Tag Archives: disorders

Basal Ganglia Disorders: Parkinson’s and Huntington’s Disease

My last post was exclusively about basal ganglia and the reason for this was to help clarify the parts of the brain directly involved in two very infamous disorders: Parkinson’s and Huntington’s Disease.

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Parkinson’s Disease

Parkinson’s disease is far more recognized that Huntington’s disease; however, thanks to the character Thirteen on the tv show House that might be changing. Parkinson’s disease effects about 1% of all people over the age of 50; however, as you can see from the video posted below, this is not always the case. Another example is actor Michael J. Fox, who was diagnosed with Parkinson’s at the age of 30. He has since become an activist for the cure of Parkinson’s, which led him to found the Michael J. Fox Foundation. It is not that uncommon to know someone with the disease. Many people can in fact recognize it based on the very characteristic tremors.

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Parkinson’s is classified by hypokinesia. The symptoms of Parkinson’s include slowness of movement or bradykinesiadifficulty in initiating ‘willed’ movements or akinesia, increases muscle tone or rigidity, and of course, tremors in the hands and jaws even at rest. Many  of those who suffer from the disease will eventually show signs of cognitive decline. More specifically, the substantia nigra’s input to the striatum. This input features the neurotransmitter dopamine, which facilitates the activity of the motor loop by activating cells in the putamen. As noted in the previous post, the putamen forms an inhibitory connection with neurons in the globus pallidus, which then forms an inhibitory connection with the thalamus (VLo). Due to the depletion of dopamine, the ‘funnel’ between VLo and the supplementary motor area (SMA) closes. As a result, the victim of Parkinson’s will have impaired motor function with symptoms such as ones listed above.

Treatment Options for Parkinson’s Disease

Even through Parkinson’s cannot be cured, therapies do exist to try to ease or deter the symptoms. Most therapies aim at enhancing the levels of dopamine delivered to the caudate nucleus and the putamen. The most common type of medication is known as L-dopa, which is a precursor for dopamine. This means that it participates the chemical reaction that produces dopamine. This treatment does alleviate some of the symptoms; however, it cannot do anything to stop the progressive course of the disease, nor slow the rate of cell degeneration in the substantia nigra. Currently, experiments are being conducted to test whether graftng non-neural cells, manipulated to produce dopamine, into the basal ganglia can help. Also, stem cell research shows promise to one day provide an effective treatment as well.

Huntington’s Disease

Whereas Parkinson’s is characterized by hypokinesia, Huntington’s is characterized by hyperkinesia or excessive movement. As tragic as Parkinson’s disease is, Huntington’s does seem far more frightening. A hereditary, progressive and always fatal disorder, Huntington’s  symptoms include dyskinesia or abnormal movements, dementia and disorder of the personality. The scariest part of the disorder is that the symptoms do not appear until adulthood, so unless the person knows that they have a history of the disorder, they can easily pass on the genes of Huntington’s to their children without even knowing that they have it. Genetic tests can be performed to find out for sure, but for many people it is too late at that point. The name Huntington’s comes from the abnormal gene carried by the patient. The first and most notable sign of the disease is known chorea: spontaneous, uncontrollable movements with rapid, irregular flow resulting a flicking movement in various parts of the body. In fact, Huntington’s disease can also be called Huntington’s Chorea. The devastating effects of the disease is due to the profound neuron loss in caudate nucleus, putamen and globus pallidus as well as cell loss in any other part of the cerebral cortex. The fact that Huntington’s can strike any part of the brain means that many patients suffer a variety of different symptoms, sometimes making it difficult to diagnose without a genetic test. Damage to the basal ganglia results in a loss of inhibitory output to the thalamus (VLo) resulting in the abnormal movements.

brainslice3Unfortunately, due to the progressive nature of the disorder and the genetic component, treatment for Huntington’s is virtually non-existent. Most patients with the disorder have their symptoms treated with various medications ranging from anti-depressants to sedatives and anti-psychotics.

 

Depression: Symptoms, Aetiology and Treatment Options

Symptoms 

Depression is a serious affective disorder that affects millions of people in the world, approximately 5% of the population. In the United States alone approximately 33 million people will suffer from depression at some point in their life (Bear, 2007). In addition, the disorder is the leading cause of suicide. Despite its high prevalence, however, stigma still also remains high. A primary reason for the stigma surrounding any mental disorder is a misunderstanding of the symptoms and causes.

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Even though depression strikes people differently, the cardinal symptoms are lowered mood and feelings of dejection, a lack of pleasure or interest rather than sadness. Accompanying symptoms include changes in appetite, fatigue, insomnia or hypersomnia, diminished concentration, feelings of worthlessness and/or guilt and recurrent thoughts of death and/or suicide (Bear, 2007). Depression can be one half of bipolar disorder but also occur on its own and in varying degrees of severity. Usually, for a diagnosis of major depression, the cardinal symptoms of depression must be present every day for approximately 2 weeks. Importantly, the cause of depression cannot be linked to a bereavement. This clear distinction is what separates depression from sadness.

Types of depression include chronic depression of dysthymia, major or clinical depression, atypical depression and manic depression. Chronic depression or dysthymia is usually less severe than major or clinical depression; however, it can be more disabling in that the symptoms are long-term (2 years+) or recurrent throughout a lifetime. Major or clinical depression is more severe; however, the symptoms do not last longer than 2 years and is not typically recurrent. Approximately 17% of sufferers have chronic symptoms.  It is important to note, however, that when depression is left untreated, recurrence is far more likely. Manic depression is found in bipolar disorder, to find out more click here. Finally, atypical depression is when a person suffers from the accompanying symptoms rather than the cardinal symptoms.

Aetiology and Treatment Options 

Biological basis 

Affective or mood disorders such as depression alter the typical function of the brain. Many different parts of the brain are usually affected at the same time, but the major system involved is the hypothalamic-pituitary-adrenal system (HPA). Exaggerated activity in the HPA system is common in people with anxiety and affective disorders. Specific to depression, blood cortisol levels are heightened as is the concentration of corticotropin-releasing hormones (CRH) in the cerebrospinal fluid.

Monoamine hypothesis

The monoamine hypothesis of depression states that a deficit in monoamines causes mood disorders. Monoamines include serotonin and catecholamines (inc. dopamine, noradrenaline, norepinephrine).  Current anti-depressants focus on this theory of depression. Anti-depressants inhibit the re-uptake of of monoamines, increasing the concentration of them in the synaptic cleft. The great benefit of anti-depressants is that they promote long-term, adaptive changes in the brain reducing the possibility of another depressive episode. Unfortunately, not all depressed people find anti-depressants effective. This can mean that either the treatment does not work for them at all or they require a greater dosage. Furthermore, it can takes week for depressants to take affect. Lastly, anti-depressants can raise levels of norepinephrine, which makes anti-depressants less effective. As anti-depressants are not always effective,  patients with prolonged depressive episodes may seek alternative treatment. Electroconvulsive therapy (ECT) and therapy are both options. ECT is mainly used in extreme cases because it can offer immediate relief. However, ECT is controversial due to the danger of memory loss. This is not surprising considering ECT is a localised seizure controlled by keeping the patient under anaesthesia. It is unknown exactly how ECT works; however, the hippocampus has been implicated. The hippocampus is involved in regulating CRH levels and the HPA system.

Types of anti-depressants include: selective serotonin re-uptake inhibitors, serotonin-noradrenaline re-uptake inhibitors, tricyclic anti-depressants and monoamine oxidase inhibitors. For people with bipolar disorder, lithium is also used to stabilise mood primarily the mania but has been shown stabilise mood overall.

Diathesis-Stress hypothesis 

The diathesis-stress hypothesis proposes that mental disorders have a genetic component that predisposes us to mental illness. Certain life stressors then makes us susceptible to mental illness actually presenting themselves. As such, traumatic childhoods full of abuse and/or neglect can leave a child at high risk for developing mental disorders. Tragically, children whose poor treatment is due to mentally ill caregivers, this cycle becomes hard to break. However, according to the diathesis-stress model, a trigger is not enough to bring forth mental illness without a genetic foundation. This genetic foundation goes hand in hand with the HPA system. Of course this does not mean that only traumatised children will suffer from mental health disorders. Individuals that have experienced a highly stressful life even such as divorce, moving away from home, changing schools, becoming ill, etc. will also be at risk are they predisposed to mental health issues.

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In a healthy individual, cortisol activates hippocampal glucocorticoid receptors, which inhibit the the HPA system. However, in a depressed individual there is a flaw in the feedback system. On a molecular level there is a diminished hippocampal response to cortisol due to reduced number of  glucocorticoid receptors. Here the genetic component of depression comes into play; glucocorticoid receptors are the product of gene expression. Hence, an individual with few glucocorticoid receptors is more susceptible. Fittingly, the amount of glucocorticoid receptors are epigentically influenced, early sensory experience can alter the number as well. This means that a childhood where we are well looked after, loved, cared for, kept safe and happy can protect us from developing depression even if we disposed to at birth. This illustrates how important the interaction of nature and nurture is. Think Voldemort vs Harry Potter. Despite the traumatic death of his parents, the one year of unconditional love and Lily’s sacrifice protected him not just magically but neurologically. Interestingly, in an interview with Oprah Winfrey, JK Rowling discuss this exact point.

 

Citation 

Antidepressants . (n.d.). Antidepressants. Retrieved July 18, 2014, from http://www.nhs.uk/conditions/Antidepressant-drugs/Pages/Introduction.aspx

Bear, M. F., Connors, B. W., & Paradiso, M. A. (Eds.). (2007). Neuroscience(Vol. 2). Lippincott Williams & Wilkins.

Pinel, J. P. (2010). Biopsychology (8th ed., International ed.). Harlow: Pearson Education.

What the Heck is an HPA Axis & What Does it Have to do with Stress?. (n.d.). About.com Fibromyalgia & Chronic Fatigue. Retrieved July 18, 2014, from http://chronicfatigue.about.com/od/cfsglossary/g/hpa_axis.htm