Sleep and ADHD

Anyone who has ever pulled an all-nighter knows that sleep is essential to brain functioning. Without adequate sleep, our cognitive performance deteriorates drastically, with difficulty concentrating and paying attention, and a diminished working memory (Higgins and George, 2007). I was struck by how these effects resemble a common disorder I see in my pediatric psychiatric clinical placement: Attention Deficit Disorder with Hyperactivity, or ADHD. To be diagnosed with ADHD, a patient must present with “a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development” (APA, 2013, p. 59). Symptoms include difficulty holding attention, forgetfulness, distractibility, trouble organizing, and trouble following through on tasks. Sound familiar? These are all consequences of insufficient sleep. These similarities, combined with the fact that children require more sleep than adults (Higgins and George, 2007), led me to turn to the literature to see what the experts say about this topic.

Corkum, Tannock, and Moldofsky (1998) found that an estimated 25% to 50% of children and adolescents with ADHD present with sleep problems, particularly in initiating and maintaining sleep. Owens (2005) reports that, “Estimates of parent-reported sleep problems in schoolage populations range from 11% of 4 to 12 year olds to 37% of elementary school-age children, making sleep issues also one of the most common complaints in pediatric practice” (p. 312). In fact, sleep disturbances used to be a key diagnostic feature of ADHD, though it has been removed in newer versions of the DSM (APA, 2013).

So which comes first? Does poor sleep lead to ADHD, or is there an element of the pathophysiology of ADHD that leads to poor sleep? Some hypothesize that sleep disturbance in children with ADHD might stem from the hyperactivity component, or that kids can’t settle down at night because of their excess energy (O’Brien et al., 2003). But other researchers say that there may be something else going on involving circadian rhythms. Indeed, sleep deficits can manifest as hyperactivity and impulsivity in children (as opposed to lethargy and sluggishness in adults), and treating sleep issues can often resolve symptoms of ADHD in children (Shur-Fen Gau, 2006).

To help parse this out, let’s first look at the areas of the brain involved in attention and hyperactivity, and how sleep impacts the functioning of these regions. Higgins and George (2007) explain that the three main areas of the brain involved in ADHD are the prefrontal cortex, the striatum, and the cerebellum. Studies show through brain imaging that patients with ADHD have decreased prefrontal gray matter, along with a smaller cerebellum and posterior parietal cortex (Durston et al., 2005; Monuteaux et al., 2008; Shaw et al., 2007). There is also evidence suggesting that there may be a connection between ADHD and specific regions of the thalamus that are specifically related to working memory and behavioral inhibition (Owens, 2005). To understand what this means in terms of behavior, it’s important to know what these areas of the brain control. The prefrontal cortex is responsible for helping us to organize our thoughts and emotions, and to make complex decisions. Lesions in this area can result in poor planning and impulsivity – a key component of ADHD. The striatum is part of the basal ganglia, a region of the brain involved in coordinating movement. The cerebellum is also involved in controlling movement, and together with the striatum is implicated in some of the hyperactivity symptoms that patients with ADHD exhibit.

So what is the overlap between the psychopathology of ADHD and the symptoms common to insufficient sleep? We all know that sleep is essential to proper functioning, but there is much dispute as to exactly why we need to sleep. Higgins and George (2007) outline the most prominent theories for us, including theories that say it’s important for our development, which is supported by the fact that infants need much more sleep than older adults. Other theories say that we need sleep because this is when our brains our able to grow new neurons and consolidate memories. Others say that it’s simple conservation of energy, and other, newer studies suggest that it’s a time for us to flush out toxins (http://www.washingtonpost.com/national/health-science/brains-flush-toxic-waste-in-sleep-including-alzheimers-linked-protein-study-of-mice-finds/2013/10/19/9af49e40-377a-11e3-8a0e-4e2cf80831fc_story.html).

But how does sleep affect those areas of the brain implicated in ADHD? The evidence clearly shows that a lack of sleep impacts functions attributed to the frontal cortex, including attention and working memory (Fallone, Owens & Dean, 2002). The thalamus, or the relay station of the brain that I mentioned above, also plays a key role in regulating non-REM sleep (Owens, 2005). There is also an overlap in neurotransmitter disruptions between ADHD and sleep disturbances, specifically in the noradrenergic and dopaminergic systems (Owens, 2005). Others studies suggest a broader disturbance involving circadian rhythms, specifically that an alteration in the CLOCK gene, or the gene that helps to regulate our sleep-wake cycle, has been found in patients with ADHD (Kissling et al., 2008). One study looked at the sleep cycles of 34 children with ADHD and 34 controls, and found that all of the children with ADHD showed a decrease in delta sleep, or that deep sleep we need to feel fully rested. Taken as a whole, this evidence has led to one possible theory that suggests that ADHD might be related to hypoarousal instead of hyperarousal, which may explain why treatment with stimulants is first line (Owens, 2005).

To answer my initial question that asked which comes first, sleep disturbance or ADHD, Owens (2005) has the most complete answer:

…the relationship between sleep problems and ADHD is essentially bidirectional and may be manifested in several ways: sleep problems may mimic ADHD symptomatology, may exacerbate underlying ADHD symptoms, may be themselves associated with or exacerbated by ADHD, and psychotropic medications used to treat ADHD may result in sleep problems. (p. 312)

There is no one answer, and much more to be done in this area of study, but the current research suggests that an important overlap exists between sleep and ADHD symptomatology. As clinicians, we need to be careful investigators into our patients’ habits surrounding sleep, and make sure that we are looking at and treating the whole person and not simply the symptoms that are present in our offices.

References

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

Durston, S., Fossella, J.A., Casey, B.J., Hulshoff Pol, H.E., Galvan, A., Schnack, H.G.,
Steenhuis, M.P., Minderaa, R.B., Buitelaar, J.K., Kahn, R.S., van Engeland, H.
(2005). Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray
matter volumes in a sample of subjects with attention deficit hyperactivity disorder,
their unaffected siblings, and controls. Molecular Psychiatry, 10, 678–
685.

Corkum, P., Tannock, R., Moldofsky, H. (1998). Sleep disturbances in children
with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and
Adolescent Psychiatry.
37, 637–646.

Fallone, G., Owens, J., Deane, J. (2002). Sleepiness in children and adolescents:
clinical implications. Sleep Medicine Reviews, 6, 287–306.

Higgins, E.S., & George, M.S. (2007). The neuroscience of clinical psychiatry: The pathophysiology of behavior and mental illness (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

Kissling, C., Retz, W., Wiemann, S., Coogan, A.N., Clement, R.M., Hunnerkopf, R.,
Conner, A.C., Freitag, C.M., Rösler, M., Thome, J. (2008). A polymorphism at the
3_-untranslated region of the CLOCK gene is associated with adult attention deficit
hyperactivity disorder. American Journal of Medical Genetics Part B:
Neuropsychiatric Genetics, 147,
333–338.

Monuteaux, M.C., Seidman, L.J., Faraone, S.V., Makris, N., Spencer, T., Valera, E.,
Brown, A., Bush, G., Doyle, A.E., Hughes, S., Helliesen, M., Mick, E., Biederman,
J. (2008). A preliminary study of dopamine D4 receptor genotype and structural
brain alterations in adults with ADHD. American Journal of Medical Genetics
Part B: Neuropsychiatric Genetics, 147B
, 1436–1441.

O’Brien, L.M., Ivanenko, A., Crabtree, V.M., Holbrook, C.R., Bruner, J.L., Klaus, C.J.,
Gozal, D. (2003). Sleep disturbances in children with attention deficit hyperactivity
disorder. Pediatric Research, 54, 237–243.

Owens, J.A. (2005). The ADHD and sleep conundrum: A review. Developmental and Behavioral Pediatrics, 26(4), 312-322.

Shaw, P., Gornick, M., Lerch, J., Addington, A., Seal, J., Greenstein, D., Sharp, W.,
Evans, A., Giedd, J.N., Castellanos, F.X., Rapoport, J.L. (2007). Polymorphisms of
the dopamine D4 receptor, clinical outcome, and cortical structure in attention deficit/
hyperactivity disorder. Archives of General Psychiatry, 64, 921–931.

Shur-Fen Gau, S. (2006). Prevalence of sleep problems and their association with inattention/hyperactivity among children aged 6-15 in Taiwan. Journal of Sleep Research, 15(4), 403-14.

Coping with Insomnia

Fundamental to our functioning as human beings, the importance of sleep cannot be overstated. In fact, we spend about a third of our lives sleeping (Higgins & George, 2007). As student psychiatric-mental health nurse practitioners, we have become accustomed to asking our patients about their sleep, knowing that many psychiatric conditions impact both the quality and quantity of patients’ sleep. Insomnia is considered both a symptom and a comorbid disorder that is associated with many psychiatric diagnoses (Haynes et al., 2011). To this end, is estimated that 35-40 percent of patients with insomnia have one or more comorbid psychiatric diagnoses. Among the most prevalent of these disorders are affective disorders, anxiety disorders, and substance abuse (Yang et al., 2006). In this post, I would like to discuss what factors contribute to insomnia, as well as a few of the medication-alternative therapies patients suffering from insomnia might benefit from.

Sleep is something that a lot of us take for granted, but it has been shown that insomnia not only precedes the development of depression, but also contributes to suicidality and excessive use of alcohol (Haynes et al., 2011). So serious is this issue, that insomnia is a stronger predictor than having a specific suicide plan in predicting near-lethal suicide attempts (McCall et al., 2010). As chronic insomnia affects approximately 10-15 percent of the adult population (Wagley et al., 2013), we as future clinicians must recognize the potential deleterious effects that accompany insomnia. Furthermore, we need to be able to offer our patients tools to help them improve their sleep.

Yang et al. (2006) identified three systems that impact sleep: the homeostatic system, the circadian system, and the arousal system.  In other words, issues with sleep arise from “an inherently weak homeostatic sleep drive, atypical circadian regulation, or constitutionally based hyperarousal” (p. 897). However, even when all three systems are working ideally, certain behaviors can still lead to poor sleep outcomes. According to Yang et al., insomnia also seems to be a “vicious cycle,” where the patient’s thoughts about sleep may perpetuate their insomnia. When a patient believes that his or her sleep will be always be of poor quality, and that all of his or her issues are related to not getting enough sleep, these thoughts frame sleep in a negative way and make it very difficult to break the cycle of insomnia. As a result, “sleeplessness further reinforces their perceived validity” (Yang et al., 2006, p. 898).

While using hypnotics on a short-term basis can be extremely helpful for many patients, relying on these medications on a long-term basis is far from ideal, especially given the fact that long-term use of sleep medications might actually reinforce beliefs patients have about the permanent nature of their inability to sleep if they are not able to rely on medications (Wagley et al., 2013). Unfortunately, however, chronic use of hypnotics is associated with rebound insomnia upon withdrawal, tolerance, and dependency (Yang et al., 2006).

So how can we help our patients achieve better sleep? Certainly, education is a good place to start. Many people are not aware that their daily habits can negatively impact their sleep. Certain behaviors, like napping during the day, spending too much time in bed, and consuming alcohol in the evening, can make sleep difficult. Yang et al. (2006) explain that “improvements in sleep hygiene are not in themselves sufficient to resolve insomnia, but rather set the stage for other, more targeted treatments to complete the task” (p. 911).

One such treatment is sleep restriction therapy, which creates a mild-to-moderate “sleep debt” in order to increase the drive to sleep. Initially, the patient keeps a sleep log in order to establish average nightly total sleep. Then, once a baseline is established, bedtime and rising times are discussed with the patient, and sleep is limited (to no less than 5 hours). The patient continues to keep a sleep log and the bedtime is subsequently adjusted according to his or her progress. The goal of this treatment is “one of prodding sleepiness into making an appearance at the right time and place” (Yang et al., 2006, p. 908).

Lastly, cognitive behavioral therapy for insomnia (CBT-I) has been shown to be an effective treatment for insomnia. This therapy combines “stimulus control, sleep restriction, sleep hygiene, and cognitive restructuring, with an added relaxation component sometimes used” (Wagley et al., 2013, p. 1044). In a study done with 30 psychiatric outpatients with poor sleep quality and residual depressive symptoms, Wagley et al. randomly assigned the participants to one group involving two sessions of CBT-I and the other group served as a control group. The results of the study provided evidence that this abbreviated cognitive behavioral treatment had positive effects on both residual insomnia and depression in long-term psychiatric outpatients.

Improving sleep hygiene, sleep restriction therapy, and CBT-I are just a few of the many treatments that should be on our radar screens as a means of promoting better sleep in patients with insomnia. With an issue as important as sleep, we owe it to our patients to find alternative ways to help them cope with with debilitating issue.

 

References:

Haynes, S.P., Kersh, B., Bootzin, R.R. (2011). Examination of insomnia and insomnia treatment in psychiatric inpatients. International Journal of Mental Health Nursing, 20, 130-136. doi: 10.1111/j.1447-0349.2010.00711.x.

Higgins, E.S., & George, M.S. (2007). The neuroscience of clinical psychiatry: The pathophysiology of behavior and mental illness (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

McCall, W.V., Blocker, J.N., D’Agostino, R., Kimball, J., Boggs, N., Lasater, B., Rosenquist, P.B. (2010). Insomnia severity is an indicator of suicidal ideation during a depression clinical trial. Sleep Medicine, 11, 822-827. doi:10.1016/j.sleep.2010.04.004.

Wagley, J.N., Rybarczyk, B., Nay, W.T., Danish, S., Lund, H.G. (2013). Effectiveness of abbreviated CBT for insomnia in psychiatric outpatients: Sleep and depression outcomes. Journal of Clinical Psychology, 69, 1043-1055. doi: 10.1002/jclp.21927

Yang, C.M., Spielman, A.J., Glovinsky, P. (2006). Nonpharmacologic strategies in the management of insomnia. Psychiatric Clinics of North America, 29, 895-919. doi: 10.1016/j.psc.2006.09.005.

Anxiety Disorders, The Forty-Four Billion Dollar Question

It is estimated that in terms of payment for psychiatric and medical treatment, workplace loss of productivity, and mortality related costs anxiety disorders have an annual price tag of about forty-four billion dollars in the United States, (Greenburg et al., 1999).  According to the National Institute of Mental Health (2013) in any given year approximately eighteen percent of the country’s adult population will suffer from an anxiety disorder.  Due to their prevalence as well as their cost in physical and emotional terms it is essential for healthcare providers to have a strong grasp on the nature of anxiety disorders.   Within this understanding the question of the causes underlying pathological anxiety is central to working towards better treatments.

Investigation for shared antecedents of anxiety disorders has mostly focused on environmental factors such as negative life events or neighborhood social context and biological determinants including genetic factors and brain abnormalities, (El-Sayed et al., 2012).  As in most mental illnesses, anxiety disorders are believed to be the result of the complex interaction between the two, with estimates of heritability across anxiety disorders ranging from thirty to sixty eight percent, (Domshcke et al., 2013).

Robust scientific evidence points to the amygdala and its links with the hippocampus, the hypothalamus, and prefrontal cortex as the core of the fear response, (Nandhra, Murphy, & Sule, 2013).  For most individuals the communication between these areas in reaction to a dangerous stimulus produces an adaptive “fight or flight” response.  In the individual with an anxiety disorder through some unknown mechanism this process is malfunctions and can cause great distress as well as impaired functioning.  One popular hypothesis, based largely on the fact that medications like benzodiazepines that potentiate the effect of the inhibitory neurotransmitter GABA are so effective at treating anxiety, is that excessive excitatory neurotransmission or impaired inhibitory neurotransmission is to blame, (Gross and Hen, 2004).  For example, researchers have found that individuals with anxiety disorders generally have lower GABA levels in the occipital cortex, the anterior cingulate and the basal ganglia compared to healthy controls, (Domshcke et al., 2013).

Epigenetics, the study of the heritable changes in gene expression and function that do not change the structure of the DNA sequence, has recently provided some clues for how these our environment may influence neurotransmission in anxiety, (Wu Ct, 2001; Domshcke et al., 2013).  El-Sayed and his peers describe epigenetic alterations as, “demonstrated to mediate the interplay between environmental stimuli and physiologic and pathophysiologic change throughout the life course,” (2012, p. 2).

In a study published last month by Domshcke and colleges, Epigenetic signature of panic disorder: A role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation, (2013), the expression of a certain gene (GAD 1) previously implicated in anxiety disorders and related to GABA synthesis in individuals with panic disorder was explored.  DNA from blood samples taken from healthy individuals and individuals with panic disorder were compared.  In very basic terms, they found that the process involved with of gene expression, methylation, varied greatly between sick and healthy individuals.  Panic patients showed significantly lower GAD 1 methylation than the control group.  Additionally the researchers collected data about life events experienced by participants in the six months prior to disease onset or twelve months prior to the study for the control group and subjectively rated as positive, negative, or neutral.  Across all participants negative life events correlated with decreased methylation of the GAD 1 gene.  It should also be noted that participants in the panic disorder group had a significantly higher percentage of negative life events and significantly lower percentage of positive life events than their healthy peers.  The researchers hypothesize that because the hypomethylation of GAD 1 would lead to an increase in GABA levels it is not a causal mechanism in panic disorder but rather a type of compensatory response to stressful life events and panic level anxiety.

While the described study and its results are considered to be preliminary they highlight the exciting prospects for future research into anxiety disorders and the role one’s experience of their environment can play in their own genetics. However, it is important to consider that this gene, its expression, and all the varied processes that influence it are just one minuet piece of the puzzle of a single hypothesis regarding the pathogenesis of an individual anxiety disorder.  It is clear that we have a long road ahead of us in building a concrete understanding of what causes anxiety disorders.  They are complex and multifaceted diseases.  Fortunately at present healthcare providers have many tools at their disposal the treat them including a variety of effective pharmacological and non-pharmacological therapies (To learn about alternative treatments for anxiety please read Jessika’s excellent recent post).  The societal cost and prevalence of anxiety disorders may not decline sharply anytime in the near future but with every new insight gained the stronger our ability to prevent and treat them will become.

References

Domschke, K., Tidow, N., Schrempf, M., Schwarte, K., Klauke, B., Reif, A., et al. (2013). Epigenetic signature of panic disorder: A role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation? Progress in Neuro-Psychopharmacology and Biological Psychiatry, 46(0), 189-196. doi:http://dx.doi.org/10.1016/j.pnpbp.2013.07.014

El-Sayed, A.M., Haloossim, M.R., Galea, S., & Koenen, K.C. (2012). Epigenetic modifications associated with suicide and common mood and anxiety disorders: a systematic review of the literature. Biology of Mood & Anxiety Disorders, 2 (10). doi:10.1186/2045-5380-2-10

Greenberg, P.E., Sisitsky, T., Kessler, R.C., Finkelstein, S.N., Berndt, E.R., Davidson,J.R., Ballenger, J.C., Fyer, A.J. (1999). The economic burden of anxiety disorders in the 1990s. Journal of Clinical Psychiatry. Jul;60(7):427-35.

Gross, C. & Hen, R. (2004). The developmental origins of anxiety. Nature Reviews Neuroscience 5, 545-552 (July 2004) | doi:10.1038/nrn1429

Nandhra, H. S., Murphy, C. L., & Sule, A. (2013). Novel pharmacological agents targeting memory and cognition in the treatment of anxiety disorders. Human Psychopharmacology: Clinical and Experimental, 28(6), 538-543. doi:10.1002/hup.2348

Wu Ct, M. (2001). Genes, genetics, and epigenetics: a correspondence. Science. Aug 10;293(5532):1103-5.

 

Alternative Anxiety Treatments

A Google search for “alternative anxiety treatment” reveals a lengthy list of herbal recommendations (Kava Kava, St. John’s Wort, Valerian Root, Chamomile, Lemon Balm etc.) among a myriad of other biologically-based and behaviorally-based therapies. As it turns out, nearly nine out of ten patients seeking psychiatric care for anxiety attacks, report using some form of complimentary and alternative medicine (CAM) (Kessler et al., 2001). This has obvious implications for us as future practitioners. We must inquire about patients’ self-treatment efforts in considering our own therapies, with special attention as to how one treatment might affect the other. The following discussion will focus on two of the most commonly used and best-studied herbal preparations: Kava Kava (Piper methysticum) and St. John’s Wort (Hypericum perforatum).

 

Kava Kava was traditionally used throughout the South Pacific to treat maladies such as gonorrhea and fatigue, in addition to relaxation and sleep induction (Pittler and Ernst, 2000). More recently, Kava has been shown to have efficacy similar to that of buspirone and opipramol, with the added benefit of limited daytime sedation and cognitive impairment over chronic benzodiazepine use; and less withdrawal or rebound problems (Sarris and Kavanagh, 2009). But before you run out to buy stock in Kava, read on. According to a 2008 editorial review by Van der Watt, Laugharne and Jance, due to hepatotoxicity association, Kava is not clinically indicated. It is worth noting that though Kava was pulled from markets in the UK and Europe as of 2002 (Sarris, Panossian, Schweitzer, Stough and Scholey, 2011), it is still readily available in the United States and was one of 1998’s best selling herbal preparations (Pittler and Ernst, 2000).  However, Sarris et al. (2011) point out multiple newly identified factors that may have erroneously associated hepatotoxicity with Kava: use of incorrect cultivars, use of plant parts higher in alkaloids, subjects’ pre-existing inability to metabolize (CYP450 3A4 and 2D6) kavalactones (Kava’s active ingredient), preparations utilizing media low in glutathione (acetonic or ethanolic media), and inadequately stored or contaminated material. To that end, Sarris et al. (2001) advise using Kava extractions obtained only from peeled roots of noble cultivars (those traditionally considered safe) through a water solute extraction process. Sarris and Kavanagh (2009) address the modulation of CYP450 (impeding or accelerating the liver’s metabolism of certain drugs, causing drugs to either become toxic or have little to no effect) by suggesting that health care professionals prescribe lower doses of standardized preparations of kavalactones for short-term or intermittent use, noting contraindications for simultaneous alcohol use or use in patients with known hepatic insufficiency or disease.

 

While I have not identified evidence supporting St. John’s Wort use in treatment of anxiety, I’ve chosen to discuss it anyway for three reasons. First, in that Google search I’d mentioned earlier, St. John’s Wort was frequently recommended for anxiety. Thus, it’s a safe bet that some patients walking through our doors will have tried it. Second, it is popular. Annual sales of St. John’s Wort in the U.S. rose by $180,000,000 between 1995 and 1997 (Gaster and Holroyd, 2000). Thirdly, it’s been widely researched. The “wort,” Old English for plant, was traditionally gathered for the Feast of St. John the Baptist (Gaster and Holroyd, 2000). For centuries, St. John’s Wort (Hypericum perforatum) was used to treat nervous conditions and depressed mood (Sarris, 2013). But is it effective? Van der Watt, Laugharne and Janca (2008, p.41) called it “the only demonstrably effective herbal treatment for mild to moderate depression.” It is used throughout Europe, and over 100 million daily doses are prescribed in Germany alone (Sarris and Kavanagh, 2009). Sarris and Kavanagh’s 2009 review also revealed that St. John’s Wort has equivalent, or superior, effects to commonly used antidepressants like sertraline, paroxetine, imipramine, citalopram, maprotiline, amitriptyline and fluoxetine. Ok, but is it safe? Schultz’s 2006 review reported that St. John’s Wort is seemingly ten times safer than synthetic antidepressants. Should I repeat that? Adverse effects reported by Gaster and Holroyd in 2000 were rare and most commonly related to reversible skin rash or nausea. However, there were case reports of mania induction or psychosis and serotonin-syndrome (Sarris, 2013). Thus, it is not recommended for patients with, or family history of, bipolar disorder. Nor is it recommended for concomitant use with antidepressants. Additionally, like Kava, this herb can interfere with blood levels of other drugs (CYP3A4 inducer, CYP2D6 inhibitor). Caution should be exercised in patients taking other medications: oral contraceptives, antibiotics, anticoagulants, benzodiazepines etc. (Bystritsky et al., 2011). While St. John’s Wort appears an effective and relatively safe option in the treatment of depression, I must remind readers that this herbal preparation is not indicated for anxiety.

 

There are hundreds of alternative therapies on the market. As we’ve seen from Kava and St. John’s Wort, both affect liver metabolism leaving room for potential harm. But what about the effects of other alternative therapies not so well studied? Anyone considering the use of any herbal preparation is strongly advised to seek the counsel of their preferred medical professional prior to use. As future nurse practitioners, we must be diligent. We must inquire regarding self-treatment efforts, and be aware as to how these may integrate with or adversely affect our own prescribed therapies. As Donna Diers put it, “the discipline of nursing is the constant attention to difference and unpredictability” (Diers, 1990). And so it is!

References

Bystritsky, Hovav, Sherbourne, Stein, Rose, Campbell-Sills, Golinelli, Sullivan, Craske, Roy-Byrne. (2012). Use of complementary and alternative medicine in a large sample of anxiety patients. Psychosomatics, 53, 266-272. doi:10.1016/j.psym.2011.11.009

Diers, D. (1990). Learning the art and craft of nursing. The American Journal of Nursing, 90, 64-66. Retrieved on 11/09/13 from http://www.jstor.org/stable/3426230

Gaster, Holroyd. (2000). St John’s Wort for depression. Archives of Internal Medicine, 160, 152. doi:10.1001/archinte.160.2.152

Kessler, Soukup, Davis, Foster, Wilkey, Van Rompay, Eisenberg. (2001). The use of complementary and alternative therapies to treat anxiety and depression in the United States. The American Journal of Psychiatry, 158, 289-294. doi:10.1176/appi.ajp.158.2.289

Pittler, Ernst. (2000). Efficacy of kava extract for treating anxiety: Systematic review and meta-analysis. Journal of Clinical Psychopharmacology, 20, 84. doi:10.1097/00004714-200002000-00014

Sarris, Panossian, Schweitzer, Stough, Scholey. (2011). Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. European Neuropsychopharmacology, 21, 841-860. doi:10.1016/j.euroneuro.2011.04.002

Sarris, Kavanagh. (2009). Kava and St. John’s Wort: current evidence for use in mood and anxiety disorders. Journal of Alternative and Complementary Medicine, 15, 827-836. doi:10.1089/acm.2009.0066

Sarris. (2013). St. John’s Wort for the treatment of psychiatric disorders. Psychiatric Clinics of North America, 36, 65-72. doi:10.1016/j.psc.2013.01.004

Schulz, V. (2006). Safety of st. john’s wort extract compared to synthetic antidepressants. Phytomedicine, 13, 199-204. doi:http://dx.doi.org/10.1016/j.phymed.2005.07.005

van der Watt, Laugharne, Janca, Aleksander. (2008). Complementary and alternative medicine in the treatment of anxiety and depression. Current Opinion in Psychiatry, 21, 37-42. doi:10.1097/YCO.0b013e3282f2d814

 

The roles of environment and genetics in ADHD

Attention deficit hyperactivity disorder (also known as ADHD) is one of the most commonly diagnosed psychiatric disorders among children (affecting 5-10% of children), with a prevalence rate among adults of 4% (Banerjee, Middleton, Faraone, 2007).  To understand ADHD one must know that the cognitive and behavioral disorder can be divided into three subtypes based on the child’s presentation: predominantly inattentive ADHD, predominantly hyperactivity-impulsive ADHD and combined inattentive hyperactive ADHD.  With the Center for Disease Control and Prevention (CDC) describing a 3% increase per year between the years of 1997 and 2006, understanding the potential causes of ADHD have been of high research interest.

Several studies have been performed to determine the potential causes of ADHD and researchers have concluded that several factors may play a role in the development of ADHD.  Lets look at some the potential players involved…

Genetics:

  • Heredity
  • The Norepinephrine Transporter Gene
  • The Dopamine Transporter Gene
  • The Choline Transporter Gene
  • 5HTTLPR, a Serotonin Transporter Gene

Environment:

  • Exposure to toxins
  • Exposure to alcohol, nicotine, and cocaine
  • Complications during pregnancy and delivery
  • Psychosocial trauma

ADHD from a Genetic Perspective

In many studies performed on the role of genetics in ADHD, it has been found that there is in fact a positive correlation between a diagnosis of ADHD among children and their parents and siblings also having the diagnosis (Banerjee, Middleton, and Faraone 2007).  On a tinier (however, more complex) level, within the three subtypes of ADHD it has been found that among the three types there is a variance in particular transporter genes for three different neurotransmitters. With predominantly inattentive ADHD, it was found that children had variation in their norepinephrine transporter gene, while children with predominantly hyperactivity-impulsive ADHD were found to have a variation in their dopamine transporter gene (Stannard, 2010). Vanderbilt University Medical Center (2009) has stated that in combined ADHD, children were found to have a variation within their choline transporter gene.   With the two predominant forms of ADHD, drugs such as Ritalin (for hyperactivity) and Strattera (for inattentiveness) have been found to be effective, while currently, there have not been any drugs discovered to treat the combined form.

In terms of the role of the serotonergic system on ADHD, Nikolas, Friderici, Waldman, Jernigan & Nigg (2010) have found that serotonin may also play a role in the development of ADHD.  They found that children possessing both low and high serotonin activity genotypes were more likely to develop disorders such as ADHD, conduct disorder and mood problems than children with an intermediate serotonin activity genotype.

ADHD from an Environmental Perspective

In a meta-analysis performed by Banerjee, Middletone, and Faraone (2007) many different environmental factors were identified that could potentially play a role in the development of ADHD in children.  They found that toxins such as mercury or manganese were shown to cause symptoms such as distractibility, hyperactivity and restlessness.

In pregnancy and delivery, traumatic events such as eclampsia, poor maternal health and even duration of labor could have a potential effect on the development of ADHD and exposure to things such as alcohol, nicotine and cocaine during the prenatal period was also found to make children more disruptive, hyperactive, and impulsive than those that were not exposed to these things (Bannerjee et al, 2007).

In terms of psychosocial trauma, Famularo, Kinscherff, and Fenton (1992) found that children who had suffered some form of maltreatment had a higher incidence rate of ADHD, oppositional disorder and PTSD than those that had not experienced maltreatment.  And, in a study performed by McLeer, Callaghan, Henry, and Wallen (1994) they found that a diagnosis for ADHD was the most frequently given diagnosis (by 46%) in children with a history of sexual abuse.

How Genetics and the Environment may work together to cause ADHD

To make this a bit more complicated, in the more recent study done by Nikolas, Friderici, Waldman, Jernigan, and Nigg (2010) they found that in 304 youth who completed the Children’s Perception of Inter-Parental Conflict (CPIC) scale to assess judgments of self blame in relation to their parents’ marital conflicts and who were each determined to have high, intermediate, or low serotonin transporter activity genotypes, they found that the children possessing high and low serotonergic activity (when coupled with psychosocial trauma) were more at risk for ADHD than children with intermediate serotonergic activity and those possessing little to no psychosocial trauma.  This study shows not only that genetics and the environment may play equal roles in the formation of ADHD, but that there is still a lot of research to be done in the field.

Conclusion

Although research has made great strides toward uncovering the causes of ADHD no one factor has been determined to be the main cause of the development of ADHD within children.  It is important to understand that no one variant in a gene or particular degree of exposure to an environmental factor will determine whether or not a child will develop ADHD however, when diagnosed, these factors, particularly variants in gene transporters may help providers to better understand how to treat a particular form of ADHD.

 

References

Attention-Deficit / Hyperactivity Disorder (ADHD). (2013, April 18). Centers for Disease Control and Prevention. Retrieved October 25, 2013, from http://www.cdc.gov/ncbddd/adhd/index.html

Banerjee, T. D., Middleton, F. and Faraone, S. V. (2007), Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatrica, 96: 1269–1274. doi: 10.1111/j.1651-2227.2007.00430.x

Famularo, R., Kinscherff, R., & Fenton, T. (1992). Psychiatric diagnoses of maltreated children: preliminary findings. Journal of the American Academy of Child & Adolescent Psychiatry, 31(5), 863-867.

McLeer, S. V., Callaghan, M., Henry, D., & Wallen, J. (1994). Psychiatric disorders in sexually abused children. Journal of the American Academy of Child & Adolescent Psychiatry, 33(3), 313-319.

Nikolas, M., Friderici, K., Waldman, I., Jernigan, K., & Nigg, J. T. (2010). Gene× environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict. Behavioral and Brain Functions, 6(1), 23.

Stannard Gromisch, E. (2010). Neurotransmitters Involved in ADHD. Psych Central. Retrieved on October 28, 2013, from http://psychcentral.com/lib/neurotransmitters-involved-in-adhd/0003300

Synder, B. (2009, December 11). Genetics may explain three types of ADHD (12/11/09). Genetics may explain three types of ADHD (12/11/09). Retrieved October 25, 2013, from http://www.mc.vanderbilt.edu/reporter/index.html?ID=7947

 

 

 

The Three A’s

While we have discussed several disorders involving memory deficits and breakdowns in cognition, it is crucial that we as future psychiatric nurse practitioners understand the importance of screening for and treating such breakdowns.  Much research is dedicated to this topic.  One journal, Memory & Cognition, covers scientific work on problem solving, thinking and information processing from a broad range of perspectives including psychology, mathematics and computer sciences.  It is an excellent resource for current topics in this field so I invite you to view the link:   http://www.springer.com/psychology/cognitive+psychology/journal/13421.  We are fortunate to attend a University that places such an emphasis on research of cognitive disorders.  In fact, Yale has an entire division dedicated to cognitive sciences.  If interested, I highly suggest viewing the research endeavors of each lab at: http://www.yale.edu/cogsci/research_labs.html

I would like to explore three conditions of neurological impairment which can be related to several diseases of memory, most notably Alzheimer’s disease.  These conditions include agnosia, aphasia and apraxia.  The Alzheimer’s Foundation of America defines agnosia as an inability to interpret information from any of the five senses.  This may include interpretation of external stimuli such as recognizing family members or internal stimuli such as pain.  Aphasia is an inability to communicate appropriately, including deficits of speech and writing.  Finally, apraxia is an inability to complete motor tasks including self-care or even swallowing/breathing when the disease has progressed to its final stages (Alzheimer’s Foundation of America, 2013).  For each topic I will present some basic deficits of neuroanatomical and neurological processes associated with the condition and a bit about potential treatments.

As previously stated, agnosia can be associated with any of the five senses.  For the purposes of this review, I will focus on visual agnosia, or an inability to recognize visual objects.  Recent research from 2013 found changes in cortical thickness across the occipital cortex with the most loss in the lateral occipital cortex (LOC), including reduced white matter connections between the LOC and other areas of the brain.  MRIs, however, do show that there are some areas of this region that are functional despite widespread damage (Bridge et al., 2013).  Perhaps training these intact areas of the brain to perform otherwise lost skills may be a goal of future psychiatric and neurological studies.  The same research, also noted that regions beyond the occipital cortex, including the somatosensory cortex, were mostly intact (Bridge et al., 2013).

Aphasia, a disorder of language including both formation of language and comprehension of language, has been studied at length.  Research from 2013 suggests that the neuroanatomy of language is organized along two specific processes.  The ventral process attributes meaning to sound, allowing an individual to understand what others say.  The dorsal process involves using sound to produce articulations, allowing an individual to produce speech (Kümmerer et al., 2013).  Much research focusing on treatment for disorders of aphasia has been based on non-invasive medical techniques including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS).  Both techniques introduce an external electrical current to the brain to either induce or reduce neural firing.  This fluctuation in firing changes the amount of oxygen/glucose required by the brain to perform, thereby changing the blood flow to these parts of the brain, and allowing for MRI evaluation of specific regions.  This allows researchers to directly manipulate and observe language performance.  Studies thus far have shown that TMS provides immediate improvement in language skills and these improvements have been sustained up to 2.4 years in some research patients.  Similarly, benefits of tDCS has been shown to immediately improve language abilities and these results have also been sustained (up to two months) (Fridriksson, Hubbard, & Hudspeth, 2012).  Further research is needed with both techniques as well as with other non-invasive procedures that can improve treatment outcomes.

Apraxia is the inability to perform specific movements, despite having the ability to do so (Ziegler, 2008).  In 28-57% of cases, apraxia results from left hemisphere brain damage.  However, in up to 34% of cases, it may be the result of specifically right sided impairment (Roy, Psych, Black, & Gonzalez, 2014).  Although apraxia refers to the inability to perform fine motor movements, it can also relate to of an inability to perform speech movements, despite the desire to do so.  This differs from aphasia in that it is not an inability to produce language, but an inability to perform the motions necessary to produce speech.  In the case of aphasia of speech, dysfunction occurs in the dominant hemisphere of the brain, the inferior portion of the precentral gyrus, the primary motor cortex and the insular cortex (Ziegler, 2008).  Techniques to treat apraxia include speech and occupational therapy.  Little research can be found on such treatment as most cases of apraxia, at least in relation to Alzheimer’s, are progressive, and tend not to resolve.  There have been measures, however, to screen for and diagnose apraxia that focus on speech motor control including speech planning and programming.  One new instrument created in 2012, the Modified Diadochokinesis Test (MDT), is such an instrument and has been shown valid in identifying issues of speech (Hurkmans, Jonkers, Boonstra, Stewart, & Reinders-Messelink, 2012).  Future research endeavors will hopefully aim to improve these instruments and focus on finding innovative techniques to help individuals with apraxia.

This is only a brief overview of the symptoms and treatment for conditions of agnosia, aphasia and apraxia.  Disorders of cognition and memory are extremely complex and thus far not very well understood by medical and research professionals.  Much of the research available focuses on specific case studies and therefore is many times not generalizable.  In many of our classes, we have examined a variety of treatment modalities for different disorders.  Do you believe any such techniques would be beneficial with these types of conditions?  Might specific behavioral or pharmacological therapies be better than others?  Hopefully through our discussion, we will become more familiar with such processes and in the future hopefully be better equipped to help patient suffering with these disorders.

References

Alzheimer’s Foundation of America (2013). About Alzheimer’s: symptoms. Retrieved from http://www.alzfdn.org/AboutAlzheimers/symptoms.html

Bridge, H., Thomas, O. M., Minini, L., Cavina-Pratesi, C., Milner, A. D., & Parker, A. J. (2013). Structural and Functional Changes across the Visual Cortex of a Patient with Visual Form Agnosia. The Journal of Neuroscience, 33(31), 12779-12791.

Fridriksson, J., Hubbard, H. I., & Hudspeth, S. G. (2012, August). Transcranial brain stimulation to treat aphasia: A clinical perspective. In Seminars in speech and language (Vol. 33, No. 03, pp. 188-202). Thieme Medical Publishers.

Hurkmans, J., Jonkers, R., Boonstra, A. M., Stewart, R. E., & Reinders‐Messelink, H. A. (2012). Assessing the treatment effects in apraxia of speech: introduction and evaluation of the Modified Diadochokinesis Test. International Journal of Language & Communication Disorders, 47(4), 427-436.

Kümmerer, D., Hartwigsen, G., Kellmeyer, P., Glauche, V., Mader, I., Klöppel, S., & Saur, D. (2013). Damage to ventral and dorsal language pathways in acute aphasia. Brain, 136(2), 619-629.

Roy, E. A., Psych, C., Black, S. E., & Gonzalez, D. (2014). Limb Apraxia: Types, Neural Correlates, and Implications for Clinical Assessment and Function in Daily Living. In The Behavioral Consequences of Stroke (pp. 51-69). Springer New York.

Ziegler, W. (2008). Apraxia of speech. Handbook of clinical neurology, 88, 269-285.