Antisocial personality disorder

Antisocial (or dissocial) personality disorder is characterized by a pervasive pattern of disregard for, or violation of, the rights of others. There may be an impoverished moral sense or conscience and a history of crime, legal problems, and impulsive and aggressive behavior.

Antisocial personality disorder (ASPD) is the name of the disorder as defined in the Diagnostic and Statistical Manual (DSM). Dissocial personality disorder is the name of a similar or equivalent concept defined in the International Statistical Classification of Diseases and Related Health Problems (ICD), where it states that the diagnosis includes antisocial personality disorder. Both manuals have similar but not identical criteria. Both have also stated that their diagnoses have been referred to, or include what is referred to, as psychopathy or sociopathy, though distinctions are sometimes made.



The APA's Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR), defines antisocial personality disorder (in Axis II Cluster B):

A) There is a pervasive pattern of disregard for and violation of the rights of others occurring since age 15 years, as indicated by three or more of the following:
  1. failure to conform to social norms with respect to lawful behaviors as indicated by repeatedly performing acts that are grounds for arrest;
  2. deception, as indicated by repeatedly lying, use of aliases, or conning others for personal profit or pleasure;
  3. impulsivity or failure to plan ahead;
  4. irritability and aggressiveness, as indicated by repeated physical fights or assaults;
  5. reckless disregard for safety of self or others;
  6. consistent irresponsibility, as indicated by repeated failure to sustain consistent work behavior or honor financial obligations;
  7. lack of remorse, as indicated by being indifferent to or rationalizing having hurt, mistreated, or stolen from another.
B) The individual is at least age 18 years.
C) There is evidence of conduct disorder with onset before age 15 years.
D) The occurrence of antisocial behavior is not exclusively during the course of schizophrenia or a manic episode.

ASPD falls under the dramatic/erratic cluster of personality disorders. In the DSM-5, the diagnosis antisocial personality disorder is kept, but it is no longer on another axis as the other mental disorders.


The WHO's International Statistical Classification of Diseases and Related Health Problems, tenth edition (ICD-10), has a diagnosis called dissocial personality disorder (F60.2):

It is characterized by at least 3 of the following:
  1. Callous unconcern for the feelings of others;
  2. Gross and persistent attitude of irresponsibility and disregard for social norms, rules, and obligations;
  3. Incapacity to maintain enduring relationships, though having no difficulty in establishing them;
  4. Very low tolerance to frustration and a low threshold for discharge of aggression, including violence;
  5. Incapacity to experience guilt or to profit from experience, particularly punishment;
  6. Marked readiness to blame others or to offer plausible rationalizations for the behavior that has brought the person into conflict with society.

The ICD states that this diagnosis includes "amoral, antisocial, asocial, psychopathic, and sociopathic personality". Although the disorder is not synonymous with conduct disorder, presence of conduct disorder during childhood or adolescence may further support the diagnosis of dissocial personality disorder. There may also be persistent irritability as an associated feature.

It is a requirement of the ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.

Further considerations


Psychopathy is commonly defined as a personality disorder characterized partly by antisocial behavior, a diminished capacity for remorse, and poor behavioral controls. Psychopathic traits are assessed using various measurement tools, including Canadian researcher Robert D. Hare's Psychopathy Checklist, Revised (PCL-R). "Psychopathy" is not the official title of any diagnosis in the DSM or ICD.

American psychiatrist Hervey Cleckley's work on psychopathy formed the basis of the diagnostic criteria for ASPD, and the DSM has stated that ASPD has also been referred to as psychopathy. However, critics have argued that ASPD is not synonymous with psychopathy as the diagnostic criteria are not exactly the same, since criteria relating to personality traits are emphasized relatively less in the former. These differences exist in part because it was believed that such traits were difficult to measure reliably and it was "easier to agree on the behaviors that typify a disorder than on the reasons why they occur".

Although the diagnosis of ASPD covers two to three times as many prisoners as are rated as psychopaths, Robert Hare believes that the PCL-R is better able to predict future criminality, violence, and recidivism than a diagnosis of ASPD. He suggests that there are differences between PCL-R-diagnosed psychopaths and non-psychopaths on "processing and use of linguistic and emotional information", while such differences are potentially smaller between those diagnosed with ASPD and without. Additionally, Hare argued that confusion regarding how to diagnose ASPD, confusion regarding the difference between ASPD and psychopathy, as well as the differing future prognoses regarding recidivism and treatability, may have serious consequences in settings such as court cases where psychopathy is often seen as aggravating the crime.

Nonetheless, psychopathy has been proposed as a specifier under an alternative model for ASPD. In the DSM-5, under "Alternative DSM-5 Model for Personality Disorders", ASPD with psychopathic features is described as characterized by "a lack of anxiety or fear and by a bold interpersonal style that may mask maladaptive behaviors (e.g., fraudulence)." Low levels of withdrawal and high levels of attention-seeking combined with low anxiety are associated with "social potency" and "stress immunity" in psychopathy. Under the specifier, affective and interpersonal characteristics are comparatively emphasized over behavioral components.

Theodore Millon's subtypes

Theodore Millon suggested five subtypes of ASPD:

Elsewhere, Millon differentiates ten subtypes (partially overlapping with the above) â€" covetous, risk-taking, malevolent, tyrannical, malignant, unprincipled, disingenuous, spineless, explosive, and abrasive â€" but specifically stresses that "the number 10 is by no means special ... Taxonomies may be put forward at levels that are more coarse or more fine-grained."


The following conditions commonly coexist with ASPD:

When combined with alcoholism, people may show frontal function deficits on neuropsychological tests greater than those associated with each condition.

Causes and pathophysiology

Personality disorders seem to be caused by a combination of these genetic and environmental influences. Genetically, it is the temperament and the kind of personality a person is born with, and environmentally, it is the way in which a person grows up and the experiences they have had.

Hormones and neurotransmitters

Traumatic events can lead to a disruption of the standard development of the central nervous system, which can generate a release of hormones that can change normal patterns of development. Aggressiveness and impulsivity are among the possible symptoms of ASPD. Testosterone is a hormone that plays an important role in aggressiveness in the brain. For instance, criminals who have committed violent crimes have higher levels of testosterone. The effect of testosterone is counteracted by cortisol which facilitates the cognitive control on impulsive tendencies.

One of the neurotransmitters that have been discussed in individuals with ASPD is serotonin. A meta-analysis of 20 studies found significantly lower 5-HIAA levels (indicating lower serotonin levels), especially in those who are younger than 30 years of age.

J.F.W. Deakin of University of Manchester's Neuroscience and Psychiatry Unit has discussed additional evidence of 5HT's connection with ASPD. Deakin suggests that low cerebrospinal fluid concentrations of 5-HIAA, and hormone responses to 5HT, have displayed that the two main ascending 5HT pathways mediate adaptive responses to post and current conditions. He states that impairments in the posterior 5HT cells can lead to low mood functioning, as seen in patients with ASPD. It is important to note that the dysregulated serotonergic function may not be the sole feature that leads to ASPD but it is an aspect of a multifaceted relationship between biological and psychosocial factors.

While it has been shown that lower levels of serotonin may be associated with ASPD, there has also been evidence that decreased serotonin function is highly correlated with impulsiveness and aggression across a number of different experimental paradigms. Impulsivity is not only linked with irregularities in 5HT metabolism but may be the most essential psychopathological aspect linked with such dysfunction. Correspondingly, the DSM classifies "impulsivity or failure to plan ahead" and "irritability and aggressiveness" as two of seven sub-criteria in category A of the diagnostic criteria of ASPD.

Some studies have found a relationship between monoamine oxidase A and antisocial behavior, including conduct disorder and symptoms of adult ASPD, in maltreated children.

Limbic neural maldevelopment

Cavum septi pellucidi (CSP) is a marker for limbic neural maldevelopment. One study found that those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls.

Cultural influences

The Socio-cultural perspective of clinical psychology view disorders as being influenced by cultural aspects, since cultural norms differ significantly, mental disorders such as ASPD are viewed differently. Robert D. Hare has suggested that the rise in ASPD that has been reported in the United States may be linked to changes in cultural mores, the latter serving to validate the behavioral tendencies of many individuals with ASPD. While the rise reported may be in part merely a byproduct of the widening use (and abuse) of diagnostic techniques, given Eric Berne's division between individuals with active and latent ASPD â€" the latter keeping themselves in check by attachment to an external source of control like the law, traditional standards, or religion â€" it has been plausibly suggested that the erosion of collective standards may indeed serve to release the individual with latent ASPD from their previously prosocial behavior.

There is also a continuous debate as to the extent to which the legal system should be involved in the identification and admittance of patients with preliminary symptoms of ASPD.


Some studies suggest that the social and home environment has contributed to the development of antisocial behavior. The parents of these children have been shown to display antisocial behavior, which could be adopted by their children.

Head injuries

Researchers have linked physical head injuries with antisocial behavior. Since the 1980s, scientists have associated traumatic brain injury, including damage to the prefrontal cortex, with an inability to make morally and socially acceptable decisions. Children with early damage in the prefrontal cortex may never fully develop social or moral reasoning and become "psychopathic individuals ... characterized by high levels of aggression and antisocial behavior performed without guilt or empathy for their victims." Additionally, damage to the amygdala may impair the ability of the prefrontal cortex to interpret feedback from the limbic system, which could result in uninhibited signals that manifest in violent and aggressive behavior.


ASPD is considered to be among the most difficult personality disorders to treat. Because of their very low or absent capacity for remorse, individuals with ASPD often lack sufficient motivation and fail to see the costs associated with antisocial acts. They may only simulate remorse rather than truly commit to change: they can be seductively charming and dishonest, and may manipulate staff and fellow patients during treatment. Studies have shown that outpatient therapy is not likely to be successful, however the extent to which persons with ASPD are entirely unresponsive to treatment may have been exaggerated.

Those with ASPD may stay in treatment only as required by an external source, such as a parole. Residential programs that provide a carefully controlled environment of structure and supervision along with peer confrontation have been recommended. There has been some research on the treatment of ASPD that indicated positive results for therapeutic interventions. Schema Therapy is also being investigated as a treatment for ASPD. A review by Charles M. Borduin features the strong influence of Multisystemic therapy (MST) that could potentially improve this imperative issue. However this treatment requires complete cooperation and participation of all family members. Some studies have found that the presence of ASPD does not significantly interfere with treatment for other disorders, such as substance abuse, although others have reported contradictory findings.

Therapists of individuals with ASPD may have considerable negative feelings toward clients with extensive histories of aggressive, exploitative, and abusive behaviors. Rather than attempt to develop a sense of conscience in these individuals, therapeutic techniques should be focused on rational and utilitarian arguments against repeating past mistakes. These approaches would focus on the tangible, material value of prosocial behavior.

No medications have been approved by the FDA to treat ASPD, although certain psychiatric medications may alleviate conditions sometimes associated with the disorder and with symptoms such as aggression, including antipsychotic, antidepressant or mood-stabilizing medications.


According to Professor Emily Simonoff, Institute of Psychiatry, "childhood hyperactivity and conduct disorder showed equally strong prediction of antisocial personality disorder (ASPD) and criminality in early and mid-adult life. Lower IQ and reading problems were most prominent in their relationships with childhood and adolescent antisocial behaviour."


ASPD is seen in 3% to 30% of psychiatric outpatients. The prevalence of the disorder is even higher in selected populations, like prisons, where there is a preponderance of violent offenders. A 2002 literature review of studies on mental disorders in prisoners stated that 47% of male prisoners and 21% of female prisoners had ASPD. Similarly, the prevalence of ASPD is higher among patients in alcohol or other drug (AOD) abuse treatment programs than in the general population (Hare 1983), suggesting a link between ASPD and AOD abuse and dependence.

A University of Colorado Colorado Springs study comparing personality disorders and Myers-Briggs Type Indicator types found that the disorder had a significant correlation with the Intuitive (N), Thinking (T), and Perceiving (P) preferences.


The first version of the DSM in 1952 listed sociopathic personality disturbance. Individuals to be placed in this category were said to be "...ill primarily in terms of society and of conformity with the prevailing milieu, and not only in terms of personal discomfort and relations with other individuals". There were four subtypes, referred to as "reactions"; antisocial, dyssocial, sexual and addiction. The antisocial reaction was said to include people who were "always in trouble" and not learning from it, maintaining "no loyalties", frequently callous and lacking responsibility, with an ability to "rationalize" their behavior. The category was described as more specific and limited than the existing concepts of "constitutional psychopathic state" or "psychopathic personality" which had had a very broad meaning; the narrower definition was in line with criteria advanced by Hervey M. Cleckley from 1941, while the term sociopathic had been advanced by George Partridge.

The DSM-II in 1968 rearranged the categories and "antisocial personality" was now listed as one of ten personality disorders but still described similarly, to be applied to individuals who are: "basically unsocialized", in repeated conflicts with society, incapable of significant loyalty, selfish, irresponsible, unable to feel guilt or learn from prior experiences, and who tend to blame others and rationalize. The manual preface contains "special instructions" including "Antisocial personality should always be specified as mild, moderate, or severe." The DSM-II warned that a history of legal or social offenses was not by itself enough to justify the diagnosis, and that a "group delinquent reaction" of childhood or adolescence or "social maladjustment without manifest psychiatric disorder" should be ruled out first. The dyssocial personality type was relegated in the DSM-II to "dyssocial behavior" for individuals who are predatory and follow more or less criminal pursuits, such as racketeers, dishonest gamblers, prostitutes, and dope peddlers. (DSM-I classified this condition as sociopathic personality disorder, dyssocial type). It would later resurface as the name of a diagnosis in the ICD manual produced by the WHO, later spelled dissocial personality disorder and considered approximately equivalent to the ASPD diagnosis.

The DSM-III in 1980 included the full term antisocial personality disorder and, as with other disorders, there was now a full checklist of symptoms focused on observable behaviors to enhance consistency in diagnosis between different psychiatrists ('inter-rater reliability'). The ASPD symptom list was based on the Research Diagnostic Criteria developed from the so-called Feighner Criteria from 1972, and in turn largely credited to influential research by sociologist Lee Robins published in 1966 as "Deviant Children Grown Up". However, Robins has previously clarified that while the new criteria of prior childhood conduct problems came from her work, she and co-researcher psychiatrist Patricia O'Neal got the diagnostic criteria they used from Lee's husband the psychiatrist Eli Robins, one of the authors of the Feighner criteria who had been using them as part of diagnostic interviews.

The DSM-IV maintained the trend for behavioral antisocial symptoms while noting "This pattern has also been referred to as psychopathy, sociopathy, or dyssocial personality disorder" and re-including in the 'Associated Features' text summary some of the underlying personality traits from the older diagnoses. The DSM-5 has the same diagnosis of antisocial personality disorder. The Pocket Guide to the DSM-5 Diagnostic Exam suggests that a person with ASPD may present "with psychopathic features" if he or she exhibits "a lack of anxiety or fear and a bold, efficacious interpersonal style".

Thirteenth Amendment to the United States Constitution

The Thirteenth Amendment to the United States Constitution abolished slavery and involuntary servitude, except as punishment for a crime. In Congress, it was passed by the Senate on April 8, 1864, and by the House on January 31, 1865. It was ratified by the required number of states on December 6, 1865. On December 18, 1865, Secretary of State William H. Seward proclaimed its adoption. It was the first of the three Reconstruction Amendments adopted following the American Civil War.

Slavery had been tacitly protected in the original Constitution through clauses such as the Three-Fifths Compromise, by which three-fifths of the slave population was counted for representation in the United States House of Representatives. Though many slaves had been declared free by Lincoln's 1863 Emancipation Proclamation, their post-war status was uncertain. On April 8, 1864, the Senate passed an amendment to abolish slavery. After one unsuccessful vote and extensive legislative maneuvering by the Lincoln administration, the House followed suit on January 31, 1865. The measure was swiftly ratified by nearly all Northern states, along with a sufficient number of border and "reconstructed" Southern states, to cause it to be adopted before the end of the year.

Though the amendment formally abolished slavery throughout the United States, factors such as Black Codes, white supremacist violence, and selective enforcement of statutes continued to subject some black Americans to involuntary labor, particularly in the South. In contrast to the other Reconstruction Amendments, the Thirteenth Amendment was rarely cited in later case law, but has been used to strike down peonage and some race-based discrimination as "badges and incidents of slavery". While the Fourteenth and Fifteenth Amendments apply only to state actors, the Thirteenth applies also to private citizens. The amendment also enables Congress to pass laws against sex trafficking and other modern forms of slavery.


Section 1. Neither slavery nor involuntary servitude, except as a punishment for crime whereof the party shall have been duly convicted, shall exist within the United States, or any place subject to their jurisdiction.

Section 2. Congress shall have power to enforce this article by appropriate legislation.

Slavery in the United States

The institution of slavery existed in all of the original thirteen British North American colonies. Prior to the Thirteenth Amendment, the United States Constitution (adopted in 1789) did not expressly use the words slave or slavery but included several provisions about unfree persons. The Three-Fifths Clause (in Article I, Section 2) allocated Congressional representation based "on the whole Number of free Persons" and "three fifths of all other Persons". This clause was a compromise between Southerners who wished slaves to be counted as 'persons' for congressional representation and northerners rejecting these out of concern of too much power for the South, because representation in the new Congress would be based on population in contrast to the one-vote-for-one-state principle in the earlier Continental Congress. Under the Fugitive Slave Clause (Article IV, Section 2), "No person held to Service or Labour in one State" would be freed by escaping to another. Article I, Section 9 allowed Congress to pass legislation outlawing the "Importation of Persons", but not until 1808. However, for purposes of the Fifth Amendmentâ€"which states that, "No person shall... be deprived of life, liberty, or property, without due process of law"â€"slaves were understood as property. Although abolitionists used the Fifth Amendment to argue against slavery, it became part of the legal basis for treating slaves as property with Dred Scott v. Sandford (1857).

Stimulated by the philosophy of the Declaration of Independence between 1777 and 1804, every Northern state provided for the immediate or gradual abolition of slavery. Most of the slaves involved were household servants. No Southern state did so, and the slave population of the South continued to grow, peaking at almost 4 million people in 1861. An abolitionist movement headed by such figures as William Lloyd Garrison grew in strength in the North, calling for the end of slavery nationwide and exacerbating tensions between North and South. The American Colonization Society, an alliance between abolitionists who felt the races should be kept separated and slaveholders who feared the presence of freed blacks would encourage slave rebellions, called for the emigration and colonization of both free blacks and slaves to Africa. Its views were endorsed by politicians such as Henry Clay, who feared that the main abolitionist movement would provoke a civil war. Proposals to eliminate slavery by constitutional amendment were introduced by Representative Arthur Livermore in 1818 and by John Quincy Adams in 1839, but failed to gain significant traction.

As the country continued to expand, the issue of slavery in its new territories became the dominant national issue. The Southern position was that slaves were property and therefore could be moved to the territories like all other forms of property. The 1820 Missouri Compromise provided for the admission of Missouri as a slave state and Maine as a free state, preserving the Senate's equality between the regions. In 1846, the Wilmot Proviso was introduced to a war appropriations bill to ban slavery in all territories acquired in the Mexicanâ€"American War; the Proviso repeatedly passed the House, but not the Senate. The Compromise of 1850 temporarily defused the issue by admitting California as a free state, instituting a stronger Fugitive Slave Act, banning the slave trade in Washington, D.C., and allowing New Mexico and Utah self-determination on the slavery issue.

Despite the compromise, tensions between North and South continued to rise over the subsequent decade, inflamed by, amongst other things, the publication of the 1852 anti-slavery novel Uncle Tom's Cabin; fighting between pro-slave and abolitionist forces in Kansas, beginning in 1854; the 1857 Dred Scott decision, which struck down provisions of the Compromise of 1850; abolitionist John Brown's 1859 attempt to start a slave revolt at Harpers Ferry and the 1860 election of slavery critic Abraham Lincoln to the presidency. The Southern states seceded from the Union in the months following Lincoln's election, forming the Confederate States of America, and beginning the American Civil War.

Proposal and ratification

Crafting the amendment

Acting under presidential war powers, Lincoln issued the Emancipation Proclamation on January 1, 1863, which proclaimed the freedom of slaves in the ten states that were still in rebellion. However, it did not affect the status of slaves in the border states that had remained loyal to the Union. That December, Lincoln again used his war powers and issued a "Proclamation for Amnesty and Reconstruction", which offered Southern states a chance to peacefully rejoin the Union if they abolished slavery and collected loyalty oaths from 10% of their voting population. Southern states did not readily accept the deal, and the status of slavery remained uncertain.

In the final years of the Civil War, Union lawmakers debated various proposals for Reconstruction. Some of these called for a constitutional amendment to abolish slavery nationally and permanently. On December 14, 1863, a bill proposing such an amendment was introduced by Representative James Mitchell Ashley. Representative James F. Wilson soon followed with a similar proposal. On January 11, 1864, Senator John B. Henderson of Missouri submitted a joint resolution for a constitutional amendment abolishing slavery. The Senate Judiciary Committee, chaired by Lyman Trumbull, became involved in merging different proposals for an amendment.

Radical Republicans led by Senator Charles Sumner and Representative Thaddeus Stevens sought a more expansive version of the amendment. On February 8, 1864, Sumner submitted a constitutional amendment stating:

“All persons are equal before the law, so that no person can hold another as a slave; and the Congress shall have power to make all laws necessary and proper to carry this declaration into effect everywhere in the United States.”

Sumner tried to promote his own more expansive wording by circumventing the Trumbull-controlled Judiciary Committee, but failed. On February 10, the Senate Judiciary Committee presented the Senate with an amendment proposal based on drafts of Ashley, Wilson and Henderson.

The Committee's version used text from the Northwest Ordinance of 1787, which stipulates, "There shall be neither slavery nor involuntary servitude in the said territory, otherwise than in the punishment of crimes whereof the party shall have been duly convicted." Though using Henderson's proposed amendment as the basis for its new draft, the Judiciary Committee removed language that would have allowed a constitutional amendment to be adopted with only a majority vote in each House of Congress and ratification by two-thirds of the states (instead of two-thirds and three-fourths, respectively).

Passage by Congress

The Senate passed the amendment on April 8, 1864, by a vote of 38 to 6. However, just over two months later on June 15, the House failed to do so, with 93 in favor and 65 against, thirteen votes short of the two-thirds vote needed for passage; the vote split largely along party lines, with Republicans supporting and Democrats opposing. In the 1864 presidential race, former Free Soil Party candidate John C. Frémont threatened a third party run opposing Lincoln, this time on a platform endorsing an anti-slavery amendment. The Republican Party platform had, as yet, failed to include a similar plank, though Lincoln endorsed the amendment in a letter accepting his nomination. Fremont withdrew from the race on September 22, 1864, and endorsed Lincoln.

With no Southern states represented, few members of Congress pushed moral and religious arguments in favor of slavery. Democrats who opposed the amendment generally made arguments based on federalism and state's rights. Some argued that the proposed change so violated the spirit of the Constitution that it would not be a valid "amendment" but would instead constitute "revolution". Some opponents warned that the amendment would lead to full citizenship for blacks.

Republicans argued that slavery was uncivilized and that abolition was a necessary step in national progress. Amendment supporters also argued that the slave system had negative effects on white people. These included the lower wages resulting from competition with forced labor, as well as repression of abolitionist whites in the South. Advocates said ending slavery would restore the First Amendment and other constitutional rights violated by censorship and intimidation in slave states.

White Northern Republicans, and some Democrats, became excited about an abolition amendment, holding meetings and issuing resolutions. Many blacks, particularly in the South, focused more on landownership and education as the key to liberation. As slavery began to seem politically untenable, an array of Northern Democrats gradually announced their support for the amendment, including Representative James Brooks, Senator Reverdy Johnson, and Tammany Hall, a powerful New York political machine.

Lincoln had been concerned that the Emancipation Proclamation might be reversed or found invalid after the war and saw constitutional amendment as a more permanent solution. He had remained outwardly neutral on the amendment because he considered it politically too dangerous. Nonetheless, Lincoln's 1864 party platform resolved to abolish slavery by constitutional amendment. After winning the election of 1864, Lincoln made the passage of the Thirteenth Amendment his top legislative priority, beginning his efforts while the "lame duck" session was still in office. Popular support for the amendment was mounting and Lincoln urged Congress on in his December 6 State of the Union speech: “there is only a question of time as to when the proposed amendment will go to the States for their action. And as it is to so go, at all events, may we not agree that the sooner the better?”

Secretary of State William H. Seward, Representative John B. Alley and others were instructed by Lincoln to procure votes by any means necessary, and promised government posts and campaign contributions to outgoing Democrats willing to switch sides. Seward had a large fund for direct bribes. Ashley, who reintroduced the measure into the House, also lobbied several Democrats to vote in favor of the measure. Representative Thaddeus Stevens commented later that "the greatest measure of the nineteenth century was passed by corruption, aided and abetted by the purest man in America"; however, Lincoln's precise role in making deals for votes remains unknown.

Republicans in Congress claimed a mandate for abolition, having gained in the elections for Senate and House. Opposition to the measure was led by the 1864 Democratic vice presidential nominee, Representative George H. Pendleton. Republicans toned down their language of radical equality in order to broaden the amendment's coalition of supporters. In order to reassure critics worried that the amendment would tear apart the social fabric, some Republicans explicitly promised that the amendment would leave patriarchy intact.

In mid-January, Speaker of the House Schuyler Colfax estimated the amendment to be five votes short of passage. Ashley postponed the vote. At this point, Lincoln intensified his push for the amendment, making direct emotional appeals to particular members of Congress. On January 31, 1865, the House called another vote on the amendment, with neither side being certain of the outcome. Every Republican supported the measure, as well as 16 Democrats, almost all of them lame ducks. The amendment finally passed by a vote of 119 to 56, narrowly reaching the required two-thirds majority. The House exploded into celebration, with some members openly weeping. Black onlookers, who had only been allowed to attend Congressional sessions since the previous year, cheered from the galleries.

President Lincoln signed the amendment on February 1, 1865. The Thirteenth Amendment is the only ratified amendment signed by a President, although James Buchanan had signed the pro-slavery Corwin Amendment, which the 36th Congress had adopted and sent to the states in March 1861. The Thirteenth Amendment's archival copy bears Lincoln's signature, under the usual signatures of the Speaker of the House and the President of the Senate, after the date. On February 7, Congress passed a resolution affirming that the Presidential signature was unnecessary.

Ratification by the states

When the Thirteenth Amendment was submitted to the states on February 1, 1865, it was quickly taken up by several legislatures. By the end of the month it had been ratified by eighteen states. Among them were the ex-confederate states of Virginia and Louisiana, where ratifications were submitted by Reconstruction governments. These, along with subsequent ratifications from Arkansas and Tennessee raised the issues of how many seceded states had legally valid legislatures, and if there were fewer legislatures than states, did Article V require ratification by three-fourths of the states or three-fourths of the legally valid state legislatures? President Lincoln in his last speech, on April 11, 1865, called the question about whether the Southern states were in or out of the Union a “pernicious abstraction.” Obviously, he declared, they were not “in their proper practical relation with the Union”; whence everyone's object should be to restore that relation. Lincoln was assassinated three days later.

With Congress out of session, the new President, Andrew Johnson, began a period known as "Presidential Reconstruction", in which he personally oversaw the creation of new state governments throughout the South. He oversaw the convening of state political conventions populated by delegates whom he deemed to be loyal. Three leading issues came before the convention: secession itself, the abolition of slavery, and the Confederate war debt. Alabama, Florida, Georgia, Mississippi, North Carolina, and South Carolina held conventions in 1865, while Texas' convention did not organize until March 1866. Johnson hoped to prevent deliberation over whether to re-admit the Southern states by accomplishing full ratification before Congress reconvened in December. He believed he could silence those who wished to deny the Southern states their place in the Union by pointing to how essential their assent had been to the successful ratification of the Thirteenth Amendment.

Direct negotiations between state governments and the Johnson administration ensued. As the summer wore on, administration officials began including assurances of the measure's limited scope with their demands for ratification. Johnson himself suggested directly to the governors of Mississippi and North Carolina that they could proactively control the allocation of rights to freedmen. Though Johnson obviously expected the freed people to enjoy at least some civil rights, including, as he specified, the right to testify in court, he wanted state lawmakers to know that the power to confer such rights would remain with the states. When South Carolina provisional governor Benjamin Franklin Perry objected to the scope of the amendment's enforcement clause, Secretary of State Seward responded by telegraph that in fact the second clause "is really restraining in its effect, instead of enlarging the powers of Congress". White politicians throughout the South were concerned that Congress might cite the amendment's enforcement powers as a way to authorize black suffrage.

When South Carolina ratified the amendment in November 1865, it issued its own interpretive declaration that "any attempt by Congress toward legislating upon the political status of former slaves, or their civil relations, would be contrary to the Constitution of the United States". Alabama and Louisiana also declared that their ratification did not imply federal power to legislate on the status of former slaves. During the first week of December, North Carolina and Georgia gave the amendment the final votes needed for it to become part of the Constitution.

The Thirteenth Amendment became part of the Constitution on December 6, 1865, based on the following ratifications:

  1. Illinois â€" February 1, 1865
  2. Rhode Island â€" February 2, 1865
  3. Michigan â€" February 3, 1865
  4. Maryland â€" February 3, 1865
  5. New York â€" February 3, 1865
  6. Pennsylvania â€" February 3, 1865
  7. West Virginia â€" February 3, 1865
  8. Missouri â€" February 6, 1865
  9. Maine â€" February 7, 1865
  10. Kansas â€" February 7, 1865
  11. Massachusetts â€" February 7, 1865
  12. Virginia â€" February 9, 1865
  13. Ohio â€" February 10, 1865
  14. Indiana â€" February 13, 1865
  15. Nevada â€" February 16, 1865
  16. Louisiana â€" February 17, 1865
  17. Minnesota â€" February 23, 1865
  18. Wisconsin â€" February 24, 1865
  19. Vermont â€" March 8, 1865
  20. Tennessee â€" April 7, 1865
  21. Arkansas â€" April 14, 1865
  22. Connecticut â€" May 4, 1865
  23. New Hampshire â€" July 1, 1865
  24. South Carolina â€" November 13, 1865
  25. Alabama â€" December 2, 1865
  26. North Carolina â€" December 4, 1865
  27. Georgia â€" December 6, 1865

Having been ratified by the legislatures of three-fourths of the several statesâ€"27 of the 36 states (including those that had been in rebellion), Secretary of State Seward, on December 18, 1865, certified that the Thirteenth Amendment had become valid, to all intents and purposes, as a part of the Constitution. Included on the enrolled list of ratifying states were the three ex-confederate states that had given their assent, but with strings attached. Seward accepted their affirmative votes, brushed aside their interpretive declarations without comment, challenge or any acknowledgment at all.

The Thirteenth Amendment was subsequently ratified by:

  • Oregon â€" December 8, 1865
  • California â€" December 19, 1865
  • Florida â€" December 28, 1865 (Reaffirmed â€" June 9, 1869)
  • Iowa â€" January 15, 1866
  • New Jersey â€" January 23, 1866 (After rejection â€" March 16, 1865)
  • Texas â€" February 18, 1870
  • Delaware â€" February 12, 1901 (After rejection â€" February 8, 1865)
  • Kentucky â€" March 18, 1976 (After rejection â€" February 24, 1865)
  • Mississippi â€" March 16, 1995; Certified â€" February 7, 2013 (After rejection â€" December 5, 1865)

The Thirteenth Amendment became part of the Constitution 61½ years after the Twelfth Amendment. To date, this is the longest interval of time between constitutional amendments.


The impact of the abolition of slavery was felt quickly. When the Thirteenth Amendment became operational, the scope of Lincoln's 1863 Emancipation Proclamation was widened to include the entire nation. Although the majority of Kentucky's slaves had been emancipated, 65,000â€"100,000 people remained to be legally freed when the Amendment went into effect on December 18. In Delaware, where a large number of slaves had escaped during the war, nine hundred people became legally free.

In addition to abolishing slavery and prohibiting involuntary servitude, except as a punishment for crime, the Thirteenth Amendment also nullified the Fugitive Slave Clause and the Three-Fifths Compromise. The population of a state originally included (for congressional apportionment purposes) all "free persons", three-fifths of "other persons" (i.e., slaves) and excluded untaxed Native Americans. The Three-Fifths Compromise was a provision in the Constitution that required three-fifths of the population of slaves be counted for purposes of apportionment of seats in the House of Representatives and taxes among the states. This compromise had the effect of increasing the political power of slave-holding states by increasing their share of seats in the House of Representatives, and consequently their share in the Electoral College (where a state's influence over the election of the President is tied to the size of its congressional delegation).

Even as the Thirteenth Amendment was working its way through the ratification process, Republicans in Congress grew increasingly concerned about the potential for there to be a large increase the congressional representation of the Democratic-dominated Southern states. Because the full population of freed slaves would be counted rather than three-fifths, the Southern states would dramatically increase their power in the population-based House of Representatives. Republicans hoped to offset this advantage by attracting and protecting votes of the newly enfranchised black population.

Political and economic change in the South

Southern culture remained deeply racist, and those blacks who remained faced a dangerous situation. J. J. Gries reported to the Joint Committee on Reconstruction: “There is a kind of innate feeling, a lingering hope among many in the South that slavery will be regalvanized in some shape or other. They tried by their laws to make a worse slavery than there was before, for the freedman has not the protection which the master from interest gave him before.” W. E. B. Du Bois wrote in 1935:

Slavery was not abolished even after the Thirteenth Amendment. There were four million freedmen and most of them on the same plantation, doing the same work that they did before emancipation, except as their work had been interrupted and changed by the upheaval of war. Moreover, they were getting about the same wages and apparently were going to be subject to slave codes modified only in name. There were among them thousands of fugitives in the camps of the soldiers or on the streets of the cities, homeless, sick, and impoverished. They had been freed practically with no land nor money, and, save in exceptional cases, without legal status, and without protection.

Official emancipation did not substantially alter the economic situation of most blacks who remained in the south.

As the amendment still permitted labor as punishment for convicted criminals, Southern states responded with what historian Douglas A. Blackmon called "an array of interlocking laws essentially intended to criminalize black life". These laws, passed or updated after emancipation, were known as Black Codes. Mississippi was the first state to pass such codes, with an 1865 law titled “An Act to confer Civil Rights on Freedmen”. The Mississippi law required black workers to contract with white farmers by January 1 of each year or face punishment for vagrancy. Blacks could be sentenced to forced labor for crimes including petty theft, using obscene language, or selling cotton after sunset. States passed new, strict vagrancy laws that were selectively enforced against blacks without white protectors. The labor of these convicts was then sold to farms, factories, lumber camps, quarries, and mines.

After its ratification of the Thirteenth Amendment in November 1865, the South Carolina legislature immediately began to legislate Black Codes. The Black Codes created a separate set of laws, punishments, and acceptable behaviors for anyone with more than one black great-grandparent. Under these Codes, Blacks could only work as farmers or servants and had few Constitutional rights. Restrictions on black land ownership threatened to make economic subservience permanent.

Some states mandated indefinitely long periods of child "apprenticeship". Some laws did not target Blacks specifically, but instead affected farm workers, most of whom were Black. At the same time, many states passed laws to actively prevent Blacks from acquiring property.

Southern business owners sought to reproduce the profitable arrangement of slavery with a system called peonage, in which (disproportionately black) workers were entrapped by loans and compelled to work indefinitely because of their debt. Peonage continued well through Reconstruction and ensnared a large proportion of black workers in the South. These workers remained destitute and persecuted, forced to work dangerous jobs and further confined legally by the racist Jim Crow laws that governed the South. Peonage differed from chattel slavery because it was not strictly hereditary and did not allow the sale of people in exactly the same fashion. However, a person's debtâ€"and by extension a personâ€"could still be sold, and the system resembled antebellum slavery in many ways.

Congressional and executive enforcement

As its first enforcement legislation, Congress passed the Civil Rights Act of 1866, which guaranteed black Americans citizenship and equal protection of the law, though not the right to vote. The Amendment was also used as authorization for several Freedmen's Bureau bills. President Andrew Johnson vetoed these bills, but a Congressional supermajoirty overrode his veto to pass the Civil Rights Act and the Second Freedmen's Bureau Bill.

Proponents of the Act including Trumbull and Wilson argued that Section 2 of the Thirteenth Amendment (enforcement power) authorized the federal government to legislate civil rights for the States. Others disagreed, maintaining that inequality conditions were distinct from slavery. Seeking more substantial justification, and fearing that future opponents would again seek to overturn the legislation, Congress and the states added additional protections to the Constitution: the Fourteenth Amendment (1868), which defined citizenship and mandated equal protection under the law, and the Fifteenth Amendment (1870), which banned racial voting restrictions.

The Freedmen's Bureau enforced the Amendment locally, providing a degree of support for people subject to the Black Codes. (Reciprocally, the Thirteenth Amendment established the Bureau's legal basis to operate in Kentucky.) The Civil Rights Act circumvented racism in local jurisdictions by allowing blacks access to the federal courts. The Enforcement Acts of 1870â€"1871 and the Civil Rights Act of 1875, in combating the violence and intimidation of white supremacy, were also part of the effort to end slave conditions for Southern blacks. However, the effect of these laws waned as political will diminished and the federal government lost authority in the South, particularly after the Compromise of 1877 ended Reconstruction in exchange for a Republican presidency.

Peonage law

With the Peonage Act of 1867, Congress abolished “the holding of any person to service or labor under the system known as peonage”, specifically banning “the voluntary or involuntary service or labor of any persons as peons, in liquidation of any debt or obligation, or otherwise.”

In 1939, the Department of Justice created the Civil Rights Section, which focused primarily on First Amendment and labor rights. The increasing scrutiny of totalitarianism in the lead-up to World War II brought increased attention to issues of slavery and involuntary servitude, abroad and at home. The U.S. sought to counter foreign propaganda and increase its credibility on the race issue by combatting the Southern peonage system. Under the leadership of Attorney General Francis Biddle, the Civil Rights Section invoked the constitutional amendments and legislation of the Reconstruction Era as the basis for its actions.

In 1947, the DOJ successfully prosecuted Elizabeth Ingalls for keeping domestic servant Dora L. Jones in conditions of slavery. The court found that Jones “was a person wholly subject to the will of defendant; that she was one who had no freedom of action and whose person and services were wholly under the control of defendant and who was in a state of enforced compulsory service to the defendant.” The Thirteenth Amendment enjoyed a swell of attention during this period, but from Brown v. Board (1954) until Jones v. Alfred H. Mayer Co. (1968) it was again eclipsed by the Fourteenth Amendment.

Human trafficking

Victims of human trafficking and other conditions of forced labor are commonly coerced by threat of legal actions to their detriment. Victims of forced labor and trafficking are protected by Title 18 of the U.S. Code.

  • Title 18, U.S.C., Section 241 â€" Conspiracy Against Rights:

Conspiracy to injure, oppress, threaten, or intimidate any person's rights or privileges secured by the Constitution or the laws of the United States

  • Title 18, U.S.C., Section 242 â€" Deprivation of Rights Under Color of Law:

It is a crime for any person acting under color of law (federal, state or local officials who enforce statutes, ordinances, regulations, or customs) to willfully deprive or cause to be deprived the rights, privileges, or immunities of any person secured or protected by the Constitution and laws of the U.S. This includes willfully subjecting or causing to be subjected any person to different punishments, pains, or penalties, than those prescribed for punishment of citizens on account of such person being an alien or by reason of his/her color or race.

Department of Justice definitions

Refers to a person in "debt servitude," or involuntary servitude tied to the payment of a debt. Compulsion to servitude includes the use of force, the threat of force, or the threat of legal coercion to compel a person to work.
Involuntary servitude
Refers to a person held by actual force, threats of force, or threats of legal coercion in a condition of slavery â€" compulsory service or labor against his or her will. This includes the condition in which people are compelled to work by a "climate of fear" evoked by the use of force, the threat of force, or the threat of legal coercion (i.e., suffer legal consequences unless compliant with demands made upon them) which is sufficient to compel service. In Bailey v. Alabama (1911), the U.S. Supreme Court ruled that peonage laws violated the amendment's ban on involuntary servitude.
Requiring specific performance as a remedy for breach of personal services contracts has been viewed as a form of involuntary servitude by some scholars and courts, though other jurisdictions and scholars have rejected this argument; it is a popular rule in academia and many local jurisdictions, but has never been upheld by higher courts.
Forced labor
Labor or service obtained by:
  • threats of serious harm or physical restraint;
  • any scheme, plan, or pattern intended to cause a person to believe he would suffer serious harm or physical restraint if he did not perform such labor or services:
  • the abuse or threatened abuse of law or the legal process.

Judicial interpretation

In contrast to the other "Reconstruction Amendments", the Thirteenth Amendment was rarely cited in later case law. As historian Amy Dru Stanley summarizes, "beyond a handful of landmark rulings striking down debt peonage, flagrant involuntary servitude, and some instances of race-based violence and discrimination, the Thirteenth Amendment has never been a potent source of rights claims".

Black slaves and their descendants

U. S. v. Rhodes (1866), one of the first Thirteenth Amendment cases, tested the Constitutionality of provisions in the Civil Rights Act of 1866 that granted blacks redress in the federal courts. Kentucky law prohibited blacks from testifying against whitesâ€"an arrangement which compromised the ability of Nancy Talbot ("a citizen of the United States of the African race") to reach justice against a white person accused of robbing her. After Talbot attempted to try the case in federal court; the Kentucky Supreme Court ruled this federal option unconstitutional. Noah Swayne (a Supreme Court justice sitting on the Kentucky Circuit Court) overturned the Kentucky decision, holding that without the material enforcement provided by the Civil Rights Act, slavery would not truly be abolished. With In Re Turner (1867), Chief Justice Salmon P. Chase ordered freedom for Elizabeth Turner, a former slave in Maryland who became indentured to her former master.

In Blyew v. U.S., (1872) the Supreme Court heard another Civil Rights Act case relating to federal courts in Kentucky. John Bylew and George Kennard were white men visiting the cabin of a black family, the Fosters. Bylew apparently became angry with sixteen-year-old Richard Foster and hit him twice in the head with an ax. Bylew and Kennard killed Richard's parents, Sallie and Jack Foster, and his blind grandmother, Lucy Armstrong. They severely wounded the Fosters' two young daughters. Kentucky courts would not allow the Foster children to testify against Blyew and Kennard. But federal courts, authorized by the Civil Rights Act, found Blyew and Kennard guilty of murder. When the Supreme Court took the case, they ruled (5â€"2) that the Foster children did not have standing in federal courts because only living people could take advantage of the Act. In doing so, the Courts effectively ruled that Thirteenth Amendment did not permit a federal remedy in murder cases. Swayne and Joseph P. Bradley dissented, maintaining that in order to have meaningful effects, the Thirteenth Amendment would have to address systemic racial oppression.

Though based on a technicality, the Blyew case set a precedent in state and federal courts that led to the erosion of Congress's Thirteenth Amendment powers. The Supreme Court continued along this path in the Slaughter-House Cases (1873), which upheld a state-sanctioned monopoly of white butchers. In United States v. Cruikshank (1876), the Court ignored Thirteenth Amendment dicta from a circuit court decision to exonerate perpetrators of the Colfax massacre and invalidate the Enforcement Act of 1870.

The Thirteenth Amendment was not solely a ban on chattel slavery, but also covers a much broader array of labor arrangements and social deprivations. As the U.S. Supreme Court explicated in the Slaughter-House Cases (1873) with respect to the Fourteenth and Fifteenth Amendment and the Thirteenth Amendment in special:

In the Civil Rights Cases (1883), the Supreme Court reviewed five consolidated cases dealing with the Civil Rights Act of 1875, which outlawed racial discrimination at "inns, public conveyances on land or water, theaters, and other places of public amusement". The Court ruled that the Thirteenth Amendment did not ban most forms of racial discrimination by non-government actors. In the majority decision, Bradley wrote (again in non-binding dicta) that the Thirteenth Amendment empowered Congress to attack "badges and incidents of slavery". However, he distinguished between "fundamental rights" of citizenship, protected by the Thirteenth Amendment, and the "social rights of men and races in the community". The majority opinion held that "it would be running the slavery argument into the ground to make it apply to every act of discrimination which a person may see fit to make as to guests he will entertain, or as to the people he will take into his coach or cab or car; or admit to his concert or theatre, or deal with in other matters of intercourse or business." In his solitary dissent, John Marshall Harlan (a Kentucky lawyer who changed his mind about civil rights law after witnessing organized racist violence) argued that "such discrimination practiced by corporations and individuals in the exercise of their public or quasi-public functions is a badge of servitude, the imposition of which congress may prevent under its power."

The Court in the Civil Rights Cases also held that appropriate legislation under the amendment could go beyond nullifying state laws establishing or upholding slavery, because the amendment "has a reflex character also, establishing and decreeing universal civil and political freedom throughout the United States" and thus Congress was empowered "to pass all laws necessary and proper for abolishing all badges and incidents of slavery in the United States." The Court stated about the scope the amendment:

Attorneys in Plessy v. Ferguson (1896) argued that racial segregation involved "observances of a servile character coincident with the incidents of slavery", in violation of the Thirteenth Amendment. In their brief to the Supreme Court, Plessy's lawyers wrote that "distinction of race and caste" was inherently unconstitutional. The Supreme Court rejected this reasoning and upheld state laws enforcing segregation under the "separate but equal" doctrine. In the (7â€"1) majority decision, the Court found that "a statute which implies merely a legal distinction between the white and colored racesâ€"a distinction which is founded on the color of the two races and which must always exist so long as white men are distinguished from the other race by colorâ€"has no tendency to destroy the legal equality of the two races, or reestablish a state of involuntary servitude." Harlan dissented, writing: "The thin disguise of 'equal' accommodations for passengers in railroad coaches will not mislead any one, nor, atone for the wrong this day done."

In Hodges v. United States (1906), the Court struck down a federal statute providing for the punishment of two or more people who "conspire to injure, oppress, threaten or intimidate any citizen in the free exercise or enjoyment of any right or privilege secured to him by the Constitution or laws of the United States". A group of white men in Arkansas conspired to violently prevent eight black workers from performing their jobs at a lumber mill; the group was convicted by a federal grand jury. The Supreme Court ruled that the federal statute, which outlawed conspiracies to deprive citizens of their liberty, was not authorized by the Thirteenth Amendment. It held that "no mere personal assault or trespass or appropriation operates to reduce the individual to a condition of slavery". Harlan dissented, maintaining his opinion that the Thirteenth Amendment should protect freedom beyond "physical restraint". Corrigan v. Buckley (1922) reaffirmed the interpretation from Hodges, finding that the amendment does not apply to restrictive covenants.

Enforcement of federal civil rights law in the South created numerous peonage cases, which slowly traveled up through the judiciary. The Supreme Court ruled in Clyatt v. United States (1905) that peonage was involuntary servitude. It held that although employers sometimes described their workers' entry into contract as voluntary, the servitude of peonage was always (by definition) involuntary.

In Bailey v. Alabama the U.S. Supreme Court again reaffirmed its holding that Thirteenth Amendment was not solely a ban on chattel slavery, but also covers a much broader array of labor arrangements and social deprivations In addition to the aforesaid the Court also ruled on Congress enforcement power under the Thirteenth Amendment. The Court said:

Jones and beyond

Legal histories cite Jones v. Alfred H. Mayer Co. (1968) as a turning point of Thirteen Amendment jurisprudence. The Supreme Court confirmed in Jones that Congress may act “rationally” to prevent private actors from imposing "badges and incidents of servitude". The Joneses were a black couple in St. Louis County, Missouri who sued a real estate company for refusing to sell them a house. The Court held:

Congress has the power under the Thirteenth Amendment rationally to determine what are the badges and the incidents of slavery, and the authority to translate that determination into effective legislation. [...] this Court recognized long ago that, whatever else they may have encompassed, the badges and incidents of slavery -- its "burdens and disabilities" -- included restraints upon "those fundamental rights which are the essence of civil freedom, namely, the same right . . . to inherit, purchase, lease, sell and convey property, as is enjoyed by white citizens." Civil Rights Cases, 109 U. S. 3, 109 U. S. 22.

Just as the Black Codes, enacted after the Civil War to restrict the free exercise of those rights, were substitutes for the slave system, so the exclusion of Negroes from white communities became a substitute for the Black Codes. And when racial discrimination herds men into ghettos and makes their ability to buy property turn on the color of their skin, then it too is a relic of slavery.

Negro citizens, North and South, who saw in the Thirteenth Amendment a promise of freedomâ€"freedom to “go and come at pleasure” and to “buy and sell when they please”â€"would be left with “a mere paper guarantee” if Congress were powerless to assure that a dollar in the hands of a Negro will purchase the same thing as a dollar in the hands of a white man. At the very least, the freedom that Congress is empowered to secure under the Thirteenth Amendment includes the freedom to buy whatever a white man can buy, the right to live wherever a white man can live. If Congress cannot say that being a free man means at least this much, then the Thirteenth Amendment made a promise the Nation cannot keep.

The Court in Jones reopened the issue of linking racism in contemporary society to the history of slavery in the United States.

The Jones precedent has been used to justify Congressional action to protect migrant workers and target sex trafficking. The direct enforcement power found in the Thirteenth Amendment contrasts with that of the Fourteenth, which allows only responses to institutional discrimination of state actors.

Other cases of involuntary servitude

The Supreme Court has taken an especially narrow view of involuntary servitude claims made by people not descended from black (African) slaves. In Robertson v. Baldwin (1897), a sailor challenged federal rules mandating the capture and return of deserters. The Court ruled that "the amendment was not intended to introduce any novel doctrine with respect to certain descriptions of service which have always been treated as exceptional." In this case, as in numerous “badges and incidents” cases, Justice Harlan authored a dissent favoring broader Thirteenth Amendment protections.

In Selective Draft Law Cases, the Supreme Court ruled that the military draft was not "involuntary servitude". In United States v. Kozminski, the Supreme Court ruled that the Thirteenth Amendment did not prohibit compulsion of servitude through psychological coercion. Kozminski defined involuntary servitude for purposes of criminal prosecution as "a condition of servitude in which the victim is forced to work for the defendant by the use or threat of physical restraint or physical injury or by the use or threat of coercion through law or the legal process. This definition encompasses cases in which the defendant holds the victim in servitude by placing him or her in fear of such physical restraint or injury or legal coercion."

U.S. Courts of Appeals, in Immediato v. Rye Neck School District, Herndon v. Chapel Hill, and Steirer v. Bethlehem School District, have ruled that the use of community service as a high school graduation requirement did not violate the Thirteenth Amendment.

Prior proposed Thirteenth Amendments

During the six decades following the 1804 ratification of the Twelfth Amendment two proposals to amend the Constitution were adopted by Congress and sent to the states for ratification. Neither has been ratified by the number of states necessary to become part of the Constitution. Commonly known as the Titles of Nobility Amendment and the Corwin Amendment, both are referred to as Article Thirteen, as was the successful Thirteenth Amendment, in the joint resolution passed by Congress.

  • The Titles of Nobility Amendment (pending before the states since May 1, 1810) would, if ratified, strip citizenship from any United States citizen who accepts a title of nobility or honor from a foreign country without the consent of Congress.
  • The Corwin Amendment (pending before the states since March 2, 1861) would, if ratified, shield "domestic institutions" of the states (in 1861 this meant slavery) from the constitutional amendment process and from abolition or interference by Congress.

DNA methylation

DNA methylation is a biochemical process where a methyl group is added to the cytosine or adenine DNA nucleotides. The rate of cytosine DNA methylation differs strongly between species, e.g. absolute quantification by mass spectrometry revealed 14% of cytosines methylated in Arabidopsis thaliana, 8% in Mus musculus, 2.3% in Escherichia coli, 0.03% in Drosophila, and virtually none (< 0.0002%) in yeast species. DNA methylation may stably alter the expression of genes in cells as cells divide and differentiate from embryonic stem cells into specific tissues. The resulting change is normally permanent and unidirectional, preventing a cell from reverting to a stem cell or converting into a different cell type. DNA methylation is typically removed during zygote formation and re-established through successive cell divisions during development. However, the latest research shows that hydroxylation of methyl groups occurs rather than complete removal of methyl groups in the zygote. Some methylation modifications that regulate gene expression are heritable and cause genomic imprinting.

DNA methylation suppresses the expression of endogenous retroviral genes and other harmful stretches of DNA that have been incorporated into the host genome over time. DNA methylation also forms the basis of chromatin structure, which enables a single cell to grow into multiple organs or perform multiple functions. DNA methylation also plays a crucial role in the development of nearly all types of cancer.

DNA methylation at the 5 position of cytosine has the specific effect of reducing gene expression and has been found in every vertebrate examined. In adult somatic cells (cells in the body, not used for reproduction), DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells, and has also been indicated in neural development.

In mammals

DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, suppression of repetitive elements, and carcinogenesis.

Between 60% and 90% of all CpGs are methylated in mammals. Methylated C residues spontaneously deaminate to form T residues over time; hence CpG dinucleotides steadily deaminate to TpG dinucleotides, which is evidenced by the under-representation of CpG dinucleotides in the human genome (they occur at only 21% of the expected frequency). (On the other hand, spontaneous deamination of unmethylated C residues gives rise to U residues, a change that is quickly recognized and repaired by the cell.)

Unmethylated CpGs are often grouped in clusters called CpG islands, which are present in the 5' regulatory regions of many genes. In many disease processes, such as cancer, gene promoter CpG islands acquire abnormal hypermethylation, which results in transcriptional silencing that can be inherited by daughter cells following cell division. Alterations of DNA methylation have been recognized as an important component of cancer development. Hypomethylation, in general, arises earlier and is linked to chromosomal instability and loss of imprinting, whereas hypermethylation is associated with promoters and can arise secondary to gene (oncogene suppressor) silencing, but might be a target for epigenetic therapy.

DNA methylation may affect the transcription of genes in two ways. First, the methylation of DNA itself may physically impede the binding of transcriptional proteins to the gene, and second, and likely more important, methylated DNA may be bound by proteins known as methyl-CpG-binding domain proteins (MBDs). MBD proteins then recruit additional proteins to the locus, such as histone deacetylases and other chromatin remodeling proteins that can modify histones, thereby forming compact, inactive chromatin, termed heterochromatin. This link between DNA methylation and chromatin structure is very important. In particular, loss of methyl-CpG-binding protein 2 (MeCP2) has been implicated in Rett syndrome; and methyl-CpG-binding domain protein 2 (MBD2) mediates the transcriptional silencing of hypermethylated genes in cancer.

Research has suggested that long-term memory storage in humans may be regulated by DNA methylation.

DNA methylation levels can be used to estimate age, forming an accurate biological clock in humans and chimpanzees.

In cancer

DNA methylation is an important regulator of gene transcription and a large body of evidence has demonstrated that genes with high levels of 5-methylcytosine in their promoter region are transcriptionally silent, and that DNA methylation gradually accumulates upon long-term gene silencing. DNA methylation is essential during embryonic development, and in somatic cells, patterns of DNA methylation are generally transmitted to daughter cells with a high fidelity. Aberrant DNA methylation patterns â€" hypermethylation and hypomethylation compared to normal tissue â€" have been associated with a large number of human malignancies. Hypermethylation typically occurs at CpG islands in the promoter region and is associated with gene inactivation. A lower level of leukocyte DNA methylation is associated with many types of cancer. Global hypomethylation has also been implicated in the development and progression of cancer through different mechanisms. Typically, there is hypermethylation of tumor suppressor genes and hypomethylation of oncogenes.

In atherosclerosis

Epigenetic modifications such as DNA methylation have been implicated in cardiovascular disease, including atherosclerosis. In animal models of atherosclerosis, vascular tissue as well as blood cells such as mononuclear blood cells exhibit global hypomethylation with gene-specific areas of hypermethylation. DNA methylation polymorphisms may be used as an early biomarker of atherosclerosis since they are present before lesions are observed, which may provide an early tool for detection and risk prevention.

Two of the cell types targeted for DNA methylation polymorphisms are monocytes and lymphocytes, which experience an overall hypomethylation. One proposed mechanism behind this global hypomethylation is elevated homocysteine levels causing hyperhomocysteinemia, a known risk factor for cardiovascular disease. High plasma levels of homocysteine inhibit DNA methyltransferases, which causes hypomethylation. Hypomethylation of DNA affects gene that alter smooth muscle cell proliferation, cause endothelial cell dysfunction, and increase inflammatory mediators, all of which are critical in forming atherosclerotic lesions. High levels of homocysteine also result in hypermethylation of CpG islands in the promoter region of the estrogen receptor alpha (ERα) gene, causing its down regulation. ERα protects against atherosclerosis due to its action as a growth suppressor, causing the smooth muscle cells to remain in a quiescent state. Hypermethylation of the ERα promoter thus allows intimal smooth muscle cells to proliferate excessively and contribute to the development of the atherosclerotic lesion.

Another gene that experiences a change in methylation status in atherosclerosis is the monocarboxylate transporter (MCT3), which produces a protein responsible for the transport of lactate and other ketone bodies out of many cell types, including vascular smooth muscle cells. In atherosclerosis patients, there is an increase in methylation of the CpG islands in exon 2, which decreases MCT3 protein expression. The down regulation of MCT3 impairs lactate transport, and significantly increases smooth muscle cell proliferation, which further contributes to the atherosclerotic lesion. An ex vivo experiment using the demethylating agent Decitabine (5-aza-2 -deoxycytidine) was shown to induce MCT3 expression in a dose dependant manner, as all hypermethylated sites in the exon 2 CpG island became demethylated after treatment. This may serve as a novel therapeutic agent to treat atherosclerosis, although no human studies have been conducted thus far.

In aging

A longitudinal study of twin children, showed that between the ages of 5 and 10 there was divergence of methylation patterns due to environmental rather than genetic influences. There is a global loss of DNA methylation during aging. But some genes become hypermethylated with age, including genes for the estrogen receptor, p16, and insulin-like growth factor 2. Biological clocks such as an epigenetic clock, are promising biomarkers of aging.

In exercise

High intensity exercise has been shown to result in reduced DNA methylation in skeletal muscle. Promoter methylation of PGC-1α and PDK4 were immediately reduced after high intensity exercise, whereas PPAR-γ methylation was not reduced until three hours after exercise. By contrast, six months of exercise in previously sedentary middle-age men resulted in increased methylation in adipose tissue. One study showed a possible increase in global genomic DNA methylation of white blood cells with more physical activity in non-Hispanics.

DNA methyltransferases

In mammalian cells, DNA methylation occurs mainly at the C5 position of CpG dinucleotides and is carried out by two general classes of enzymatic activities â€" maintenance methylation and de novo methylation.

Maintenance methylation activity is necessary to preserve DNA methylation after every cellular DNA replication cycle. Without the DNA methyltransferase (DNMT), the replication machinery itself would produce daughter strands that are unmethylated and, over time, would lead to passive demethylation. DNMT1 is the proposed maintenance methyltransferase that is responsible for copying DNA methylation patterns to the daughter strands during DNA replication. Mouse models with both copies of DNMT1 deleted are embryonic lethal at approximately day 9, due to the requirement of DNMT1 activity for development in mammalian cells.

It is thought that DNMT3a and DNMT3b are the de novo methyltransferases that set up DNA methylation patterns early in development. DNMT3L is a protein that is homologous to the other DNMT3s but has no catalytic activity. Instead, DNMT3L assists the de novo methyltransferases by increasing their ability to bind to DNA and stimulating their activity. Finally, DNMT2 (TRDMT1) has been identified as a DNA methyltransferase homolog, containing all 10 sequence motifs common to all DNA methyltransferases; however, DNMT2 (TRDMT1) does not methylate DNA but instead methylates cytosine-38 in the anticodon loop of aspartic acid transfer RNA.

Since many tumor suppressor genes are silenced by DNA methylation during carcinogenesis, there have been attempts to re-express these genes by inhibiting the DNMTs. 5-Aza-2'-deoxycytidine (decitabine) is a nucleoside analog that inhibits DNMTs by trapping them in a covalent complex on DNA by preventing the β-elimination step of catalysis, thus resulting in the enzymes' degradation. However, for decitabine to be active, it must be incorporated into the genome of the cell, which can cause mutations in the daughter cells if the cell does not die. In addition, decitabine is toxic to the bone marrow, which limits the size of its therapeutic window. These pitfalls have led to the development of antisense RNA therapies that target the DNMTs by degrading their mRNAs and preventing their translation. However, it is currently unclear whether targeting DNMT1 alone is sufficient to reactivate tumor suppressor genes silenced by DNA methylation.

In plants

Significant progress has been made in understanding DNA methylation in the model plant Arabidopsis thaliana. DNA methylation in plants differs from that of mammals: while DNA methylation in mammals mainly occurs on the cytosine nucleotide in a CpG site, in plants the cytosine can be methylated at CpG, CpHpG, and CpHpH sites, where H represents any nucleotide but guanine. Overall, Arabidopsis DNA is highly methylated, mass spectrometry analysis estimated 14% of cytosines to be modified.

The principal Arabidopsis DNA methyltransferase enzymes, which transfer and covalently attach methyl groups onto DNA, are DRM2, MET1, and CMT3. Both the DRM2 and MET1 proteins share significant homology to the mammalian methyltransferases DNMT3 and DNMT1, respectively, whereas the CMT3 protein is unique to the plant kingdom. There are currently two classes of DNA methyltransferases: 1) the de novo class, or enzymes that create new methylation marks on the DNA; and 2) a maintenance class that recognizes the methylation marks on the parental strand of DNA and transfers new methylation to the daughters strands after DNA replication. DRM2 is the only enzyme that has been implicated as a de novo DNA methyltransferase. DRM2 has also been shown, along with MET1 and CMT3 to be involved in maintaining methylation marks through DNA replication. Other DNA methyltransferases are expressed in plants but have no known function (see the Chromatin Database).

It is not clear how the cell determines the locations of de novo DNA methylation, but evidence suggests that, for many (though not all) locations, RNA-directed DNA methylation (RdDM) is involved. In RdDM, specific RNA transcripts are produced from a genomic DNA template, and this RNA forms secondary structures called double-stranded RNA molecules. The double-stranded RNAs, through either the small interfering RNA (siRNA) or microRNA (miRNA) pathways direct de-novo DNA methylation of the original genomic location that produced the RNA. This sort of mechanism is thought to be important in cellular defense against RNA viruses and/or transposons, both of which often form a double-stranded RNA that can be mutagenic to the host genome. By methylating their genomic locations, through an as yet poorly understood mechanism, they are shut off and are no longer active in the cell, protecting the genome from their mutagenic effect.

In fungi

Many fungi have low levels (0.1 to 0.5%) of cytosine methylation, whereas other fungi have as much as 5% of the genome methylated. This value seems to vary both among species and among isolates of the same species. There is also evidence that DNA methylation may be involved in state-specific control of gene expression in fungi. However, at a detection limit of 250 attomoles by using ultra-high sensitive mass spectrometry DNA methylation was not confirmed in single cellular yeast species such as Saccharomyces cerevisiae or Schizosaccharomyces pombe, indicating that yeasts do not possess this DNA modification.

Although brewers' yeast (Saccharomyces) and fission yeast (Schizosaccharomyces) have no detectable DNA methylation, the model filamentous fungus Neurospora crassa has a well-characterized methylation system. Several genes control methylation in Neurospora and mutation of the DNA methyl transferase, dim-2, eliminates all DNA methylation but does not affect growth or sexual reproduction. While the Neurospora genome has very little repeated DNA, half of the methylation occurs in repeated DNA including transposon relics and centromeric DNA. The ability to evaluate other important phenomena in a DNA methylase-deficient genetic background makes Neurospora an important system in which to study DNA methylation.

In insects

DNA methylation is debated in insects, Drosophila melanogaster for instance seems to possess a very low level of DNA methylation only that is however too low to be studied by methods such as bisulphite sequencing. Takayama et al. developed a sensitive method that allowed to find that the fly genome DNA sequence patterns that associate with methylation are very different from the patterns seen in humans, or in other animal or plant species to date. Genome methylation in D. melanogaster was found at specific short motifs (concentrated in specific 5-base sequence motifs that are CA- and CT-rich but depleted of guanine) and is independent of DNMT2 activity.

In bacteria

Adenine or cytosine methylation is part of the restriction modification system of many bacteria, in which specific DNA sequences are methylated periodically throughout the genome. A methylase is the enzyme that recognizes a specific sequence and methylates one of the bases in or near that sequence. Foreign DNAs (which are not methylated in this manner) that are introduced into the cell are degraded by sequence-specific restriction enzymes and cleaved. Bacterial genomic DNA is not recognized by these restriction enzymes. The methylation of native DNA acts as a sort of primitive immune system, allowing the bacteria to protect themselves from infection by bacteriophage.

E. coli DNA adenine methyltransferase (Dam) is an enzyme of ~32 kDa that does not belong to a restriction/modification system. The target recognition sequence for E. coli Dam is GATC, as the methylation occurs at the N6 position of the adenine in this sequence (G meATC). The three base pairs flanking each side of this site also influence DNAâ€"Dam binding. Dam plays several key roles in bacterial processes, including mismatch repair, the timing of DNA replication, and gene expression. As a result of DNA replication, the status of GATC sites in the E. coli genome changes from fully methylated to hemimethylated. This is because adenine introduced into the new DNA strand is unmethylated. Re-methylation occurs within two to four seconds, during which time replication errors in the new strand are repaired. Methylation, or its absence, is the marker that allows the repair apparatus of the cell to differentiate between the template and nascent strands. It has been shown that altering Dam activity in bacteria results in increased spontaneous mutation rate. Bacterial viability is compromised in dam mutants that also lack certain other DNA repair enzymes, providing further evidence for the role of Dam in DNA repair.

One region of the DNA that keeps its hemimethylated status for longer is the origin of replication, which has an abundance of GATC sites. This is central to the bacterial mechanism for timing DNA replication. SeqA binds to the origin of replication, sequestering it and thus preventing methylation. Because hemimethylated origins of replication are inactive, this mechanism limits DNA replication to once per cell cycle.

Expression of certain genes, for example those coding for pilus expression in E. coli, is regulated by the methylation of GATC sites in the promoter region of the gene operon. The cells' environmental conditions just after DNA replication determine whether Dam is blocked from methylating a region proximal to or distal from the promoter region. Once the pattern of methylation has been created, the pilus gene transcription is locked in the on or off position until the DNA is again replicated. In E. coli, these pilus operons have important roles in virulence in urinary tract infections. It has been proposed that inhibitors of Dam may function as antibiotics.

On the other hand, DNA cytosine methylase targets CCAGG and CCTGG sites to methylate cytosine at the C5 position (C meC(A/T) GG). The other methylase enzyme, EcoKI, causes methylation of adenines in the sequences AAC(N6)GTGC and GCAC(N6)GTT.

Molecular cloning

Most strains used by molecular biologists are derivatives of E. coli K-12, and possess both Dam and Dcm, but there are commercially available strains that are dam-/dcm- (lack of activity of either methylase). In fact, it is possible to unmethylate the DNA extracted from dam+/dcm+ strains by transforming it into dam-/dcm- strains. This would help digest sequences that are not being recognized by methylation-sensitive restriction enzymes.

The Restriction enzyme DpnI can recognize 5'-GmeATC-3'sites and digest the methylated DNA. Being such a short motif, it occurs frequently in sequences by chance, and as such its primary use for researchers is to degrade template DNA following PCR reactions (PCR products lack methylation, as no methylases are present in the reaction). Similarly, some commercially available restriction enzymes are sensitive to methylation at their cognate restriction sites, and must as mentioned previously be used on DNA passed through a dam-/dcm- strain to allow cutting.


DNA methylation can be detected by the following assays currently used in scientific research:

  • Mass spectrometry is a very sensitive and reliable analytical method to detect DNA methylation. MS in general is however not informative about the sequence context of the methylation, thus limited in studying the function of this DNA modification.
  • Methylation-Specific PCR (MSP), which is based on a chemical reaction of sodium bisulfite with DNA that converts unmethylated cytosines of CpG dinucleotides to uracil or UpG, followed by traditional PCR. However, methylated cytosines will not be converted in this process, and primers are designed to overlap the CpG site of interest, which allows one to determine methylation status as methylated or unmethylated.
  • Whole genome bisulfite sequencing, also known as BS-Seq, which is a high-throughput genome-wide analysis of DNA methylation. It is based on aforementioned sodium bisulfite conversion of genomic DNA, which is then sequenced on a Next-generation sequencing platform. The sequences obtained are then re-aligned to the reference genome to determine methylation states of CpG dinucleotides based on mismatches resulting from the conversion of unmethylated cytosines into uracil.
  • The HELP assay, which is based on restriction enzymes' differential ability to recognize and cleave methylated and unmethylated CpG DNA sites.
  • ChIP-on-chip assays, which is based on the ability of commercially prepared antibodies to bind to DNA methylation-associated proteins like MeCP2.
  • Restriction landmark genomic scanning, a complicated and now rarely used assay based upon restriction enzymes' differential recognition of methylated and unmethylated CpG sites; the assay is similar in concept to the HELP assay.
  • Methylated DNA immunoprecipitation (MeDIP), analogous to chromatin immunoprecipitation, immunoprecipitation is used to isolate methylated DNA fragments for input into DNA detection methods such as DNA microarrays (MeDIP-chip) or DNA sequencing (MeDIP-seq).
  • Pyrosequencing of bisulfite treated DNA. This is sequencing of an amplicon made by a normal forward primer but a biotinylated reverse primer to PCR the gene of choice. The Pyrosequencer then analyses the sample by denaturing the DNA and adding one nucleotide at a time to the mix according to a sequence given by the user. If there is a mis-match, it is recorded and the percentage of DNA for which the mis-match is present is noted. This gives the user a percentage methylation per CpG island.
  • Molecular break light assay for DNA adenine methyltransferase activity â€" an assay that relies on the specificity of the restriction enzyme DpnI for fully methylated (adenine methylation) GATC sites in an oligonucleotide labeled with a fluorophore and quencher. The adenine methyltransferase methylates the oligonucleotide making it a substrate for DpnI. Cutting of the oligonucleotide by DpnI gives rise to a fluorescence increase.
  • Methyl Sensitive Southern Blotting is similar to the HELP assay, although uses Southern blotting techniques to probe gene-specific differences in methylation using restriction digests. This technique is used to evaluate local methylation near the binding site for the probe.
  • MethylCpG Binding Proteins (MBPs) and fusion proteins containing just the Methyl Binding Domain (MBD) are used to separate native DNA into methylated and unmethylated fractions. The percentage methylation of individual CpG islands can be determined by quantifying the amount of the target in each fraction. Extremely sensitive detection can be achieved in FFPE tissues with abscription-based detection.
  • High Resolution Melt Analysis (HRM or HRMA), is a post-PCR analytical technique. The target DNA is treated with sodium bisulfite, which chemically converts unmethylated cytosines into uracils, while methylated cytosines are preserved. PCR amplification is then carried out with primers designed to amplify both methylated and unmethylated templates. After this amplification, highly methylated DNA sequences contain a higher number of CpG sites compared to unmethylated templates, which results in a different melting temperature that can be used in quantitative methylation detection.

Differentially methylated regions (DMRs)

Differentially methylated regions (DMRs), are genomic regions with different methylation statuses among multiple samples (tissues, cells, individuals or others), are regarded as possible functional regions involved in gene transcriptional regulation. The identification of DMRs among multiple tissues (T-DMRs) provides a comprehensive survey of epigenetic differences among human tissues. DMRs between cancer and normal samples (C-DMRs) demonstrate the aberrant methylation in cancers. It is well known that DNA methylation is associated with cell differentiation and proliferation. Many DMRs have been found in the development stages (D-DMRs) and in the reprogrammed progress (R-DMRs). In addition, there are intra-individual DMRs (Intra-DMRs) with longitudinal changes in global DNA methylation along with the increase of age in a given individual. There are also inter-individual DMRs (Inter-DMRs) with different methylation patterns among multiple individuals.

QDMR (Quantitative Differentially Methylated Regions) is a quantitative approach to quantify methylation difference and identify DMRs from genome-wide methylation profiles by adapting Shannon entropy ( The platform-free and species-free nature of QDMR makes it potentially applicable to various methylation data. This approach provides an effective tool for the high-throughput identification of the functional regions involved in epigenetic regulation. QDMR can be used as an effective tool for the quantification of methylation difference and identification of DMRs across multiple samples.

Gene-set analysis (a.k.a pathway analysis; usually performed tools such as DAVID, GoSeq or GSEA) has been shown to be severely biased when applied to high-throughput methylation data (e.g. MeDIP-seq, MeDIP-ChIP, HELP-seq etc.), and a wide range of studies have thus mistakenly reported hyper-methylation of genes related to development and differentiation; it has been suggested that this can be corrected using sample label permutations or using a statistical model to control for differences in the numberes of CpG probes / CpG sites that target each gene.

Computational prediction

DNA methylation can also be detected by computational models through sophisticated algorithms and methods. Computational models can facilitate the global profiling of DNA methylation across chromosomes, and often such models are faster and cheaper to perform than biological assays. Such up-to-date computational models include Bhasin, et al., Bock, et al., and Zheng, et al. Together with biological assay, these methods greatly facilitate the DNA methylation analysis.

Pick%27s disease

Pick's disease, a type of Frontotemporal Dementia, is a rare neurodegenerative disease that causes progressive destruction of nerve cells in the brain. Symptoms include dementia and loss of speech (aphasia). While some of the symptoms can initially be alleviated, the disease progresses and patients often die within two to ten years. A defining characteristic of the disease is build-up of tau proteins in neurons, accumulating into silver-staining, spherical aggregations known as "Pick bodies".

While the term Pick's disease was once used to represent a class of clinical syndromes with symptoms attributable to frontal and temporal lobe dysfunction, it is now used among professionals to mean a specific pathology that is one of the causes of frontotemporal lobar degeneration. Some people use the term Pick's disease to mean the more general clinical syndrome of frontotemporal lobar degeneration, but this has previously led to confusion among professionals and patients and so its use should be restricted to the specific pathological subtype described below. It is also known as Pick disease and PiD (not to be confused with pelvic inflammatory disease (PID) or Parkinson's disease (PD)).

Signs and symptoms

The symptoms of Pick's disease include difficulty in speech and thinking, efforts to dissociate from family, behavioral changes, unwarranted anxiety, impaired regulation of social conduct (e.g., breaches of etiquette, tactlessness, dis-inhibition, misperception), passivity, inertia, over-activity, pacing and wandering. The changes in personality allow doctors to distinguish between Pick's disease and Alzheimer's disease. Pick's disease is one of the causes of the clinical syndrome of frontotemporal lobar degeneration which has three subtypes. Pick's disease pathology is associated more with the frontotemporal dementia and progressive nonfluent aphasia subtypes than the semantic dementia subtype.


While other pathologies causing frontotemporal lobar degeneration are associated with a genetic cause, evidence is not conclusive in modern research on whether classical Pick's disease pathology has or does not have a direct genetic link, or whether it has been shown to run in families or certain ethnic or gender specific subgroups.


PiD was first recognized as a distinct disease separate from other neurodegenerative diseases because of the presence of large, dark-staining aggregates of proteins in neurological tissue as well as the aforementioned ballooned cells, which are known as Pick cells. Pick bodies are almost universally present in patients with PiD, but some new cases of atypical Pick’s disease have come to light that lack noticeable Pick bodies. A variety of stains can aid in the visualization of Pick bodies and Pick cells, but immunohistochemical staining using anti-tau and anti-ubiquitin antibodies have proven the most efficient and specific. Hematoxylin and eosin staining allows visualization of another population of Pick cells, which are both tau and ubiquitin protein negative. Several silver impregnation stains have been used, including the Bielschowsky, Bodian, and Gallyas methods. The latter two techniques are sensitive enough to allow PiD to be distinguished from Alzheimer's disease as the Bodian will bind preferentially to cells with PiD as compared to the Gallyas method, which preferentially binds to the cells with Alzheimer's.

Numerous areas of the brain are affected by PiD, but the specific areas that are affected allow for differentiation between PiD and Alzheimer’s disease. Pick bodies are almost always found in several places in the brain, including the dentate gyrus, the pyramidial cells of the CA1 sector and subiculum of the hippocampus, and the neocortex as well as a plurality of other nuclei. Interestingly, it is the location in the layers of the brain as well as the anatomical placement that demonstrates some of the unique features of PiD. A striking feature is that in the neocortex the Pick bodies are in the II and IV layers of the cortex, which send neurons within the cortex and to thalamic synapses, respectively. While layers III and V have very few if any Pick bodies they show extreme neuronal loss that can, in some cases, be so severe as to leave a void in the brain altogether. Other regions that are involved include the caudate, which is severely affected, the dorsomedial region of the putamen, the globus pallidus, and locus coeruleus. The hypothalamic lateral tuberal nucleus is also very severely affected. The cerebellar elements that are important in receiving input, including the mossy fibers as well as the monodendritic brush cells in the granule cell layer, and generating output signals, most notably the dentate nucleus, are stricken with lots of tau protein inclusions. Strangely, the substantia nigra is most often uninvolved or only mildly involved, but cases of extreme degeneration do exist.

PiD has several unique biochemical characteristics that allow for identification of Pick’s disease as opposed to other pathological subtypes of frontotemporal lobar degeneration. The most striking of these is that this disease, which has tau protein tangles present in many affected neurons, contains only one or as many as two of the six isoforms of the tau protein. All of these isoforms result from alternative splicing of the same gene. Pick bodies typically have the 3R isoform of tau proteins as not only the most abundant form but the only form of this protein, but a recent study has shown that a much greater number of tau isoforms including 4R and mixed 3R/4R can be present in the Pick bodies. Not only do these tangles have the 3R tau protein predominately, they are characteristically shaped with a round body; there is often an indentation in the area that faces the nucleus of the cell.

The Pick bodies are able to be labeled by N-terminal amyloid precursor protein segment, hyperphosphorylated tau, ubiquitin, Alz-50, neurofiliment proteins, clathrin, synaptophysin and neuronal surface glycoside (A2B5) specific stains. Moreover βII tubulin proteins are suspected in playing a role in the formation of phosphor-tau aggregates that are seen in PiD as well as AD.

Differences from Alzheimer’s disease

In Alzheimer's disease, all six isoforms of tau proteins are expressed. In addition, the presence of neurofibrillary tangles that are a hallmark of Alzheimer’s can be stained with antibodies to basic fibroblast growth factor, amyloid P, and heparan sulfate glycosaminoglycan.

Another difference is that in Pick's disease, a personality change occurs before any form of memory loss, unlike Alzheimer's, where memory loss typically presents first. This is used clinically to determine whether a patient is suffering from Alzheimer's or Pick's.


Pick's disease is named after Arnold Pick, a professor of psychiatry from the University of Prague who first discovered and described the disease in 1892 by examining the brain tissue of several deceased patients with histories of dementia. As a result, the characteristic histological feature of this diseaseâ€"a protein tangle that appears as a large body in neuronal tissueâ€"is named a Pick body. In 1911, Alois Alzheimer noted the complete absence of senile plaques and neurofilbrillary tangles as well as the presence of Pick bodies and occasional ballooned neurons.

Notable cases

  • Don Cardwell (1935â€"2008), Major League baseball pitcher
  • Rocco "Rocky" Catena (1929â€"2006), music industry executive, former senior VP, Capitol Records, in charge of marketing The Beatles and other top recording stars in the U.S. Suffered from Pick's disease for 20+ years.
  • Jerry Corbetta (1947-), original lead singer and keyboardist for the group Sugarloaf
  • Ted Darling (c.1935â€"1996), voice of the Buffalo Sabres
  • Robert W. Floyd (1936â€"2001), computer scientist
  • Colleen Howe (1933â€"2009), wife of Hockey Hall of Famer Gordie Howe
  • Kazi Nazrul Islam (1899â€"1976), Bengali poet and musician (Known as rebel poet), who pioneered poetic works espousing intense rebellion against fascism and oppression, was a lifelong sufferer of this disease (approximately 1941â€"1976)
  • Ralph Klein (1942â€"2013), former premier of Alberta, Canada
  • Kevin Moore (1958â€"2013), English footballer
  • Nic Potter (1951â€"2013), British bassist for Van der Graaf Generator
  • David Rumelhart (1942â€"2011), American cognitive psychologist
  • Colin Savage, father of footballer Robbie Savage
  • Ernie Moss (born 1949), English footballer.