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Friday, March 22, 2019

Health insurance in the United States

From Wikipedia, the free encyclopedia

Health insurance in the United States is any program that helps pay for medical expenses, whether through privately purchased insurance, social insurance, or a social welfare program funded by the government. Synonyms for this usage include "health coverage", "health care coverage", and "health benefits". In a more technical sense, the term "health insurance "is used to describe any form of insurance providing protection against the costs of medical services. This usage includes private insurance and social insurance programs such as Medicare, which pools resources and spreads the financial risk associated with major medical expenses across the entire population to protect everyone, as well as social welfare programs like Medicaid and the Children's Health Insurance Program, which both provide assistance to people who cannot afford health coverage.

In addition to medical expense insurance, "health insurance" may also refer to insurance covering disability or long-term nursing or custodial care needs. Different health insurance provides different levels of financial protection and the scope of coverage can vary widely, with more than 40% of insured individuals reporting that their plans do not adequately meet their needs as of 2007.

The share of Americans without health insurance has been cut in half since 2013. Many of the reforms instituted by the Affordable Care Act of 2010 were designed to extend health care coverage to those without it; however, high cost growth continues unabated. National health expenditures are projected to grow 4.7% per person per year from 2016 to 2025. Public healthcare spending was 29% of federal mandated spending in 1990 and 35% of it in 2000. It is also projected to be roughly half in 2025.

Enrollment and the uninsured

Gallup issued a report in July 2014 stating that the uninsured rate for adults 18 and over declined from 18% in 2013 to 13.4% by in 2014, largely because there were new coverage options and market reforms under the Affordable Care Act. Rand Corporation had similar findings.

Trends in private coverage

The proportion of non-elderly individuals with employer-sponsored cover fell from 66% in 2000 to 56% in 2010, then stabilized following the passage of the Affordable Care Act. Employees who worked part-time (less than 30 hours a week) were less likely to be offered coverage by their employer than were employees who worked full-time (21% vs. 72%).

A major trend in employer sponsored cover has been increasing premiums, deductibles, and co-payments for medical services, and increasing the costs of using out-of-network health providers rather than in-network providers.

Trends in public coverage

Public insurance cover increased from 2000–2010 in part because of an aging population and an economic downturn in the latter part of the decade. Funding for Medicaid and CHIP expanded significantly under the 2010 health reform bill. The proportion of individuals covered by Medicaid increased from 10.5% in 2000 to 14.5% in 2010 and 20% in 2015. The proportion covered by Medicare increased from 13.5% in 2000 to 15.9% in 2010, then decreased to 14% in 2015.

Status of the uninsured

The uninsured proportion was stable at 14–15% from 1990 to 2008, then rose to a peak of 18% in Q3 2013 and rapidly fell to 11% in 2015. The proportion without insurance has stabilized at 9%.

A 2011 study found that there were 2.1 million hospital stays for uninsured patients, accounting for 4.4% ($17.1 billion) of total aggregate inpatient hospital costs in the United States. The costs of treating the uninsured must often be absorbed by providers as charity care, passed on to the insured via cost-shifting and higher health insurance premiums, or paid by taxpayers through higher taxes.

Death

Since people who lack health insurance are unable to obtain timely medical care, they have a 40% higher risk of death in any given year than those with health insurance, according to a study published in the American Journal of Public Health. The study estimated that in 2005 in the United States, there were 45,000 deaths associated with lack of health insurance. A 2008 systematic review found consistent evidence that health insurance increased utilization of services and improved health.

A study at Johns Hopkins Hospital found that heart transplant complications occurred most often amongst the uninsured, and that patients who had private health plans fared better than those covered by Medicaid or Medicare.

Reform

The Affordable Care Act of 2010 was designed primarily to extend health coverage to those without it by expanding Medicaid, creating financial incentives for employers to offer coverage, and requiring those without employer or public coverage to purchase insurance in newly created health insurance exchanges. This requirement for almost all individuals to maintain health insurance is often referred to as the "individual mandate." The CBO has estimated that roughly 33 million who would have otherwise been uninsured will receive coverage because of the act by 2022.

Repeal of the Individual Mandate

The Tax Cuts and Jobs Act of 2017 effectively repealed the individual mandate, meaning that individuals will no longer be penalized for failing to maintain health coverage starting in 2019. The CBO projects that this change will result in four million more uninsured by 2019, 13 million more by 2027.

History

Accident insurance was first offered in the United States by the Franklin Health Assurance Company of Massachusetts. This firm, founded in 1850, offered insurance against injuries arising from railroad and steamboat accidents. Sixty organizations were offering accident insurance in the US by 1866, but the industry consolidated rapidly soon thereafter. While there were earlier experiments, sickness coverage in the US effectively dates from 1890. The first employer-sponsored group disability policy was issued in 1911, but this plan's primary purpose was replacing wages lost because the worker was unable to work, not medical expenses.

Before the development of medical expense insurance, patients were expected to pay all other health care costs out of their own pockets, under what is known as the fee-for-service business model. During the middle to late 20th century, traditional disability insurance evolved into modern health insurance programs. Today, most comprehensive private health insurance programs cover the cost of routine, preventive, and emergency health care procedures, and also most prescription drugs, but this was not always the case. The rise of private insurance was accompanied by the gradual expansion of public insurance programs for those who could not acquire coverage through the market.

Hospital and medical expense policies were introduced during the first half of the 20th century. During the 1920s, individual hospitals began offering services to individuals on a pre-paid basis, eventually leading to the development of Blue Cross organizations in the 1930s. The first employer-sponsored hospitalization plan was created by teachers in Dallas, Texas in 1929. Because the plan only covered members' expenses at a single hospital, it is also the forerunner of today's health maintenance organizations (HMOs).

In 1935 the decision was made by the Roosevelt Administration not to include a large-scale health insurance program as part of the new Social Security program. The problem was not an attack by any organized opposition, such as the opposition from the American Medical Association that derailed Truman's proposals in 1949. Instead, there was a lack of active popular, congressional, or interest group support. Roosevelt's strategy was to wait for a demand and a program to materialize, and then if he thought it popular enough to throw his support behind it. His Committee on Economic Security (CES) deliberately limited the health segment of Social Security to the expansion of medical care and facilities. It considered unemployment insurance to be the major priority. Roosevelt assured the medical community that medicine would be kept out of politics. Jaap Kooijman says he succeeded in "pacifying the opponents without discouraging the reformers." The right moment never came for him to reintroduce the topic.

The rise of employer-sponsored coverage

Employer-sponsored health insurance plans dramatically expanded as a direct result of wage controls imposed by the federal government during World War II. The labor market was tight because of the increased demand for goods and decreased supply of workers during the war. Federally imposed wage and price controls prohibited manufacturers and other employers from raising wages enough to attract workers. When the War Labor Board declared that fringe benefits, such as sick leave and health insurance, did not count as wages for the purpose of wage controls, employers responded with significantly increased offers of fringe benefits, especially health care coverage, to attract workers.

President Harry S. Truman proposed a system of public health insurance in his November 19, 1945, address. He envisioned a national system that would be open to all Americans, but would remain optional. Participants would pay monthly fees into the plan, which would cover the cost of any and all medical expenses that arose in a time of need. The government would pay for the cost of services rendered by any doctor who chose to join the program. In addition, the insurance plan would give cash to the policy holder to replace wages lost because of illness or injury. The proposal was quite popular with the public, but it was fiercely opposed by the Chamber of Commerce, the American Hospital Association, and the AMA, which denounced it as "socialism".

Foreseeing a long and costly political battle, many labor unions chose to campaign for employer-sponsored coverage, which they saw as a less desirable but more achievable goal, and as coverage expanded the national insurance system lost political momentum and ultimately failed to pass. Using health care and other fringe benefits to attract the best employees, private sector, white-collar employers nationwide expanded the U.S. health care system. Public sector employers followed suit in an effort to compete. Between 1940 and 1960, the total number of people enrolled in health insurance plans grew seven-fold, from 20,662,000 to 142,334,000, and by 1958, 75% of Americans had some form of health coverage.

Kerr-Mills Act

Still, private insurance remained unaffordable or simply unavailable to many, including the poor, the unemployed, and the elderly. Before 1965, only half of seniors had health care coverage, and they paid three times as much as younger adults, while having lower incomes. Consequently, interest persisted in creating public health insurance for those left out of the private marketplace.

The 1960 Kerr-Mills Act provided matching funds to states assisting patients with their medical bills. In the early 1960s, Congress rejected a plan to subsidize private coverage for people with Social Security as unworkable, and an amendment to the Social Security Act creating a publicly run alternative was proposed. Finally, President Lyndon B. Johnson signed the Medicare and Medicaid programs into law in 1965, creating publicly run insurance for the elderly and the poor. Medicare was later expanded to cover people with disabilities, end-stage renal disease, and ALS.

State risk pools

In 1976, some states began providing guaranteed-issuance risk pools, which enable individuals who are medically uninsurable through private health insurance to purchase a state-sponsored health insurance plan, usually at higher cost, with high deductibles and possibly lifetime maximums. Minnesota was the first to offer such a plan; 34 states (Alabama, Alaska, Arkansas, California, Colorado, Connecticut, Florida, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maryland, Minnesota, Mississippi, Missouri, Montana, Nebraska, New Hampshire, New Mexico, North Carolina, North Dakota, Oklahoma, Oregon, South Carolina, South Dakota, Tennessee, Texas, Utah, Washington, West Virginia, Wisconsin, Wyoming) now offer them. Plans vary greatly from state to state, both in their costs and benefits to consumers and in their methods of funding and operations.

These risk pools allowed people with pre-existing conditions such as cancer, diabetes, heart disease or other chronic illnesses to be able to switch jobs or seek self-employment without fear of being without health care benefits. While details of the plans varied from state to state, the plans were expensive, with premiums that can be double the average policy, and the pools currently cover only 1 in 25 of the so-called "uninsurable" population—about 182,000 people in the U.S. as of 2004, and about 200,000 in 2008. Additionally, even plans which are not expensive can leave those enrolled with little real health insurance beyond "catastrophic" insurance; for example, one insurance plan through Minnesota's high-risk pool, while costing only $215 per quarter, includes a $10,000 deductible with no preventative or other health care covered unless and until the enrollee has spent $10,000 of their own money during the year on health care. Very sick people can accumulate large medical bills during mandatory waiting periods before their medical expenses are covered, and there are often lifetime expenditure caps (maximums), after which the risk pool no longer pays for any medical expenses.

Efforts to pass a national pool were unsuccessful for many years, but some federal tax money has been awarded to states to innovate and improve their plans. With the Patient Protection and Affordable Care Act, effective from 2014, it has been easier for people with pre-existing conditions to afford regular insurance, since all insurers are fully prohibited from discriminating against or charging higher rates for any individuals based on pre-existing medical conditions. Therefore, most of the state-based pools shut down. Some remain due to statutes which have not been updated, but the also may cover people with gaps in coverage such as undocumented immigrants or Medicare-eligible individuals under the age of 65.

Pre-existing Condition Insurance Plan

The Pre-existing Condition Insurance Plan, or PCIP, is a transitional program created in the Patient Protection and Affordable Care Act (PPACA). Those eligible for PCIP are citizens of the United States or those legally residing in the U.S., who have been uninsured for the last 6 months and "have a pre-existing condition or have been denied health coverage because of their health condition." However, if one has health insurance or is enrolled in a state high risk pool, they are not eligible for PCIP, even if that coverage does not cover their medical condition. PCIP is run by the individual states or through the U.S. Department of Health and Human Services, which has a contract with the Government Employees Health Association, or GEHA, to administer benefits. Both will be funded by the federal government and provide three plan options. These options are the standard, extended, and the Health Savings Account option. PCIP only covers the individual enrollee and does not include family members or dependents. In 2014, the Affordable Care Act provision banning discrimination based on pre-existing conditions will be implemented and PCIP enrollees will be transitioned into new state-based health care exchanges.

Towards universal coverage

Persistent lack of insurance among many working Americans continued to create pressure for a comprehensive national health insurance system. In the early 1970s, there was fierce debate between two alternative models for universal coverage. Senator Ted Kennedy proposed a universal single-payer system, while President Nixon countered with his own proposal based on mandates and incentives for employers to provide coverage while expanding publicly run coverage for low-wage workers and the unemployed. Compromise was never reached, and Nixon's resignation and a series of economic problems later in the decade diverted Congress's attention away from health reform.

The numbers of uninsured Americans and the uninsured rate from 1987 to 2008.
 
Shortly after his inauguration, President Clinton offered a new proposal for a universal health insurance system. Like Nixon's plan, Clinton's relied on mandates, both for individuals and for insurers, along with subsidies for people who could not afford insurance. The bill would have also created "health-purchasing alliances" to pool risk among multiple businesses and large groups of individuals. The plan was staunchly opposed by the insurance industry and employers' groups and received only mild support from liberal groups, particularly unions, which preferred a single payer system. Ultimately it failed after the Republican takeover of Congress in 1994.

Finally achieving universal health coverage remained a top priority among Democrats, and passing a health reform bill was one of the Obama Administration's top priorities. The Patient Protection and Affordable Care Act was similar to the Nixon and Clinton plans, mandating coverage, penalizing employers who failed to provide it, and creating mechanisms for people to pool risk and buy insurance collectively. Earlier versions of the bill included a publicly run insurer that could compete to cover those without employer sponsored coverage (the so-called public option), but this was ultimately stripped to secure the support of moderates. The bill passed the Senate in December 2009 with all Democrats voting in favor and the House in March 2010 with the support of most Democrats. Not a single Republican voted in favor of it either time.

State and federal regulation

Historically, health insurance has been regulated by the states, consistent with the McCarran-Ferguson Act. Details for what health insurance could be sold were up to the states, with a variety of laws and regulations. Model acts and regulations promulgated by the National Association of Insurance Commissioners (NAIC) provide some degree of uniformity state to state. These models do not have the force of law and have no effect unless they are adopted by a state. They are, however, used as guides by most states, and some states adopt them with little or no change.

However, with the Patient Protection and Affordable Care Act, effective since 2014, federal laws have created some uniformity in partnership with the existing state-based system. Insurers are prohibited from discriminating against or charging higher rates for individuals based on pre-existing medical conditions and must offer a standard set of coverage.

California

In 2007, 87% of Californians had some form of health insurance. Services in California range from private offerings: HMOs, PPOs to public programs: Medi-Cal, Medicare, and Healthy Families (SCHIP). Insurers can pay providers a capitation only in the case of HMOs.

California developed a solution to assist people across the state and is one of the few states to have an office devoted to giving people tips and resources to get the best care possible. California's Office of the Patient Advocate was established July 2000 to publish a yearly Health Care Quality Report Card on the top HMOs, PPOs, and Medical Groups and to create and distribute helpful tips and resources to give Californians the tools needed to get the best care.

Additionally, California has a Help Center that assists Californians when they have problems with their health insurance. The Help Center is run by the Department of Managed Health Care, the government department that oversees and regulates HMOs and some PPOs.

Massachusetts

The state passed healthcare reform in 2006 in order to greater decrease the uninsured rate among its citizens. The federal Patient Protection and Affordable Care Act (colloquially known as "Obamacare") is largely based on Massachusetts' health reform. Due to that colloquialism, the Massachusetts reform has been nicknamed as "Romneycare" after then-Governor Mitt Romney.

As of 2017, Massachusetts has the highest rate of insured citizens in the United States at 97%.

Public health care coverage

Public programs provide the primary source of coverage for most seniors and also low-income children and families who meet certain eligibility requirements. The primary public programs are Medicare, a federal social insurance program for seniors (generally persons aged 65 and over) and certain disabled individuals; Medicaid, funded jointly by the federal government and states but administered at the state level, which covers certain very low income children and their families; and CHIP, also a federal-state partnership that serves certain children and families who do not qualify for Medicaid but who cannot afford private coverage. Other public programs include military health benefits provided through TRICARE and the Veterans Health Administration and benefits provided through the Indian Health Service. Some states have additional programs for low-income individuals. In 2011, approximately 60 percent of stays were billed to Medicare and Medicaid—up from 52 percent in 1997.

Medicare

In the United States, Medicare is a federal social insurance program that provides health insurance to people over the age of 65, individuals who become totally and permanently disabled, end stage renal disease (ESRD) patients, and people with ALS. Recent research has found that the health trends of previously uninsured adults, especially those with chronic health problems, improves once they enter the Medicare program. Traditional Medicare requires considerable cost-sharing, but ninety percent of Medicare enrollees have some kind of supplemental insurance—either employer-sponsored or retiree coverage, Medicaid, or a private Medigap plan—that covers some or all of their cost-sharing. With supplemental insurance, Medicare ensures that its enrollees have predictable, affordable health care costs regardless of unforeseen illness or injury. 

As the population covered by Medicare grows, its costs are projected to rise from slightly over 3 percent of GDP to over 6 percent, contributing substantially to the federal budget deficit. In 2011, Medicare was the primary payer for an estimated 15.3 million inpatient stays, representing 47.2 percent ($182.7 billion) of total aggregate inpatient hospital costs in the United States. The Affordable Care Act took some steps to reduce Medicare spending, and various other proposals are circulating to reduce it further.

Medicare Advantage

Medicare Advantage plans expand the health insurance options for people with Medicare. Medicare Advantage was created under the Balanced Budget Act of 1997, with the intent to better control the rapid growth in Medicare spending, as well as to provide Medicare beneficiaries more choices. But on average, Medicare Advantage plans cost 12% more than traditional Medicare. The ACA took steps to align payments to Medicare Advantage plans with the cost of traditional Medicare.

There is some evidence that Medicare Advantage plans select patients with low risk of incurring major medical expenses to maximize profits at the expense of traditional Medicare.

Medicare Part D

Medicare Part D provides a private insurance option to allow Medicare beneficiaries to purchase subsidized coverage for the costs of prescription drugs. It was enacted as part of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) and went into effect on January 1, 2006.

Medicaid

Medicaid was instituted for the very poor in 1965. Since enrollees must pass a means test, Medicaid is a social welfare or social protection program rather than a social insurance program. Despite its establishment, the percentage of US residents who lack any form of health insurance has increased since 1994. It has been reported that the number of physicians accepting Medicaid has decreased in recent years because of lower reimbursement rates.

The Affordable Care Act dramatically expanded Medicaid. The program will now cover everyone with incomes under 133% of the federal poverty level who does not qualify for Medicare, provided this expansion of coverage has been accepted by the state where the person resides. Meanwhile, Medicaid benefits must be the same as the essential benefit in the newly created state exchanges. The federal government will fully fund the expansion of Medicaid initially, with some of the financial responsibility gradually devolving back to the states by 2020. 

In 2011, there were 7.6 million hospital stays billed to Medicaid, representing 15.6% (approximately $60.2 billion) of total aggregate inpatient hospital costs in the United States.

Children's Health Insurance Program (CHIP)

The Children's Health Insurance Program (CHIP) is a joint state/federal program to provide health insurance to children in families who earn too much money to qualify for Medicaid, yet cannot afford to buy private insurance. The statutory authority for CHIP is under title XXI of the Social Security Act. CHIP programs are run by the individual states according to requirements set by the federal Centers for Medicare and Medicaid Services, and may be structured as independent programs separate from Medicaid (separate child health programs), as expansions of their Medicaid programs (CHIP Medicaid expansion programs), or combine these approaches (CHIP combination programs). States receive enhanced federal funds for their CHIP programs at a rate above the regular Medicaid match.

Military health benefits

Health benefits are provided to active duty service members, retired service members and their dependents by the Department of Defense Military Health System (MHS). The MHS consists of a direct care network of Military Treatment Facilities and a purchased care network known as TRICARE. Additionally, veterans may also be eligible for benefits through the Veterans Health Administration.

Indian health service

The Indian Health Service (IHS) provides medical assistance to eligible American Indians at IHS facilities, and helps pay the cost of some services provided by non-IHS health care providers.

Private health care coverage

Private health insurance may be purchased on a group basis (e.g., by a firm to cover its employees) or purchased by individual consumers. Most Americans with private health insurance receive it through an employer-sponsored program. According to the United States Census Bureau, some 60% of Americans are covered through an employer, while about 9% purchase health insurance directly. Private insurance was billed for 12.2 million inpatient hospital stays in 2011, incurring approximately 29% ($112.5 billion) of the total aggregate inpatient hospital costs in the United States.

The US has a joint federal and state system for regulating insurance, with the federal government ceding primary responsibility to the states under the McCarran-Ferguson Act. States regulate the content of health insurance policies and often require coverage of specific types of medical services or health care providers. State mandates generally do not apply to the health plans offered by large employers, because of the preemption clause of the Employee Retirement Income Security Act.

Employer sponsored

Employer-sponsored health insurance is paid for by businesses on behalf of their employees as part of an employee benefit package. Most private (non-government) health coverage in the US is employment-based. Nearly all large employers in America offer group health insurance to their employees. The typical large-employer PPO plan is typically more generous than either Medicare or the Federal Employees Health Benefits Program Standard Option.

The employer typically makes a substantial contribution towards the cost of coverage. Typically, employers pay about 85% of the insurance premium for their employees, and about 75% of the premium for their employees' dependents. The employee pays the remaining fraction of the premium, usually with pre-tax/tax-exempt earnings. These percentages have been stable since 1999. Health benefits provided by employers are also tax-favored: Employee contributions can be made on a pre-tax basis if the employer offers the benefits through a section 125 cafeteria plan.

Workers who receive employer-sponsored health insurance tend to be paid less in cash wages than they would be without the benefit, because of the cost of insurance premiums to the employer and the value of the benefit to the worker. The value to workers is generally greater than the wage reduction because of economies of scale, a reduction in adverse selection pressures on the insurance pool (premiums are lower when all employees participate rather than just the sickest), and reduced income taxes. Disadvantages to workers include disruptions related to changing jobs, the regressive tax effect (high-income workers benefit far more from the tax exemption for premiums than low-income workers), and increased spending on healthcare.

Costs for employer-paid health insurance are rising rapidly: between 2001 and 2007, premiums for family coverage have increased 78%, while wages have risen 19% and inflation has risen 17%, according to a 2007 study by the Kaiser Family Foundation. Employer costs have risen noticeably per hour worked, and vary significantly. In particular, average employer costs for health benefits vary by firm size and occupation. The cost per hour of health benefits is generally higher for workers in higher-wage occupations, but represent a smaller percentage of payroll. The percentage of total compensation devoted to health benefits has been rising since the 1960s. Average premiums, including both the employer and employee portions, were $4,704 for single coverage and $12,680 for family coverage in 2008.

However, in a 2007 analysis, the Employee Benefit Research Institute concluded that the availability of employment-based health benefits for active workers in the US is stable. The "take-up rate," or percentage of eligible workers participating in employer-sponsored plans, has fallen somewhat, but not sharply. EBRI interviewed employers for the study, and found that others might follow if a major employer discontinued health benefits. Effective by January 1, 2014, the Patient Protection and Affordable Care Act will impose a $2000 per employee tax penalty on employers with over 50 employees who do not offer health insurance to their full-time workers. (In 2008, over 95% of employers with at least 50 employees offered health insurance.) On the other hand, public policy changes could also result in a reduction in employer support for employment-based health benefits.

Although much more likely to offer retiree health benefits than small firms, the percentage of large firms offering these benefits fell from 66% in 1988 to 34% in 2002.

Small employer group coverage

According to a 2007 study, about 59% of employers at small firms (3–199 workers) in the US provide employee health insurance. The percentage of small firms offering coverage has been dropping steadily since 1999. The study notes that cost remains the main reason cited by small firms who do not offer health benefits. Small firms that are new are less likely to offer coverage than ones that have been in existence for a number of years. For example, using 2005 data for firms with fewer than 10 employees, 43% of those that had been in existence at least 20 years offered coverage, but only 24% of those that had been in existence less than 5 years did. The volatility of offer rates from year to year also appears to be higher for newer small businesses.

The types of coverage available to small employers are similar to those offered by large firms, but small businesses do not have the same options for financing their benefit plans. In particular, self-funded health care (whereby an employer provides health or disability benefits to employees with its own funds rather than contracting an insurance company) is not a practical option for most small employers. A RAND Corporation study published in April 2008 found that the cost of health care coverage places a greater burden on small firms, as a percentage of payroll, than on larger firms. A study published by the American Enterprise Institute in August 2008 examined the effect of state benefit mandates on self-employed individuals, and found that "the larger the number of mandates in a state, the lower the probability that a self-employed person will be a significant employment generator." Beneficiary cost sharing is, on average, higher among small firms than large firms.

When small group plans are medically underwritten, employees are asked to provide health information about themselves and their covered family members when they apply for coverage. When determining rates, insurance companies use the medical information on these applications. Sometimes they will request additional information from an applicant's physician or ask the applicants for clarification.

States regulate small group premium rates, typically by placing limits on the premium variation allowable between groups (rate bands). Insurers price to recover their costs over their entire book of small group business while abiding by state rating rules. Over time, the effect of initial underwriting "wears off" as the cost of a group regresses towards the mean. Recent claim experience—whether better or worse than average—is a strong predictor of future costs in the near term. But the average health status of a particular small employer group tends to regress over time towards that of an average group. The process used to price small group coverage changes when a state enacts small group reform laws.

Insurance brokers play a significant role in helping small employers find health insurance, particularly in more competitive markets. Average small group commissions range from 2 percent to 8 percent of premiums. Brokers provide services beyond insurance sales, such as assisting with employee enrollment and helping to resolve benefits issues.

College-sponsored health insurance for students

Many colleges, universities, graduate schools, professional schools and trade schools offer a school-sponsored health insurance plan. Many schools require that you enroll in the school-sponsored plan unless you are able to show that you have comparable coverage from another source. 

Effective group health plan years beginning after September 23, 2010, if an employer-sponsored health plan allows employees' children to enroll in coverage, then the health plan must allow employees' adult children to enroll as well as long as the adult child is not yet age 26. Some group health insurance plans may also require that the adult child not be eligible for other group health insurance coverage, but only before 2014.

This extension of coverage will help cover one in three young adults, according to White House documents.

Federal employees health benefit plan (FEHBP)

In addition to such public plans as Medicare and Medicaid, the federal government also sponsors a health benefit plan for federal employees—the Federal Employees Health Benefits Program (FEHBP). FEHBP provides health benefits to full-time civilian employees. Active-duty service members, retired service members and their dependents are covered through the Department of Defense Military Health System (MHS). FEHBP is managed by the federal Office of Personnel Management.

COBRA coverage

The Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA) enables certain individuals with employer-sponsored coverage to extend their coverage if certain "qualifying events" would otherwise cause them to lose it. Employers may require COBRA-qualified individuals to pay the full cost of coverage, and coverage cannot be extended indefinitely. COBRA only applies to firms with 20 or more employees, although some states also have "mini-COBRA" laws that apply to small employers.

Association Health Plan (AHP)

In the late 1990s federal legislation had been proposed to "create federally-recognized Association Health Plans which was then "referred to in some bills as 'Small Business Health Plans.' The National Association of Insurance Commissioners (NAIC), which is the "standard-setting and regulatory of chief insurance regulators from all states, the District of Columbia and territories, cautioned against implementing AHPs citing "plan failures like we saw The Multiple Employer Welfare Arrangements (MEWAs) in the 1990s." "[S]mall businesses in California such as dairy farmers, car dealers, and accountants created AHPs "to buy health insurance on the premise that a bigger pool of enrollees would get them a better deal." A November 2017 article in the Los Angeles Times described how there were only 4 remaining AHPs in California. Many of the AHPs filed for bankruptcy, "sometimes in the wake of fraud." State legislators were forced to pass "sweeping changes in the 1990s" that almost made AHPs extinct.

According to a 2000 Congressional Budget Office (CBO) report, Congress passed legislation creating "two new vehicles Association Health Plans (AHPs) and HealthMarts, to facilitate the sale of health insurance coverage to employees of small firms" in response to concerns about the "large and growing number of uninsured people in the United States."

In 2003, according to the Heartland Institute's Merrill Matthews, association group health insurance plans offered affordable health insurance to "some 6 million Americans." Matthews responded to the criticism that said that some associations work too closely with their insurance providers. He said, "You would expect the head of AARP to have a good working relationship with the CEO of Prudential, which sells policies to AARP's seniors."

In March 2017, the U.S. House of Representatives passed The Small Business Health Fairness Act (H.R. 1101), which established "requirements for creating a federally-certified AHP, including for certification itself, sponsors and boards of trustees, participation and coverage, nondiscrimination, contribution rates, and voluntary termination."

AHPs would be "exempt from most state regulation and oversight, subject only to Employee Retirement Income Security Act (ERISA) and oversight by the U.S. Department of Labor, and most proposals would also allow for interstate plans."

Critics said that "Exemptions would lead to market instability and higher premiums in the traditional small-group market. AHPs exempt from state regulation and oversight would enable them to be more selective about who they cover. They will be less likely to cover higher-risk populations, which would cause an imbalance in the risk pool for other small business health plans that are part of the state small group risk pool. Adverse selection would likely abound and Association Health Plans would be selling an unregulated product alongside small group plans, which creates an unlevel playing field." According to the Congressional Budget Office (CBO), "[p]remiums would go up for those buying in the traditional small-group market." competing against AHPs that offer less expensive and less comprehensive plans.

The National Association of Insurance Commissioners (NAIC), the National Governors' Association and "several insurance and consumer groups" opposed the AHP legislation. The NAIC issued a Consumer Alert regarding AHPs, as proposed in Developing the Next Generation of Small Businesses Act of 2017. H.R. 1774. Their statement said that AHP's "[t]hreaten the stability of the small group market" and provide "inadequate benefits and insufficient protection to consumers." Under AHPs, "[f]ewer consumers would have their rights protected, "AHPs would also be exempt from state solvency requirements, putting consumers at serious risk of incurring medical claims that cannot be paid by their Association Health Plan."

In November 2017, President Trump directed "the Department of Labor to investigate ways that would "allow more small businesses to avoid many of the [Affordable Care Act's] costly requirements." Under the ACA, small-employer and individual markets had "gained important consumer protections under the ACA and state health laws — including minimum benefit levels." In a December 28, 2017 interview with the New York Times, Trump explained that, "We've created associations, millions of people are joining associations. ...That were formerly in Obamacare or didn't have insurance. Or didn't have health care. ...It could be as high as 50 percent of the people. So now you have associations, and people don't even talk about the associations. That could be half the people are going to be joining up...So now you have associations and the individual mandate. I believe that because of the individual mandate and the association".

Final rules were released by the Department of Labor on June 19, 2018.

Individually purchased

Prior to the ACA, effective in 2014, the individual market was often subject to medical underwriting which made it difficult for individuals with pre-existing conditions to purchase insurance. The ACA prohibited medical underwriting in the individual market for health insurance marketplace plans.

Prior to the ACA as of 2007, about 9% of Americans were covered under health insurance purchased directly, with average out-of-pocket spending is higher in the individual market, with higher deductibles, co-payments and other cost-sharing provisions. While self-employed individuals receive a tax deduction for their health insurance and can buy health insurance with additional tax benefits, most consumers in the individual market do not receive any tax benefit.

Types of medical insurance

Traditional indemnity or fee-for-service

Early hospital and medical plans offered by insurance companies paid either a fixed amount for specific diseases or medical procedures (schedule benefits) or a percentage of the provider's fee. The relationship between the patient and the medical provider was not changed. The patient received medical care and was responsible for paying the provider. If the service was covered by the policy, the insurance company was responsible for reimbursing or indemnifying the patient based on the provisions of the insurance contract ("reimbursement benefits"). Health insurance plans that are not based on a network of contracted providers, or that base payments on a percentage of provider charges, are still described as indemnity or fee-for-service plans.

Blue Cross Blue Shield Association

The Blue Cross Blue Shield Association (BCBSA) is a federation of 38 separate health insurance organizations and companies in the United States. Combined, they directly or indirectly provide health insurance to over 100 million Americans. BCBSA insurance companies are franchisees, independent of the association (and traditionally each other), offering insurance plans within defined regions under one or both of the association's brands. Blue Cross Blue Shield insurers offer some form of health insurance coverage in every U.S. state, and also act as administrators of Medicare in many states or regions of the United States, and provide coverage to state government employees as well as to federal government employees under a nationwide option of the Federal Employees Health Benefit Plan.

Health Maintenance Organizations

A health maintenance organization (HMO) is a type of managed care organization (MCO) that provides a form of health care coverage that is fulfilled through hospitals, doctors, and other providers with which the HMO has a contract. The Health Maintenance Organization Act of 1973 required employers with 25 or more employees to offer federally certified HMO options. Unlike traditional indemnity insurance, an HMO covers only care rendered by those doctors and other professionals who have agreed to treat patients in accordance with the HMO's guidelines and restrictions in exchange for a steady stream of customers. Benefits are provided through a network of providers. Providers may be employees of the HMO ("staff model"), employees of a provider group that has contracted with the HMO ("group model"), or members of an independent practice association ("IPA model"). HMOs may also use a combination of these approaches ("network model").

Managed care

The term managed care is used to describe a variety of techniques intended to reduce the cost of health benefits and improve the quality of care. It is also used to describe organizations that use these techniques ("managed care organization"). Many of these techniques were pioneered by HMOs, but they are now used in a wide variety of private health insurance programs. Through the 1990s, managed care grew from about 25% US employees with employer-sponsored coverage to the vast majority.

Rise of managed care in the US
1998 14% 27% 35% 24%
1999 10% 28% 39% 24%
2000 8% 29% 42% 21%
2001 7% 24% 46% 23%
2002 4% 27% 52% 18%
2003 5% 24% 54% 17%
2004 5% 25% 55% 15%
2005 3% 21% 61% 15%
2006 3% 20% 60% 13% 4%
2007 3% 21% 57% 15% 5%
2008 2% 20% 58% 12% 8%
2009 1% 20% 60% 10% 8%
2010 1% 19% 58% 8% 13%
2011 1% 17% 55% 10% 17%
2012 <1 span=""> 16% 56% 9% 19%
2013 <1 span=""> 14% 57% 9% 20%
2014 <1 span=""> 13% 55% 23% 27%
2015 1% 17% 50% 26% 26%
2016 2% 23% 35% 32% 28%
Network-based managed care
Many managed care programs are based on a panel or network of contracted health care providers. Such programs typically include:
  • A set of selected providers that furnish a comprehensive array of health care services to enrollees;
  • Explicit standards for selecting providers;
  • Formal utilization review and quality improvement programs;
  • An emphasis on preventive care; and
  • Financial incentives to encourage enrollees to use care efficiently.
Provider networks can be used to reduce costs by negotiating favorable fees from providers, selecting cost effective providers, and creating financial incentives for providers to practice more efficiently. A survey issued in 2009 by America's Health Insurance Plans found that patients going to out-of-network providers are sometimes charged extremely high fees.

Network-based plans may be either closed or open. With a closed network, enrollees' expenses are generally only covered when they go to network providers. Only limited services are covered outside the network—typically only emergency and out-of-area care. Most traditional HMOs were closed network plans. Open network plans provide some coverage when an enrollee uses non-network provider, generally at a lower benefit level to encourage the use of network providers. Most preferred provider organization plans are open-network (those that are not are often described as exclusive provider organizations, or EPOs), as are point of service (POS) plans. 

The terms "open panel" and "closed panel" are sometimes used to describe which health care providers in a community have the opportunity to participate in a plan. In a "closed panel" HMO, the network providers are either HMO employees (staff model) or members of large group practices with which the HMO has a contract. In an "open panel" plan the HMO or PPO contracts with independent practitioners, opening participation in the network to any provider in the community that meets the plan's credential requirements and is willing to accept the terms of the plan's contract.
Other managed care techniques
Other managed care techniques include such elements as disease management, case management, wellness incentives, patient education, utilization management and utilization review. These techniques can be applied to both network-based benefit programs and benefit programs that are not based on a provider network. The use of managed care techniques without a provider network is sometimes described as "managed indemnity."

Blurring lines

Over time, the operations of many Blue Cross and Blue Shield operations have become more similar to those of commercial health insurance companies. However, some Blue Cross and Blue Shield plans continue to serve as insurers of last resort. Similarly, the benefits offered by Blues plans, commercial insurers, and HMOs are converging in many respects because of market pressures. One example is the convergence of preferred provider organization (PPO) plans offered by Blues and commercial insurers and the point of service plans offered by HMOs. Historically, commercial insurers, Blue Cross and Blue Shield plans, and HMOs might be subject to different regulatory oversight in a state (e.g., the Department of Insurance for insurance companies, versus the Department of Health for HMOs). Today, it is common for commercial insurance companies to have HMOs as subsidiaries, and for HMOs to have insurers as subsidiaries (the state license for an HMO is typically different from that for an insurance company). At one time the distinctions between traditional indemnity insurance, HMOs and PPOs were very clear; today, it can be difficult to distinguish between the products offered by the various types of organization operating in the market.

The blurring of distinctions between the different types of health care coverage can be seen in the history of the industry's trade associations. The two primary HMO trade associations were the Group Health Association of America and the American Managed Care and Review Association. After merging, they were known as American Association of Health Plans (AAHP). The primary trade association for commercial health insurers was the Health Insurance Association of America (HIAA). These two have now merged, and are known as America's Health Insurance Plans (AHIP).

New types of medical plans

In recent years, various new types of medical plans have been introduced.
High-deductible health plan (HDHP)
Plans with much higher deductibles than traditional health plans—primarily providing coverage for catastrophic illness—have been introduced. Because of the high deductible, these provide little coverage for everyday expenses—and thus have potentially high out-of-pocket expenses—but do cover major expenses. Couple with these are various forms of savings plans.
Tax-preferenced health care spending account
Coupled with high-deductible plans are various tax-advantaged savings plans—funds (such as salary) can be placed in a savings plan, and then go to pay the out-of-pocket expenses. This approach to addressing increasing premiums is dubbed "consumer driven health care", and received a boost in 2003, when President George W. Bush signed into law the Medicare Prescription Drug, Improvement, and Modernization Act. The law created tax-deductible Health Savings Accounts (HSAs), untaxed private bank accounts for medical expenses, which can be established by those who already have health insurance. Withdrawals from HSAs are only penalized if the money is spent on non-medical items or services. Funds can be used to pay for qualified expenses, including doctor's fees, Medicare Parts A and B, and drugs, without being taxed.
Consumers wishing to deposit pre-tax funds in an HSA must be enrolled in a high-deductible insurance plan (HDHP) with a number of restrictions on benefit design; in 2007, qualifying plans must have a minimum deductible of US$1,050. Currently, the minimum deductible has risen to $1.200 for individuals and $2,400 for families. HSAs enable healthier individuals to pay less for insurance and deposit money for their own future health care, dental and vision expenses.
HSAs are one form of tax-preferenced health care spending accounts. Others include Flexible Spending Accounts (FSAs), Archer Medical Savings Accounts (MSAs), which have been superseded by the new HSAs (although existing MSAs are grandfathered), and Health Reimbursement Accounts (HRAs). These accounts are most commonly used as part of an employee health benefit package. While there are currently no government-imposed limits to FSAs, legislation currently being reconciled between the House of Representatives and Senate would impose a cap of $2,500. While both the House and Senate bills would adjust the cap to inflation, approximately 7 million Americans who use their FSAs to cover out-of-pocket health care expenses greater than $2,500 would be forced to pay higher taxes and health care costs.
In July 2009, Save Flexible Spending Plans, a national grassroots advocacy organization, was formed to protect against the restricted use of FSAs in health care reform efforts, Save Flexible Spending Accounts is sponsored by the Employers Council on Flexible Compensation (ECFC), a non-profit organization "dedicated to the maintenance and expansion of the private employee benefits on a tax-advantaged basis". ECFC members include companies such as WageWorks Inc., a benefits provider based in San Mateo, California.
Most FSA participants are middle income Americans, earning approximately $55,000 annually. Individuals and families with chronic illnesses typically receive the most benefit from FSAs; even when insured, they incur annual out-of-pocket expenses averaging $4,398. Approximately 44 percent of Americans have one or more chronic conditions.
Limited benefit plan
Opposite to high-deductible plans are plans which provide limited benefits—up to a low level—have also been introduced. These limited medical benefit plans pay for routine care and do not pay for catastrophic care, they do not provide equivalent financial security to a major medical plan. Annual benefit limits can be as low as $2,000. Lifetime maximums can be very low as well.
Discount medical card
One option that is becoming more popular is the discount medical card. These cards are not insurance policies, but provide access to discounts from participating health care providers. While some offer a degree of value, there are serious potential drawbacks for the consumer.
Short term
Short term health insurance plans have a short policy period (typically months) and are intended for people who only need insurance for a short time period before longer term insurance is obtained. Short term plans typically cost less than traditional plans and have shorter application processes, but do not cover pre-existing conditions.
Health care sharing
A Health care sharing ministry is an organization that facilitates sharing of health care costs between individual members who have common ethical or religious beliefs. Though a health care sharing ministry is not an insurance company, members are exempted from the individual responsibility requirements of the Patient Protection and Affordable Care Act.

Health care markets and pricing

The US health insurance market is highly concentrated, as leading insurers have carried out over 400 mergers from the mid-1990s to the mid-2000s (decade). In 2000, the two largest health insurers (Aetna and UnitedHealth Group) had total membership of 32 million. By 2006 the top two insurers, WellPoint and UnitedHealth, had total membership of 67 million. The two companies together had more than 36% of the national market for commercial health insurance. The AMA has said that it "has long been concerned about the impact of consolidated markets on patient care." A 2007 AMA study found that in 299 of the 313 markets surveyed, one health plan accounted for at least 30% of the combined health maintenance organization (HMO)/preferred provider organization (PPO) market. In 90% of markets, the largest insurer controls at least 30% of the market, and the largest insurer controls more than 50% of the market in 54% of metropolitan areas. The US Department of Justice has recognized this percentage of market control as conferring substantial monopsony power in the relations between insurer and physicians.

Most provider markets (especially hospitals) are also highly concentrated—roughly 80%, according to criteria established by the FTC and Department of Justice—so insurers usually have little choice about which providers to include in their networks, and consequently little leverage to control the prices they pay. Large insurers frequently negotiate most-favored nation clauses with providers, agreeing to raise rates significantly while guaranteeing that providers will charge other insurers higher rates.

According to some experts, such as Uwe Reinhardt, Sherry Glied, Megan Laugensen, Michael Porter, and Elizabeth Teisberg, this pricing system is highly inefficient and is a major cause of rising health care costs. Health care costs in the United States vary enormously between plans and geographical regions, even when input costs are fairly similar, and rise very quickly. Health care costs have risen faster than economic growth at least since the 1970s. Public health insurance programs typically have more bargaining power as a result of their greater size and typically pay less for medical services than private plans, leading to slower cost growth, but the overall trend in health care prices have led public programs' costs to grow at a rapid pace as well.

Other types of health insurance (non-medical)

While the term "health insurance" is most commonly used by the public to describe coverage for medical expenses, the insurance industry uses the term more broadly to include other related forms of coverage, such as disability income and long-term care insurance.

Disability income insurance

Disability income (DI) insurance pays benefits to individuals who become unable to work because of injury or illness. DI insurance replaces income lost while the policyholder is unable to work during a period of disability (in contrast to medical expense insurance, which pays for the cost of medical care). For most working age adults, the risk of disability is greater than the risk of premature death, and the resulting reduction in lifetime earnings can be significant. Private disability insurance is sold on both a group and an individual basis. Policies may be designed to cover long-term disabilities (LTD coverage) or short-term disabilities (STD coverage). Business owners can also purchase disability overhead insurance to cover the overhead expenses of their business while they are unable to work.

A basic level of disability income protection is provided through the Social Security Disability Insurance (SSDI) program for qualified workers who are totally and permanently disabled (the worker is incapable of engaging in any "substantial gainful work" and the disability is expected to last at least 12 months or result in death).

Long-term care insurance

Long-term care (LTC) insurance reimburses the policyholder for the cost of long-term or custodial care services designed to minimize or compensate for the loss of functioning due to age, disability or chronic illness. LTC has many surface similarities to long-term disability insurance. There are at least two fundamental differences, however. LTC policies cover the cost of certain types of chronic care, while long-term-disability policies replace income lost while the policyholder is unable to work. For LTC, the event triggering benefits is the need for chronic care, while the triggering event for disability insurance is the inability to work.

Private LTC insurance is growing in popularity in the US. Premiums have remained relatively stable in recent years. However, the coverage is quite expensive, especially when consumers wait until retirement age to purchase it. The average age of new purchasers was 61 in 2005, and has been dropping.

Supplemental coverage

Private insurers offer a variety of supplemental coverages in both the group and individual markets. These are not designed to provide the primary source of medical or disability protection for an individual, but can assist with unexpected expenses and provide additional peace of mind for insureds. Supplemental coverages include Medicare supplement insurance, hospital indemnity insurance, dental insurance, vision insurance, accidental death and dismemberment insurance and specified disease insurance.

Supplemental coverages are intended to:
  • Supplement a primary medical expense plan by paying for expenses that are excluded or subject to the primary plan's cost-sharing requirements (e.g., co-payments, deductibles, etc.);
  • Cover related expenses such as dental or vision care;
  • Assist with additional expenses that may be associated with a serious illness or injury.

Medicare Supplement Coverage (Medigap)

Medicare Supplement policies are designed to cover expenses not covered (or only partially covered) by the "original Medicare" (Parts A & B) fee-for-service benefits. They are only available to individuals enrolled in Medicare Parts A & B. Medigap plans may be purchased on a guaranteed issue basis (no health questions asked) during a six-month open enrollment period when an individual first becomes eligible for Medicare. The benefits offered by Medigap plans are standardized.

Hospital indemnity insurance

Hospital indemnity insurance provides a fixed daily, weekly or monthly benefit while the insured is confined in a hospital. The payment is not dependent on actual hospital charges, and is most commonly expressed as a flat dollar amount. Hospital indemnity benefits are paid in addition to any other benefits that may be available, and are typically used to pay out-of-pocket and non-covered expenses associated with the primary medical plan, and to help with additional expenses (e.g., child care) incurred while in the hospital.

Scheduled health insurance plans

Scheduled health insurance plans are an expanded form of Hospital Indemnity plans. In recent years, these plans have taken the name mini-med plans or association plans. These plans may provide benefits for hospitalization, surgical, and physician services. However, they are not meant to replace a traditional comprehensive health insurance plan. Scheduled health insurance plans are more of a basic policy providing access to day-to-day health care such as going to the doctor or getting a prescription drug, but these benefits will be limited and are not meant to be effective for catastrophic events. Payments are based upon the plan's "schedule of benefits" and are usually paid directly to the service provider. These plans cost much less than comprehensive health insurance. Annual benefit maximums for a typical scheduled health insurance plan may range from $1,000 to $25,000.

Dental insurance

Dental insurance helps pay for the cost of necessary dental care. Few medical expense plans include coverage for dental expenses. About 97% of dental benefits in the United States is provided through separate policies from carriers—both stand-alone and medical affiliates—that specialize in this coverage. Typically, these dental plans offer comprehensive preventive benefits. However, major dental expenses, such as crowns and root canals, are just partially covered. Also, most carriers offer a lower rate if you select a plan that utilizes their Network providers. Discount dental programs are also available. These do not constitute insurance, but provide participants with access to discounted fees for dental work.

Vision care insurance

Vision care insurance provides coverage for routine eye care and is typically written to complement other medical benefits. Vision benefits are designed to encourage routine eye examinations and ensure that appropriate treatment is provided.

Specified disease

Specified disease provides benefits for one or more specifically identified conditions. Benefits can be used to fill gaps in a primary medical plan, such as co-payments and deductibles, or to assist with additional expenses such as transportation and child care costs.

Accidental death and dismemberment insurance

AD&D insurance is offered by group insurers and provides benefits in the event of accidental death. It also provides benefits for certain specified types of bodily injuries (e.g., loss of a limb or loss of sight) when they are the direct result of an accident.
  • Insurance companies have high administrative costs. Private health insurers are a significant portion of the U.S. economy directly employing (in 2004) almost 470,000 people at an average salary of $61,409.
  • Health insurance companies are not actually providing traditional insurance, which involves the pooling of risk, because the vast majority of purchasers actually do face the harms that they are "insuring" against. Instead, as Edward Beiser and Jacob Appel have separately argued, health insurers are better thought of as low-risk money managers who pocket the interest on what are really long-term healthcare savings accounts.
  • According to a study by a pro-health reform group published February 11, the nation's largest five health insurance companies posted a 56 percent gain in 2009 profits over 2008. The insurers (Wellpoint, UnitedHealth, Cigna, Aetna and Humana) cover the majority of Americans with health insurance.

Adult neurogenesis

From Wikipedia, the free encyclopedia

BrdU (red), a marker of DNA replication, highlights neurogenesis in the subgranular zone of hippocampal dentate gyrus. Fragment of an illustration from Faiz et al., 2005.
 
Doublecortin expression in the rat dentate gyrus, 21st postnatal day. Oomen et al., 2009.
 
Adult neurogenesis is the process by which neurons are generated from neural stem cells in the adult. This process is different from the embryonic development of neurogenesis

In most mammals, new neurons are continually born throughout adulthood in two regions of the brain:
More attention has been given to neurogenesis in the dentate gyrus than in the striatum. In rodents, many of the newborn dentate gyrus neurons die shortly after they are born, but a number of them become functionally integrated into the surrounding brain tissue. The amount of neurons born in the human hippocampus remains controversial; some studies have reported that in adult humans about 700 new neurons are added in the hippocampus every day, while other studies show that adult hippocampal neurogenesis does not exist in humans, or, if it does, it is at undetectable levels. The role of new neurons in adult brain function thus remains unclear. Adult neurogenesis is reported to play a role in learning and memory, emotion, stress, depression, response to injury, and other conditions.

Mechanism

Adult neural stem cells

Neural stem cells (NSCs) are the self-renewing, multipotent cells that generate the main phenotypes of the nervous system.

Lineage reprogramming (trans-differentiation)

Emerging evidence suggests that neural microvascular pericytes, under instruction from resident glial cells, are reprogrammed into interneurons and enrich local neuronal microcircuits. This response is amplified by concomitant angiogenesis.

Model organisms of neurogenesis

Planarian

Planarian are one of the earliest model organisms used to study regeneration with Pallas as the forefather of planarian studies. Planarian are a classical invertebrate model that in recent decades have been used to examine neurogenesis. The central nervous system of a planarian is simple, though fully formed with two lobes located in the head and two ventral nerve cords. This model reproduces asexually producing a complete and fully functioning nervous system after division allowing for consistent examination of neurogenesis.

Axolotl

The axolotl is less commonly used than other vertebrates, but is still a classical model for examining regeneration and neurogenesis. Though the axolotl has made its place in biomedical research in terms of limb regeneration, the model organism has displayed a robust ability to generate new neurons following damage. Axolotls have contributed as a bridge organism between invertebrates and mammals, as the species has the regenerative capacity to undergo complete neurogenesis forming a wide range of neuronal populations not limited to a small niche, yet the complexity and architecture is complex and analogous in many ways to human neural development.

Zebrafish

Zebrafish have long been a classical developmental model due to their transparency during organogenesis and have been utilized heavily in early development neurogenesis.). The zebrafish displays a strong neurogenerative capacity capable of regenerating a variety of tissues and complete neuronal diversity (with the exception of astrocytes, as they have yet to be identified within the zebrafish brain) with continued neurogenesis through the life span. In recent decades the model has solidified its role in adult regeneration and neurogenesis following damage. The zebrafish, like the axolotl, has played a key role as a bridge organism between invertebrates and mammals. The zebrafish is a rapidly developing organism that is relatively inexpensive to maintain, while providing the field ease of genetic manipulation and a complex nervous system.

Chick

Though avians have been used primarily to study early embryonic development, in recent decades the developing chick has played a critical role in the examination of neurogenesis and regeneration as the young chick is capable of neuronal-turnover at a young age, but loses the neurogenerative capacity into adulthood. The loss of neuroregenerative ability over maturation has allowed investigators to further examine genetic regulators of neurogenesis.

Rodent

Rodents, mice and rats, have been the most prominent model organism since the discovery of modern neurons by Santiago Ramon y Cajal. Rodents have a very similar architecture and a complex nervous system with very little regenerative capacity similar to that found in humans. For that reason, rodents have been heavily used in pre-clinical testing. Rodents display a wide range of neural circuits responsible for complex behaviors making them ideal for studies of dendritic pruning and axonal shearing. While the organism makes for a strong human analog, the model has its limitations not found in the previous models: higher cost of maintenance, lower breeding numbers, and the limited neurogenerative abilities.

Tracking neurogenesis

The creation of new functional brain cells can be measured in several ways, summarized in the following sections.

DNA labelling

Labelled DNA can trace dividing cell's lineage, and determine the location of its daughter cells. A nucleic acid analog is inserted into the genome of a neuron-generating cell (such as a glial cell or neural stem cell). Thymine analogs (3H) thymidine and BrdU are commonly used DNA labels, and are used for radiolabelling and immunohistochemistry respectively.

Fate determination via neuronal lineage markers

DNA labeling can be used in conjunction with neuronal lineage markers to determine the fate of new functional brain cells. First, incorporated labeled nucleotides are used to detect the populations of newly divided daughter cells. Specific cell types are then determined with unique differences in their expression of proteins, which can be used as antigens in an immunoassay. For example, NeuN/Fox3 and GFAP are antigens commonly used to detect neurons, glia, and ependymal cells. Ki67 is the most commonly used antigen to detect cell proliferation. Some antigens can be used to measure specific stem cell stages. For example, stem cells requires the sox2 gene to maintain pluripotency and is used to detect enduring concentrations of stem cells in CNS tissue. The protein nestin is an intermediate filament, which is essential for the radial growth of axons, and is therefore used to detect the formation of new synapses.

Cre-Lox recombination

Some genetic tracing studies utilize cre-lox recombination to bind a promoter to a reporter gene, such as lacZ or GFP gene. This method can be used for long term quantification of cell division and labeling, whereas the previously mentioned procedures are only useful for short-term quantification.

Viral Vectors

It has recently become more common to use recombinant viruses to insert the genetic information encoding specific markers (usually protein fluorophores such as GFP) that are only expressed in cells of a certain kind. The marker gene is inserted downstream of a promoter, leading to transcription of that marker only in cells containing the transcription factor(s) that bind to that promoter. For example, a recombinant plasmid may contain the promoter for doublecortin, a protein expressed predominantly by neurons, upstream of a sequence coding for GFP, thereby making infected cells fluoresce green upon exposure to light in the blue to ultraviolet range while leaving non doublecortin expressing cells unaffected, even if they contain the plasmid. Many cells will contain multiple copies of the plasmid and the fluorphore itself, allowing the fluorescent properties to be transferred along an infected cell's lineage

By labeling a cell that gives rise to neurons, such as a neural stem cells or neural precursor cells, one can track the creation, proliferation, and even migration of newly created neurons. It is important to note, however, that while the plasmid is stable for long periods of time, its protein products may have highly variable half lives and their fluorescence may decrease as well as become too diluted to be seen depending on the number of round of replication they have undergone, making this method more useful for tracking self-similar neural precursor or neural stem cells rather than neurons themselves. The insertion of genetic material via a viral vector tends to be sporadic and infrequent relative to the total number of cells in a given region of tissue, making quantification of cell division inaccurate. However, the above method can provide highly accurate data with respect to when a cell was born as well as full cellular morphologies.

Methods for inhibiting neurogenesis

Many studies analyzing the role of adult neurogenesis utilize a method of inhibiting cell proliferation in specific brain regions, mimicking an inhibition of neurogenesis, to observe the effects on behavior.

Pharmacological inhibition

Pharmacological inhibition is widely used in various studies, as it provides many benefits. It is generally inexpensive as compared to other methods, such as irradiation, can be used on various species, and does not require any invasive procedures or surgeries for the subjects. 

However, it does pose certain challenges, as these inhibitors can't be used to inhibit proliferation in specific regions, thus leading to nonspecific effects from other systems being affected. To avoid these effects, more work must be done to determine optimal doses in order to minimize the effects on systems unrelated to neurogenesis. 

A common pharmacological inhibitor for adult neurogenesis is methylazoxymethanol acetate (MAM), a chemotherapeutic agent. Other cell division inhibitors commonly used in studies are cytarabine and temozolomide.

Pharmacogenetics

Another method used to study the effects of adult neurogenesis is using pharmacogenetic models. These models provide different benefits from the pharmacological route, as it allows for more specificity by targeting specific precursors to neurogenesis and specific stem cell promoters. It also allows for temporal specificity with the interaction of certain drugs. This is beneficial in looking specifically at neurogenesis in adulthood, after normal development of other regions in the brain. 

The herpes simplex virus thymidine kinase (HSV-TK) has been used in studies in conjunction with antiviral drugs to inhibit adult neurogenesis. It works by targeting stem cells using glial fibrillary acidic proteins and nestin expression. These targeted stem cells undergo cell death instead of cell proliferation when exposed to antiviral drugs.

Cre protein is also commonly used in targeting stem cells that will undergo gene changes upon treatment with tamoxifen.

Irradiation

Irradiation is a method that allows for very specific inhibition of adult neurogenesis. It can be targeted to the brain to avoid affecting other systems and having nonspecific effects. It can even be used to target specific brain regions, which is important in determining how adult neurogenesis in different areas of the brain affects behavior. 

However, irradiation is more expensive than the other methods and also requires large equipment with trained individuals.

Inhibition of adult neurogenesis in the hippocampus

Many studies have observed how inhibiting adult neurogenesis in other mammals, such as rats and mice, affect their behavior. Inhibition of adult neurogenesis in the hippocampus has been shown to have various affects on learning and memory, conditioning, and investigative behaviors. 

Impaired fear conditioning has been seen in studies involving rats with a lack of adult neurogenesis in the hippocampus. Inhibition of adult neurogenesis in the hippocampus has also been linked to changes in behavior in tasks involving investigation. Rats also show decreased contextualized freezing behaviors in response to contextualized fear and impairment in learning spatial locations when lacking adult neurogenesis.

Effects on pattern separation

The changes in learning and memory seen in the studies mentioned previously are thought to be related to the role of adult neurogenesis in regulating pattern separation. Pattern separation is defined as, "a process to remove redundancy from similar inputs so that events can be separated from each other and interference can be reduced, and in addition can produce a more orthogonal, sparse, and categorized set of outputs."

This impairment in pattern separation could explain the impairments seen in other learning and memory tasks. A decreased ability in reducing interference could lead to greater difficulty in forming and retaining new memories, although it's hard to discriminate between effects of neurogenesis in learning and pattern separation due to limitations in the interpretation behavioral results."

Studies show that rats with inhibited adult neurogenesis demonstrate difficulty in differentiating and learning contextualized fear conditioning. Rats with blocked adult neurogenesis also show impaired differential freezing when they are required to differentiate between similar contexts. This also affects their spatial recognition in radial arm maze tests when the arms are closer together rather than when they are further apart. A meta-analysis of behavioral studies evaluating the effect of neurogenesis in different pattern separation tests has shown a consistent effect of neurogenesis ablation on performance, although there are exceptions in the literature."

Effects on behavioral inhibition

Behavioral inhibition is important in rats and other animals in halting whatever they are currently doing in order to reassess a situation in response to a threat or anything else that may require their attention.

Rats with lesioned hippocampi show less behavioral inhibition when exposed to threats, such as cat odor. The disruption of normal cell proliferation and development of the dentate gyrus in developing rats also impairs their freezing response, which is an example of behavior inhibition, when exposed to an unfamiliar adult male rat.

This impairment in behavioral inhibition also ties into the process of learning and memory, as repressing wrong answers or behaviors requires the ability to inhibit that response.

Implications

Role in learning

The functional relevance of adult neurogenesis is uncertain, but there is some evidence that hippocampal adult neurogenesis is important for learning and memory. Multiple mechanisms for the relationship between increased neurogenesis and improved cognition have been suggested, including computational theories to demonstrate that new neurons increase memory capacity, reduce interference between memories, or add information about time to memories. Experiments aimed at ablating neurogenesis have proven inconclusive, but several studies have proposed neurogenic-dependence in some types of learning, and others seeing no effect. Studies have demonstrated that the act of learning itself is associated with increased neuronal survival. However, the overall findings that adult neurogenesis is important for any kind of learning are equivocal.

Alzheimer's disease

Some studies suggest that decreased hippocampal neurogenesis can lead to development of Alzheimer's disease (AD). Yet, others hypothesize that AD patients have increased neurogenesis in the CA1 region of Ammon's horn (the principal region of AD hippocampal pathology) in order to compensate for neuronal loss. While the exact nature of the relationship between neurogenesis and Alzheimer's disease is unknown, insulin-like growth factor 1-stimulated neurogenesis produces major changes in hippocampal plasticity and seems to be involved in Alzheimer's pathology. Allopregnanolone, a neurosteroid, aids the continued neurogenesis in the brain. Levels of allopregnanolone in the brain decline in old age and Alzheimer's disease. Allopregnanolone has been shown through reversing impairment of neurogenesis to reverse the cognitive deficits in a mouse model of Alzheimer's disease. Eph receptors and ephrin signaling have been shown to regulate adult neurogenesis in the hippocampus and have been studied as potential targets to treat some symptoms of AD. Molecules associated with the pathology of AD, including ApoE, PS1 and APP, have also been found to impact adult neurogenesis in the hippocampus.

Role in schizophrenia

Studies suggest that people with schizophrenia have a reduced hippocampus volume, which is believed to be caused by a reduction of adult neurogenesis. Correspondingly, this phenomenon might be the underlying cause of many of the symptoms of the disease. Furthermore, several research papers referred to four genes, dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), disrupted in schizophrenia 1 (DISC1), and neuregulin 1 receptor (ERBB4), as being possibly responsible for this deficit in the normal regeneration of neurons. Similarities between depression and schizophrenia suggest a possible biological link between the two diseases. However, further research must be done in order to clearly demonstrate this relationship.

Adult Neurogenesis and Major Depressive Disorder

Research indicates that adult hippocampal neurogenesis is inversely related to Major Depressive Disorder (MDD). Neurogenesis is decreased in the hippocampus of animal models of major depressive disorder, and many treatments for the disorder, including antidepressant medication and electroconvulsive therapy, increase hippocampal neurogenesis. It has been theorized that decreased hippocampal neurogenesis in individuals with major depressive disorder may be related to the high levels of stress hormones called glucocorticoids, which are also associated with the disorder. The hippocampus instructs the hypothalamic-pituitary-adrenal axis to produce less glucocorticoids when glucocorticoid levels are high. A malfunctioning hippocampus, therefore, might explain the chronically high glucocorticoid levels in individuals with major depressive disorder. However, some studies have indicated that hippocampal neurogenesis is not lower in individuals with major depressive disorder and that blood glucocorticoid levels do not change when hippocampal neurogenesis changes, so the associations are still uncertain.

Stress and depression

Many now believe stress to be the most significant factor for the onset of depression, aside from genetics. As discussed above, hippocampal cells are sensitive to stress which can lead to decreased neurogenesis. This area is being considered more frequently when examining the causes and treatments of depression. Studies have shown that removing the adrenal gland in rats caused increased neurogenesis in the dentate gyrus. The adrenal gland is responsible for producing cortisol in response to a stressor, a substance that when produced in chronic amounts causes the down regulation of serotonin receptors and suppresses the birth of neurons. It was shown in the same study that administration of corticosterone to normal animals suppressed neurogenesis, the opposite effect. The most typical class of antidepressants administered for this disease are selective serotonin reuptake inhibitors (SSRIs) and their efficacy may be explained by neurogenesis. In a normal brain, an increase in serotonin causes suppression of the corticotropin-releasing hormone (CRH) through connection to the hippocampus. It directly acts on the paraventricular nucleus to decrease CRH release and down regulate norepinephrine functioning in the locus coeruleus. Because CRH is being repressed, the decrease in neurogenesis that is associated with elevated levels of it is also being reversed. This allows for the production of more brain cells, in particular at the 5-HT1a receptor in the dentate gyrus of the hippocampus which has been shown to improve symptoms of depression. It normally takes neurons approximately three to six weeks to mature, which is approximately the same amount of time it takes for SSRIs to take effect. This correlation strengthens the hypothesis that SSRIs act through neurogenesis to decrease the symptoms of depression. Some neuroscientists have expressed skepticism that neurogenesis is functionally significant, given that a tiny number of nascent neurons are actually integrated into existing neural circuitry. However, a recent study used the irradiation of nascent hippocampal neurons in non-human primates (NHP) to demonstrate that neurogenesis is required for antidepressant efficacy.

Adult-born neurons appear to have a role in the regulation of stress. Studies have linked neurogenesis to the beneficial actions of specific antidepressants, suggesting a connection between decreased hippocampal neurogenesis and depression. In a pioneer study, scientists demonstrated that the behavioral benefits of antidepressant administration in mice is reversed when neurogenesis is prevented with x-irradiation techniques. In fact, newborn neurons are more excitable than older neurons due to a differential expression of GABA receptors. A plausible model, therefore, is that these neurons augment the role of the hippocampus in the negative feedback mechanism of the HPA-axis (physiological stress) and perhaps in inhibiting the amygdala (the region of brain responsible for fearful responses to stimuli). Indeed, suppression of adult neurogenesis can lead to an increased HPA-axis stress response in mildly stressful situations. This is consistent with numerous findings linking stress-relieving activities (learning, exposure to a new yet benign environment, and exercise) to increased levels of neurogenesis, as well as the observation that animals exposed to physiological stress (cortisol) or psychological stress (e.g. isolation) show markedly decreased levels of newborn neurons. Under chronic stress conditions, the elevation of newborn neurons by antidepressants improves the hippocampal-dependent control on the stress response; without newborn neurons, antidepressants are unable to restore the regulation of the stress response and recovery becomes impossible.

Some studies have hypothesized that learning and memory are linked to depression, and that neurogenesis may promote neuroplasticity. One study proposes that mood may be regulated, at a base level, by plasticity, and thus not chemistry. Accordingly, the effects of antidepressant treatment would only be secondary to change in plasticity. However another study has demonstrated an interaction between antidepressants and plasticity; the antidepressant fluoxetine has been shown to restore plasticity in the adult rat brain. The results of this study imply that instead of being secondary to changes in plasticity, antidepressant therapy could promote it.

Effects of sleep reduction

One study has linked lack of sleep to a reduction in rodent hippocampal neurogenesis. The proposed mechanism for the observed decrease was increased levels of glucocorticoids. It was shown that two weeks of sleep deprivation acted as a neurogenesis-inhibitor, which was reversed after return of normal sleep and even shifted to a temporary increase in normal cell proliferation. More precisely, when levels of corticosterone are elevated, sleep deprivation inhibits this process. Nonetheless, normal levels of neurogenesis after chronic sleep deprivation return after 2 weeks, with a temporary increase of neurogenesis. While this is recognized, overlooked is the blood glucose demand exhibited during temporary diabetic hypoglycemic states. The American Diabetes Association amongst many documents the pseudosenilia and agitation found during temporary hypoglycemic states. Much more clinical documentation is needed to competently demonstrate the link between decreased hematologic glucose and neuronal activity and mood.

Possible use in treating Parkinson's disease

Parkinson's disease is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Transplantation of fetal dopaminergic precursor cells has paved the way for the possibility of a cell replacement therapy that could ameliorate clinical symptoms in affected patients. In recent years, scientists have provided evidence for the existence of neural stem cells with the potential to produce new neurons, particularly of a dopaminergic phenotype, in the adult mammalian brain. Experimental depletion of dopamine in rodents decreases precursor cell proliferation in both the subependymal zone and the subgranular zone. Proliferation is restored completely by a selective agonist of D2-like (D2L) receptors. Neural stem cells have been identified in the neurogenic brain regions, where neurogenesis is constitutively ongoing, but also in the non-neurogenic zones, such as the midbrain and the striatum, where neurogenesis is not thought to occur under normal physiological conditions. Newer research has shown that there in fact is neurogenesis in the striatum. A detailed understanding of the factors governing adult neural stem cells in vivo may ultimately lead to elegant cell therapies for neurodegenerative disorders such as Parkinson's disease by mobilizing autologous endogenous neural stem cells to replace degenerated neurons.

Traumatic Brain Injury

Traumatic brain injuries vary in their mechanism of injury, producing a blunt or penetrating trauma resulting in a primary and secondary injury with excitotoxicity and relatively wide spread neuronal death. Due to the overwhelming number of traumatic brain injuries as a result of the War on Terror, tremendous amounts of research have been placed towards a better understanding of the pathophysiology of traumatic brain injuries as well as neuroprotective interventions and possible interventions prompting restorative neurogenesis. Hormonal interventions, such as progesterone, estrogen, and allopregnanolone have been examined heavily in recent decades as possible neuroprotective agents following traumatic brain injuries to reduce the inflammation response stunt neuronal death. In rodents, lacking the regenerative capacity for adult neurogenesis, the activation of stem cells following administration of α7 nicotinic acetylcholine receptor agonist, PNU-282987, has been identified in damaged retinas with follow-up work examining activation of neurogenesis in mammals after traumatic brain injury. Currently, there is no medical intervention that has passed phase-III clinical trials for use in the human population.

Factors affecting

Changes in old age

Neurogenesis is substantially reduced in the hippocampus of aged animals, raising the possibility that it may be linked to age-related declines in hippocampal function. For example, the rate of neurogenesis in aged animals is predictive of memory. However, new born cells in aged animals are functionally integrated. Given that neurogenesis occurs throughout life, it might be expected that the hippocampus would steadily increase in size during adulthood, and that therefore the number of granule cells would be increased in aged animals. However, this is not the case, indicating that proliferation is balanced by cell death. Thus, it is not the addition of new neurons into the hippocampus that seems to be linked to hippocampal functions, but rather the rate of turnover of granule cells.

Effects of exercise

Scientists have shown that physical activity in the form of voluntary exercise results in an increase in the number of newborn neurons in the hippocampus of mice and rats. These and other studies have shown that learning in both species can be enhanced by physical exercise. Recent research has shown that brain-derived neurotrophic factor and insulin-like growth factor 1 are key mediators of exercise-induced neurogenesis. Exercise increases the production of BDNF, as well as the NR2B subunit of the NMDA receptor. Exercise increases the uptake of IGF-1 from the bloodstream into various brain regions, including the hippocampus. In addition, IGF-1 alters c-fos expression in the hippocampus. When IGF-1 is blocked, exercise no longer induces neurogenesis. Other research demonstrated that exercising mice that did not produce beta-endorphin, a mood-elevating hormone, had no change in neurogenesis. Yet, mice that did produce this hormone, along with exercise, exhibited an increase in newborn cells and their rate of survival. While the association between exercise-mediated neurogenesis and enhancement of learning remains unclear, this study could have strong implications in the fields of aging and/or Alzheimer's disease.

Effects of cannabinoids

Some studies have shown that the stimulation of the cannabinoids results in the growth of new nerve cells in the hippocampus from both embryonic and adult stem cells. In 2005 a clinical study of rats at the University of Saskatchewan showed regeneration of nerve cells in the hippocampus. Studies have shown that a synthetic drug resembling THC, the main psychoactive ingredient in marijuana, provides some protection against brain inflammation, which might result in better memory at an older age. This is due to receptors in the system that can also influence the production of new neurons. Nonetheless, a study directed at Rutgers University demonstrated how synchronization of action potentials in the hippocampus of rats was altered after THC administration. Lack of synchronization corresponded with impaired performance in a standard test of memory. Recent studies indicate that a natural cannabinoid of cannabis, cannabidiol (CBD), increases adult neurogenesis while having no effect on learning. THC however impaired learning and had no effect on neurogenesis. A greater CBD to THC ratio in hair analyses of cannabis users correlates with protection against gray matter reduction in the right hippocampus. CBD has also been observed to attenuate the deficits in prose recall and visuo-spatial associative memory of those currently under the influence of cannabis, implying neuroprotective effects against heavy THC exposure. Neurogenesis might play a role in its neuroprotective effects, but further research is required.

Regulation

Summary of the signalling pathways in the neural stem cell microenvironment.
 
Many factors may affect the rate of hippocampal neurogenesis. Exercise and an enriched environment have been shown to promote the survival of neurons and the successful integration of newborn cells into the existing hippocampus. Another factor is central nervous system injury since neurogenesis occurs after cerebral ischemia, epileptic seizures, and bacterial meningitis. On the other hand, conditions such as chronic stress, viral infection. and aging can result in a decreased neuronal proliferation. Circulating factors within the blood may reduce neurogenesis. In healthy aging humans, the plasma and cerebrospinal fluid levels of certain chemokines are elevated. In a mouse model, plasma levels of these chemokines correlate with reduced neurogenesis, suggesting that neurogenesis may be modulated by certain global age-dependent systemic changes. These chemokines include CCL11, CCL2 and CCL12, which are highly localized on mouse and human chromosomes, implicating a genetic locus in aging. Another study implicated the cytokine, IL-1beta, which is produced by glia. That study found that blocking IL-1 could partially prevent the severe impairment of neurogenesis caused by a viral infection.

Epigenetic regulation also plays a large role in neurogenesis. DNA methylation is critical in the fate-determination of adult neural stem cells in the subventricular zone for post-natal neurogenesis through the regulation of neuronic genes such as Dlx2, Neurog2, and Sp8. Many microRNAs such as miR-124 and miR-9 have been shown to influence cortical size and layering during development.

History

Early neuroanatomists, including Santiago Ramón y Cajal, considered the nervous system fixed and incapable of regeneration. The first evidence of adult mammalian neurogenesis in the cerebral cortex was presented by Joseph Altman in 1962, followed by a demonstration of adult neurogenesis in the dentate gyrus of the hippocampus in 1963. In 1969, Joseph Altman discovered and named the rostral migratory stream as the source of adult generated granule cell neurons in the olfactory bulb. Up until the 1980s, the scientific community ignored these findings despite use of the most direct method of demonstrating cell proliferation in the early studies, i.e. 3H-thymidine autoradiography. By that time, Shirley Bayer (and Michael Kaplan) again showed that adult neurogenesis exists in mammals (rats), and Nottebohm showed the same phenomenon in birds sparking renewed interest in the topic. Studies in the 1990s finally put research on adult neurogenesis into a mainstream pursuit. Also in the early 1990s hippocampal neurogenesis was demonstrated in non-human primates and humans. More recently, neurogenesis in the cerebellum of adult rabbits has also been characterized. Further, some authors (particularly Elizabeth Gould) have suggested that adult neurogenesis may also occur in regions within the brain not generally associated with neurogenesis including the neocortex. However, others have questioned the scientific evidence of these findings, arguing that the new cells may be of glial origin. Recent research has elucidated the regulatory effect of GABA on neural stem cells. GABA's well-known inhibitory effects across the brain also affect the local circuitry that triggers a stem cell to become dormant. They found that diazepam (Valium) has a similar effect.

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