings et al., 1991), serotonin (Lee et al., 2005) and GABA (Feusner et al., 2001) genes have been implicated as suspected players in genetic vulnerability to PTSD; however, the research is extremely limited and often contradictory.

Environmental risk factors like having experienced abuse, domestic violence or low socioeconomic status in childhood puts the individual in danger of developing PTSD during their lifetime (Enlow, Blood & Egeland, 2013).  Further, Heim & Nemeroff (1999) believe that early exposure to these kinds of stressors during critical developmental periods creates a brain neurochemically susceptible to stress, predisposing them to the toxic and lasting effects trauma can potentially have.  Though genetic research in PTSD is currently inadequate, it is probable that genetic and environmental factors interplay and moderate each other as in other psychiatric illnesses, which then leads to one’s susceptibility to develop PTSD after a traumatic event.

What is going on in my brain when these symptoms occur?

Though a number of circuits are undoubtedly involved, the literature shows compelling evidence for the role of the locus coeruleus-norepinephrine system in explaining a number of the symptoms observed in PTSD (Krystal & Neumeister, 2009; Valentino & Van Bockstaele, 2008).  Norepinephrine is a neurotransmitter released by the locus coeruleus in reaction to a threatening stimulus that prepares your body for the “fight-or-flight” response by getting your heart beating and your blood pumping.

Your locus coeruleus communicates with 3 brain structures heavily involved in handling impulses, regulating emotions, storing memories and responding to stress called the amygdala, hippocampus and prefrontal cortex (Ravindran & Stein, 2009).  In PTSD, the communication goes awry as there is a consistent overabundance of norepinephrine both in the brain and the body, resulting in a constant “fight-or-flight” state of hyperarousal mixed with intense fear (Geracioti et al., 2001; Kosten et al., 1987; Yehuda et al., 1992).  For the PTSD patient, this may feel like a recurring experience of their trauma.

The amygdala normally links threats with appropriate fear responses but with the locus coeruleus pumping out unregulated amounts of norepinephrine, the prefrontal cortex loses its usual inhibitory control over the amygdala (Ravindran & Stein, 2009).  Arnsten (1997) explains that when this control is lost, the amygdala makes frequent mistakes where incongruent associations are made between innocuous stimuli and primitive fear responses.  Mistakes are ultimately stored in the hippocampus, and recalling these memories can result in impulsivity, as well as intensely fearful thoughts and feelings that the PTSD sufferer may actively try to avoid (Ravindran & Stein, 2009; Sherin & Nemeroff, 2011).




American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

Arnsten, A. (1997) Review catecholamine regulation of the prefrontal cortex. Journal of Psychopharmacology, 11(2): 151-62.

Bremner, J., Southwick, S., Darnell, A. & Charney, D. (1996). Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse. American Journal of Psychiatry, 153(3): 369-75.

Comings, D., Comings, B., Muhleman, D., Dietz, G., Shahbahrami, B., Tast, D., Knell, E., Kocsis, P., Baumgarten, R. & Kovacs, B. (1991). The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. Journal of the American Medical Association, 266(13): 1793-800.

Ditlevsen, D. & Elklit, A. (2010). The combined effect of gender and age on post traumatic stress disorder: do men and women show differences in the lifespan distribution of the disorder. Annals of General Psychiatry, 9(32).

Enlow, M., Blood, E. & Egeland, B. (2013). Sociodemographic risk, developmental, competence, and PTSD symptoms in young children exposed to interpersonal trauma in early life. Journal of Traumatic Stress, 26(6): 686-694.

Feusner, J., Ritchie, T., Lawford, B., Young, R., Kann, B. & Noble, E. (2001). GABA(A) receptor beta 3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population. Psychiatric Research, 104(2): 109-17.

Geracioti, T., Baker, D., Ekhator, N., West, S., Hill, K., Bruce, A., Schmidt, D., Rounds-Kugler, B., Yehuda, R., Keck, P. & Kasckow, J. (2001). CSF norepinephrine concentrations in posttraumatic stress disorder. American Journal of Psychiatry, 158(8): 1227-30.

Heim, C. & Nemeroff, C. (1999). The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. Biological Psychiatry, 46(11): 1509-22.

Jacobsen, L., Southwick, S. & Kosten, T. (2001). Substance use disorders in patients with posttraumatic stress disorders: a review of the literature. American Journal of Psychiatry, 158(8): 1184-90.

Karstoft, K., Armour, C., Elklit, A. & Solomon, Z. (2013). Long-term trajectories of posttraumatic stress disorder in veterans: the role of social resources. Journal of Clinical Psychiatry, 74(12): 1163-8.

Kessler, R., Sonnega, A., Bromet, E., Hughes, M. & Nelson, C. (1995). Posttraumatic stress disorder in the national comorbidity survey. Archives of General Psychiatry, 52(12): 1048-60.

Kosten, T., Wahby, V., Giller, E. & Mason, J. (1987). Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder. Psychoneuroendocrinology, 12: 13-20.

Krystal, J. & Neumeister, A. (2009). Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Research, 1293: 13-23.

Lee, H., Lee, M., Kang, R., Kim, H., Kim, S., Kee, B., Kim, Y., Kim, YK., Kim, J., Yeon, B., Oh, K., Oh, B., Yoon, J., Lee, C., Jung, H., Chee, I. & Paik, I. (2005). Influence of the serotonin transporter promoter gene polymorphism on susceptibility to posttraumatic stress disorder. Journal of Depression & Anxiety, 21(3): 135-9.

Lehavot, K., Molina, Y. & Simoni, J. (2012). Childhood trauma, adult sexual assault, and adult gender expression among lesbian and bisexual women. Sex Roles, 67(5-6): 272-284.

Logrip, M., Zorrilla, E. & Koob, G. (2012). Stress modulation of drug self-administration: implications for addiction comorbidity with post-traumatic stress disorder. Neuropharmacology, 65: 552-564.

Lyons, M., Goldberg, J., Eisen, S., True, W., Tsuang, M. & Meyer, J. (1993).  Do genes influence exposure to trauma: a twin study of combat. American Journal of Medical Genetics, 48(22).

Petrakis, I., Rosenheck, R. & Desai, R. (2011). Substance use comorbidity among veterans with posttraumatic stress disorder and other psychiatric illness. The American Journal on Addictions, 20(3): 185-189.

Ravindran, L. & Stein, M. (2009). Pharmacotherapy of PTSD: premises, principles, and priorities. Brain Research, 1293: 24-39.

Roberts, A., Rosario, M., Corliss, H., Koenen, K. & Austin, S. (2012). Elevated risk of posttraumatic stress in sexual minority youths: mediation by childhood abuse and gender nonconformity. American Journal of Public Health, 102(8): 1587-93.

Sack, W., Clarke, G. & Seeley, J. (1995) Posttraumatic stress disorder across two generations of Cambodian refugees. Journal of the American Academy of Child and Adolescent Psychiatry, 34: 1160-1166.

Shalev, A. (2009). Posttraumatic stress disorders (PTSD) and stress related disorders. Psychiatric Clinics of North America, 32(3): 687-704.

Sherin, J. & Nemeroff, C. (2011). Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues in Clinical Neuroscience, 13(3): 263-278.

Valentino, R. & Van Bockstaele, E. (2009). Convergent regulation of locus coeruleus activity as an adaptive response to stress. European Journal of Pharmacology, 583(2-3): 194-203.

Yahuda, R., Halligan, S. & Bierer, L. (2002). Cortisol levels in adult offspring of Holocaust survivors: relation to PTSD symptom severity in the parent and child. Psychoneuroendocrinology, 27(1-2): 171-80.

Yehuda, R., Southwick, S., Giller, E., Ma, X. & Mason, J. (1992). Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. The Journal of Nervous and Mental Disease, 180: 321–325.

Self-harm, Pain, and the Brain

In discussing personality disorders, I’d like to build on earlier post by a classmate, Jaime Biava. He discussed the idea that individuals diagnosed with Borderline Personality Disorder (BPD) may show changes in the HPA axis area of the brain. A person diagnosed with BPD may manifest outward behaviors such as cutting, suicidal gestures, bulimia, and substance abuse. Commonly, BPD is found in people who suffered maltreatment and neglect in childhood (Cohen, et al, 2006), or long-term exposure to stress (Leichsenring, et al, 2011). Yet, BPD is a relatively new diagnosis in psychiatry; in the past, persons fitting the criteria were often diagnosed with ‘pseudo-neurotic schizophrenia’, or ‘hysteria’, prior to the disorder being studied and subsequently classified by Otto Kernberg in the 1960s (Friedel, 2004; Kernberg, 1967). Indeed, there are even psychiatric professionals today who do not believe that Borderline Personality Disorder exists. Thus, more recent findings of actual changes in the brain that are unique to persons with BPD not only add weight to the validity of the diagnosis, but also may assist professionals and the public to become more accepting of  the true suffering that people with Borderline Personality Disorder  endure.

To review, Borderline Personality Disorder is found in approximately 1-5% of all persons (Leichsenring, et al, 2011). Currently the most effective therapies- mentalization therapy or dialectical behavior therapy– assist with repair of coping mechanisms disrupted by trauma. When a child’s brain is repeatedly exposed to stress or trauma, their psychological and emotional development may be forestalled or maladapted (O’Neill & Frodl, 2012). For many years, it seemed as if most of the research about BPD focused on these psycho-social factors. Along the same lines, the thinking on drug and alcohol addiction used to be that individuals were psychologically immature or weak, and this was why they used substances (Khantzian, 1985). The germ of truth in such thinking is that a dearth of coping skills coupled with unmet emotional needs does seem to strengthen the grip of addiction, or addictive behavior (Farber, 1997). Repetitive self-harming behavior (such as cutting, bulimia or substance abuse) in persons with BPD may be conceptualized as addictive because the goal of the behavior not only serves powerful emotional needs, but also may be produced by changes in the brain.

Over the last fifteen years a number of studies have shown that there is a reduction in the volume of both the hippocampus and the amygdala in persons with Borderline Personality Disorder, although these changes appear to be most common in persons who are diagnosed with both Post Traumatic Stress Disorder (PTSD) and BPD (Leichsenring, et al, 2011). Moreover, studies using brain imaging have shown that the amygdala and frontal area of the brain (called the medial prefrontal cortex, or MPFC) were excessively stimulated in persons with BPD (Koenigsberg, et al, 2009; Silbersweig, et al, 2007). Occupational therapists using neuro-imaging have found that the MPFC, which is also used to process pain sensations, is impaired in children with autism, and have theorized that persons with BPD who self-injure are perhaps using a form of self-stimulation (as children with autism do) in a misguided attempt to regulate their emotions (Brown, Shankar, & Smith, 2009). Another possibility is that part of the difficulty people with BPD have with self-regulation has to do with a sensory processing disorder (Brown, et al, 2009).

Finding structural and chemical differences in the brains of persons with BPD helps to refute the notion that self-harming behavior is willful or something that can be controlled by ‘mind over matter’.  There is a fair amount of research that speaks to the idea of self-harm in people suffering from Borderline Personality Disorder as being a method to self-medicate (Farber, 1988; Brown, et al, 2009).  The original hypothesis of self-medication for emotional pain came from Khantzian (1985), who in studying addiction concluded that persons abusing drugs seek to medicate painful emotional states, and that the inability to regulate those moods is often rooted in a stressful or abusive childhood history. Thus, when a person burns or cuts their arm, that sensation is preferable to enduring the emotional pain they are experiencing. The concept of palliating emotional pain by cutting can be difficult to accept when viewing someone whose arm is so scarred that it

appearspic as if an ace bandage has been wrapped around it.

Those who participate in repetitive self-harming behavior have offered another explanation: that they attempt to numb emotional pain by cutting/burning themselves (Farber,1985), almost as a means of potent distraction. Yet the relationship between pain and the BPD diagnosis may be more complex. A recent study asked test subjects to immerse their hand in frigid water; the longer subjects were able to withstand the frozen water determined the level of pain tolerance. These results revealed that individuals with BPD had a much higher pain tolerance than people with no mental health condition, or even than persons diagnosed with major depression (Pavony, & Lenzenweger, 2013). It remains to be seen how having a high pain tolerance would play a part in compelling repetitive self-harming behavior. At the present time, we only know that regardless of why self-harming behavior happens, therapy does assist individuals in gaining insight and learning less destructive coping methods; hardly a panacea, but offering hope to those who struggle with Borderline Personality Disorder.


Brown, S., Shankar, R., & Smith, K. (2009). Borderline personality disorder and sensory processing impairment. Progress in Neurology and Psychiatry, 13, 4, 10-16.

Cohen, R. A., Grieve, S., Hoth, K. F., Paul, R. H., Sweet, L., Tate, D., Gunstad, J., … Williams, L. M. (2006). Early Life Stress and Morphometry of the Adult Anterior Cingulate Cortex and Caudate Nuclei. Biological Psychiatry, 59, 10, 975-982.

Farber, S. K. (1998). Self-Medication, Traumatic Reenactment, and Somatic Expression in Bulimic and Self-Mutilating Behavior. Clinical Social Work Journal, 25, 1, 87-106.

Friedel, R. O. (2004). Borderline personality disorder demystified: An essential guide for understanding and living with BPD. New York: Marlowe & Co.

Kernberg OF (1967): Borderline personality organization. J Am Psychoanal Assoc 15:641–685.

Khantzian, E. J. (1985). The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. The American Journal of Psychiatry, 142, 11, 1259-64.

Koenigsberg, H. W., Fan, J., Ochsner, K. N., Liu, X., Guise, K. G., Pizzarello, S., Dorantes, C., … Siever, L. J. (2009). Neural correlates of the use of psychological distancing to regulate responses to negative social cues: a study of patients with borderline personality disorder. Biological Psychiatry, 66, 9, 854-63.

Leichsenring, F., Leibing, E., Kruse, J., New, A. S., & Leweke, F. ( 2011). Borderline personality disorder. The Lancet, 377, 9759, 74-84.

O’Neill, A., & Frodl, T. (2012). Brain structure and function in borderline personality disorder. Brain Structure & Function, 217, 4, 767-82.

Pavony, M. T., & Lenzenweger, M. F. (2013). Somatosensory Processing and Borderline Personality Disorder: Pain Perception and a Signal Detection Analysis of Proprioception and Exteroceptive Sensitivity. Personality Disorders: Theory, Research, and Treatment.

Silbersweig, D., Clarkin, J. F., Goldstein, M., Kernberg, O. F., Tuescher, O., Levy, K. N., Brendel, G., … Stern, E. (January 01, 2007). Failure of frontolimbic inhibitory function in the context of negative emotion in borderline personality disorder. The American Journal of Psychiatry, 164, 12, 1832-41.


Traumatic Memory in Schizophrenia

Over the past few decades, there has been increasing interest in the relationship between traumatizing events and the manner in which traumatized individuals attribute meaning to those events –a process often called ‘appraisal’. Other researches have broadened this focus to examine the interrelationship of trauma, appraisal and psychosis. Such studies frequently center around the question of causation. Does trauma cause psychosis? Can psychosis cause trauma? How does appraisal mediate either process? Of all individuals with schizophrenia, an estimated 29% suffer from comorbid PTSD. (Buckley et al, 2009). Given these numbers, studies of psychosis, appraisal, and trauma have directed particular attention to this population.

Cognitive models of psychosis have proposed that appraisal plays a critical role in determining whether an unusual event of the mind will be experienced only as such, or will be transformed into a psychosis that is debilitating and requires care. (Morrison, 2001). Others go so far as to claim that the development of psychosis will only occur as a result of certain forms of appraisal: specifically, the appraisal must attribute to the occurrence of an anomalous perception some external cause, and one which carries with it a personal significance. (Garety et al, 2001). The same study demonstrated that individuals who appraised similar events within a psychological and/or normalizing framework were less likely to develop psychosis. Further evidence suggests that personalizing appraisals play a significant role in the development of persecutory delusions, which in turn contribute to the development of psychosis. (Kindermann & Bentall, 1997). Distinctions between ‘anomalous events of perception’ and diagnosable psychosis (e.g. auditory hallucinations) can begin to seem arbitrary. Nevertheless, the prevalent association between debilitating psychosis and certain forms of appraisal deserves attention.

If appraisal plays a role in the development of psychosis, how does trauma fit in?
There is strong evidence to support the idea that trauma may induce psychosis. One study found that victims of childhood sexual abuse, interpersonal violence and physical violence together accounted for roughly 70% of ‘voice-hearers’: that is, among those who experienced chronic auditory hallucinations (AH), their psychosis was preceded by an identified traumatic event. (Romme & Escher, 1989). Correlation does not imply causation, but the sequence of events is suggestive. A second study found the same correlation (onset of AH preceded by some trauma or its reenactment) among patients with schizophrenia, patients with dissociative identity disorder, and individuals who were not in treatment but regularly experienced AH. (Honig et al, 1998). So, strong support exists for the idea that trauma might induce psychosis; is the reverse possible?

Traditional conceptions of trauma have focused on the effect of some external event on the individual. More recent research has sought to expand our view of trauma by examining whether internal events like psychosis can themselves be traumatizing. A review of the relevant literature in 2003 reported that multiple, independent studies using different methodologies found high rates of PTSD in response to psychosis. (Morrison et al, 2003). Despite the review’s criticism of certain methodologies the authors concluded that it is likely individuals do develop what has come to be termed ‘post-psychotic PTSD.’ (Morrison et al).

A last and unlikely source of trauma for patients with schizophrenia is found in the treatment they receive. Acute inpatient care can involve sedation, restraint, seclusion, involuntary admission, all of which can be experienced (and construed) as violent. In a relatively small sample of 34 psychiatric patients treated in an inpatient setting, 44% were found to have developed PTSD as a result of their admission. (Horowitz et al, 1979). Of special note, the same Morrison review found that the implementation of sedation, restraint, and seclusion served to “heighten the person’s sense of fear, victimization and helplessness over their experiences.” (Morrison et al, 334). Again, the mediation of appraisal seems to be at play in the development of individual, traumatic experiences.

Trauma and psychosis each appear capable of causing the other; and appraisal seems to be implicated in the process. How is this explained on a neurobiological level? Although both positive (hallucinations, delusions) and negative symptoms (apathy, reduced motivation) in schizophrenia are impairing, the associated cognitive deficits (attention, memory, executive function) are sometimes regarded as the most impairing of all. (Higgins & George, 2013). And some of the cognitive deficits that characterize schizophrenia are also present in PTSD. One study out of Australia set out to determine whether the dysfunction of working memory present in each disorder was driven by the same mechanisms. (Galletly et al, 2008). They were motivated by the possibility that pathologies of apparently different origin might share some underlying neurobiological basis –more exactly, that the patterns of neuroelectrical activity associated with dysfunctional working memory might be identical in the individual with schizophrenia and the individual with PTSD. Using event-related brain electrical field potentials (ERPs) they were able to compare the electrical activity of three groups (schizophrenia, PTSD, control) by the millisecond during the performance of the same tasks, under the same conditions. They found that the abnormalities giving rise to working memory dysfunction were ultimately distinct. One of the tasks –called ‘controlled stimulus processing’ – tested activation of a specific, visually evoked ERP named Visual N1. Activation of Visual N1 has been shown to reflect control and direction of attention as well as a kind of automatic processing of the physical make-up of a given stimulus. (Naatanen & Picton, 1989). In the Galletly study there were marked differences in activation of Visual N1 across the two pathologies. In individuals with PTSD, N1 amplitude was normal. Individuals with schizophrenia, however, displayed abnormally reduced early stimulus processing suggesting “difficulty forming an internal physical representation of the stimulus.” (Galletly, 202). While this is admittedly a very small distinction, it suggests real differences in the neurobiology of pathologies generating clinically indistinguishable deficits.

It is interesting to speculate how such a small difference might manifest itself for the patient with schizophrenia in his or her appraisal of the kinds of ‘anomalous events of perception’ mentioned before. Garety et al observed that those most likely to transform such an event into a clinically significant psychosis often attributed the experience to some external cause. No doubt, a persistent “difficulty forming an internal physical representation” of the phenomena around you must lead to the sense of a profound loss of control.


Buckley, P.F., Miller, B.J., Lehrer, D.S., and Castle, D.J. (2009). Psychiatric Comorbidities and Schizophrenia. Schizophrenia Bulletin 35: 383-402.

Galletly, C.A., McFarlane, A.D., Clark, R., (2008). Differentiating cortical patterns of cognitive dysfunction in schizophrenia and posttraumatic stress disorder. Psychiatry Research 159: 196-206.

Garety PA, Kuipers E, Fowler D, Freeman D, Bebbington PE (2001) A cognitive model of the positive symptoms of psychosis. Psychological Medicine. 31:189–195.

Higgins, E.S., George, M.S., (2013). The neuroscience of clinical psychiatry. Lippincott, Williams, and Wilkins: Philadelphia.

Honig, A., Romme, M. A., Ensink, B. J., Escher, S. D., Pennings, M. H., & deVries, M. W. (1998). Auditory hallucinations: A comparison between patients and nonpatients. Journal of Nervous and Mental Disease 186: 646–651.

Horowitz, M., Wilner, N., & Alvarez, W. (1979). Impact of events scale: A measure of subjective stress. Psychosomatic Medicine 41: 209–218.

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Morrison, A.P., (2001) The interpretation of intrusions in psychosis: An integrative cognitive approach to hallucinations and delusions. Behavioral Cognitive Psychotherapy. 29: 257–276

Morrison, A.P., Frame, L., Larkin, W., (2003). Relationships between trauma and psychosis: A review and integration. British Journal of Clinical Psychology 42: 331-353.

Naatanen, R., Picton, T., 1987. The N1 wave of the human electric and magnetic response to sound, a review and an analysis of the component structure. Psychophysiology 24: 375–425.

Romme, M. A. J., & Escher, A. D. M. A. C. (1989). Hearing voices. Schizophrenia Bulletin 15: 209–216.