title: Benazir Bhutto

text: In 1998, India tested its first nuclear weapon; Bhutto responded with an editorial for the "Los Angeles Times" in which she argued that the international community should go further than imposing economic sanctions on India, but should launch a preemptive bomb strike on India's nuclear facilities. She called on Sharif to retaliate with a series of Pakistani military tests. After Sharif's government did so, Bhutto called for Pakistan to sign the Comprehensive Nuclear-Test-Ban Treaty and arrive at a bilateral agreement on nuclear proliferation with India. Tensions between India and Pakistan resulted in the Kargil War of 1999; the conflict humiliated Pakistan both militarily and politically and left the country with a very poor international standing. Bhutto observed the conflict from abroad, describing it as "Pakistan's biggest blunder".


title: Benazir Bhutto

text: In April 1999, the Ehtesab Bench of the Lahore High Court convicted Bhutto "in absentia", giving her a five years prison sentence, an $8.6 million fine, and disqualifying her from public office. The Pakistani authorities unsuccessfully tried to secure her arrest and extradition through Interpol. Bhutto claimed that this was politically motivated. She was in London at the time of the judgment, and rather than returning to Pakistan she relocated to Dubai. She decided on Dubai because Zayed bin Sultan Al Nahyan, the President of the United Arab Emirates, had been a longstanding friend of her family. She brought her mother and three children to live there with her, settling into a villa in the Emirates Hills given to her by the Emirati government. She claimed that were she to return to Pakistan then she would be imprisoned and then murdered.


title: Benazir Bhutto

text: She remained in Dubai for eight years, for five of which her husband remained imprisoned in Pakistan. She remained head of the PPP,


title: Benazir Bhutto

text: and spent much of her time in exile fighting the corruption charges that were being brought against her and her husband. Two years later a retrial was ordered after it was ascertained that undue political bias was exerted on the judges. Bhutto also campaigned for Zardari's release from prison. Some of her close political advisers suggested that she abandon him for the sake of her political career, but she refused. While in Dubai, she also focused on raising her children and caring for her mother, whose Alzheimer's disease had progressed to a severe stage.


title: Benazir Bhutto

text: In October 1999, the chair of the Joint Chiefs of Staff, Pervez Musharraf, launched a military coup which ousted Sharif from power. Bhutto called the coup "disturbing" and "distressing" but noted that it had got rid of Sharif, "an unpopular despot who was hounding the press, the judiciary, the opposition, the foreign investors." She called on Western countries to push for a return to electoral democracy in Pakistan. Musharraf stated that both Sharif and Bhutto had "misgoverned the country" and had failed to allow internal democracy within their own parties, pointing to Bhutto's appointment as chair for life of the PPP, something he compared to "the old African dictators".


title: Benazir Bhutto

text: In April 2000, Sharif was convicted of treason and sentenced to life imprisonment. At the request of the Saudi monarch, Sharif was released from prison after a year and exiled to Saudi Arabia; he was also disqualified from holding public office. In 2002, Musharraf amended the constitution to ban anyone serving more than two terms as Prime Minister, thus disqualifying both Bhutto and Sharif, whom he called "useless politicians". Musharraf also consolidated power around himself; in June 2001 he appointed himself to the Presidency, holding this position alongside his positions as chief executive and chief of the army staff. He talked about the need for a return to democracy and to respect human rights. He was a secularist and repealed the Hudood Ordinances, an achievement Bhutto had been unable to make. In an April 2002 referendum, Musharraf extended his presidential mandate for a further five years. Bhutto expressed concern that with mainstream politicians removed from Pakistan's political arena, the vacuum would be filled by Islamist extremists.


title: Benazir Bhutto

text: She was in Dubai while the PPP contested the October 2002 general election; it received the largest number of votes but only 63 seats in the National Assembly. Musharraf agreed to release Zardari in November 2004 as a symbol of good will; following his release, Zardari travelled to New York for medical treatment. Bhutto flew to New York roughly every three weeks to visit him. The couple did not officially acknowledge it, but their relationship was essentially over. Figures in the PPP alleged that Musharraf held a longstanding animosity towards Bhutto and her family because, under her father, Musharraf's father had been sacked from his position, accused of involvement in a scam.


title: Benazir Bhutto

text: In June 1997, the Pakistani government formally requested that the Swiss government review bank accounts owned by Bhutto and her husband. In 1998, a Swiss magistrate, Daniel Devaud, seized a safe-deposit box containing a $190,000 necklace that Bhutto had purchased in London's Bond Street the previous year. Over the following six years, he investigated how Bhutto had obtained the money used to buy this item. His investigations were followed by a BBC documentary team led by Owen Bennett-Jones. Devaud's investigations revealed a range of corrupt deals that Zardari had been involved with. It was discovered that Dassault, a French aircraft manufacturer, had agreed to pay Zardari and another Pakistani man $200 million to ensure he would facilitate a $4 billion sales of fighter jets. It was also revealed that in both Bhutto and Zardari had taken approximately $15 million in exchange for awarding a customs contract to the Swiss firms SGS/Cotecna when she was Prime Minister. Devaud concluded that Bhutto "knew she was acting in a criminally reprehensible manner by abusing her role in order to obtain for herself and for her husband considerable sums in the interest of her family at the cost of the Islamic Republic of Pakistan".


title: Benazir Bhutto

text: Benazir Bhutto was embroiled in a number of cases being pursued by Nawaz Sharif's government in 1997. She termed those cases as a part of Sharif's plan to eliminate her from politics. In an effort to challenge Sharif government's "ehtesab drive", Ms Bhutto along with other PPP leaders visited the Ehtesab Commission, Islamabad, where she handed over corruption references against then PM Nawaz Sharif and his brother Shehbaz Sharif to Abdul Jaleel, Director Special Enquiries at the Ehtesab Commission. These references contained charges of corruptions against Sharif family and Saif-ur-Rehman who was a close aide of Nawaz Sharif. Ms Bhutto gave full statements of facts of complaints. In 1998, Switzerland issued a request for the arrest of Bhutto on suspicion of money laundering. The Geneva City Court subsequently charged Zardari "in absentia" with laundering money and taking bribes of $15 million from SGS and Cotecna. A Swiss court ordered her to turn over $11.9 million to the Pakistani state and to serve 180 days in prison. 17 Swiss bank accounts owned by the Zardari-Bhutto family were frozen by the country's government. In 2004, a UK court ruled that Rockwood Estate in Surrey—which Zardari owned, despite his repeated denials—should be sold and the proceeds given to the Pakistani state, who were the rightful owners. Zardari protested, admitting that he owned the property and that he should receive the proceeds of its sale.


title: Benazir Bhutto

text: Through a spokesman, Bhutto said that the charges against her represented a witch hunt and compared them to McCarthyism. She expressed bemusement as to why many thought her spending was lavish: "I mean, what is poor and what is rich? If you mean, am I rich by European standards, do I have a billion dollars, or even a hundred million dollars, even half that, no, I do not. But if you mean that I'm ordinary rich, yes, my father had three children studying at Harvard as undergraduates at the same time. But this wealth never meant anything to my brothers or me." She maintained that the charges against her and her husband were purely political. Bhutto ignored the summons to travel to Switzerland to serve her sentence. She challenged the court ruling and secured a retrial which overturned the previous ruling. However, Allen commented: "no one seriously suggested that the evidence had been fixed or that Bhutto and Zardari were not thieves on a grand scale.".


title: Benazir Bhutto

text: Bhutto was a client of Mossack Fonseca, whose customer records were disclosed in the Panama Papers leak. 7 September 2001 London law firm Richard Rooney and Co told MF-BVI (Mossack Fonseca British Virgin Islands) to create Petroline International Inc in the British Virgin Islands. Petroline International Inc is owned by Bhutto, her nephew Hassan Ali Jaffery Bhutto, and her aide and head of security Rehman Malik, who later became a Senator and Interior Minister in the government of Yousaf Raza Gillani. Mossack Fonseca had declined to do business with Bhutto's first company, similarly named Petrofine FZC, established in Sharjah, United Arab Emirates (UAE) in 2000. The Petrofine was "politically sensitive," they said, and "declined to accept Mrs. Bhutto as a client". A United Nations committee chaired by former head of the US Federal Reserve, Paul Volcker, concluded in a 2005 investigation into abuses of the oil-for-food program that Petrofine FZC had paid US$2 million to the Iraqi government of Saddam Hussein to obtain US$115–145 million in oil contracts.


title: Benazir Bhutto

text: In 2006, the Pakistani National Accountability Bureau (NAB) accused Bhutto, Malik and Ali Jaffery of owning Petrofine. Bhutto and the PPP denied this. In April 2006 an NAB court froze assets owned in Pakistan and elsewhere by Bhutto and Zardari. The $1.5 billion in assets were acquired through corrupt practices, the NAB said, and noting that the 1997 Swiss charges of criminal money-laundering were still in litigation.


title: Benazir Bhutto

text: At Pakistan's request, Interpol issued notices—but not arrest warrants—for Bhutto and her husband. On 27 January 2007, she was invited by the United States to speak to President George W. Bush and Congressional and State Department officials.


title: Benazir Bhutto

text: The US and UK had supported Musharraf because of his role in assisting their War on Terror—especially the War in Afghanistan—but they gradually lost faith in his ability to rule successfully. His domestic popularity was slipping; a mid-2007 poll gave him only a 26% approval rating. In 2007, mass anti-Musharraf protests broke out in what was known as the Lawyers' Movement. Pakistan was also experiencing growing levels of violence from Islamist militants, such as the Siege of Lal Masjid. Official figures held that eight suicide bombings took place in 2006 and 44 in 2007. The US government increasingly saw Bhutto as an important figure who could help to constrain Pakistan's domestic problems. They nevertheless wanted a power-sharing deal and did not want Musharraf removed from power completely, regarding him as a vital ally in their War on Terror.


title: Benazir Bhutto

text: Assisted by Luis Ayala, the secretary-general of the Socialist International, in 2006 Bhutto and Sharif began a process of reconciliation. Ayala believed that this was a prerequisite for ensuring Pakistan's transition back to democratic elections. Both Bhutto and Sharif had residences in London, not far from one another. Facilitated by the lawyer Aitzaz Ahsan, the pair developed a joint plan of action. In May 2006 they both signed a Charter of Democracy, a document calling for an end to military rule. They established a committee consisting of four Pakistani senators, two from the PPP and two from the Pakistan Muslim League (Nawaz). Henceforth, Bhutto avoided openly criticizing Sharif as she once had.


title: Benazir Bhutto

text: Concerned about the instability of their ally, the US government pushed Musharraf to meet with Bhutto and come to an arrangement that might strengthen his legitimacy. This was also encouraged by the UK government. In January 2007, Musharraf held his first meeting with Bhutto at a hotel in Abu Dhabi, followed by further talks in June. As a result of their discussions, it was agreed that the Pakistani authorities would drop all charges of corruption against both Bhutto and her husband. This was achieved through the introduction of the National Reconciliation Ordinance, a measure which nullified all pending criminal proceedings against politicians. The Ordinance also lifted Musharraf's ban on individuals serving more than two terms as Prime Minister.


title: Benazir Bhutto

text: It was agreed that if Musharraf stepped down from his military positions and was elected as a civilian President, then Bhutto would be willing to serve under him as Prime Minister. Many of Musharraf's close allies had reservations about his concessions to Bhutto.


title: Benazir Bhutto

text: The United States' Condoleezza Rice and the UK's Jack Straw worked together to ensure a transition back to electoral democracy in Pakistan. The UK and Spain both dropped criminal investigations into Bhutto's corruption, although Switzerland refused to do so. In August 2007, the U.S. ambassador to the United Nations, Zalmay Khalizad, had several meetings with Bhutto in New York City. There, Bhutto also gave a public talk at the Council of Foreign Relations. Bhutto and Khalizad also traveled to a luncheon in Aspen, Colorado to meet with prominent U.S. political and business leaders. In October 2007, Musharraf was elected president by Pakistan's parliament. In keeping with the agreement made by Bhutto and Musharraf, the PPP representatives abstained rather than voting against Musharraf's nomination.


title: Benazir Bhutto

text: The US publisher HarperCollins paid Bhutto half a million dollars to produce a book, to be titled "Reconciliation". Co-written with the U.S. political scientist and journalist Mark Siegel, it would be published in 2008 as "Reconciliation: Islam, Democracy and the West". "Reconciliation" was partly a response to the Clash of Civilisations theory that had been popularised by the American political scientist Samuel P. Huntington during the 1990s. She argued that Huntington's theory denied the universality of democratic ideals and created a "self-fulfilling prophecy of fear" whereby it provoked the conflicts that it claimed to predict. In "Reconciliation" she proposed that Western countries finance a new "Marshall Plan" to aid the poor in Muslim-majority countries, believing that this would improve Islamic attitudes toward the West.


title: Benazir Bhutto

text: Bhutto returned to Pakistan in October 2007, arriving in Karachi. It was widely thought that she had a strong chance of becoming the country's next Prime Minister in the 2008 national elections, although her deal with Musharraf and links with the U.S. had dented her popularity and Sharif—still in Saudi Arabia—was more popular in the opinion polls. Musharraf was annoyed at her arrival, having requested that she return only after the election. Her husband and daughters remained in Dubai, while her son was still studying at Oxford.


title: Benazir Bhutto

text: Bhutto described the main problem facing her country as the clash between "moderation and extremism", and was pessimistic about her safety. Musharraf himself had survived several assassination attempts by Islamist militants, and warned Bhutto that she too would be a target. She requested that the US or UK take responsibility for her security, but they refused, and her security detail was instead organised by Musharraf. While her cavalcade was making its way through a crowd in Karachi, two bombs exploded, killing 149 and injuring 402. Bhutto herself was physically unharmed. Bhutto alleged that there were four suicide squads that had been dispatched to eliminate her and that there were key officials in the government involved in the plot; she sent a list naming these officials to Musharraf. Bhutto requested that Musharraf bring in the British Scotland Yard or the United States' Federal Bureau of Investigation to investigate the crime, but he refused.


title: Benazir Bhutto

text: Relations between the pair were further strained when Musharraf declared a state of emergency and suspended the constitution in November, at which point Bhutto was visiting Dubai. The PPP and PML-N launched protests at Musharraf's actions. Against the warnings of some of her advisors, Bhutto quickly returned to Pakistan, where she was briefly placed under house arrest. She then publicly denounced Musharraf, fearing that any association with him would damage her credibility. On 26 November, Sharif returned from exile; that same day, Bhutto filed papers to contest two parliamentary seats in the Larkana constituency. As he had previously agreed with Bhutto, Musharraf then retired as army chief and was sworn in as Pakistan's civilian president.


title: Benazir Bhutto

text: In early December, Bhutto met with Sharif to publicise their demand that Musharraf fulfil his promise to lift the state of emergency before January's parliamentary elections, threatening to boycott the vote if he failed to comply. On 16 December, Musharraf did so.


title: Benazir Bhutto

text: Bhutto announced that the PPP would campaign on "the five E's": employment, education, energy, environment, and equality. The PPP's manifesto called for greater civilian oversight of, and restrictions on, the military and intelligence agencies. They also vowed to rid the intelligence services of elements driven by political or religious motives.


title: Benazir Bhutto

text: On the morning of 27 December 2007, Bhutto met with Afghan President Hamid Karzai. In the afternoon, she gave a speech at a PPP rally held in Rawalpindi's Liaquat National Bagh. On leaving in a bulletproof vehicle, she opened the car's escape hatch and stood up to wave to the surrounding crowds. A man standing within two to three metres of the car fired three gunshots at her and detonated a suicide vest packed with ball bearings. Bhutto was fatally injured; reports differ as to whether she was hit by bullets or by shrapnel from the explosion. Twenty-two others also died. Bhutto was rushed to Rawalpindi General Hospital but was clinically dead on arrival and attempts at resuscitation were unsuccessful. No autopsy was conducted, and the body was swiftly transported to Chaklala Air Base. The following day, she was buried next to her father in the Bhutto family mausoleum, Garhi Khuda Bakhsh, her family graveyard near Larkana. Musharraf declared a three-day period of mourning, while PPP supporters rioted in various parts of Pakistan, leading to at least 50 deaths.


title: Benazir Bhutto

text: Authorities claimed that the assassin had been a teenage boy from South Waziristan. They claimed to have proof that the attack had been masterminded by Baitullah Mehsud, leader of the Pakistani Taliban. The United States Central Intelligence Agency concurred that this was probable, although Mehsud denied the accusation. Mehsud nevertheless had a motive; he believed that Bhutto's pro-American and secularist agenda would undermine the Pakistani Taliban's control of South Waziristan and hinder the growth of Sunni Islamist radicalism. Al-Qaeda commander Mustafa Abu al-Yazid claimed responsibility for the assassination, declaring that "We terminated the most precious American asset which vowed to defeat [the] mujahideen." The PPP accused the government of a cover-up, with several PPP figures claiming that Bhutto had been killed by a sniper linked to the intelligence agencies. Within Pakistan, there was also public speculation that the attack might have been masterminded by India or the United States. Musharraf agreed to invite Britain's Scotland Yard to investigate the assassination, although its eventual report proved inconclusive. Requests for the body to be exhumed for an autopsy were rejected by Zardari.


title: Benazir Bhutto

text: In Bhutto's political will, she had designated her son Bilawal, who was then 19, as her political heir as chair of the PPP. It also specified that her husband should serve as custodial chairman until Bilawal completed his formal education. Zardari became co-chair of the PPP. The academic Anna Suvorova specified that Bhutto's assassination created "a real family cult", one which was "fuelled by various apocrypha, rituals, and relics". In the wake of Bhutto's death, the election was postponed from January to February 2008, when it resulted in the formation of a coalition government bringing together the PPP and the Pakistan Muslim League (Nawaz). The new coalition put forth PPP member Yousuf Raza Gilani as Prime Minister. Musharraf, facing likely impeachment, resigned as president in August. He fled to London although, in February 2011, a Rawalpindi court issued a subpoena for him on the grounds that he had not acted on known threats to Bhutto and had provided insufficient security to protect her. In September 2008, Zardari was elected President of Pakistan by the country's electoral college; he remained in that position until 2013.


title: Benazir Bhutto

text: As president, Zardari called for a United Nations investigation into his wife's assassination. In 2009, the UN Secretary General Ban Ki-moon established a three-person team to lead the investigation comprising the Chilean Heraldo Muñoz, Irish Peter FitzGerald, and Indonesian Marzuki Darusman. Although it was not in the commission's remit to identify a culprit, Muñoz later expressed the view that the assassination was likely carried out by the Pakistani Taliban, perhaps with the support of Mehsud, and that they may well have been assisted by rogue elements in the country's intelligence agencies. He also expressed the view that the original police investigation had been deliberately botched. In February 2012, the Pakistani official enquiry issued its final report, placing responsibility for the attack with 27 different militant groups. In May 2013, the state's main prosecutor in the Bhutto case, Zulfikar Ali, was himself assassinated in Islamabad. There was never a smoking gun in the Bhutto investigation. Many in Pakistan had reasons for wanting Bhutto dead; some saw her as corrupt, and her killing was considered advantageous to both the military establishment and to the Islamic fundamentalists who despised her.


title: Benazir Bhutto

text: Bhutto was committed to democracy and modernisation, and believed that the future of the Islamic world lay in the embrace of these processes. However, Allen thought that it was "hard to pin down" what Bhutto's "core political values" actually were. Bhatia described Bhutto as having "liberal convictions" and a "self-evidently progressive outlook", while Suvorova thought that Bhutto presented herself as "the outpost of universal liberal values in conservative Pakistan" for a Western audience. Bhutto biographer G. S. Bhargava thought that in the context of Pakistani politics, she could "pass" for a social democrat. Her friend Catherine Drucker, who knew her while the two women were at Oxford University, said Bhutto's political views were then akin to those "commonplace" within the "mild leftism of the day". Bhargava added that, through her education in governance and politics at Harvard and then Oxford, Bhutto had "a thorough exposure to political theory and practice, in historical perspective as well as in the contemporary setting".


title: Benazir Bhutto

text: Bhutto admired the Thatcherite economic policies pursued by Prime Minister Margaret Thatcher in the United Kingdom; she was, according to biographer Mushtaq Ahmed, a "zealous convert" to privatisation and market economics. Bhutto advocated the creation of an expanded economically and politically stable middle class in Pakistan, believing that this was needed in order to sustain a stable democratic state. Allen commented that although the PPP had once been officially socialist in ideology, Bhutto "was not a natural socialist, or even as adept at talking the talk as Zulfikar had been". She disagreed with her father's socialist economic policies, and when in power sought to privatise various industries that had been nationalised in the 1970s. Ahmed thus suggested that while under Bhutto the PPP continued to profess ideals of egalitarianism and claimed it would enhance the welfare of peasants and workers, such "progressive phraseology" couched an absence of economic policies to benefit the poor. Instead, Ahmed thought, its policies primarily benefited "the privileged classes" and was thus a right-wing rather than left-wing party.


title: Benazir Bhutto

text: During her years in office Bhutto also did nothing to seriously challenge the feudal nature of rural Pakistan. Under Bhutto, Ahmed wrote, people from the wealthy feudal class dominated the PPP "both at the federal and provincial levels". Bhargava suggested that, because of the period in which she was operating, Bhutto did not need to engage in the "verbal radicalism" employed by her father, not needing to "clamor for a socialist identity" in order to win votes and allowing her to be "a pragmatist in both word and deed". Lamb described Bhutto at being skilled in using populist strategies in election campaigns. In a 2007 article for the "Los Angeles Times", Bhutto's niece, Fatima Bhutto, called her "a puppet 'democrat linked to the U.S. government's neoconservative agenda.


title: Benazir Bhutto

text: Under Bhutto's leadership, the PPP was officially secular, as were the governments which she led. However, in Pakistan at the time, the term "secularisation" was often understood not as reflecting the separation of religious institutions and the state, but rather had connotations of atheism and irreligion. Thus, Suvorova argued, Bhutto opposed the secularisation of Islamic societies. Bhutto also took a hard stance against militant Islamism. Although she had to compromise with Pakistan's powerful Islamist lobby, she favored a secular government for the country. Allen wrote that "at no time in her years in power did Bhutto, Westernized though she was, feel comfortable in seriously challenging Pakistan's Islamists". Although during her campaigns she vowed to abolish the "hudud" restrictions on women that Zia had introduced, she never did so; instead these were revoked by Musharraf in 2006.


title: Benazir Bhutto

text: Bhutto was indignant when faced with sexism, and regarded herself as an ardent supporter of women's rights; however, Suvorova stated that she was "never a feminist in theory or practice". Bhutto expressed the view that there were differences between male and female leaders, and that "women leaders are more generous and forgiving, male leaders tend to be more inflexible and more rigid." In contrast to those Islamic clerics who insisted that her involvement in politics contrasted with Islamic values, she insisted that there was no conflict. In her view, "it was men's interpretation of our religion that restricted women's opportunities, not our religion itself. Islam in fact had been quite progressive towards women from its inception." Bhutto described her main role model as Fatimah, the daughter of the Islamic prophet Muhammad, stating that she admired her piety, wisdom, and courage. She also described the Indian Prime Minister Indira Gandhi as a political inspiration.


title: Benazir Bhutto

text: According to Bhutto biographer Shyam Bhatia, Bhutto possessed a desire to be liked and to be popular, and for this reason "was prepared to be all things to all people", having a "chameleon-like" quality to blend into her environment. Muñoz concurred, describing Bhutto as "a woman of contradictions". Suvorova similarly observed that Bhutto presented herself differently when in the West compared to when she was in Pakistan. While in Pakistan Bhutto presented herself as a conservative Muslim who always wore her head covered, but as a student in Oxford she had adopted a more liberal lifestyle, tending to wear a T-shirt and jeans and occasionally drinking wine. As a politician, she was conscious of how her image was presented in Pakistan; she dressed modestly, was never photographed with a glass lest it is interpreted as containing alcohol, and would refuse to shake men's hands. In the country, she also wore a white dupatta on her head to placate Islamist opposition; her mother and other female family members had not covered their hair in this manner.


title: Benazir Bhutto

text: The journalist Christina Lamb believed that in being raised in a wealthy and aristocratic family, Bhutto was unable to appreciate the struggles of Pakistan's poorest. The Islamic studies scholar Akbar S. Ahmed, who went to school with Bhutto, wrote that she was a "pampered and precocious" child. Bhatia claimed that at Oxford, where he first met her, Bhutto was spoilt, self-obsessed, and prone to throwing temper tantrums, although at the same time was humorous and generous, willing to pay for her friends' meals whenever at a restaurant. Allen suggested that Bhutto retained her "characteristic "de haut en bas" arrogance, a relic of her feudal upbringing", arguing that her key character flaw had been "a belief in the special, almost sacred destiny of herself and the Bhutto family" and that accordingly, while she "spoke like a democrat ... she thought and felt as a dynast". In later life, Bhutto was accused of being addicted to power, although Allen thought it more accurate to state that she was "addicted to adulation", suggesting that this stemmed from a narcissistic element to Bhutto's personality.


title: Benazir Bhutto

text: Commentators and biographers have said that Bhutto shared her father's charisma but also his arrogance, and that like him she was impatient with criticism. The connection between Bhutto and her father was endorsed by Allen, who stated that they "had much in common: strength, charisma, political instinct, and the courage, part, and parcel of their arrogance, that was so characteristic of both". Allen also believed that Bhutto was so dedicated to her father that "psychologically", she was "unable to admit to any imperfection" in him. After his death she repeatedly presented his execution as a martyrdom. Bhutto imitated many of her father's mannerisms and his style of speech; the journalist Carla Hall referred to her having a "vaguely British accent". She was an accomplished orator, having honed her skill at public speaking while president of the Oxford Debating Society.


title: Benazir Bhutto

text: Having encountered her later in life, Muñoz regarded Bhutto as a "charming and intelligent" woman. Close friends called her "BB", a name with which she signed some of her personal letters. Her parents gave her the childhood nickname of "Pinkie", possibly alluding to her rosy complexion.


title: Benazir Bhutto

text: Allen described Bhutto as "a woman of action rather than an intellectual". Bhutto's choice of reading material was usually either utilitarian or pleasurable rather than intellectual; she enjoyed reading Mills & Boon romance novels and the celebrity-focused "Hello!" magazine. She read a number of self-help books, telling a friend that "for all the lows in my life, those self-help books helped me survive, I can tell you". Her father had also encouraged her to read the writings of various prominent political figures, among them Napoleon Bonaparte, Otto von Bismarck, Vladimir Lenin, Mustafa Kemal Atatürk, and Mao Zedong. She had a love of French and Italian cuisine, and was a great fan of the music of American singer Neil Diamond.


title: Benazir Bhutto

text: In a 2002 interview with "The Guardian", Bhutto described her allegiance to the Sufi branch of Sunni Islam. Allen thought her to have "some genuine, if unorthodox, religious belief, mixed up with superstition". Bhargava stated that Bhutto was "dedicated and devout in her religious principles but modern and emancipated in her behavior and outlook". In conversation, she often used the phrase "inshallah", and insisted that the Quran supported the equality of the sexes. Bhutto was anti-abortion and spoke forcefully against abortion, most notably at the 1994 meeting of the International Conference on Population and Development in Cairo, where she accused the West of "seeking to impose adultery, abortion, intercourse education and other such matters on individuals, societies, and religions which have their own social ethos".


title: Benazir Bhutto

text: Bhutto was the oldest of four children. Of these, her younger sister Sanam, or "Sunny", remained close to her throughout her life.


title: Benazir Bhutto

text: On returning to Pakistan in 1987, Bhutto's mother arranged for her marriage to the businessman Asif Ali Zardari. Many of her friends were surprised that Bhutto acquiesced to Islamic tradition given her liberal attitudes, however, she later related that she "felt obligations to my family and my religion" to go through with it and that her high public profile made it difficult for her to find a husband through other means. She consistently presented an image of respect and loyalty for her husband, throughout the many accusations and periods of imprisonment he faced. Allen commented that it would probably never be known how happy the couple's marriage was, for Bhutto "always projected support and loyalty for her unpopular mate".


title: Benazir Bhutto

text: In the final years of Bhutto's life, she and her husband lived apart. According to Allen, she would have been aware that a divorce or a public separation would have resulted in the end of her political career in Pakistan due to social stigma around the subject. In a 2007 interview, Bhutto said that she and her husband were living apart because of his medical requirements, adding that she visited him every month in New York. Regarding the rumors of separation, in 2008 Bhutto's friend Victoria Schofield said that the marriage should not be judged by ordinary standards. According to Schofield, after Zardari's return from prison, the Bhuttos' marriage was going through a process of "readjustment". In 2018, Bhutto's friend Ron Suskind described the marriage as "probably not all bad", although added that Bhutto did not consider her husband to be an equal partner in the marriage.


title: Benazir Bhutto

text: The couple had three children: a son, Bilawal, was born in September 1988, while she was campaigning for that year's election. She also had two daughters, Bakhtawar (born on 25 January 1990) and Aseefa (born on 3 February 1993). When she gave birth to Bakhtawar, she became the first elected head of government to give birth while in office. Bhutto was devoted to her father and husband. In later life, she increasingly came to see success through the prism of her family.


title: Benazir Bhutto

text: Muñoz described Bhutto as "one of Pakistan's most important political figures, a respected world leader, and the leading stateswoman in the Islamic world". Allen suggested that although Bhutto's record in office was that of a "corrupt, compromised politician", she displayed admirable qualities, especially valor in the face of opposition. Within the Islamic world, Bhutto was often regarded as "a genuine Muslim political leader" and recognised as the head of Pakistan's most popular political party. Bhargava expressed the view that at the time of her initial election, Bhutto's "personal popularity" was "tremendous", larger than any that her father had previously achieved, with Suvorova suggesting that at this point in her life Bhutto was often regarded as a "quasi-saint" by her supporters. In 1996, the Guinness Book of Records named her the most popular international politician of the year, and she also received such awards at the French Legion of Honour and Oxford University's Doctor Honours Causa.


title: Benazir Bhutto

text: At the same time there were many Pakistanis who despised her, disliking her popularity, her ties to Western nations, and her modernizing agenda. Extremist Sunni Islamist elements opposed her because of their belief that female leaders are un-Islamic, and because they thought she was a Shia Muslim. They maintained that her participation in politics meant associating with men to whom she was not related and that this compromised the modesty required by Islam. Conservative clerical opponents also claimed that by being prime minister, Bhutto was failing her religious duty, which was to focus her energies on having as many children as possible.


title: Benazir Bhutto

text: Ahmed stated that Bhutto was one of the very few political leaders who had been able to "assume the iconic status of a political martyr in the West while simultaneously evoking strong sentiments in the Muslim world". He therefore contrasted her with contemporaries like Iraq's Saddam Hussein who were popular domestically but hated in the West, and those like Egypt's Hosni Mubarak who curried favor with Western governments while alienating their domestic audience. Bhutto gained popularity in Western nations in part because she could present herself as being "part of their world", speaking a high standard of English and having been educated at Harvard and Oxford. While her Western supporters sometimes had doubts about her ability to govern, they generally viewed her as a progressive figure who could advance democracy and counter-terrorism in Pakistan.


title: Benazir Bhutto

text: Allen commented that "the cards might have been stacked in Bhutto's favor—she was rich, educated, aristocratic, the favored daughter of a very powerful father—nevertheless, her achievement was a remarkable one" given the male-dominated environment of late-20th century Pakistani society. Mushtaq Ahmed similarly believed that "for a woman to win an election in a male-dominated society was an achievement", and that "her victory over the forces of reaction and persecution was an unprecedented accomplishment in political history." Ahmed thought that the election of a female Prime Minister in a Muslim-majority country served as "a proclamation that Islam was a forward-thinking religion". He added that as a pioneering female leader, Bhutto had "barely half a dozen" parallels, among them Indira Gandhi, Thatcher, Golda Meir, Chandrika Kumaratunga, and Corazon Aquino. Comparisons with Aquino were often made — and welcomed by Bhutto — because both women had fought against a military dictatorship and spent time in exile.


title: Benazir Bhutto

text: She became a global icon for women's rights, and inspired many Pakistani girls and women by her example. The Pakistani women's rights activist Malala Yousafzai—who received the 2014 Nobel Peace Prize—cited Bhutto as a personal inspiration. Writing in "The American Prospect" magazine, the journalist Adele M. Stan called Bhutto "An Imperfect Feminist", commenting that despite her efforts towards women's rights, these were sometimes offset by her compromises with Pakistan's Islamists and her support of the Taliban's rise to power in neighbouring Afghanistan.


title: Benazir Bhutto

text: Assessing her legacy, William Dalrymple wrote in "The Guardian" that "it's wrong for the West simply to mourn Benazir Bhutto as a martyred democrat since her legacy was far murkier and more complex". Despite her western and positive image in the world, Bhutto's controversial policies and support have made her legacy much more complicated. Benazir Bhutto failed to revert the controversial Hudood Ordinance – a contentious presidential ordinance which suppressed women's rights, making them subordinate to men. In 2009, CBS News described her legacy as "mixed", and commented that: "it's only in death that she will become an icon—in some ways, people will look at her accomplishments through rose-tinted glasses rather than remembering the corruption charges, her lack of achievements or how much she was manipulated by other people." Jason Burke, writing in "The Guardian" about Benazir, termed her "[both] a victim, as well as in part a culprit, of its [Pakistan's] chronic instability".


title: Benazir Bhutto

text: Several universities and public buildings in Pakistan have been named after her. The Pakistani government honored Bhutto on her birthday by renaming Islamabad's airport Benazir Bhutto International Airport, Muree Road of Rawalpindi as Benazir Bhutto Road and Rawalpindi General Hospital as Benazir Bhutto Hospital. Prime Minister Yousaf Raza Gillani, a member of Bhutto's PPP, asked Musharraf to pardon convicts on death row on her birthday in honour of Bhutto. Several months after Bhutto's death, a series of Pakistani postage stamps were announced to mark her 55th birthday.


title: Serotonin

text: Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction. Approximately 90% of the serotonin that the body produces is in the intestinal tract.


title: Serotonin

text: Biochemically, the indoleamine molecule derives from the amino acid tryptophan, via the (rate-limiting) hydroxylation of the 5 position on the ring (forming the intermediate 5-hydroxytryptophan), and then decarboxylation to produce serotonin. Serotonin is primarily found in the enteric nervous system located in the gastrointestinal tract (GI tract). However, it is also produced in the central nervous system (CNS), specifically in the raphe nuclei located in the brainstem, Merkel cells located in the skin, pulmonary neuroendocrine cells and taste receptor cells in the tongue. Additionally, serotonin is stored in blood platelets and is released during agitation and vasoconstriction, where it then acts as an agonist to other platelets.


title: Serotonin

text: Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the GI tract, where it regulates intestinal movements. About 8% is found in platelets and 1–2% in the CNS. The serotonin is secreted luminally and basolaterally, which leads to increased serotonin uptake by circulating platelets and activation after stimulation, which gives increased stimulation of myenteric neurons and gastrointestinal motility. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning.


title: Serotonin

text: Several classes of antidepressants, such as the SSRIs and the SNRIs among others, interfere with the normal reabsorption of serotonin after it is done with the transmission of the signal, therefore augmenting the neurotransmitter levels in the synapses.


title: Serotonin

text: Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, where it can serve as a vasoconstrictor or a vasodilator while regulating hemostasis and blood clotting. In high concentrations, serotonin acts as a vasoconstrictor by contracting endothelial smooth muscle directly or by potentiating the effects of other vasoconstrictors (e.g. angiotensin II, norepinephrine). The vasoconstrictive property is mostly seen in pathologic states affecting the endotheliumsuch as atherosclerosis or chronic hypertension. In physiologic states, vasodilation occurs through the serotonin mediated release of nitric oxide from endothelial cells. Additionally, it inhibits the release of norepinephrine from adrenergic nerves. Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. There are various serotonin receptors.


title: Serotonin

text: Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. The rate-limiting step is hydride transfer from serotonin to the flavin cofactor. There follows oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic-acid derivative. The latter is then excreted by the kidneys.


title: Serotonin

text: Besides mammals, serotonin is found in all bilateral animals including worms and insects, as well as in fungi and in plants. Serotonin's presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection. Serotonin is produced by pathogenic amoebae, and its effect in the human gut is diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.


title: Serotonin

text: Serotonin is involved in numerous physiological processes, including sleep, thermoregulation, learning and memory, pain, (social) behavior, sex, feeding, motor activity, biological rhythms and possibly others. In less complex animals, such as some invertebrates, serotonin regulates feeding and other processes. In plants serotonin synthesis seems to be associated with stress signals.


title: Serotonin

text: Serotonin primarily acts through its receptors and its effects depend on which cells and tissues express these receptors (see below).


title: Serotonin

text: The 5-HT receptors, the receptors for serotonin, are located on the cell membrane of nerve cells and other cell types in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and psychedelic drugs. Except for the 5-HT receptor, a ligand-gated ion channel, all other 5-HT receptors are G-protein-coupled receptors (also called seven-transmembrane, or heptahelical receptors) that activate an intracellular second messenger cascade.


title: Serotonin

text: Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake, including cocaine, dextromethorphan (an antitussive), tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). A 2006 study conducted by the University of Washington suggested that a newly discovered monoamine transporter, known as PMAT, may account for "a significant percentage of 5-HT clearance".


title: Serotonin

text: Contrasting with the high-affinity SERT, the PMAT has been identified as a low-affinity transporter, with an apparent K of 114 micromoles/l for serotonin; approximately 230 times higher than that of SERT. However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport 'capacity' than SERT, "resulting in roughly comparable uptake efficiencies to SERT in heterologous expression systems." The study also suggests some SSRIs, such as fluoxetine and sertraline anti-depressants, inhibit PMAT but at IC values which surpass the therapeutic plasma concentrations by up to four orders of magnitude. Therefore, SSRI monotherapy is "ineffective" in PMAT inhibition. At present, no known pharmaceuticals are known to appreciably inhibit PMAT at normal therapeutic doses. The PMAT also suggestively transports dopamine and norepinephrine, albeit at K values even higher than that of 5-HT (330–15,000 μmoles/L).


title: Serotonin

text: Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins. This process underlies serotonin's effects upon platelet-forming cells (thrombocytes) in which it links to the modification of signaling enzymes called GTPases that then trigger the release of vesicle contents by exocytosis. A similar process underlies the pancreatic release of insulin.


title: Serotonin

text: The effects of serotonin upon vascular smooth muscle tonethe biological function after which serotonin was originally nameddepend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.


title: Serotonin

text: The neurons of the raphe nuclei are the principal source of 5-HT release in the brain. There are nine raphe nuclei, designated B1–B9, which contain the majority of serotonin-containing neurons (some scientists chose to group the "nuclei raphes lineares" into one nucleus), all of which are located along the midline of the brainstem, and centered on the reticular formation. Axons from the neurons of the raphe nuclei form a neurotransmitter system reaching almost every part of the central nervous system. Axons of neurons in the lower raphe nuclei terminate in the cerebellum and spinal cord, while the axons of the higher nuclei spread out in the entire brain.


title: Serotonin

text: The serotonin nuclei may also be divided into two main groups, the rostral and caudal containing three and four nuclei respectively. The rostral group consists of the caudal linear nuclei (B8), the dorsal raphe nuclei (B6 and B7) and the median raphe nuclei (B5, B8 and B9), that project into multiple cortical and subcortical structures. The caudal group consists of the nucleus raphe magnus (B3), raphe obscurus nucleus (B2), raphe pallidus nucleus (B1), and lateral medullary reticular formation, that project into the brainstem.


title: Serotonin

text: The serotonergic pathway is involved in sensorimotor function, with pathways projecting both into cortical (Dorsal and Median Raphe Nuclei), subcortical, and spinal areas involved in motor activity. Pharmacological manipulation suggests that serotonergic activity increases with motor activity while firing rates of serotonergic neurons increase with intense visual stimuli. Animal models suggest that kainate signaling negatively regulates serotonin actions in the retina, with possible implications for the control of the visual system. The descending projections form a pathway that inhibits pain called the "descending inhibitory pathway" that may be relevant to a disorder such as fibromyalgia, migraine, and other pain disorders, and the efficacy of antidepressants in them.


title: Serotonin

text: Serotonergic projections from the caudal nuclei are involved in regulating mood and emotion, and hypo- or hyper-serotonergic states may be involved in depression and sickness behavior.


title: Serotonin

text: Serotonin is released into the synapse, or space between neurons, and diffuses over a relatively wide gap (>20 nm) to activate 5-HT receptors located on the dendrites, cell bodies, and presynaptic terminals of adjacent neurons.


title: Serotonin

text: When humans smell food, dopamine is released to increase the appetite. But, unlike in worms, serotonin does not increase anticipatory behaviour in humans; instead, the serotonin released while consuming activates 5-HT2C receptors on dopamine-producing cells. This halts their dopamine release, and thereby serotonin decreases appetite. Drugs that block 5-HT receptors make the body unable to recognize when it is no longer hungry or otherwise in need of nutrients, and are associated with weight gain, especially in people with a low number of receptors. The expression of 5-HT receptors in the hippocampus follows a diurnal rhythm, just as the serotonin release in the ventromedial nucleus, which is characterised by a peak at morning when the motivation to eat is strongest.


title: Serotonin

text: In macaques, alpha males have twice the level of serotonin in the brain as subordinate males and females (measured by the concentration of 5-HIAA in the cerebrospinal fluid (CSF)). Dominance status and CSF serotonin levels appear to be positively correlated. When dominant males were removed from such groups, subordinate males begin competing for dominance. Once new dominance hierarchies were established, serotonin levels of the new dominant individuals also increased to double those in subordinate males and females. The reason why serotonin levels are only high in dominant males, but not dominant females has not yet been established.


title: Serotonin

text: In humans, levels of 5-HT receptor inhibition in the brain show negative correlation with aggression, and a mutation in the gene that codes for the 5-HT receptor may double the risk of suicide for those with that genotype. Serotonin in the brain is not usually degraded after use, but is collected by serotonergic neurons by serotonin transporters on their cell surfaces. Studies have revealed nearly 10% of total variance in anxiety-related personality depends on variations in the description of where, when and how many serotonin transporters the neurons should deploy.


title: Serotonin

text: Serotonin has been implicated in cognition, mood, anxiety and psychosis, but strong clarity has not been achieved.


title: Serotonin

text: In regards to research for neurotransmitters and effects on patients with Autism Spectrum Disorder (ASD), 5-HT has been studied the most in terms of research efforts and investigations. As noted, 5-HT signaling does facilitate many neural processes including that of neurogenesis, cell migration and survival, synaptogenesis, and synaptic plasticity. It was noted that 45% of tested ASD subjects contained high levels of 5-HT in their blood. In addition, investigations performed on ASD-like animal models reported that hyperserotonemia significantly reduced the motivation for social interest through inhibition of separation distress, which could be related in the ASD patients that have social impairments.


title: Serotonin

text: Serotonin regulates gastrointestinal function. The gut is surrounded by enterochromaffin cells, which release serotonin in response to food in the lumen. This makes the gut contract around the food. Platelets in the veins draining the gut collect excess serotonin. There are often serotonin abnormalities in gastrointestinal disorders such as constipation and irritable bowel syndrome.


title: Serotonin

text: If irritants are present in the food, the enterochromaffin cells release more serotonin to make the gut move faster, i.e., to cause diarrhea, so the gut is emptied of the noxious substance. If serotonin is released in the blood faster than the platelets can absorb it, the level of free serotonin in the blood is increased. This activates 5-HT3 receptors in the chemoreceptor trigger zone that stimulate vomiting. Thus, drugs and toxins stimulate serotonin release from enterochromaffin cells in the gut wall. The enterochromaffin cells not only react to bad food but are also very sensitive to irradiation and cancer chemotherapy. Drugs that block 5HT3 are very effective in controlling the nausea and vomiting produced by cancer treatment, and are considered the gold standard for this purpose.


title: Serotonin

text: In mice and humans, alterations in serotonin levels and signalling have been shown to regulate bone mass. Mice that lack brain serotonin have osteopenia, while mice that lack gut serotonin have high bone density. In humans, increased blood serotonin levels have been shown to be significant negative predictor of low bone density. Serotonin can also be synthesized, albeit at very low levels, in the bone cells. It mediates its actions on bone cells using three different receptors. Through 5-HT receptors, it negatively regulates bone mass, while it does so positively through 5-HT receptors and 5-HT receptors. There is very delicate balance between physiological role of gut serotonin and its pathology. Increase in the extracellular content of serotonin results in a complex relay of signals in the osteoblasts culminating in FoxO1/ Creb and ATF4 dependent transcriptional events. Very recently following the seminal finidings that gut serotonin regulates bone mass in 2008, the mechanistic investigations into what regulates serotonin synthesis from the gut in the regulation of bone mass have started. Piezo1 has been shown to sense RNA in the gut and relay this information through serotonin synthesis to the bone. This study by Sugisawa et al., showed that cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse "Piezo1" profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of "Piezo1" increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders. These studies of Yadav et al., Cell 2008, Nat Med 2010 and more recently Sugisawa et al., Cell 2019 have opened a new area of serotonin research in bone metabolism that can be potentially harnessed to treat bone mass disorders.


title: Serotonin

text: Since serotonin signals resource availability it is not surprising that it affects organ development. Many human and animal studies have shown that nutrition in early life can influence, in adulthood, such things as body fatness, blood lipids, blood pressure, atherosclerosis, behavior, learning, and longevity. Rodent experiment shows that neonatal exposure to SSRIs makes persistent changes in the serotonergic transmission of the brain resulting in behavioral changes, which are reversed by treatment with antidepressants. By treating normal and knockout mice lacking the serotonin transporter with fluoxetine scientists showed that normal emotional reactions in adulthood, like a short latency to escape foot shocks and inclination to explore new environments were dependent on active serotonin transporters during the neonatal period.


title: Serotonin

text: Human serotonin can also act as a growth factor directly. Liver damage increases cellular expression of 5-HT2A and 5-HT2B receptors, mediating liver compensatory regrowth (see ) Serotonin present in the blood then stimulates cellular growth to repair liver damage.


title: Serotonin

text: 5HT2B receptors also activate osteocytes, which build up bone However, serotonin also inhibits osteoblasts, through 5-HT1B receptors.


title: Serotonin

text: Serotonin, in addition, evokes endothelial nitric oxide synthase activation and stimulates, through a 5-HT1B receptor-mediated mechanism, the phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures. In blood, serotonin is collected from plasma by platelets, which store it. It is thus active wherever platelets bind in damaged tissue, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic (growth factor), to aid healing.


title: Serotonin

text: Pulmonary neuroendocrine cells are specialized epithelial cells that occur as solitary cells or as clusters called neuroepithelial bodies in the lung. Pulmonary neuroendocrine cells are also known as "Kulchitsky cells" or "K cells".


title: Serotonin

text: Several classes of drugs target the 5-HT system, including some antidepressants, antipsychotics, anxiolytics, antiemetics, and antimigraine drugs, as well as, the psychedelic drugs and empathogens.


title: Serotonin

text: At rest, serotonin is stored within the vesicles of presynaptic neurons. When stimulated by nerve impulses, serotonin is released as a neurotransmitter into the synapse, reversibly binding to the postsynaptic receptor to induce a nerve impulse on the postsynaptic neuron. Serotonin can also bind to auto-receptors on the presynaptic neuron to regulate the synthesis and release of serotonin. Normally serotonin is taken back into the presynaptic neuron to stop its action, then reused or broken down by monoamine oxidase.


title: Serotonin

text: The serotonergic psychedelic drugs psilocin/psilocybin, DMT, mescaline, psychedelic mushroom and LSD are agonists, primarily at 5HT receptors. The empathogen-entactogen MDMA releases serotonin from synaptic vesicles of neurons.


title: Serotonin

text: Drugs that alter serotonin levels are used in treating depression, generalized anxiety disorder, and social phobia. Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamine neurotransmitters (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. MAOI therapy is associated with many adverse drug reactions, and patients are at risk of hypertensive emergency triggered by foods with high tyramine content, and certain drugs. Some drugs inhibit the re-uptake of serotonin, making it stay in the synaptic cleft longer. The tricyclic antidepressants (TCAs) inhibit the reuptake of both serotonin and norepinephrine. The newer selective serotonin reuptake inhibitors (SSRIs) have fewer side-effects and fewer interactions with other drugs.


title: Serotonin

text: Certain SSRI medications have been shown to lower serotonin levels below the baseline after chronic use, despite initial increases. The "5-HTTLPR" gene codes for the number of serotonin transporters in the brain, with more serotonin transporters causing decreased duration and magnitude of serotonergic signaling. The 5-HTTLPR polymorphism (l/l) causing more serotonin transporters to be formed is also found to be more resilient against depression and anxiety.


title: Serotonin

text: Extremely high levels of serotonin can cause a condition known as serotonin syndrome, with toxic and potentially fatal effects. In practice, such toxic levels are essentially impossible to reach through an overdose of a single antidepressant drug, but require a combination of serotonergic agents, such as an SSRI with a MAOI, which may occur in therapeutic doses. The intensity of the symptoms of serotonin syndrome vary over a wide spectrum, and the milder forms are seen even at nontoxic levels. It is estimated that 14% of patients experiencing serotonin syndrome overdose on SSRIs; meanwhile the fatality rate is between 2% to 12%.


title: Serotonin

text: Some 5-HT antagonists, such as ondansetron, granisetron, and tropisetron, are important antiemetic agents. They are particularly important in treating the nausea and vomiting that occur during anticancer chemotherapy using cytotoxic drugs. Another application is in the treatment of postoperative nausea and vomiting.


title: Serotonin

text: Some serotonergic agonist drugs cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as cardiac valve fibrosis.


title: Serotonin

text: In the past, three groups of serotonergic drugs have been epidemiologically linked with these syndromes. These are the serotonergic vasoconstrictive antimigraine drugs (ergotamine and methysergide), the serotonergic appetite suppressant drugs (fenfluramine, chlorphentermine, and aminorex), and certain anti-Parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT receptors. These include pergolide and cabergoline, but not the more dopamine-specific lisuride.


title: Serotonin

text: As with fenfluramine, some of these drugs have been withdrawn from the market after groups taking them showed a statistical increase of one or more of the side effects described. An example is pergolide. The drug was declining in use since it was reported in 2003 to be associated with cardiac fibrosis.


title: Serotonin

text: Two independent studies published in "The New England Journal of Medicine" in January 2007 implicated pergolide, along with cabergoline, in causing valvular heart disease. As a result of this, the FDA removed pergolide from the United States market in March 2007. (Since cabergoline is not approved in the United States for Parkinson's Disease, but for hyperprolactinemia, the drug remains on the market. Treatment for hyperprolactinemia requires lower doses than that for Parkinson's Disease, diminishing the risk of valvular heart disease).


title: Serotonin

text: Several plants contain serotonin together with a family of related tryptamines that are methylated at the amino (NH) and (OH) groups, are "N"-oxides, or miss the OH group. These compounds do reach the brain, although some portion of them are metabolized by monoamine oxidase enzymes (mainly MAO-A) in the liver. Examples are plants from the genus "Anadenanthera" that are used in the hallucinogenic yopo snuff. These compounds are widely present in the leaves of many plants, and may serve as deterrents for animal ingestion. Serotonin occurs in several mushrooms of the genus "Panaeolus".


title: Serotonin

text: Serotonin is used by a variety of single-cell organisms for various purposes. SSRIs have been found to be toxic to algae. The gastrointestinal parasite "Entamoeba histolytica" secretes serotonin, causing a sustained secretory diarrhea in some people. Patients infected with "E. histolytica" have been found to have highly elevated serum serotonin levels, which returned to normal following resolution of the infection. "E. histolytica" also responds to the presence of serotonin by becoming more virulent. This means serotonin secretion not only serves to increase the spread of enteamoebas by giving the host diarrhea but also serves to coordinate their behaviour according to their population density, a phenomenon known as quorum sensing. Outside the gut of a host, there is nothing that the entoamoebas provoke to release serotonin, hence the serotonin concentration is very low. Low serotonin signals to the entoamoebas they are outside a host and they become less virulent to conserve energy. When they enter a new host, they multiply in the gut, and become more virulent as the enterochromaffine cells get provoked by them and the serotonin concentration increases.


title: Serotonin

text: In drying seeds, serotonin production is a way to get rid of the buildup of poisonous ammonia. The ammonia is collected and placed in the indole part of -tryptophan, which is then decarboxylated by tryptophan decarboxylase to give tryptamine, which is then hydroxylated by a cytochrome P450 monooxygenase, yielding serotonin.


title: Serotonin

text: However, since serotonin is a major gastrointestinal tract modulator, it may be produced in the fruits of plants as a way of speeding the passage of seeds through the digestive tract, in the same way as many well-known seed and fruit associated laxatives. Serotonin is found in mushrooms, fruits, and vegetables. The highest values of 25–400 mg/kg have been found in nuts of the walnut ("Juglans") and hickory ("Carya") genera. Serotonin concentrations of 3–30 mg/kg have been found in plantains, pineapples, banana, kiwifruit, plums, and tomatoes. Moderate levels from 0.1–3 mg/kg have been found in a wide range of tested vegetables.


title: Serotonin

text: Serotonin is one compound of the poison contained in stinging nettles ("Urtica dioica"), where it causes pain on injection in the same manner as its presence in insect venoms (see below). It is also naturally found in "Paramuricea clavata", or the Red Sea Fan.


title: Serotonin

text: Serotonin and tryptophan have been found in chocolate with varying cocoa contents. The highest serotonin content (2.93 µg/g) was found in chocolate with 85% cocoa, and the highest tryptophan content (13.27–13.34 µg/g) was found in 70–85% cocoa. The intermediate in the synthesis from tryptophan to serotonin, 5-hydroxytryptophan, was not found.


title: Serotonin

text: Root development in "Arabidopsis thaliana" is stimulated and modulated by serotonin - in various ways at various concentrations.


title: Serotonin

text: Serotonin serves as a plant defense chemical against fungi. When infected with Fusarium crown rot ("Fusarium pseudograminearum"), wheat ("Triticum aestivum") greatly increases its production of tryptophan to synthesize new serotonin. The function of this is poorly understood but wheat also produces serotonin when infected by "Stagonospora nodorum" - in that case to retard spore production. The model cereal "Brachypodium distachyon" - used as a research substitute for wheat and other production cereals - also produces serotonin, coumaroyl-serotonin, and feruloyl-serotonin in response to "F. graminearum". This produces a slight antimicrobial effect. "B. distachyon" produces more serotonin (and conjugates) in response to deoxynivalenol (DON)-producing "F. graminearum" than non-DON-producing. "Solanum lycopersicum" produces many AA conjugates - including several of serotonin - in its leaves, stems, and roots in response to "Ralstonia solanacearum" infection.


title: Serotonin

text: For example, in the roundworm "Caenorhabditis elegans", which feeds on bacteria, serotonin is released as a signal in response to positive events, such as finding a new source of food or in male animals finding a female with which to mate. When a well-fed worm feels bacteria on its cuticle, dopamine is released, which slows it down; if it is starved, serotonin also is released, which slows the animal down further. This mechanism increases the amount of time animals spend in the presence of food. The released serotonin activates the muscles used for feeding, while octopamine suppresses them. Serotonin diffuses to serotonin-sensitive neurons, which control the animal's perception of nutrient availability.


title: Serotonin

text: If lobsters are injected with serotonin, they behave like dominant individuals whereas octopamine causes subordinate behavior. A crayfish that is frightened may flip its tail to flee, and the effect of serotonin on this behavior depends largely on the animal's social status. Serotonin inhibits the fleeing reaction in subordinates, but enhances it in socially dominant or isolated individuals. The reason for this is social experience alters the proportion between serotonin receptors (5-HT receptors) that have opposing effects on the fight-or-flight response. The effect of 5-HT receptors predominates in subordinate animals, while 5-HT receptors predominates in dominants.


title: Serotonin

text: Serotonin is a common component of invertebrate venoms, salivary glands, nervous tissues, and various other tissues, across molluscs, insects, crustaceans, scorpions, various kinds of worms, and jellyfish. Adult "Rhodnius prolixus" - hematophagous on vertebrates - secrete lipocalins into the wound during feeding. These lipocalins were demonstrated to sequester serotonin to prevent vasoconstriction (and possibly coagulation) in the host by Andersen et al. 2003.


title: Serotonin

text: Serotonin is evolutionarily conserved and appears across the animal kingdom. It is seen in insect processes in roles similar to in the human central nervous system, such as memory, appetite, sleep, and behavior. Some circuits in mushroom bodies are serotonergic. (See specific "Drosophila" example below, Dipterans.)


title: Serotonin

text: Locust swarming is initiated "but not maintained" by serotonin, with release being triggered by tactile contact between individuals. This transforms social preference from aversion to a gregarious state that enables coherent groups. Learning in flies and honeybees is affected by the presence of serotonin.


title: Serotonin

text: Insect 5-HT receptors have similar sequences to the vertebrate versions, but pharmacological differences have been seen. Invertebrate drug response has been far less characterized than mammalian pharmacology and the potential for species selective insecticides has been discussed.


title: Serotonin

text: Wasps and hornets have serotonin in their venom, which causes pain and inflammation as do scorpions. "Pheidole dentata" takes on more and more tasks in the colony as it gets older, which requires it to respond to more and more olfactory cues in the course of performing them. This olfactory response broadening was demonstrated by Seid and Traniello 2006 to go along with increased serotonin and dopamine, but not octopamine.


title: Serotonin

text: If flies are fed serotonin, they are more aggressive; flies depleted of serotonin still exhibit aggression, but they do so much less frequently. In their crops it plays a vital role in digestive motility produced by contraction. Serotonin that acts on the crop is exogenous to the crop itself and was shown by Liscia et al. 2012 to probably originate in the serotonin neural plexus in the thoracic-abdominal synganglion. A "Drosophila" serotonergic mushroom body was found by Lee et al. 2011 to work in concert with "Amnesiac" to form memories. Dierick and Greenspan 2007 found serotonin to promote aggression in "Diptera", which was counteracted by neuropeptide F - a surprising find given that they both promote courtship, which is usually similar to aggression in most respects.


title: Serotonin

text: Serotonin, also referred to as 5-hydroxytryptamine (5-HT), is a neurotransmitter most known for its involvement in mood disorders in humans. It is also a widely present neuromodulator among vertebrates and invertebrates. Serotonin has been found having associations with many physiological systems such as cardiovascular, thermoregulation, and behavioral functions, including: circadian rhythm, appetite, aggressive and sexual behavior, sensorimotor reactivity and learning, and pain sensitivity. Serotonin's function in neurological systems along with specific behaviors among vertebrates found to be strongly associated with serotonin will be further discussed. Two relevant case studies are also mentioned regarding serotonin development involving teleost fish and mice.


title: Serotonin

text: In mammals, 5-HT is highly concentrated in the substantia nigra, ventral tegmental area and raphe nuclei. Lesser concentrated areas include other brain regions and the spinal cord. 5-HT neurons are also shown to be highly branched, indicating that they are structurally prominent for influencing multiple areas of the CNS at the same time, although this trend is exclusive solely to mammals.


title: Serotonin

text: Vertebrates are multicellular organisms in the phylum Chordata that possess a backbone and a nervous system. This includes mammals, fish, reptiles, birds, etc. In humans, the nervous system is composed of the central and peripheral nervous system, with little known about the specific mechanisms of neurotransmitters in most other vertebrates. However, it is known that while serotonin is involved in stress and behavioral responses, it is also important in cognitive functions. Brain organization in most vertebrates includes 5-HT cells in the hindbrain. In addition to this, 5-HT is often found in other sections of the brain in non-placental vertebrates, including the basal forebrain and pretectum. Since location of serotonin receptors contribute to behavioral responses, this suggests serotonin is part of specific pathways in non-placental vertebrates that are not present in amniotic organisms. Teleost fish and mice are organisms most often used to study the connection between serotonin and vertebrate behavior. Both organisms show similarities in the effect of serotonin on behavior, but differ in the mechanism in which the responses occur.


title: Serotonin

text: There are few studies of serotonin in dogs. One study reported serotonin values were higher at dawn than at dusk. In another study, serum 5-HT levels did not seem to be associated with dogs' behavioural response to a stressful situation. Urinary serotonin/creatinine ratio in bitches tended to be higher 4 weeks after surgery. In addition, serotonin was positively correlated with both cortisol and progesterone but not with testosterone after ovariohysterectomy.


title: Serotonin

text: Like non-placental vertebrates, teleost fish also possess 5-HT cells in other sections of the brain, including the basal forebrain. "Danio rerio" (zebra fish) are a species of teleost fish often used for studying serotonin within the brain. Despite much being unknown about serotonergic systems in vertebrates, the importance in moderating stress and social interaction is known. It is hypothesized that AVT and CRF cooperate with serotonin in the hypothalamic-pituitary-interrenal axis. These neuropeptides influence the plasticity of the teleost, affecting its ability to change and respond to its environment. Subordinate fish in social settings show a drastic increase in 5-HT concentrations. High levels of 5-HT long term influence the inhibition of aggression in subordinate fish.


title: Serotonin

text: Researchers at the Department of Pharmacology and Medical Chemistry used serotonergic drugs on male mice to study the effects of selected drugs on their behavior. Mice in isolation exhibit increased levels of agonistic behavior towards one another. Results found that serotonergic drugs reduce aggression in isolated mice while simultaneously increasing social interaction. Each of the treatments use a different mechanism for targeting aggression, but ultimately all have the same outcome. While the study shows that serotonergic drugs successfully target serotonin receptors, it does not show specifics of the mechanisms that affect behavior, as all types of drugs tended to reduce aggression in isolated male mice. Aggressive mice kept out of isolation may respond differently to changes in serotonin reuptake.


title: Serotonin

text: Like in humans, serotonin is extremely involved in regulating behavior in most other vertebrates. This includes not only response and social behaviors, but also influencing mood. Defects in serotonin pathways can lead to intense variations in mood, as well as symptoms of mood disorders, which can be present in more than just humans.


title: Serotonin

text: One of the most researched aspects of social interaction in which serotonin is involved is aggression. Aggression is regulated by the 5-HT system, as serotonin levels can both induce or inhibit aggressive behaviors, as seen in mice (see section on Mice) and crabs. While this is widely accepted, it is unknown if serotonin interacts directly or indirectly with parts of the brain influencing aggression and other behaviors. Studies of serotonin levels show that they drastically increase and decrease during social interactions, and they generally correlate with inhibiting or inciting aggressive behavior. The exact mechanism of serotonin influencing social behaviors is unknown, as pathways in the 5-HT system in various vertebrates can differ greatly.


title: Serotonin

text: Serotonin is important in environmental response pathways, along with other neurotransmitters. Specifically, it has been found to be involved in auditory processing in social settings, as primary sensory systems are connected to social interactions. Serotonin is found in the IC structure of the midbrain, which processes specie specific and non-specific social interactions and vocalizations. It also receives acoustic projections that convey signals to auditory processing regions. Research has proposed that serotonin shapes the auditory information being received by the IC and therefore is influential in the responses to auditory stimuli. This can influence how an organism responds to the sounds of predatory or other impactful species in their environment, as serotonin uptake can influence aggression and/or social interaction.


title: Serotonin

text: We can describe mood not as specific to an emotional status, but as associated with a relatively long-lasting emotional state. Serotonin's association with mood is most known for various forms of depression and bipolar disorders in humans. Disorders caused by serotonergic activity potentially contribute to the many symptoms of major depression, such as overall mood, activity, suicidal thoughts and sexual and cognitive dysfunction. Selective serotonin reuptake inhibitors (SSRI's) are a class of drugs demonstrated to be an effective treatment in major depressive disorder and are the most prescribed class of antidepressants. SSRI's function is to block the reuptake of serotonin, making more serotonin available to absorb by the receiving neuron. Animals have been studied for decades in order to understand depressive behavior among species. One of the most familiar studies, the forced swimming test (FST), was performed to measure potential antidepressant activity. Rats were placed in an inescapable container of water, at which point time spent immobile and number of active behaviors (such as splashing or climbing) were compared before and after a panel of anti-depressant drugs were administered. Antidepressants that selectively inhibit NE reuptake were shown to reduce immobility and selectively increase climbing without affecting swimming. However, results of the SSRI's also show reduced immobility but increased swimming without affecting climbing. This study demonstrated the importance of behavioral tests for antidepressants, as they can detect drugs with an effect on core behavior along with behavioral components of species.


title: Serotonin

text: In the nematode "C. elegans", artificial depletion of serotonin or the increase of octopamine cues behavior typical of a low-food environment: "C. elegans" becomes more active, and mating and egg-laying are suppressed, while the opposite occurs if serotonin is increased or octopamine is decreased in this animal. Serotonin is necessary for normal nematode male mating behavior, and the inclination to leave food to search for a mate. The serotonergic signaling used to adapt the worm's behaviour to fast changes in the environment affects insulin-like signaling and the TGF beta signaling pathway, which control long-term adaption.


title: Serotonin

text: In the fruit fly insulin both regulates blood sugar as well as acting as a growth factor. Thus, in the fruit fly, serotonergic neurons regulate the adult body size by affecting insulin secretion. Serotonin has also been identified as the trigger for swarm behavior in locusts. In humans, though insulin regulates blood sugar and IGF regulates growth, serotonin controls the release of both hormones, modulating insulin release from the beta cells in the pancreas through serotonylation of GTPase signaling proteins. Exposure to SSRIs during Pregnancy reduces fetal growth.


title: Serotonin

text: Genetically altered "C. elegans" worms that lack serotonin have an increased reproductive lifespan, may become obese, and sometimes present with arrested development at a dormant larval state.


title: Serotonin

text: Serotonin is known to regulate aging, learning and memory. The first evidence comes from the study of longevity in "C. elegans". During early phase of aging, the level of serotonin increases, which alters locomotory behaviors and associative memory. The effect is restored by mutations and drugs (including mianserin and methiothepin) that inhibit serotonin receptors. The observation does not contradict with the notion that the serotonin level goes down in mammals and humans, which is typically seen in late but not early phase of aging.


title: Serotonin

text: In animals including humans, serotonin is synthesized from the amino acid -tryptophan by a short metabolic pathway consisting of two enzymes, tryptophan hydroxylase (TPH) and aromatic amino acid decarboxylase (DDC), and the coenzyme pyridoxal phosphate. The TPH-mediated reaction is the rate-limiting step in the pathway.


title: Serotonin

text: TPH has been shown to exist in two forms: TPH1, found in several tissues, and TPH2, which is a neuron-specific isoform.


title: Serotonin

text: Serotonin can be synthesized from tryptophan in the lab using "Aspergillus niger" and "Psilocybe coprophila" as catalysts. The first phase to 5-hydroxytryptophan would require letting tryptophan sit in ethanol and water for 7 days, then mixing in enough HCl (or other acid) to bring the pH to 3, and then adding NaOH to make a pH of 13 for 1 hour. "Asperigillus niger" would be the catalyst for this first phase. The second phase to synthesizing tryptophan itself from the 5-hydroxytryptophan intermediate would require adding ethanol and water, and letting sit for 30 days this time. The next two steps would be the same as the first phase: adding HCl to make the pH = 3, and then adding NaOH to make the pH very basic at 13 for 1 hour. This phase uses the "Psilocybe coprophila" as the catalyst for the reaction.


title: Serotonin

text: Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system, because it does not cross the blood–brain barrier. However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, do cross the blood–brain barrier. These agents are available as dietary supplements and in various foods, and may be effective serotonergic agents.


title: Serotonin

text: One product of serotonin breakdown is 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine. Serotonin and 5-HIAA are sometimes produced in excess amounts by certain tumors or cancers, and levels of these substances may be measured in the urine to test for these tumors.


title: Serotonin

text: Indium tin oxide is recommended for the electrode material in electrochemical investigation of concentrations produced, detected, or consumed by microbes. A laser desorption ionization mass spectrometry technique was developed by Bertazzo et al. 1994 to measure the molecular weight of both natural and synthetic serotonins.


title: Serotonin

text: It had been known to physiologists for over a century that a vasoconstrictor material appears in serum when blood was allowed to clot. In 1935, Italian Vittorio Erspamer showed an extract from enterochromaffin cells made intestines contract. Some believed it contained adrenaline, but two years later, Erspamer was able to show it was a previously unknown amine, which he named "enteramine". In 1948, Maurice M. Rapport, Arda Green, and Irvine Page of the Cleveland Clinic discovered a vasoconstrictor substance in blood serum, and since it was a serum agent affecting vascular tone, they named it serotonin.


title: Serotonin

text: In 1952, enteramine was shown to be the same substance as serotonin, and as the broad range of physiological roles was elucidated, the abbreviation 5-HT of the proper chemical name 5-hydroxytryptamine became the preferred name in the pharmacological field. Synonyms of serotonin include: 5-hydroxytriptamine, thrombotin, enteramin, substance DS, and 3-(β-Aminoethyl)-5-hydroxyindole. In 1953, Betty Twarog and Page discovered serotonin in the central nervous system. Page regarded Erspamer's work on "Octopus vulgaris", "Discoglossus pictus", "Hexaplex trunculus", "Bolinus brandaris", "Sepia", "Mytilus", and "Ostrea" as valid and fundamental to understanding this newly identified substance, but regarded his earlier results in various models - especially those from rat blood - to be too confounded by the presence of other MAs, including some other vasoactives.


title: Sarah, Duchess of York

text: Sarah, Duchess of York (born Sarah Margaret Ferguson; 15 October 1959), also known by the nickname Fergie, is a member of the British royal family. She is the former wife of Prince Andrew, Duke of York, the younger brother of King Charles III.


title: Sarah, Duchess of York

text: She was raised in Dummer, Hampshire, and attended the Queen's Secretarial College. She later worked for public relations firms in London, and then for a publishing company. Ferguson began a relationship with Prince Andrew in 1985, and they were married on 23 July 1986 at Westminster Abbey. They have two daughters, the princesses Beatrice and Eugenie. Their marriage, separation in 1992, and divorce in 1996 attracted much media coverage.


title: Sarah, Duchess of York

text: Both during and after her marriage, Sarah has been involved with several charities as a patron and spokesperson. Her charity work primarily revolves around helping cancer patients and children. She has been the patron of Teenage Cancer Trust since 1990 and has founded Children in Crisis. In the years after her divorce, Sarah was the subject of scandals that affected her relationship with the royal family, but she has appeared in various royal events in recent years. She has authored several books for children and adults and has worked as a TV personality and film producer.


title: Sarah, Duchess of York

text: Sarah Margaret Ferguson was born on 15 October 1959 at London Welbeck Hospital in London. She is the second daughter of Major Ronald Ferguson (1931–2003) and Susan Barrantes (née Wright; 1937–1998). She has one older full sister, Jane. After Ferguson's parents divorced in 1974, her mother married polo player Héctor Barrantes in 1975 and moved to Trenque Lauquen in the Argentine pampas. Sarah stayed at the Dummer Down Farm at Dummer, Hampshire, her father's home since age 8. Major Ferguson married Susan Deptford in 1976 and had three more children: Andrew, Alice, and Elizabeth. Sarah later mentioned that at the age of 12, when her parents' marriage started to fall apart, she developed an eating disorder and "turned to overeating for comfort".


title: Sarah, Duchess of York

text: Known informally as "Fergie", she once described her family as "country gentry with a bit of old money". She is a descendant of King Charles II of England via three of his illegitimate children: Charles Lennox, 1st Duke of Richmond; James Scott, 1st Duke of Monmouth; and Anne Lennard, Countess of Sussex. She has aristocratic ancestry, being the great-great-granddaughter of the 6th Duke of Buccleuch, a great-granddaughter of the 8th Viscount Powerscourt, and a descendant of the 1st Duke of Abercorn and the 4th Duke of Devonshire. Ferguson is distantly related to Prince Andrew, as they are both descended from the Duke of Devonshire as well as King James VI and I.


title: Sarah, Duchess of York

text: Ferguson attended Daneshill School, Stratfield Turgis. The staff of the school described her as a "courageous, bubbly and outgoing little girl". She then attended Hurst Lodge School in Ascot. She did not shine academically but showed talent in swimming and tennis. At a young age, she developed an interest in skiing and later briefly worked as a chalet girl. In her teenage years, she worked both as a cleaner and waitress. After finishing a course at Queen's Secretarial College at the age of eighteen, Ferguson went to work for an art gallery. Later she worked in two public relations firms in London, and then for a publishing company. During her youth, she dated Kim Smith-Bingham, a stockbroker, and Paddy McNally, a motor racing manager more than 20 years her senior.


title: Sarah, Duchess of York

text: On 19 March 1986, Prince Andrew (fourth in line to the throne at the time) and Sarah Ferguson announced their engagement. Prince Andrew had known Ferguson since childhood, and they had met occasionally at polo matches and became reacquainted with each other at Royal Ascot in 1985. Also prior to their engagement, Ferguson had accompanied Diana, Princess of Wales, during her official tour of Andrew's ship HMS "Brazen". Prince Andrew designed the engagement ring himself. It consisted of ten diamonds surrounding a Burmese ruby. He chose the Burmese ruby to complement Sarah's red hair. With her fun spirit and friendly approach, she was initially considered to be a good addition to the royal family.


title: Sarah, Duchess of York

text: After securing the Queen's consent (which at that time was required by the Royal Marriages Act 1772 for all descendants of King George III), Andrew and Sarah were married in Westminster Abbey on 23 July 1986. The Queen bestowed the title Duke of York upon Prince Andrew, and, as his new wife, Sarah automatically assumed her husband's royal and ducal status and became "Her Royal Highness The Duchess of York". As Duchess of York, Sarah joined her husband in carrying out royal engagements, including official overseas visits.


title: Sarah, Duchess of York

text: In 1987, the Duke and Duchess of York undertook a 25-day tour of Canada. In February 1987, Sarah got a private pilot's license and, after passing a 40-hour training course that was paid for by Lord Hanson as a wedding gift, was presented with her wings at RAF Benson in December. On 22 January 1988, during the trip to New York to attend a fundraising event, Sarah was attacked by a young man at the entrance of her hotel. The man, who was screaming "murderers 3/8" and had the Irish Republican Army flag in his hands when he rushed at Sarah, was "charged with attempted assault on the Duchess and assault on a federal agent". Later, a State Department press officer stated that "she was unharmed in the incident". In March 1988, the Duke and Duchess of York visited California. The trip was described by two British newspapers as a "brash, vulgar, excessive, weak-humored exhibition by two royals". The couple was defended by city officials of Los Angeles who stated that the criticism was "awful" and offensive, and observers described the Duke and his wife's behaviour as friendly and said that they fulfilled their duties. In May 1989, Sarah went on an official solo trip to Berlin.


title: Sarah, Duchess of York

text: The couple became parents on 8 August 1988, with the birth of their daughter Beatrice. Sarah suffered from high blood pressure and excessive water retention during her pregnancy. In September, Sarah joined her husband in Australia for an official visit. The decision to leave her newborn daughter at home in the UK while she was touring the country brought her criticism from the press and media. Their second child, another daughter, Eugenie, was born on 23 March 1990 by caesarean section. During her marriage, the tabloid press ridiculed the Duchess of York for her weight (which climbed to (220 lbs) during her first pregnancy), labelling her the "Duchess of Pork" and "Fat Fergie". She vowed to lose weight after the birth of her first daughter. In 1989 Sarah was credited with kickstarting the UK popularity of exercise regime Callanetics after it was widely reported that founder Callan Pinckney had given her private tuition. Sarah received praise for her weight loss and some criticism for not gaining enough weight during her second pregnancy. Sarah later discussed the negative effect of the press stories about her weight on her self-esteem and added that they made her eating disorder worse.


title: Sarah, Duchess of York

text: Biographer Sarah Bradford described how Andrew's duties as a naval officer required him to stay away from home for long periods. According to Sarah's account, the couple saw each other 40 days a year in the first five years of their marriage. By 1991, the marriage was in trouble, as Sarah was finding life as a member of the royal family increasingly difficult. Her friendship with Texan multimillionaire Steve Wyatt (son of Lynn Wyatt) gained much publicity when photographs, including one of Wyatt with Sarah's toddler daughter, appeared in newspapers in January 1992. The Duke and Duchess of York announced their separation on 19 March 1992. Following the separation, the palace announced that Sarah would no longer carry out public engagements on behalf of the Queen. Furthermore, the Queen announced in a statement that she would not take responsibility for Sarah's debts. Sarah separated her residence from her husband and moved to Romenda Lodge on the Wentworth Estate, Surrey, in 1992.


title: Sarah, Duchess of York

text: In August 1992, the British tabloid "Daily Mirror" published surreptitiously taken photographs of John Bryan, an American financial manager, kissing Sarah's toes as she sunbathed topless. Sarah endured widespread public ridicule, contributing to her further estrangement from the British royal family. French magazine "Paris Match" was ordered to pay £84,000 in damages for publishing the photographs, though the original amount sought was £1.32 million. In 1995, Prince Andrew's aunt Princess Margaret, who had received a bouquet of flowers sent by Sarah, reportedly wrote in a letter to Sarah: "You have done more to bring shame on the family than could ever have been imagined".


title: Sarah, Duchess of York

text: After four years of official separation, the Duke and Duchess announced their mutual decision to divorce in 1996. In the years after her divorce, Sarah claimed that she had received £15,000 a year as a divorce settlement and cited her deal as a spokeswoman with Weight Watchers as her main "source of income". However, subsequent information given by senior officials to "The Sunday Telegraph" revealed that Sarah had received £350,000 in cash, £500,000 from the Queen to buy a new house for her and the children, and a monthly allowance that was estimated to have reached £500,000 in total by 2010. The couple shared custody of their children. In a 2007 interview, as to why they finalised their divorce she said, "I wanted to work; it's not right for a princess of the royal house to be commercial, so Andrew and I decided to make the divorce official so I could go off and get a job."


title: Sarah, Duchess of York

text: The decree nisi was granted on 17 April 1996 and the divorce was finalised on 30 May 1996, after which she legally retained the style "Her Royal Highness" with the style of other divorced peeresses. However, it was announced in April that Sarah had chosen not to use the style "Her Royal Highness" and would relinquish it under the divorce terms. In accordance with letters patent issued in August 1996 regulating post-divorce royal titles, Sarah formally ceased being a "Royal Highness" and was re-styled Sarah, Duchess of York.


title: Sarah, Duchess of York

text: Since the divorce, Sarah has attended some functions with her daughters, such as the investitures of the Duke of York into the Royal Victorian Order and the Order of the Garter, and Royal Ascot, and on those occasions, she is afforded the courtesy of treatment as a member of the royal family. Sarah hinted at the idea of remarrying Andrew in several interviews. In August 2013, she was invited to stay at Balmoral Castle with Prince Andrew and their daughters as guests of the Queen, and in September 2013, in response to a question about the possibility of remarrying Andrew, Sarah said, "He's still my handsome prince, he'll always be my handsome prince."


title: Sarah, Duchess of York

text: She was not invited to the 1999 wedding of Prince Edward and Sophie Rhys-Jones or the 2011 wedding of Prince William and Catherine Middleton, but she attended the wedding of Prince Harry and Meghan Markle in 2018. However, she did not receive an invitation to the evening reception at Frogmore House hosted by Prince Charles, and was reportedly "deeply upset" by her exclusion.


title: Sarah, Duchess of York

text: The Lord Chamberlain's Office has listed Sarah as a member of the royal family, along with other extended family members such as Daniel Chatto and Mike Tindall. she is not, however, listed on a section of the royal family's website titled "Members of the Royal Family". She attended the state funeral of Queen Elizabeth II in September 2022, and was seated by her daughters' side.