Schizophrenia is a complex disorder that is associated with multiple candidate genes. No single gene has been identified as the sole cause of schizophrenia, and it is believed that the more genes involved, the greater the risk. Some of the important candidate genes for schizophrenia include DTNBP1, COMT, NRG1, G72, RGS4, DAOA, DISC1, and DRD2. Among these, neuregulin, dysbindin, and DISC1 are the most replicated and plausible genes, with COMT being the strongest candidate gene due to its role in dopamine metabolism. Low activity of the COMT gene has been associated with obsessive-compulsive disorder and schizophrenia. Neuregulin 1 is a growth factor that stimulates neuron development and differentiation, and increased neuregulin signaling in schizophrenia may suppress the NMDA receptor, leading to lowered glutamate levels. Dysbindin is involved in the biogenesis of lysosome-related organelles, and its expression is decreased in schizophrenia. DISC1 encodes a multifunctional protein that influences neuronal development and adult brain function, and it is disrupted in schizophrenia. It is located at the breakpoint of a balanced translocation identified in a large Scottish family with schizophrenia, schizoaffective disorder, and other major mental illnesses.

Piaget’s theory of cognitive development highlights that Preoperational children are egocentric, meaning they view the world solely from their own perspective and cannot comprehend that others may have different viewpoints. Piaget believed that cognitive development is a result of the interplay between innate abilities and environmental factors, and progresses through four distinct stages: the sensorimotor stage, Preoperational stage, concrete operational stage, and formal operational stage. While Piaget’s theory has greatly contributed to our understanding of cognitive development, it has also faced criticism over time. Other notable theories in this field include Vygotsky’s theory, Bruner’s theory, and the information-processing approach. Vygotsky’s theory, for instance, examines human development across three levels: cultural, interpersonal, and individual.

Genomic Imprinting and its Role in Psychiatric Disorders

Genomic imprinting is a phenomenon where a piece of DNA behaves differently depending on whether it is inherited from the mother of the father. This is because DNA sequences are marked of imprinted in the ovaries and testes, which affects their expression. In psychiatry, two classic examples of genomic imprinting disorders are Prader-Willi and Angelman syndrome.

Prader-Willi syndrome is caused by a deletion of chromosome 15q when inherited from the father. This disorder is characterized by hypotonia, short stature, polyphagia, obesity, small gonads, and mild mental retardation. On the other hand, Angelman syndrome, also known as Happy Puppet syndrome, is caused by a deletion of 15q when inherited from the mother. This disorder is characterized by an unusually happy demeanor, developmental delay, seizures, sleep disturbance, and jerky hand movements.

Overall, genomic imprinting plays a crucial role in the development of psychiatric disorders. Understanding the mechanisms behind genomic imprinting can help in the diagnosis and treatment of these disorders.

Mitgehen, also known as the ‘anglepoise sign’, refers to a phenomenon where a patient moves in response to very slight pressure, indicating a lack of resistance of rigidity in their muscles. This can be observed in various conditions, including Parkinson’s disease and catatonia.

To obtain an accurate measurement of the QT interval, it is recommended to measure it in lead II of leads V5-6. The Bazett formula may not provide accurate corrections for heart rates above 100 bpm of below 60 bpm, but it can be used to estimate the QT interval at a standard heart rate of 60 bpm through the corrected QT interval (QTc).

QTc Prolongation: Risks and Identification

The QT interval is a measure of the time it takes for the ventricles to repolarize and is calculated from the beginning of the QRS complex to the end of the T wave. However, the QT interval varies with the heart rate, making it difficult to use a single number as a cut-off for a prolonged QT. Instead, a corrected QT interval (QTc) is calculated for each heart rate using various formulas. A QTc over the 99th percentile is considered abnormally prolonged, with approximate values of 470 ms for males and 480 ms for females.

Prolonged QT intervals can lead to torsade de pointes (TdP), a polymorphic ventricular tachycardia that can be fatal if it degenerates into ventricular fibrillation. TdP is characterized by a twisting of the QRS complexes around an isoelectric line and is often asymptomatic but can also be associated with syncope and death. An accurate diagnosis requires an ECG to be recorded during the event. It is important to note that an increase in the QT interval due to a new conduction block should not be considered indicative of acquired LQTS and risk for TdP.

Antidepressants and Their Cardiac Effects

SSRIs are generally recommended for patients with cardiac disease as they may protect against myocardial infarction (MI). Untreated depression worsens prognosis in cardiovascular disease. Post MI, SSRIs and mirtazapine have either a neutral of beneficial effect on mortality. Sertraline is recommended post MI, but other SSRIs and mirtazapine are also likely to be safe. However, citalopram is associated with Torsades de pointes (mainly in overdose). Bupropion, citalopram, escitalopram, moclobemide, lofepramine, and venlafaxine should be used with caution of avoided in those at risk of serious arrhythmia (those with heart failure, left ventricular hypertrophy, previous arrhythmia, of MI).

Tricyclic antidepressants (TCAs) have established arrhythmogenic activity which arises as a result of potent blockade of cardiac sodium channels and variable activity at potassium channels. ECG changes produced include PR, QRS, and QT prolongation and the Brugada syndrome. Lofepramine is less cardiotoxic than other TCAs and seems to lack the overdose arrhythmogenicity of other TCAs. QT changes are not usually seen at normal clinical doses of antidepressants (but can occur, particularly with citalopram/escitalopram). The arrhythmogenic potential of TCAs and other antidepressants is dose-related.

Overall, SSRIs are recommended for patients with cardiac disease, while caution should be exercised when prescribing TCAs and other antidepressants, especially in those at risk of serious arrhythmia. It is important to monitor patients closely for any cardiac effects when prescribing antidepressants.

Multiple Sclerosis: An Overview

Multiple sclerosis is a neurological disorder that is classified into three categories: primary progressive, relapsing-remitting, and secondary progressive. Primary progressive multiple sclerosis affects 5-10% of patients and is characterized by a steady progression with no remissions. Relapsing-remitting multiple sclerosis affects 20-30% of patients and presents with a relapsing-remitting course but does not lead to serious disability. Secondary progressive multiple sclerosis affects 60% of patients and initially presents with a relapsing-remitting course but is then followed by a phase of progressive deterioration.

The disorder typically begins between the ages of 20 and 40 and is characterized by multiple demyelinating lesions that have a preference for the optic nerves, cerebellum, brainstem, and spinal cord. Patients with multiple sclerosis present with a variety of neurological signs that reflect the presence and distribution of plaques. Ocular features of multiple sclerosis include optic neuritis, internuclear ophthalmoplegia, and ocular motor cranial neuropathy.

Multiple sclerosis is more common in women than in men and is seen with increasing frequency as the distance from the equator increases. It is believed to be caused by a combination of genetic and environmental factors, with monozygotic concordance at 25%. Overall, multiple sclerosis is a predominantly white matter disease that can have a significant impact on a patient’s quality of life.

The thalamus is considered the relay station for sensory and motor stimuli. There are three basic types of thalamic nuclei: relay nuclei, association nuclei and non-specific nuclei. Relay nuclei receive very well defined inputs and project this signal to functionally distinct areas of the cerebral cortex. These include the nuclei that relay primary sensations and also the nuclei involved in feedback of cerebellar signals and basal gangliar output.

Without prior knowledge, it would be difficult to accurately answer this question. However, one could make an educated guess by eliminating the options of 5, 9, and: and narrowing down the possible answers.

Pharmacological management of dementia involves the use of acetylcholinesterase inhibitors (AChE inhibitors) and memantine. AChE inhibitors prevent the breakdown of acetylcholine, which is deficient in Alzheimer’s due to the loss of cholinergic neurons. Donepezil, galantamine, and rivastigmine are commonly used AChE inhibitors in the management of Alzheimer’s. However, gastrointestinal side effects such as nausea and vomiting are common with these drugs.

Memantine, on the other hand, is an NMDA receptor antagonist that blocks the effects of pathologically elevated levels of glutamate that may lead to neuronal dysfunction. It has a half-life of 60-100 hours and is primarily renally eliminated. Common adverse effects of memantine include somnolence, dizziness, hypertension, dyspnea, constipation, headache, and elevated liver function tests.

Overall, pharmacological management of dementia aims to improve cognitive function and slow down the progression of the disease. However, it is important to note that these drugs do not cure dementia and may only provide temporary relief of symptoms.

Understanding Prosody and Aprosodias

Prosody refers to the emotional tone of language, which is conveyed through the melodious quality and inflections in the voice. It is affected by various psychiatric and neuropsychiatric illnesses, and disorders in the ability to express of understand the emotional overlay of speech are called aprosodias. Aprosodias are typically caused by dysfunction in areas of the non-dominant hemisphere, usually the right side of the brain.

Executive aprosody, which is the ability to express emotions in speech, can be tested by asking the patient to repeat a neutral sentence with different emotions. It is affected by lesions of the right premotor cortex of the basal ganglia. On the other hand, receptive aprosody, which is the ability to understand emotions in speech, can be tested by asking the patient to identify the emotion conveyed in a neutral sentence with different emotional inflections. It is affected by lesions of the posterior superior right temporal lobe.

Abnormalities of prosody are not specific to any particular disorder, but patients with severe depression, schizophrenia, and pervasive developmental disorders often present with characteristic abnormalities of prosody. For instance, severely depressed patients may have a monotonous, affect-neutral pattern of speech, while patients with schizophrenia may present with abnormal modulation of emphasis and volume of unusual accents. Patients with autism and Asperger’s disorder may have speech patterns that are monotonous, robotic, of singsong in quality.

Cranial Nerve Reflexes

When it comes to questions on cranial nerve reflexes, it is important to match the reflex to the nerves involved. Here are some examples:

– Pupillary light reflex: involves the optic nerve (sensory) and oculomotor nerve (motor).
– Accommodation reflex: involves the optic nerve (sensory) and oculomotor nerve (motor).
– Jaw jerk: involves the trigeminal nerve (sensory and motor).
– Corneal reflex: involves the trigeminal nerve (sensory) and facial nerve (motor).
– Vestibulo-ocular reflex: involves the vestibulocochlear nerve (sensory) and oculomotor, trochlear, and abducent nerves (motor).

Another example of a cranial nerve reflex is the gag reflex, which involves the glossopharyngeal nerve (sensory) and the vagus nerve (motor). This reflex is important for protecting the airway from foreign objects of substances that may trigger a gag reflex. It is also used as a diagnostic tool to assess the function of these nerves.

The muscle spindle is supplied by both sensory and motor nerves. Sensory supply is via Type Ia fibers whereas the motor supply is via gamma motor neurons.

CYP1A2 is responsible for metabolizing caffeine, and it competes with other drugs that are also metabolized by this enzyme. When caffeine is consumed excessively, it can deplete the CYP1A2, leaving none available to metabolize clozapine, resulting in increased levels of clozapine. However, this is not a common issue in clinical settings.

The Cytochrome P450 system is a group of enzymes that metabolize drugs by altering their functional groups. The system is located in the liver and small intestine and is involved in drug interactions through enzyme induction of inhibition. Notable inducers include smoking, alcohol, and St John’s Wort, while notable inhibitors include grapefruit juice and some SSRIs. CYP2D6 is important due to genetic polymorphism, and CYP3A4 is the most abundant subfamily and is commonly involved in interactions. Grapefruit juice inhibits both CYP1A2 and CYP3A4, while tobacco smoking induces CYP1A2. The table summarizes the main substrates, inhibitors, and inducers for each CYP enzyme.

Debrisoquine hydroxylase is responsible for the metabolism of several antidepressants such as tricyclics, SSRIs, venlafaxine, and others. Poor metabolisers may experience more side effects from these medications, while ultra-rapid metabolisers may require higher doses.

The Cytochrome P450 system is a group of enzymes that metabolize drugs by altering their functional groups. The system is located in the liver and small intestine and is involved in drug interactions through enzyme induction of inhibition. Notable inducers include smoking, alcohol, and St John’s Wort, while notable inhibitors include grapefruit juice and some SSRIs. CYP2D6 is important due to genetic polymorphism, and CYP3A4 is the most abundant subfamily and is commonly involved in interactions. Grapefruit juice inhibits both CYP1A2 and CYP3A4, while tobacco smoking induces CYP1A2. The table summarizes the main substrates, inhibitors, and inducers for each CYP enzyme.

Tau and Tauopathies

Tau proteins are essential for maintaining the stability of microtubules in neurons. Microtubules provide structural support to the cell and facilitate the transport of molecules within the cell. Tau proteins are predominantly found in the axons of neurons and are absent in dendrites. The gene that codes for tau protein is located on chromosome 17.

When tau proteins become hyperphosphorylated, they clump together, forming neurofibrillary tangles. This process leads to the disintegration of cells, which is a hallmark of several neurodegenerative disorders collectively known as tauopathies.

The major tauopathies include Alzheimer’s disease, Pick’s disease (frontotemporal dementia), progressive supranuclear palsy, and corticobasal degeneration. These disorders are characterized by the accumulation of tau protein in the brain, leading to the degeneration of neurons and cognitive decline. Understanding the role of tau proteins in these disorders is crucial for developing effective treatments for these devastating diseases.

QTc Prolongation: Risks and Identification

The QT interval is a measure of the time it takes for the ventricles to repolarize and is calculated from the beginning of the QRS complex to the end of the T wave. However, the QT interval varies with the heart rate, making it difficult to use a single number as a cut-off for a prolonged QT. Instead, a corrected QT interval (QTc) is calculated for each heart rate using various formulas. A QTc over the 99th percentile is considered abnormally prolonged, with approximate values of 470 ms for males and 480 ms for females.

Prolonged QT intervals can lead to torsade de pointes (TdP), a polymorphic ventricular tachycardia that can be fatal if it degenerates into ventricular fibrillation. TdP is characterized by a twisting of the QRS complexes around an isoelectric line and is often asymptomatic but can also be associated with syncope and death. An accurate diagnosis requires an ECG to be recorded during the event. It is important to note that an increase in the QT interval due to a new conduction block should not be considered indicative of acquired LQTS and risk for TdP.

Serotonin (5-hydroxytryptamine, 5-HT) receptors are primarily G protein receptors, except for 5-HT3, which is a ligand-gated receptor. It is important to remember that 5-HT3 is most commonly associated with nausea. Additionally, 5-HT7 is linked to circadian rhythms. The stimulation of 5-HT2 receptors is believed to be responsible for the side effects of insomnia, agitation, and sexual dysfunction that are associated with the use of selective serotonin reuptake inhibitors (SSRIs).

Courtesy stigma, also known as stigma by association, is a genuine type of stigma that targets individuals who are connected to those with mental health issues, such as family members and healthcare providers. The remaining terms are not valid.

Stigma is a term used to describe the negative attitudes and beliefs that people hold towards individuals who are different from them. There are several types of stigma, including discredited and discreditable stigma, felt stigma, enacted stigma, and courtesy stigma. Discredited stigma refers to visible stigmas such as race, gender, of physical disability, while discreditable stigma refers to concealable stigmas such as mental illness of HIV infection. Felt stigma is the shame and fear of discrimination that prevents people from seeking help, while enacted stigma is the experience of unfair treatment by others. Finally, courtesy stigma refers to the stigma that attaches to those who are associated with a stigmatized person.

The First Pass Effect in Psychiatric Drugs

The first-pass effect is a process in drug metabolism that significantly reduces the concentration of a drug before it reaches the systemic circulation. This phenomenon is related to the liver and gut wall, which absorb and metabolize the drug before it can enter the bloodstream. Psychiatric drugs are not exempt from this effect, and some undergo a significant reduction in concentration before reaching their target site. Examples of psychiatric drugs that undergo a significant first-pass effect include imipramine, fluphenazine, morphine, diazepam, and buprenorphine. On the other hand, some drugs undergo little to no first-pass effect, such as lithium and pregabalin.

Orally administered drugs are the most affected by the first-pass effect. However, there are other routes of administration that can avoid of partly avoid this effect. These include sublingual, rectal (partly avoids first pass), intravenous, intramuscular, transdermal, and inhalation. Understanding the first-pass effect is crucial in drug development and administration, especially in psychiatric drugs, where the concentration of the drug can significantly affect its efficacy and safety.

The only factor that indicates a poor prognosis in schizophrenia is the presence of severe negative symptoms at the onset. On the other hand, good prognostic indicators include acute onset, being married, and female gender. Age of onset and first rank symptoms do not have consistent evidence as prognostic indicators. However, if severe negative symptoms are present at onset, it is likely that the individual will have a poor quality of life and impaired psychosocial functioning at the two-year follow-up.

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.

Freud’s The Psychopathology of Everyday Life was written in 1901, while The Interpretation of Dreams was written in 1899, Mourning and Melancholia in 1917, and The Ego and the Id in 1923. Man and Superman was a play written by George Bernard Shaw in 1903 and is unrelated to Freud’s works.

The cortex is composed of neurons, with the majority being pyramidal neurons that are excitatory and contain glutamate. Grey matter is where neural cell bodies are located, while white matter mainly consists of myelinated axon tracts. The color contrast between the two is due to the white appearance of myelin.

The Cerebral Cortex and Neocortex

The cerebral cortex is the outermost layer of the cerebral hemispheres and is composed of three parts: the archicortex, paleocortex, and neocortex. The neocortex accounts for 90% of the cortex and is involved in higher functions such as thought and language. It is divided into 6-7 layers, with two main cell types: pyramidal cells and nonpyramidal cells. The surface of the neocortex is divided into separate areas, each given a number by Brodmann (e.g. Brodmann’s area 17 is the primary visual cortex). The surface is folded to increase surface area, with grooves called sulci and ridges called gyri. The neocortex is responsible for higher cognitive functions and is essential for human consciousness.

Agomelatine is a newly developed antidepressant that primarily targets the melatonin receptors, but its antidepressant properties stem from its ability to block serotonin receptors.

The hypoglossal nerve (nerve XII) is responsible for controlling the motor functions of the tongue and the muscles surrounding the hyoid bone. As a result, when there is a lesion on the right side, the tongue will tend to deviate towards that side. It is important to note that the hypoglossal nerve is purely a motor nerve and does not have any sensory component.

Overview of Cranial Nerves and Their Functions

The cranial nerves are a complex system of nerves that originate from the brain and control various functions of the head and neck. There are twelve cranial nerves, each with a specific function and origin. The following table provides a simplified overview of the cranial nerves, including their origin, skull exit, modality, and functions.

The first cranial nerve, the olfactory nerve, originates from the telencephalon and exits through the cribriform plate. It is a sensory nerve that controls the sense of smell. The second cranial nerve, the optic nerve, originates from the diencephalon and exits through the optic foramen. It is a sensory nerve that controls vision.

The third cranial nerve, the oculomotor nerve, originates from the midbrain and exits through the superior orbital fissure. It is a motor nerve that controls eye movement, pupillary constriction, and lens accommodation. The fourth cranial nerve, the trochlear nerve, also originates from the midbrain and exits through the superior orbital fissure. It is a motor nerve that controls eye movement.

The fifth cranial nerve, the trigeminal nerve, originates from the pons and exits through different foramina depending on the division. It is a mixed nerve that controls chewing and sensation of the anterior 2/3 of the scalp. It also tenses the tympanic membrane to dampen loud noises.

The sixth cranial nerve, the abducens nerve, originates from the pons and exits through the superior orbital fissure. It is a motor nerve that controls eye movement. The seventh cranial nerve, the facial nerve, also originates from the pons and exits through the internal auditory canal. It is a mixed nerve that controls facial expression, taste of the anterior 2/3 of the tongue, and tension on the stapes to dampen loud noises.

The eighth cranial nerve, the vestibulocochlear nerve, originates from the pons and exits through the internal auditory canal. It is a sensory nerve that controls hearing. The ninth cranial nerve, the glossopharyngeal nerve, originates from the medulla and exits through the jugular foramen. It is a mixed nerve that controls taste of the posterior 1/3 of the tongue, elevation of the larynx and pharynx, and swallowing.

The tenth cranial nerve, the vagus nerve, also originates from the medulla and exits through the jugular foramen. It is a mixed nerve that controls swallowing, voice production, and parasympathetic supply to nearly all thoracic and abdominal viscera. The eleventh cranial nerve, the accessory nerve, originates from the medulla and exits through the jugular foramen. It is a motor nerve that controls shoulder shrugging and head turning.

The twelfth cranial nerve, the hypoglossal nerve, originates from the medulla and exits through the hypoglossal canal. It is a motor nerve that controls tongue movement. Overall, the cranial nerves play a crucial role in controlling various functions of the head and neck, and any damage of dysfunction can have significant consequences.

Undoing and sublimation are two psychological concepts that are often mistaken for each other. While both involve a person’s attempt to deal with negative thoughts of emotions, there is a key difference between the two.

In undoing, a person tries to undo of neutralize their own unacceptable thoughts, emotions, of behaviors. This is often driven by feelings of guilt or remorse over something they have done of felt. The goal is to make amends and alleviate the negative feelings associated with their actions.

On the other hand, sublimation involves turning negative emotions into positive ones. However, unlike undoing, the person does not necessarily feel guilty of remorseful about their emotions. Instead, they may see their emotions as justified and seek to channel them into more positive outlets.

Therefore, while both undoing and sublimation involve coping with negative emotions, the key difference lies in the underlying motivation and feelings associated with the process.

Intermediate Mechanism: Rationalisation

Rationalisation is a defense mechanism commonly used by individuals to create false but credible justifications for their behavior of actions. It involves the use of logical reasoning to explain away of justify unacceptable behavior of feelings. The individual may not be aware that they are using this mechanism, and it can be difficult to identify in oneself.

Rationalisation is considered an intermediate mechanism, as it is common in healthy individuals from ages three to ninety, as well as in neurotic disorders and in mastering acute adult stress. It can be dramatically changed by conventional psychotherapeutic interpretation.

Examples of rationalisation include a student who fails an exam and blames the teacher for not teaching the material well enough, of a person who cheats on their partner and justifies it by saying their partner was neglectful of unaffectionate. It allows the individual to avoid taking responsibility for their actions and to maintain a positive self-image.

Overall, rationalisation can be a useful defense mechanism in certain situations, but it can also be harmful if it leads to a lack of accountability and an inability to learn from mistakes.

Childhood separation anxiety disorder is linked to a higher likelihood of developing affective and neurotic disorders in the future, but it is not considered a cause of schizophrenia. The development of schizophrenia is thought to be influenced by various factors, including a family history of the disorder, specific genes that increase the risk, complications during birth, infections experienced by the mother of child, malnutrition during pregnancy, being born in the winter, having an older father, delayed developmental milestones, and substance abuse, particularly cannabis.

The examiner’s use of minimal force to move the patient’s arm is an instance of automatic obedience, but it can be categorized more precisely as mitgehen, which represents a heightened form of automatic obedience.

– Catatonia is a psychiatric syndrome characterized by disturbed motor functions, mood, and thought.
– Key behaviors associated with catatonia include stupor, posturing, waxy flexibility, negativism, automatic obedience, mitmachen, mitgehen, ambitendency, psychological pillow, forced grasping, obstruction, echopraxia, aversion, mannerisms, stereotypies, motor perseveration, echolalia, and logorrhoea.
– These behaviors are often tested in exam questions.
– Karl Ludwig Kahlbaum is credited with the original clinical description of catatonia.

Autism and Genetics

Research has shown that there is a strong genetic component to autism. In fact, siblings of individuals with autism are significantly more likely to develop the disorder than someone in the general population. Twin studies have also demonstrated the high heritability of autism, but have also highlighted the genetic complexity of the disorder. Monozygotic twins have a concordance rate of 60-90%, while dizygotic twins have a concordance rate closer to 30%. Despite this, the molecular genetics of autism is still not well understood. Copy number variations (CNVs) have been implicated, along with a number of candidate genes. Further research is needed to fully understand the genetic basis of autism.

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.