Tuesday 29 January 2013

Dopamine in Schizophrenia & Parkinson's Disease

This is a paper I wrote for my 2nd year Psychology degree. It concerns biological psychology. As ever, if you require the reference list, please get in touch, I'll be happy to provide the full bibliography.


Compare and contrast the role of dopamine in Schizophrenia and Parkinson's disease.

In 1908, Paul Eugen Bleuler coined the term ‘Schizophrenia’ (SZ) to describe a mental disorder which brings about disunity in personality and a ‘split’ from reality (Fusar-Poli & Politi, 2008). More recent explanations categorise the symptomology of the disorder into three types; Positive, Negative and Cognitive (Mueser & McGurk, 2004).

The DSM-IV states positive symptoms are the presence of abnormal symptoms (i.e. hallucinations) whilst negative symptoms are characterised as the absence of normal behaviours (i.e. anhedonia). Cognitive issues pertaining to SZ are generally cognitive deficits (i.e. low psycho-motor speed). According to Van Os and Kapur (2009), schizophrenia has a global prevalence rate of 0.30-0.66 per cent.

Parkinson’s disease (PD) on the other hand is an idiopathic degenerative neurological disorder that is typified by rigidity and slowness in movement, cognitive impairment (i.e. memory) and postural instability (Lang & Lozano, 1998). Post, Merkus and de Haan (2007) note that old-age is the best predictor of PD and continues to be the foremost risk factor in acquiring the disease.

Dopamine (DA) has been implicated in both diseases frequently and the DA hypothesis of SZ stems from two foundational premises. Firstly, medication that increases DA availability, such as amphetamine, can cause schizophrenic symptoms in normal populations (Angrist & Gershon, 1970) and secondly, drugs that alleviate schizophrenic symptoms are DA receptor antagonists and their efficacy is related to their aptitude in blocking DA D2 receptors (Carlsson, 1978). Essentially, the hypothesis proposes SZ is caused by excessive DA activity (Matthysse, 1974; Grace, 1993).

The paranoia experienced by schizophrenics has also been implicated with DA. Schultz (2007) suggests that dopaminergic neurons fire in direct response to novel environmental rewards and consequently, the heightened DA leads to fixation on the rewarding situation. This fixation then injects motivational significance to the stimuli. The patient then draws conclusions which are plausible (in their minds) to make sense of the situation, commonly they are being plotted against or wanted by the police.

Most commonly, the DA D2 receptor is implicated in SZ. However, recent studies suggest other DA receptors are associated with SZ. Many studies have examined D1 receptor binding in the prefrontal cortex (PFC) of schizophrenics and although they have produced mixed results (Knable et al. 1996; Okubo et al. 1997), Abi-Dargham et al. (2002) postulate SZ may be correlated with greater amounts of D1 receptors in the dorsolateral prefrontal cortex.

Dopamine has also been linked to the aetiology of PD. PD is typified by deterioration of dopaminergic neurons in the substantia nigra and a consequent decrease in DA levels in the striatum which lead to symptoms of PD (Radad, Gille & Rausch, 2005). An alternative, but related explanation describes the abnormal accumulation of the mutated protein alpha-synuclein. Alpha-synuclein is the primary constituent of the larger Lewy body found in the cytoplasm of neurons in the pars compacta of the substantia nigra in sufferers of PD. Collectively; they cause neural degeneration that is typical in PD (Engelender, 2008). More specifically, the striatum which is secondary to the substantia nigra, is responsible for posture and muscle movement. As this area is impaired by the presence of Lewy bodies, PD sufferers experience muscular rigidity and poor postural stability (Marsden, 1990).

In healthy humans, cells in the ventral tegmental area (VTA) project to the limbic and cortical areas whilst, neurons of the substantia nigra project to the striatum. In PD however, dopaminergic nerve cells in the substantia nigra build up nerve cell loss, and its depletion and the consequential striatal dopamine decrease are accountable the motor defects (Carlson, 2010).

Aside from DA, which is limited in its explanatory power (i.e. only adequate in explaining the positive symptoms of SZ), glutamate has also been implicated in both diseases. The glutamate hypothesis of schizophrenia suggests there is strong evidence corroborating a link between glutamate and schizophrenic symptoms (Goff & Coyle, 2001; Jentsch & Roth, 1999). Dysfunctional glutamate receptors can play a role in psychosis in that the drug phencyclidine (PCP) blocks certain ionotroopic glutamate receptors such as N -methyl-D-aspartate (NMDA) receptors inducing psychotic symptoms (i.e. hallucinations) (Javitt & Zukin, 1991). Therefore, the hypo-glutamate hypothesis proposes stimulation of glutamate receptors to ease the symptoms of schizophrenia.

Support for this theory comes from PCP psychosis that has been directly implicated with the positive/negative symptoms of SZ (Egan & Weinberger, 1997; Tsai et al., 1995), whilst Kay and Sevy (1990) draw accurate parallels between PCP induced psychosis and the cognitive deficits experienced by schizophrenics.

Fig. 1. Mean ventricular size in SZ patients and controls.
Taken from Weinberger & Wyatt 1982
Although many commentators have proposed that SZ is a psychiatric disorder, there is evidence for a neurological basis in the assessment of brain abnormalities in SZ patients. Weinberger and Wyatt (1982), through MRI and CT scans found a significant discrepancy in lateral ventricular size between SZ patients and controls (see figure 1). The premise of brain abnormality is further strengthened by the work Hulshoff-Pol et al. (2002) who found that the rate of cerebral gray matter deterioration is greater in SZ patients than the rate of natural decline experienced during old-age.

Brain abnormality has also been implicated in PD. Grafton (2004) by way of functional imaging, has shown that akinesia (movement difficulty found in PD) is linked to the diminished activation of the respective motor area in the brain. Abnormal pons, midbrain, cerebellum and thalamus were also directly associated with parkinsonian tremors.

However, although these studies seem confirmatory and well-founded, there is the matter of cause and effect. It is not known whether SZ causes brain abnormalities or if in fact it is the abnormalities in the pons and midbrain that cause tremors that are typical of PD.

As both diseases are similar in that SZ is an excess of DA and PD is a deficiency, both can be managed by particular drugs. The main form of treatment in SZ is the use of first-generation antipsychotic drugs (i.e. Chlorpromazine) that alleviate schizophrenic symptoms by blocking the DA D2 receptors. Baldessarini (1977) concludes that the effectiveness of such drugs is well established as they have been confirmed by numerous double-blind experiments. However, first-generation antipsychotics only soothe positive symptoms of SZ and can cause side effects such as long-term tardive dyskinesia (Kapur & Mamo, 2003). A wider drawback of the medication is that the consumption of these drugs can lead to stigmatisation as noted by van Zelst (2009).

However, medication is not the only answer. Antipsychotic drugs are most effective when administered in a psycho-social support context (Zygmunt et al, 2002). When coupled with support, reduction of around 80% of patients’ symptoms can be attained, particularly if management is commenced early (Robinson et al, 1999).

Whilst SZ treatments rely on the decrease of DA to alleviate symptoms, PD therapies are concerned with the increase of striatal DA. L-Dopa is a precursor to DA that stimulates the remaining dopaminergic neurons to increase output. However, the body naturally metabolises most of the L-Dopa and to combat this, L-Dopa is administered with dopa decarboxylase inhibitor to increase the proportion passing through the blood-brain barrier (National Collaborating Centre for Chronic Conditions, 2006).

However, due to peripheral intake of L-Dopa by the body, there are side-effects. The most common side-effect is motor complications; patients can experience severe difficulty in movement. Also, it is typical to experience a ‘wearing-off’ effect of the drug. For this reason, physicians usually delay onset of medication and/or initially provide an alternative (National Collaborating Centre for Chronic Conditions, 2006).

Throughout the text, from causation to therapies of both diseases, clear likenesses emerge. The most salient is the disabling effect both disorders induce in terms of patients’ thinking, feeling and behaviour. However, none of the aforementioned explanations are absolute. It is improbable that any sole neurotransmitter theory is satisfactory to wholly elucidate such multifaceted disorders like SZ or PD.

Greenamyre (1993) proposes the marked synthesis between dopaminergic agents and glutamate receptor antagonists can offer a way of utilizing low doses of the two drugs in tandem to cure Parkinson's disease and lessen side effects.
The forthcoming studies on the exact effect of DA in SZ ought to concentrate on first-episode neuroleptic-naive schizophrenic patients. Such studies represent the greatest chance of examining specific changes in the dopaminergic pathways and connecting them in a significant manner to numerous scopes of psychopathology observed in schizophrenic patients (Hietala & Syvälahti, 1996).

Foyzul Rahman - 30/01/2012
Recommended citation: Rahman, F. (2012). Dopamine, the role of, in Schizophrenia and Parkinson's Disease. http://knowledge-fozrahman.blogspot.com/2013/01/dopamine-in-schizophrenia-parkinsons.html

3 comments:

  1. I was diagnosed with Parkinson’s disease a year ago at the age of 68. For several months I had noticed tremors in my right hand and the shaking of my right foot when I was sitting. My normally beautiful cursive writing was now small cramped printing. And I tended to lose my balance. Neurologist had me walk down the hall and said I didn’t swing my right arm. I had never noticed! I was in denial for a while as there is no history in my family of parents and five older siblings, but now accept I had classic symptoms. I was taking pramipexole (Sifrol), carbidopa/levodopa and Biperiden, 2 mg. and started physical therapy to strengthen muscles. nothing was really working to help my condition.I went off the Siferol (with the doctor’s knowledge) and started on parkinson’s herbal formula i ordered from Solution Health Herbal Clinic, my symptoms totally declined over a 5 weeks use of the Parkinsons disease natural herbal formula. i am now almost 70 and doing very well, the disease is totally reversed!! Visit there website www.solutionhealthherbalclinic.com or E-mail: solutionsherbalclinic@gmail.com

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  2. My symptoms started at the age of 47. My fingers on my left hand were stiff and were difficult to move. People noticed that my walk was not normal. I was often asked did I hurt. I noticed nothing different about my walk. It was difficult getting up from` a chair and getting out of a car. I was diagnosed a year later ,it was the onset of tremors starting in my right hand that caused my other symptoms to be recognized as Parkinson's.. I am now 59. With the new herbal medicine i purchase from totalcureherbsfoundation .c om  was my only way to get rid of my PD,the herbal formula effectively reverse my condition and alleviate all symptoms. 

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  3. I am a 51 year old female that just found out I have Parkinson's about a year and half, but I have been having signs of it for years, tremors, depression, body weakness. ECT. I honestly don't think my doctor was reading the signs because of my gender and age. A few years ago I had my shoulder lock up on me and I was sent to a P.T since x-rays didn't show any physical damage. My shaking was getting worse and I began falling. Only when my speech became so bad that it brought concern to my dentist was Parkinson's even considered. He phoned my doctor with his concerns about my shaking and balance problems. By this time I was forgoing shots in the back of my neck for back and neck pain to which once again I was sent to a P.T (although x-rays showed no damage) I was told I had a few spurs which were most likely causing the pain. Here I was feeling like my whole body was falling apart and doctor could not find anything wrong, maybe in was all in my head? My doctor even seemed annoyed with me and things just kept progressing and I just kept it to myself, why bother going through testing and them finding nothing? Well, it was after my second P.T called my doctor about the weakness in my legs and arms, by this time I have developed a gait in my walk and I fell more frequently. Only then did my doctor send me to a specialist and it was found that I had Parkinson's, and that I have had it for awhile. I think because I was a woman that my signs and symptoms weren't taken seriously and therefor left untreated for so long,I was taking pramipexole dihydrochloride three times daily, I Was on carbidopa levodopa but only lasted 90 minutes then wore off.I found that none of the current medications worked effective for me.I got tired of using those medication so I decided to apply natural herbs formula that was prescribed to me by my second P.T, i purchase the herbal formula from totalcureherbsfoundation. com, There has been huge progression ever since I start the treatment plan which will last for 15 weeks usage.all the symptoms and sign has begin to disappear .

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