Punding is compulsive performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting objects. It can also apply to digital objects, such as computer files and data. The term was originally coined to describe complex, prolonged, purposeless, and stereotyped behaviour in phenmetrazine and chronic amphetamine users, by Swedish forensic psychiatrist G. Rylander, in 1968. [1] It was later described in Parkinson's disease, [2] [3] but mainly in cases of patients being treated with dopaminergic drugs. [4] It has also been described in methamphetamine and cocaine users, as well as in some patients with gambling addictions, and hypersexuality. [5]
For example, punding may consist of activities such as collecting pebbles and lining them up as perfectly as possible; disassembling and reassembling wristwatches; or conducting extended monologues devoid of context. [6]
People engaging in punding find immersion in such activities comforting, even when it serves no purpose, and generally find it very frustrating to be diverted from them. They are not generally aware that there is a compulsive element, but will continue even when they have good reason to stop. Rylander describes a burglar who started punding and could not stop, even though he was suffering from an increasing apprehension of being caught. [7] Interrupting can lead to various responses, including anger or rage, sometimes to the point of violence. [8]
Punding has been linked primarily to an overstimulation of the dopamine D1 receptors and, to a lesser extent, of D2 receptors, which has been proposed to lead to substantial changes in the striatum (especially its dorsal and ventral areas) and the nucleus accumbens, some of the main dopaminergic areas of the brain regulating psychomotoric functions and reward mechanisms. On the other hand, it has been noted that patients with Parkinson's disease treated with dopaminergic drugs that selectively activate only D3 receptors are the least likely to develop punding. [4]
Treatment is mostly the same as for the dopamine dysregulation syndrome, but will vary depending on the cause: for patients with Parkinson's disease, doses of dopaminergic drugs such as levodopa must be reduced; [9] [10] while people addicted to dopaminergic stimulants like cocaine or amphetamines should be counseled on their issues of addiction and referred to an appropriate drug rehabilitation program. [11]
Medications that have proven effective in the treatment of punding are atypical antipsychotics like quetiapine or clozapine. [12] [11] Amantadine has also reported to be fairly effective, while memantine, an analog of amantadine with a more targeted pharmacological profile has not been evaluated but would presumably have similar efficacy to amantadine. [11] [4] [13] Selective serotonin reuptake inhibitors have been found to be of virtually no use, although in a handful of cases they have led to the resolution of symptoms, especially sertraline but only in high doses (the fact that sertraline also activates Dopamine D2 receptors is presumably involved). [10]
While treating the root cause is considered to be the mainstay of treatment, in cases where a reduction in the consumption of dopaminergic substances of any kind (medications or drugs) is unacceptable (such as when reducing the dose of levodopa in a patient with Parkinson's disease would lead to an unacceptable worsening of the symptoms), are the type of situations when medications are most frequently considered, usually as add-on therapies. [10]
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotic (neuroleptic) medications. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures.
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower extremities. Discoordination can also occur internally especially with the respiratory muscles and it often goes unrecognized. Dyskinesia is a symptom of several medical disorders that are distinguished by their underlying cause.
Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because of widespread drug resistance. It acts as a nicotinic antagonist, dopamine agonist, and noncompetitive NMDA antagonist. The antiviral mechanism of action is antagonism of the influenzavirus A M2 proton channel, which prevents endosomal escape.
A stereotypy is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are found especially in people with autism spectrum disorders and visually impaired children, and are also found in intellectual disabilities, tardive dyskinesia and stereotypic movement disorder, yet may also be encountered in neurotypical individuals as well. Studies have shown stereotypies associated with some types of schizophrenia. Frontotemporal dementia is also a common neurological cause of repetitive behaviors and stereotypies. Several causes have been hypothesized for stereotypy, and several treatment options are available.
Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinson's disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases.
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.
Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.
A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. The use of dopamine agonists is associated with impulse control disorders and dopamine agonist withdrawal syndrome (DAWS).
In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. At present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms.
Dihydroergocryptine (DHEC), sold under the brand names Almirid and Cripar among others, is a dopamine agonist of the ergoline group that is used as an antiparkinson agent in the treatment of Parkinson's disease. It is taken by mouth.
Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dopamine agonist medications for an extended period of time. It is characterized by problems such as addiction to medication, gambling, or sexual behavior.
Parkinson's disease (PD), or simply Parkinson's, is a chronic degenerative disorder of the central nervous system that affects both the motor system and non-motor systems. The symptoms usually emerge slowly, and as the disease progresses, non-motor symptoms become more common. Early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Problems may also arise with cognition, behaviour, sleep, and sensory systems. Parkinson's disease dementia is common in advanced stages.
Levodopa-induced dyskinesia (LID) is a form of dyskinesia associated with levodopa (l-DOPA), used to treat Parkinson's disease. It often involves hyperkinetic movements, including chorea, dystonia, and athetosis.
Pardoprunox (INN) is an antiparkinsonian drug developed by Solvay for the treatment of Parkinson's disease that reached phase III clinical trials before being discontinued. It was also being investigated for the treatment of depression and anxiety but these indications appear to have been abandoned as well.
Sarizotan (EMD-128,130) is a selective 5-HT1A receptor agonist and D2 receptor antagonist, which has antipsychotic effects, and has also shown efficacy in reducing dyskinesias resulting from long-term anti-Parkinsonian treatment with levodopa.
OSU-6162 (PNU-96391) is a compound which acts as a partial agonist at both dopamine D2 receptors and 5-HT2A receptors. It acts as a dopamine stabilizer in a similar manner to the closely related drug pridopidine, and has antipsychotic, anti-addictive and anti-Parkinsonian effects in animal studies. Both enantiomers show similar activity but with different ratios of effects, with the (S) enantiomer (–)-OSU-6162 that is more commonly used in research, having higher binding affinity to D2 but is a weaker partial agonist at 5-HT2A, while the (R) enantiomer (+)-OSU-6162 has higher efficacy at 5-HT2A but lower D2 affinity.
Mevidalen (developmental code name LY-3154207) is a dopaminergic drug which is under development for the treatment of Lewy body disease, including those with Parkinson's disease. It acts as a selective positive allosteric modulator (PAM) of the dopamine D1 receptor. The drug is orally active and crosses the blood–brain barrier. It is a tetrahydroisoquinoline and is a close analogue of DETQ, another D1 receptor PAM. Mevidalen has been found to have wakefulness-promoting effects in sleep-deprived humans. Side effects of mevidalen have been reported to include increased heart rate and blood pressure, insomnia, dizziness, nausea, vomiting, anxiety, nervousness, fatigue, headaches, palpitations, and contact dermatitis, as well as falls in those with dementia. As of March 2022, mevidalen is in phase 2 clinical trials for the treatment of Lewy body disease. Besides for movement disorders and dementia, D1 receptor PAMs like mevidalen might have value in the treatment of certain neuropsychiatric disorders, such as depression, excessive somnolence, and attention deficit hyperactivity disorder.