House of Mind

"Biology gives you a brain. Life turns it into a mind" - Jeffrey Eugenides

  • 20th November
    2011
  • 20
  • 24th June
    2011
  • 24
Daily Diseases and Disorders: Huntington's Disease

dailydiseasesanddisorders:

Huntington’s disease is a neurodegenerative genetic disorder that greatly affects muscle coordination and cognition. The nerve cells in the brain slowly breakdown and atrophy. Huntington’s disease affects the striatum of the brain as well as the hippocampus, purkinje cells, and the cerebellum. 

Huntington’s is an autosomal dominant genetic disease that results from a defect on chromosome #4. The defect causes a repeat in a CAG sequence on the DNA to occur many more times than normal. In person without Huntington’s, the CAG sequence is repeated 10 to 35 times. In an individual with Huntington’s disease, the repeat can be repeated 36-120 times. The repeated sequence is expanded as it is passed through one generation to the next, lengthening the sequence in each offspring. Therefore, the disease becomes progressively juvenile. If one parent has Huntington’s, the child has a 50% chance of having the disease as well. 

There are two types of Huntington’s: juvenile which appears in children and the much more common form, adult-onset Huntington’s which appears in an individual aged 30 to 40. 

Huntington’s disease has become a target due to the ethical issues associated with it. Many question when an individual should be tested for the disease, if at all. Preimplantation genetic diagnosis has been used as a selective form of abortion. Some individuals who might have the disease may opt to not have the disease diagnosed. 

Worldwide, 5-10 people out of 100,000 have the disease.

After the first onset of symptoms, an individual typically has a life span of twenty more years of life. Huntington’s has no cure and ultimately leads to death. Suicide is one of the greatest cause of fatalies in the disease with 7.3% with Huntington’s taking their own lives and up to 27% attempting suicide. 

Diagnosis: A genetic counselor can determine if the child will have Huntington’s disease using genetic testing. The geneticist will look at the number of CAG repeats and determine the likelihood of the person developing Huntington’s in their life. In most cases, the affected individual will have an idea of when the symptoms will onset. A physical diagnosis that analyzes the symptoms of Huntington’s is also effective for most patients. Medical imaging of the brain can also show which areas of the brain have atrophied. 

Symptoms: Huntington’s disease affects many parts of the body. Movement disorders can include involuntary jerking, sustained contraction of muscles, rigidity, diffulty with speech, posture problems, and difficulty swallowing. Cognitive disorders include difficulty with organization, emotional flexibility, lack of focus and reasonable thinking, and various other symptoms. Lastly, psychiatric disorders include sadness, unhappiness, social withdrawal, loss of interest, fatigue, feelings of guilt, reduced appetite, and reduced sex drive.

Treatment: There is no cure for Huntington’s disease. Some of the symptoms can be controlled with various antidepressants and other drugs that reduce the amount of involuntary muscle jerking. 

Additional Information: Huntington’s disease has become prominent in different media sources and has appeared in Everwood, House, Private Practice, ER, and Scrubs. 

  • 27th May
    2011
  • 27
Attention-Deficit/Hyperactivity Disorder In the US, ADHD has a prevalence of around 5-12% during childhood. Approx. 5 million children and adolescents in the US have ADHD, while only 2 million are being treated (mostly through psychostimulants). ADHD has long been characterized by its well-known pervasive behavioral symptoms: hyperactivity, impulsivity and inattention, which begin in childhood. There are 2 types of ADHD according to the DSM-IV: Hyperactive/Impulsive ADHD and Inattention ADHD. Hyperactive/Impulsive ADHD Symptoms: ADHD 1 Fidgeting/squirming Inability to remain seated Restless Loud and noisy (difficulty playing quietly) Excessive talking Impulsive Intrusive  “Always on the go” Inattention Symptoms: ADHD2 Careless errors Inattention to detail Sustains attention poorly Appears to not be listening Disorganized Trouble following through with directions/obligations Loses needed objects Dislikes sustained mental effort Easily distracted  Forgetful In order for criteria to be met, +6 of the symptoms mentioned above (according to ADHD type) need to be present for 6 months or more and cause impairments in more than 1 setting (social, academic, occupational). These symptoms must also not be attributable to any other condition (i.e. depression, anxiety, substance use, etc)  and can cause impairment in children by the age of 7. Other characteristics that are important in the understanding and diagnosis of ADHD patients include: age, sex, comorbidity with other psychiatric disorders, intelligence, prematurity, exposure to toxins during early life, locomotor hyperactivity, differences in delay aversion, reward salience, motor inhibition tasks, error processing and working memory compared to controls. Moreover, ADHD is a disorder that’s characterized by high intra-subject variability (which is thought to be mediated by competition among functional neural networks).  Although the underlying cause of ADHD is currently unknown, there is a belief that both genetic (mostly dopaminergic and noradrenergic genes) and environmental factors (i.e. parental smoking, brain injury) play a role in ADHD. Moreover, some have suggested that gene-environment interactions account for about 70-80% of ADHD cases.  ADHD has strongly been linked to developmental, volumetric and functional differences in several brain structures/areas. For example, brain imaging studies of children with ADHD have found smaller sizes in the corpus callosum, caudate nucleus, and right frontal cortex. Overall, the brains of children with ADHD are significantly smaller and that the brain volume reduction in ADHD is widespread and also affects the cerebrum and cerebellum. Other studies from different disciplines have implicated disruption of the frontostriatal pathway and other circuitry in diverse areas like the prefrontal cortex, the basal ganglia and the cerebellum. Additionally, other studies have found delayed cortical maturation in children with ADHD-meaning that they take longer and are slower to develop compared to normal brains. More recently, disruptions in other brain networks and their relation to ADHD are starting to be explored. The diagram above is taken from Castellanos et. al (2008). Dr. Castellanos is an NYU clinician who employs neuroimaging techniques like fMRI to study differences in brain circuitry and wiring in patients with ADHD. In the ADHD brain, the precuneus (red part towards the posterior end of the brain), which is involved in high-level integration of posterior association processes with anterior executive function, appears to be enlarged. ADHD related differences in brain regions are shown at the right. The authors suggest that functional circuits linking the anterior cingulate cortex to the precuneus and posterior cingulate cortex and their long range connections should be considered as dysfunctional center in the ADHD brain.  Sources: Castellanos et. al. 2008. Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biological Psychiatry. 63 (3): 332-7.  Castellanos and Tannock. 2002. Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes. Nature Reviews Neuroscience. 3: 617-626.  Castellanos, XF. 2011. The Restless Brain: Spontaneous Brain Fluctuations and Variability in ADHD. Disorders of the Nervous System Lecture.  Kieling et. al. 2008. Neurobiology of attention deficit hyperactivity disorder. Child and Adolescent Psychiatric Clin N America. 17: 285-307. 

Attention-Deficit/Hyperactivity Disorder

In the US, ADHD has a prevalence of around 5-12% during childhood. Approx. 5 million children and adolescents in the US have ADHD, while only 2 million are being treated (mostly through psychostimulants). ADHD has long been characterized by its well-known pervasive behavioral symptoms: hyperactivity, impulsivity and inattention, which begin in childhood. There are 2 types of ADHD according to the DSM-IV: Hyperactive/Impulsive ADHD and Inattention ADHD.

Hyperactive/Impulsive ADHD Symptoms: ADHD 1

  • Fidgeting/squirming
  • Inability to remain seated
  • Restless
  • Loud and noisy (difficulty playing quietly)
  • Excessive talking
  • Impulsive
  • Intrusive 
  • “Always on the go”

Inattention Symptoms: ADHD2

  • Careless errors
  • Inattention to detail
  • Sustains attention poorly
  • Appears to not be listening
  • Disorganized
  • Trouble following through with directions/obligations
  • Loses needed objects
  • Dislikes sustained mental effort
  • Easily distracted 
  • Forgetful

In order for criteria to be met, +6 of the symptoms mentioned above (according to ADHD type) need to be present for 6 months or more and cause impairments in more than 1 setting (social, academic, occupational). These symptoms must also not be attributable to any other condition (i.e. depression, anxiety, substance use, etc)  and can cause impairment in children by the age of 7. Other characteristics that are important in the understanding and diagnosis of ADHD patients include: age, sex, comorbidity with other psychiatric disorders, intelligence, prematurity, exposure to toxins during early life, locomotor hyperactivity, differences in delay aversion, reward salience, motor inhibition tasks, error processing and working memory compared to controls. Moreover, ADHD is a disorder that’s characterized by high intra-subject variability (which is thought to be mediated by competition among functional neural networks). 

Although the underlying cause of ADHD is currently unknown, there is a belief that both genetic (mostly dopaminergic and noradrenergic genes) and environmental factors (i.e. parental smoking, brain injury) play a role in ADHD. Moreover, some have suggested that gene-environment interactions account for about 70-80% of ADHD cases. 

ADHD has strongly been linked to developmental, volumetric and functional differences in several brain structures/areas. For example, brain imaging studies of children with ADHD have found smaller sizes in the corpus callosum, caudate nucleus, and right frontal cortex. Overall, the brains of children with ADHD are significantly smaller and that the brain volume reduction in ADHD is widespread and also affects the cerebrum and cerebellum. Other studies from different disciplines have implicated disruption of the frontostriatal pathway and other circuitry in diverse areas like the prefrontal cortex, the basal ganglia and the cerebellum. Additionally, other studies have found delayed cortical maturation in children with ADHD-meaning that they take longer and are slower to develop compared to normal brains.

More recently, disruptions in other brain networks and their relation to ADHD are starting to be explored. The diagram above is taken from Castellanos et. al (2008). Dr. Castellanos is an NYU clinician who employs neuroimaging techniques like fMRI to study differences in brain circuitry and wiring in patients with ADHD. In the ADHD brain, the precuneus (red part towards the posterior end of the brain), which is involved in high-level integration of posterior association processes with anterior executive function, appears to be enlarged. ADHD related differences in brain regions are shown at the right. The authors suggest that functional circuits linking the anterior cingulate cortex to the precuneus and posterior cingulate cortex and their long range connections should be considered as dysfunctional center in the ADHD brain. 

Sources:

Castellanos et. al. 2008. Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biological Psychiatry. 63 (3): 332-7. 

Castellanos and Tannock. 2002. Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes. Nature Reviews Neuroscience. 3: 617-626. 

Castellanos, XF. 2011. The Restless Brain: Spontaneous Brain Fluctuations and Variability in ADHD. Disorders of the Nervous System Lecture. 

Kieling et. al. 2008. Neurobiology of attention deficit hyperactivity disorder. Child and Adolescent Psychiatric Clin N America. 17: 285-307. 

  • 18th January
    2011
  • 18
  • 8th October
    2010
  • 08
I think it’s interesting that the tree’s root is stemming from the dorso-caudal part of the skull. This spot is also where the cerebellum, also referred to as the “tree of life”, is located in the human brain.  The cerebellum’s functions include: motor coordination (particularly voluntary movement), balance, and muscle tone. It is also implicated in some cognitive functions. 

I think it’s interesting that the tree’s root is stemming from the dorso-caudal part of the skull. This spot is also where the cerebellum, also referred to as the “tree of life”, is located in the human brain. 

The cerebellum’s functions include: motor coordination (particularly voluntary movement), balance, and muscle tone. It is also implicated in some cognitive functions. 

(via articulomortis)