Neurological disorder

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Neurological_disorder 

 

Neurological disorder
Neurons in person with epilepsy, 40x magnified.
Specialty	Neurology

A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor coordination, loss of sensation, seizures, confusion, pain and altered levels of consciousness. There are many recognized neurological disorders, some relatively common, but many rare. They may be assessed by neurological examination, and studied and treated within the specialities of neurology and clinical neuropsychology.

Interventions for neurological disorders include preventive measures, lifestyle changes, physiotherapy or other therapy, neurorehabilitation, pain management, medication, operations performed by neurosurgeons or a specific diet. The World Health Organization estimated in 2006 that neurological disorders and their sequelae (direct consequences) affect as many as one billion people worldwide, and identified health inequalities and social stigma/discrimination as major factors contributing to the associated disability and suffering.

Causes

Part of the causal chain leading to Alzheimer's disease.

Although the brain and spinal cord are surrounded by tough membranes, enclosed in the bones of the skull and spinal vertebrae, and chemically isolated by the blood–brain barrier, they are very susceptible if compromised. Nerves tend to lie deep under the skin but can still become exposed to damage. Individual neurons, and the neural circuits and nerves into which they form, are susceptible to electrochemical and structural disruption. Neuroregeneration may occur in the peripheral nervous system and thus overcome or work around injuries to some extents, but it is thought to be rare in the brain and spinal cord.

The specific causes of neurological problems vary, but can include genetic disorders, congenital abnormalities or disorders, infections, lifestyle or environmental health problems including malnutrition, and brain injury, spinal cord injury, nerve injury and gluten sensitivity (with or without intestinal damage or digestive symptoms). Metal poisoning, where metals accumulate in the human body and disrupt biological processes, has been reported to induce neurological problems, at least in the case of lead. The neurological problem may start in another body system that interacts with the nervous system. For example, cerebrovascular disorders involve brain injury due to problems with the blood vessels (cardiovascular system) supplying the brain; autoimmune disorders involve damage caused by the body's own immune system; lysosomal storage diseases such as Niemann-Pick disease can lead to neurological deterioration. The National Institutes of Health recommend considering the evaluation of an underlying celiac disease in people with unexplained neurological symptoms, particularly peripheral neuropathy or ataxia.

In a substantial minority of cases of neurological symptoms, no neural cause can be identified using current testing procedures, and such "idiopathic" conditions can invite different theories about what is occurring.

Numerous examples have been described of neurological disorders that are associated with mutated DNA repair genes. Inadequate repair of DNA damages can lead directly to cell death and neuron depletion as well as disruptions in the pattern of epigenetic alterations required for normal neuronal function.

Classification

Deaths due to neurological conditions per million persons 2012

  18-52

  53-68

  69-84

  85-99

  100-131

  132-157

  158-186

  187-243

  244-477

  478-1,482

Neurological disorders can be categorized according to the primary location affected, the primary type of dysfunction involved, or the primary type of cause. The broadest division is between central nervous system disorders and peripheral nervous system disorders. The Merck Manual lists brain, spinal cord and nerve disorders in the following overlapping categories:

Nervous system
The Human Nervous System.
Identifiers
MeSH	D009422
Anatomical terminology

• Brain:
  • Brain damage according to cerebral lobe (see also 'lower' brain areas such as basal ganglia, cerebellum, brainstem):
    • Frontal lobe damage
    • Parietal lobe damage
    • Temporal lobe damage
    • Occipital lobe damage
  • Brain dysfunction according to type:
    • Aphasia (language)
    • Dysgraphia (writing)
    • Dysarthria (speech)
    • Apraxia (patterns or sequences of movements)
    • Agnosia (identifying things or people)
    • Amnesia (memory)
• Spinal cord disorders (see spinal pathology, injury, inflammation)
• Peripheral neuropathy and other Peripheral nervous system disorders
• Cranial nerve disorder such as Trigeminal neuralgia
• Autonomic nervous system disorders such as dysautonomia, multiple system atrophy
• Seizure disorders such as epilepsy
• Movement disorders of the central and peripheral nervous system such as Parkinson's disease, essential tremor, amyotrophic lateral sclerosis, Tourette's syndrome, multiple sclerosis and various types of peripheral neuropathy
• Sleep disorders such as narcolepsy
• Migraines and other types of headache such as cluster headache and tension headache
• Lower back and neck pain (see back pain)
• Central neuropathy (see neuropathic pain)
• Neuropsychiatric illnesses (diseases and/or disorders with psychiatric features associated with known nervous system injury, underdevelopment, biochemical, anatomical, or electrical malfunction, and/or disease pathology e.g. attention deficit hyperactivity disorder, autism, Asperger syndrome, Tourette's syndrome and some cases of obsessive compulsive disorder as well as the neurobehavioral associated symptoms of degeneratives of the nervous system such as Parkinson's disease, essential tremor, Huntington's disease, Alzheimer's disease, multiple sclerosis and organic psychosis.)

Many of the diseases and disorders listed above have neurosurgical treatments available (e.g. Tourette's syndrome, Parkinson's disease, essential tremor and obsessive compulsive disorder).

• Delirium and dementia such as Alzheimer's disease
• Dizziness and vertigo
• Stupor and coma
• Head injury
• Stroke (CVA, cerebrovascular attack)
• Tumors of the nervous system (e.g. cancer)
• Multiple sclerosis and other demyelinating diseases
• Infections of the brain or spinal cord (including meningitis)
• Prion diseases (a type of infectious agent)
• Complex regional pain syndrome (a chronic pain condition)

Neurological disorders in non-human animals are treated by veterinarians.

Mental functioning

A neurological examination can, to some extent, assess the impact of neurological damage and disease on brain function in terms of behavior, memory or cognition. Behavioral neurology specializes in this area. In addition, clinical neuropsychology uses neuropsychological assessment to precisely identify and track problems in mental functioning, usually after some sort of brain injury or neurological impairment.

Alternatively, a condition might first be detected through the presence of abnormalities in mental functioning, and further assessment may indicate an underlying neurological disorder. There are sometimes unclear boundaries in the distinction between disorders treated within neurology, and mental disorders treated within the other medical specialty of psychiatry, or other mental health professions such as clinical psychology. In practice, cases may present as one type but be assessed as more appropriate to the other. Neuropsychiatry deals with mental disorders arising from specific identified diseases of the nervous system.

One area that can be contested is in cases of idiopathic neurological symptoms - conditions where the cause cannot be established. It can be decided in some cases, perhaps by exclusion of any accepted diagnosis, that higher-level brain/mental activity is causing symptoms, rather than the symptoms originating in the area of the nervous system from which they may appear to originate. Classic examples are "functional" seizures, sensory numbness, "functional" limb weakness and functional neurological deficit ("functional" in this context is usually contrasted with the old term "organic disease"). Such cases may be contentiously interpreted as being "psychological" rather than "neurological". Some cases may be classified as mental disorders, for example as conversion disorder, if the symptoms appear to be causally linked to emotional states or responses to social stress or social contexts.

On the other hand, dissociation refers to partial or complete disruption of the integration of a person's conscious functioning, such that a person may feel detached from one's emotions, body and/or immediate surroundings. At one extreme this may be diagnosed as depersonalization disorder. There are also conditions viewed as neurological where a person appears to consciously register neurological stimuli that cannot possibly be coming from the part of the nervous system to which they would normally be attributed, such as phantom pain or synesthesia, or where limbs act without conscious direction, as in alien hand syndrome. Theories and assumptions about consciousness, free will, moral responsibility and social stigma can play a part in this, whether from the perspective of the clinician or the patient.

Some of the fields that contribute to understanding mental functioning

Conditions that are classed as mental disorders, or learning disabilities and forms of intellectual disability, are not themselves usually dealt with as neurological disorders. Biological psychiatry seeks to understand mental disorders in terms of their basis in the nervous system, however. In clinical practice, mental disorders are usually indicated by a mental state examination, or other type of structured interview or questionnaire process. At the present time, neuroimaging (brain scans) alone cannot accurately diagnose a mental disorder or tell the risk of developing one; however, it can be used to rule out other medical conditions such as a brain tumor. In research, neuroimaging and other neurological tests can show correlations between reported and observed mental difficulties and certain aspects of neural function or differences in brain structure. In general, numerous fields intersect to try to understand the basic processes involved in mental functioning, many of which are brought together in cognitive science. The distinction between neurological and mental disorders can be a matter of some debate, either in regard to specific facts about the cause of a condition or in regard to the general understanding of brain and mind.

Moreover, the definition of disorder in medicine or psychology is sometimes contested in terms of what is considered abnormal, dysfunctional, harmful or unnatural in neurological, evolutionary, psychometric or social terms.

Essential tremor

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Essential_tremor 

 

Essential tremor
Other names	Idiopathic tremor
Archimedean spiral drawings from a man with a unilateral essential tremor. The spiral on the left was drawn by the subject using the left hand, and the one on the right using the right hand.
Specialty	Neurology
Usual onset	Any age, but typically after 40
Causes	Unknown
Risk factors	Family history, exposure to particular toxins
Diagnostic method	Based on symptoms
Differential diagnosis	Cerebellar tremor, dystonic tremor, multiple sclerosis, Parkinson's disease
Treatment	Medications, surgery
Medication	Beta blockers, primidone, anti-epileptics, topiramate, gabapentin, levetiracetam, benzodiazepines
Frequency	Annual incidence of 23.7 per 100,000 (2010)

Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations (oscillations or twitching movements) of certain muscle groups in one or more body parts of unknown cause. It typically is symmetrical, and affects the arms, hands, or fingers; but sometimes involves the head, vocal cords, or other body parts.  Essential tremor is either an action (intention) tremor—it intensifies when one tries to use the affected muscles during voluntary movements such as eating and writing—or it is a postural tremor, present with sustained muscle tone. This means that it is distinct from a resting tremor, such as that caused by Parkinson's disease, which is not correlated with movement.

Essential tremor is a progressive neurological disorder, and the most common movement disorder. Its onset is usually after age 40, but it can occur at any age. The cause is unknown. Diagnosis is by observing the typical pattern of the tremor coupled with the exclusion of known causes of such a tremor.

While essential tremor is distinct from Parkinson's disease, which causes a resting tremor, essential tremor is nevertheless sometimes misdiagnosed as Parkinson's disease. Some patients have been found to have both essential tremors and resting tremors.

Treatments for essential tremor include medications, typically given sequentially to determine which is most effective coupled with which has the least troublesome side effects. Clostridium botulinum toxin (Botox) injections and ultrasound are also sometimes used for cases refractory to medications.

Signs and symptoms

In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in vibrato, and difficulty doing small, precise tasks such as threading a needle. Even simple tasks such as cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a person's activities of daily living, including feeding, dressing, and taking care of personal hygiene. Essential tremor generally presents as a rhythmic tremor (4–12 Hz) that occurs only when the affected muscle is exerting effort. Any sort of physical or mental stress tends to make the tremor worse.

The tremor may also occur in the head (neck), jaw, and voice, as well as other body regions, with the general pattern being that the tremor begins in the arms and then spreads to these other regions in some people. Women are more likely to develop the head tremor than are men. Other types of tremor may also occur, including postural tremor of the outstretched arms, intention tremor of the arms, and rest tremor in the arms. Some people may have unsteadiness and problems with gait and balance.

ET-related tremors do not occur during sleep, but people with ET sometimes complain of an especially coarse tremor upon awakening that becomes noticeably less coarse within the first few minutes of wakefulness. Tremor and disease activity/intensity can worsen in response to fatigue, strong emotions, low blood sugar, cold and heat, caffeine, lithium salts, some antidepressants, and other factors. Typically, the tremor worsens in "performance" situations, such as when writing a cheque for payment at a store or giving a presentation.

Parkinson's disease and parkinsonism can also occur simultaneously with ET. The degree of tremor, rigidity, and functional disability did not differ from patients with idiopathic Parkinson's disease. Hand tremor predominated (as it did in Parkinson’s disease), and occurred in nearly all cases, followed by head tremor, voice tremor, neck, face, leg, tongue, and trunk tremor. Most other tremors occurred in association with hand tremor. More severe tremors, a lower sleep disorder frequency, and a similar prevalence of other non-motor symptoms also can occur.

Walking difficulties in essential tremor are common. About half of patients have associated dystonia, including cervical dystonia, writer's cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. Olfactory dysfunction (loss of sense of smell) is common in Parkinson’s disease, and has also been reported to occur in patients with essential tremor. A number of patients with essential tremor also exhibit many of the same neuropsychiatric disturbances seen in idiopathic Parkinson's disease.

Essential tremor with tremor onset after the age of 65 has been associated with mild cognitive impairment, as well as dementia; although the link between these conditions, if any, is still not understood.

Essential tremor has two tremor components, central and peripheral. These two tremor components were identified by measuring the tremor of ET patients once with no weights on their hands and then with 1-lb weights on their hands. The addition of the weights resulted in a tremor spectrum with two peaks, one that maintained the same frequency (the central tremor) and one that decreased in frequency (the peripheral tremor). Only with the addition of the weights was the peripheral tremor distinguishable from the central tremor.

Cause

Genetic

The underlying cause of essential tremor is not clear, but many cases seem to be familial. About half of the cases are due to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission. No genes have been identified yet, but genetic linkage has been established with several chromosomal regions.

Toxins

Some environmental factors, including toxins, are also under active investigation, as they may play a role in the disease's cause.

Pathophysiology

In terms of pathophysiology, clinical, physiological and imaging studies point to an involvement of the cerebellum and/or cerebellothalamocortical circuits. Changes in the cerebellum could also be mediated by alcoholic beverage consumption. Purkinje cells are especially susceptible to ethanol excitotoxicity. Impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor. Some cases have Lewy bodies in the locus ceruleus. ET cases that progress to Parkinson's disease are less likely to have had cerebellar problems. Recent neuroimaging studies have suggested that the efficiency of the overall brain functional network in ET is disrupted.

Recent post mortem studies have evidenced alterations in (leucine-rich repeat and Ig domain containing 1 (LINGO1) gene and GABA receptors in the cerebellum of people with essential tremor. HAPT1 mutations have also been linked to ET, as well as to Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

In 2012, the National Toxicology Program concluded that sufficient evidence exists of an association between blood lead exposure at levels >10 μg/dl and essential tremor in adults, and limited evidence at blood lead levels >5 μg/dl.

Diagnosis

Usually, the diagnosis is established on clinical grounds. Tremors can start at any age, from birth through advanced ages (senile tremor). Any voluntary muscle in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the neck (causing the person's head to shake), tongue, and legs. A resting tremor of the hands is sometimes present. Tremor occurring in the legs might be diagnosable as orthostatic tremor.

ET occurs within multiple neurological disorders besides Parkinson's disease. This includes migraine disorders, where co-occurrences between ET and migraines have been examined.

Terminology

This type of tremor is often referred to as "kinetic tremor". Essential tremor has been known as "benign essential tremor", but the adjective "benign" has been removed in recognition of the sometimes disabling nature of the disorder.

Treatment

General measures

Not all individuals with ET require treatment, but many treatment options are available depending on symptom severity. Caffeine and stress should be avoided, and adequate good-quality sleep is recommended.

Oral medications

First-line

When symptoms are sufficiently troublesome to warrant treatment, the first medication choices are beta blockers such as propranolol or alternately, nadolol and timolol. Atenolol and pindolol are not effective for tremor. The anti-epileptic primidone may also be effective.

Propranolol and primidone only have tremor-reducing effects on about half of ET patients, and the effects are moderate.

Second-line

Second-line medications are the anti-epileptics topiramate, gabapentin (as monotherapy) or levetiracetam, or benzodiazepines such as alprazolam.

Third-line

Third-line medications are clonazepam and mirtazapine.

Fourth-line

Theophylline has been used by some practitioners to treat ET, though it may also induce tremor. However, its use is debated due to conflicting data on its efficacy. Some evidence shows that low doses may lead to improvement.

Ethanol has shown superior efficacy to those of benzodiazepines in small trials. It improves tremor in small doses and its effects are usually noticeable within 20 minutes for 3–5 hours, but occasionally appears in a rebound tremor augmentation later.

Some systematic reviews of medications for the treatment of ET have been conducted. A 2017 review of topiramate found limited data and low quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects, a 2017 review of zonisamide found insufficient information to assess efficacy and safety, and a 2016 review of pregabalin determined the effects to be uncertain due to the low quality of evidence.

Botulinum injection

When medications do not control the tremor or the person does not tolerate medication, C. botulinum toxin, deep brain stimulation, or occupational therapy can be helpful. The electrodes for deep brain stimulation are usually placed in the "tremor center" of the brain, the ventral intermediate nucleus of the thalamus.

Ultrasound

Additionally, MRI-guided high-intensity focused ultrasound is a nonsurgical treatment option for people with essential tremor who are medication refractory. MRI-guided high-intensity focused ultrasound does not achieve healing, but can improve the quality of life. While its long-term effects are not yet established, the improvement in tremor score from baseline was durable at 1 year and 2 years following the treatment. To date, reported adverse events and side effects have been mild to moderate. Possible adverse events include gait difficulties, balance disturbances, paresthesias, headache, skin burns with ulcerations, skin retraction, scars, and blood clots. This procedure is contraindicated in pregnant women, persons who have non-MRI compatible implanted metallic devices, allergy to MR contrast agents, cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis, heart conditions, severe hypertension, and ethanol or substance abuse, among others. The US Food and Drug Administration (FDA) approved Insightec’s Exablate Neuro system to treat essential tremor in 2016.

Another treatment for essential tremor is a surgical option; deep brain stimulation is used.

Prognosis

Although essential tremor is often mild, people with severe tremor have difficulty performing many of their routine activities of daily living. ET is generally progressive in most cases (sometimes rapidly, sometimes very slowly), and can be disabling in severe cases.

Epidemiology

ET is one of the most common neurological diseases, with a prevalence around 4% in persons age 40 and older and considerably higher among persons in their 60s, 70s, 80s, with an estimated 20% of individuals in their 90s and over. Aside from enhanced physiological tremor, it is the most common type of tremor and one of the most commonly observed movement disorders.

Society and culture

Actress Katharine Hepburn (1907–2003) had an essential tremor, which she inherited from her grandfather, that caused her head—and sometimes her hands—to shake. The tremor was noticeable by the time of her performance in the 1979 film The Corn is Green, when critics mentioned the "palsy that kept her head trembling". Hepburn's tremor worsened in her later life.

In 2010, musician Daryl Dragon of The Captain and Tennille was diagnosed with essential tremor, with the condition becoming so severe that Dragon was forced to retire from music.

Director-writer-producer-comedian Adam McKay was diagnosed with essential tremor.

Downton Abbey creator Julian Fellowes has the condition, as does the show's character Charlie Carson 

Research

Harmaline is a widely used model of essential tremor (ET) in rodents. Harmaline is thought to act primarily on neurons in the inferior olive. Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally. Harmane or harmaline has been implicated not only in essential tremors, but is also found in greater quantities in the brain fluid of Parkinson's disease sufferers as well as cancer. Higher levels of the neurotoxin are associated with greater severity of the tremors. Harmane is particularly abundant in meats, and certain cooking practices (e.g., long cooking times) increase its concentration, however, at least one study has shown that harmane blood concentrations do not go up after meat consumption in ET patients with already elevated harmane levels, where as the control group's harmane levels increase accordingly, suggesting that another factor, like a metabolic defect, may be responsible for the higher harmane levels in E.T. patients.

Caprylic acid is being researched as a possible treatment for essential tremor. It has currently been approved by the FDA and designated as GRAS, and is used as a food additive and has been studied as part of a ketogenic diet for treatment of epilepsy in children. Research on caprylic acid as a possible treatment for ET begun because researchers recognized that ethanol was effective in reducing tremor, and because of this, they looked into longer-chain alcohols reducing tremor. They discovered that 1-octanol reduced tremor and did not have the negative side effects of ethanol. Pharmacokinetic research on 1-octanol lead to the discovery that 1-octanol metabolized into caprylic acid in the body and that caprylic acid actually was the tremor-reducing agent. Many studies of the effects of caprylic acid on essential tremor have been done, including a dose-escalation study on ET patients and a study testing the effects of caprylic acid on central and peripheral tremor. The dose-escalation study examined doses of 8 mg/kg to 128 mg/kg and determined that these concentrations were safe with mild side effects. The maximum tolerated dose was not reached in this study. The study testing the effects of caprylic acid on central and peripheral tremors determined that caprylic acid reduced both.

Mesolimbic pathway

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Mesolimbic_pathway

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.

The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates incentive salience (e.g. motivation and desire for rewarding stimuli) and facilitates reinforcement and reward-related motor function learning; it may also play a role in the subjective perception of pleasure. The dysregulation of the mesolimbic pathway and its output neurons in the nucleus accumbens plays a significant role in the development and maintenance of an addiction.

Anatomy

The mesolimbic pathway and its positioning in relation to the other dopaminergic pathways

The mesolimbic pathway is a collection of dopaminergic (i.e., dopamine-releasing) neurons that project from the ventral tegmental area (VTA) to the ventral striatum, which includes the nucleus accumbens (NAcc) and olfactory tubercle. It is one of the component pathways of the medial forebrain bundle, which is a set of neural pathways that mediate brain stimulation reward.

The VTA is located in the midbrain and consists of dopaminergic, GABAergic, and glutamatergic neurons. The dopaminergic neurons in this region receive stimuli from both cholinergic neurons in the pedunculopontine nucleus and the laterodorsal tegmental nucleus as well as glutamatergic neurons in other regions such as the prefrontal cortex. The nucleus accumbens and olfactory tubercle are located in the ventral striatum and are primarily composed of medium spiny neurons. The nucleus accumbens is subdivided into limbic and motor subregions known as the NAcc shell and NAcc core. The medium spiny neurons in the nucleus accumbens receive input from both the dopaminergic neurons of the VTA and the glutamatergic neurons of the hippocampus, amygdala, and medial prefrontal cortex. When they are activated by these inputs, the medium spiny neurons' projections release GABA onto the ventral pallidum.

Function

The mesolimbic pathway regulates incentive salience, motivation, reinforcement learning, and fear, among other cognitive processes.

The mesolimbic pathway is involved in motivation cognition. Depletion of dopamine in this pathway, or lesions at its site of origin, decrease the extent to which an animal is willing to go to obtain a reward (e.g. the number of lever presses for intravenous nicotine delivery in rats or time spent searching for food). Dopaminergic drugs are also able to increase the extent an animal is willing to go to obtain a reward. Moreover, the firing rate of neurons in the mesolimbic pathway increases during anticipation of reward, which may explain craving. Mesolimbic dopamine release was once thought to be the primary mediator of pleasure, but is now believed to have only a minor or secondary role in pleasure perception.

Clinical significance

Mechanisms of addiction

The mesolimbic pathway and a specific set of the pathway's output neurons (e.g. D1-type medium spiny neurons within the nucleus accumbens) play a central role in the neurobiology of addiction. Drug addiction is an illness caused by habitual substance abuse that induces chemical changes in the brain's circuitry. Commonly abused substances such as cocaine, alcohol, and nicotine have been shown to increase extracellular levels of dopamine within the mesolimbic pathway, preferentially within the nucleus accumbens. The mechanisms by which these drugs do so vary depending on the drug prototype. For example, cocaine precludes the re-uptake of synaptic dopamine through blocking the presynaptic dopamine transporter. Another stimulant, amphetamine, promotes increased dopamine from the synaptic vesicles. Non-stimulant drugs typically bind with ligand-gated channels or G protein-coupled receptors. Such drugs include alcohol, nicotine, and tetrahydrocannabinol (THC).

These dopaminergic activations of the mesolimbic pathway are accompanied by the perception of reward. This stimulus-reward association shows a resistance to extinction and creates an increased motivation to repeat that same behavior that caused it.

In relation, a 2017 study found that abusive (emotional, physical, and sexual) and adverse life events were associated with a heightened limbic response to cocaine. In other words, individuals who had previously suffered abuse were more likely to have a brain pathway primed for cocaine or drug use.

Relation to neurological and psychological disorders

The mesolimbic pathway is implicated in schizophrenia, depression, and Parkinson's disease. It is also theorized to be implicated in overuse of digital media. Each involves distinct structural changes within the mesolimbic pathway.

Libido

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Libido

Libido (/lɪˈbiːdoʊ/; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. In psychoanalytic theory libido is psychic drive or energy, particularly associated with sexual instinct, but also present in other instinctive desires and drives. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act upon the nucleus accumbens (primarily testosterone and dopamine, respectively) regulate libido in humans. Social factors, such as work and family, and internal psychological factors, such as personality and stress, can affect libido. Libido can also be affected by medical conditions, medications, lifestyle and relationship issues, and age (e.g., puberty). A person who has extremely frequent or a suddenly increased sex drive may be experiencing hypersexuality, while the opposite condition is hyposexuality.

A person may have a desire for sex, but not have the opportunity to act on that desire, or may on personal, moral or religious reasons refrain from acting on the urge. Psychologically, a person's urge can be repressed or sublimated. Conversely, a person can engage in sexual activity without an actual desire for it. Multiple factors affect human sex drive, including stress, illness, pregnancy, and others. A 2001 review found that, on average, men have a higher desire for sex than women.

Sexual desires are often an important factor in the formation and maintenance of intimate relationships in humans. A lack or loss of sexual desire can adversely affect relationships. Changes in the sexual desires of any partner in a sexual relationship, if sustained and unresolved, may cause problems in the relationship. The infidelity of a partner may be an indication that a partner's changing sexual desires can no longer be satisfied within the current relationship. Problems can arise from disparity of sexual desires between partners, or poor communication between partners of sexual needs and preferences.

There is no widely accepted measure of what is a healthy level for sex desire. Some people want to have sex every day, or more than once a day; others once a year or not at all. However, a person who lacks a desire for sexual activity for some period of time may be experiencing a hypoactive sexual desire disorder or may be asexual.

Psychological perspectives

Psychoanalysis

Psychoanalysis

Sigmund Freud

Sigmund Freud, who is considered the originator of the modern use of the term, defined libido as "the energy, regarded as a quantitative magnitude... of those instincts which have to do with all that may be comprised under the word 'love'." It is the instinctual energy or force, contained in what Freud called the id, the strictly unconscious structure of the psyche. He also explained that it is analogous to hunger, the will to power, and so on insisting that it is a fundamental instinct that is innate in all humans.

Freud developed the idea of a series of developmental phases in which the libido fixates on different erogenous zones—first in the oral stage (exemplified by an infant's pleasure in nursing), then in the anal stage (exemplified by a toddler's pleasure in controlling his or her bowels), then in the phallic stage, through a latency stage in which the libido is dormant, to its reemergence at puberty in the genital stage. (Karl Abraham would later add subdivisions in both oral and anal stages.)

Freud pointed out that these libidinal drives can conflict with the conventions of civilised behavior, represented in the psyche by the superego. It is this need to conform to society and control the libido that leads to tension and disturbance in the individual, prompting the use of ego defenses to dissipate the psychic energy of these unmet and mostly unconscious needs into other forms. Excessive use of ego defenses results in neurosis. A primary goal of psychoanalysis is to bring the drives of the id into consciousness, allowing them to be met directly and thus reducing the patient's reliance on ego defenses.

Freud viewed libido as passing through a series of developmental stages within the individual. Failure to adequately adapt to the demands of these different stages could result in libidinal energy becoming 'dammed up' or fixated in these stages, producing certain pathological character traits in adulthood. Thus the psychopathologized individual for Freud was an immature individual, and the goal of psychoanalysis was to bring these fixations to conscious awareness so that the libido energy would be freed up and available for conscious use in some sort of constructive sublimation.

Analytical psychology

According to Swiss psychiatrist Carl Gustav Jung, the libido is identified as the totality of psychic energy, not limited to sexual desire. As Jung states in "The Concept of Libido," "[libido] denotes a desire or impulse which is unchecked by any kind of authority, moral or otherwise. Libido is appetite in its natural state. From the genetic point of view it is bodily needs like hunger, thirst, sleep, and sex, and emotional states or affects, which constitute the essence of libido." The Duality (opposition) creates the energy (or libido) of the psyche, which Jung asserts expresses itself only through symbols: "It is the energy that manifests itself in the life process and is perceived subjectively as striving and desire." (Ellenberger, 697) These symbols may manifest as "fantasy-images" in the process of psychoanalysis which embody the contents of the libido, otherwise lacking in any definite form. Desire, conceived generally as a psychic longing, movement, displacement and structuring, manifests itself in definable forms which are apprehended through analysis.

Defined more narrowly, libido is the mental energy. If is it conserved an individual may gain many benefits

Factors that affect libido

Endogenous compounds

Libido is governed primarily by activity in the mesolimbic dopamine pathway (ventral tegmental area and nucleus accumbens). Consequently, dopamine and related trace amines (primarily phenethylamine) that modulate dopamine neurotransmission play a critical role in regulating libido.

Other neurotransmitters, neuropeptides, and sex hormones that affect sex drive by modulating activity in or acting upon this pathway include:

• Testosterone (directly correlated) – and other androgens
• Estrogen (directly correlated) – and related female sex hormones
• Progesterone (inversely correlated)
• Oxytocin (directly correlated)
• Serotonin (inversely correlated)
• Norepinephrine
• Acetylcholine

Sex hormone levels and the menstrual cycle

A woman's desire for sex is correlated to her menstrual cycle, with many women experiencing a heightened sexual desire in the several days immediately before ovulation, which is her peak fertility period, which normally occurs two days before until two days after the ovulation. This cycle has been associated with changes in a woman's testosterone levels during the menstrual cycle. According to Gabrielle Lichterman, testosterone levels have a direct impact on a woman's interest in sex. According to her, testosterone levels rise gradually from about the 24th day of a woman's menstrual cycle until ovulation on about the 14th day of the next cycle, and during this period the woman's desire for sex increases consistently. The 13th day is generally the day with the highest testosterone levels. In the week following ovulation, the testosterone level is the lowest and as a result women will experience less interest in sex.

Also, during the week following ovulation, progesterone levels increase, resulting in a woman experiencing difficulty achieving orgasm. Although the last days of the menstrual cycle are marked by a constant testosterone level, women's libido may get a boost as a result of the thickening of the uterine lining which stimulates nerve endings and makes a woman feel aroused. Also, during these days, estrogen levels decline, resulting in a decrease of natural lubrication.

Although some specialists disagree with this theory, menopause is still considered by the majority a factor that can cause decreased sex desire in women. The levels of estrogen decrease at menopause and this usually causes a lower interest in sex and vaginal dryness which makes intercourse painful. However, the levels of testosterone increase at menopause and this may be why some women may experience a contrary effect of an increased libido.

Psychological and social factors

Certain psychological or social factors can reduce the desire for sex. These factors can include lack of privacy or intimacy, stress or fatigue, distraction or depression. Environmental stress, such as prolonged exposure to elevated sound levels or bright light, can also affect libido. Other causes include experience of sexual abuse, assault, trauma, or neglect, body image issues, and anxiety about engaging in sexual activity.

Individuals with PTSD may find themselves with reduced sexual desire. Struggling to find pleasure, as well as having trust issues, many with PTSD experience feelings of vulnerability, rage and anger, and emotional shutdowns, which have been shown to inhibit sexual desire in those with PTSD. Reduced sex drive may also be present in trauma victims due to issues arising in sexual function. For women, it has been found that treatment can improve sexual function, thus helping restore sexual desire. Depression and libido decline often coincide, with reduced sex drive being one of the symptoms of depression. Those suffering from depression often report the decline in libido to be far reaching and more noticeable than other symptoms. In addition, those with depression often are reluctant to report their reduced sex drive, often normalizing it with cultural/social values, or by the failure of the physician to inquire about it.

Physical factors

Physical factors that can affect libido include endocrine issues such as hypothyroidism, the effect of certain prescription medications (for example flutamide), and the attractiveness and biological fitness of one's partner, among various other lifestyle factors.

In males, the frequency of ejaculations affects the levels of serum testosterone, a hormone which promotes libido. A study of 28 males aged 21–45 found that all but one of them had a peak (145.7% of baseline [117.8%–197.3%]) in serum testosterone on the 7th day of abstinence from ejaculation.

Anemia is a cause of lack of libido in women due to the loss of iron during the period.

Smoking, alcohol abuse, and the use of certain drugs can also lead to a decreased libido. Moreover, specialists suggest that several lifestyle changes such as exercising, quitting smoking, lowering consumption of alcohol or using prescription drugs may help increase one's sexual desire.

Medications

Some people purposefully attempt to decrease their libido through the usage of anaphrodisiacs. Aphrodisiacs, such as dopaminergic psychostimulants, are a class of drugs which can increase libido. On the other hand, a reduced libido is also often iatrogenic and can be caused by many medications, such as hormonal contraception, SSRIs and other antidepressants, antipsychotics, opioids and beta blockers.

Many SSRIs can cause a long term decrease in libido and other sexual functions, even after users of those drugs have shown improvement in their depression and have stopped usage. Multiple studies have shown that with the exception of bupropion (Wellbutrin), trazodone (Desyrel) and nefazodone (Serzone), antidepressants generally will lead to lowered libido. SSRIs that typically lead to decreased libido are fluoxetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa) and sertraline (Zoloft). There are several ways to try and reap the benefits of the antidepressants while maintaining high enough sex drive levels. Some antidepressant users have tried decreasing their dosage in the hopes of maintaining an adequate sex drive. Results of this are often positive, with both drug effectiveness not reduced and libido preserved. Other users try enrolling in psychotherapy to solve depression-related issues of libido. However, the effectiveness of this therapy is mixed, with lots reporting that it had no or little effect on sexual drive.

Testosterone is one of the hormones controlling libido in human beings. Emerging research is showing that hormonal contraception methods like oral contraceptive pills (which rely on estrogen and progesterone together) are causing low libido in females by elevating levels of sex hormone binding globulin (SHBG). SHBG binds to sex hormones, including testosterone, rendering them unavailable. Research is showing that even after ending a hormonal contraceptive method, SHBG levels remain elevated and no reliable data exists to predict when this phenomenon will diminish.

Oral contraceptives lower androgen levels in users, and lowered androgen levels generally lead to a decrease in sexual desire. However, usage of oral contraceptives has shown to typically not have a connection with lowered libido in women. Multiple studies have shown that usage of oral contraceptives is associated with either a small increase or decrease in libido, with most users reporting a stable sex drive.

Effects of age

Males reach the peak of their sex drive in their teenage years, while females reach it in their thirties. The surge in testosterone hits the male at puberty resulting in a sudden and extreme sex drive which reaches its peak at age 15–16, then drops slowly over his lifetime. In contrast, a female's libido increases slowly during adolescence and peaks in her mid-thirties. Actual testosterone and estrogen levels that affect a person's sex drive vary considerably.

Some boys and girls will start expressing romantic or sexual interest by age 10–12. The romantic feelings are not necessarily sexual, but are more associated with attraction and desire for another. For boys and girls in their preteen years (ages 11–12), at least 25% report "thinking a lot about sex". By the early teenage years (ages 13–14), however, boys are much more likely to have sexual fantasies than girls. In addition, boys are much more likely to report an interest in sexual intercourse at this age than girls. Masturbation among youth is common, with prevalence among the population generally increasing until the late 20s and early 30s. Boys generally start masturbating earlier, with less than 10% boys masturbating around age 10, around half participating by age 11–12, and over a substantial majority by age 13–14. This is in sharp contrast to girls where virtually none are engaging in masturbation before age 13, and only around 20% by age 13–14.

People in their 60s and early 70s generally retain a healthy sex drive, but this may start to decline in the early to mid-70s. Older adults generally develop a reduced libido due to declining health and environmental or social factors. In contrast to common belief, postmenopausal women often report an increase in sexual desire and an increased willingness to satisfy their partner. Women often report family responsibilities, health, relationship problems, and well-being as inhibitors to their sexual desires. Aging adults often have more positive attitudes towards sex in older age due to being more relaxed about it, freedom from other responsibilities, and increased self-confidence. Those exhibiting negative attitudes generally cite health as one of the main reasons. Stereotypes about aging adults and sexuality often regard seniors as asexual beings, doing them no favors when they try to talk about sexual interest with caregivers and medical professionals. Non-western cultures often follow a narrative of older women having a much lower libido, thus not encouraging any sort of sexual behavior for women. Residence in retirement homes has affects on residents' libidos. In these homes, sex occurs, but it is not encouraged by the staff or other residents. Lack of privacy and resident gender imbalance are the main factors lowering desire. Generally, for older adults, being excited about sex, good health, sexual self-esteem and having a sexually talented partner.

Sexual desire disorders

A sexual desire disorder is more common in women than in men, and women tend to exhibit less frequent and less intense sexual desires than men. Erectile dysfunction may happen to the penis because of lack of sexual desire, but these two should not be confused. For example, large recreational doses of amphetamine or methamphetamine can simultaneously cause erectile dysfunction and significantly increase libido. However, men can also experience a decrease in their libido as they age.

The American Medical Association has estimated that several million US women suffer from a female sexual arousal disorder, though arousal is not at all synonymous with desire, so this finding is of limited relevance to the discussion of libido. Some specialists claim that women may experience low libido due to some hormonal abnormalities such as lack of luteinising hormone or androgenic hormones, although these theories are still controversial. Also, women commonly lack sexual desire in the period immediately after giving birth. Moreover, any condition affecting the genital area can make women reject the idea of having intercourse. It has been estimated that half of women experience different health problems in the area of the vagina and vulva, such as thinning, tightening, dryness or atrophy. Frustration may appear as a result of these issues and because many of them lead to painful sexual intercourse, many women prefer not having sex at all. Surgery or major health conditions such as arthritis, cancer, diabetes, high blood pressure, coronary artery disease or infertility may have the same effect in women. Surgery that affects the hormonal levels in women include oophorectomies.