"He (Knut) and his companion Gianna are definitely displaying behavioural problems," said researcher Frank Albrecht, from the animal welfare group People for the Ethical Treatment of Animals (Peta).
Knut, who became an international media sensation in 2007, even making the cover of glossy US magazine Vanity Fair, suffers from panic attacks and "sways to and fro" in an abnormal manner, Albrecht said.
The first public appearance of "Cute Knut" attracted 100 camera crews from around the world and the cub generated millions of euros for Berlin Zoo in lucrative merchandising and extra entrance fees.
But now Knut is a strapping three-and-a-half year old and experts have been saying for some time that all the attention has altered his behaviour, even to the extent of his imitating people taking photos with his paws.
And for Peta, Knut is the tip of the iceberg, with between 75% and 90% of the 34 polar bears in captivity in 11 German zoos showing signs of being disturbed - particularly those in newer, slightly larger enclosures.
Birth rates are falling and the mortality rates of those cubs that are born are "extremely high". Once adult, 75% die before their 15th birthday, compared with life expectancy in the wild of between 15 and 18 years.
"Our organisation therefore calls for an immediate halt to breeding (of polar bears in captivity), and in the long term, an end to keeping polar bears in Germany," Peta said.
"It is clear to anyone who reads our research that polar bears do not belong in captivity."
Heiner Kloes from Berlin Zoo slammed the claims as "ridiculous", telling the Bild daily: "Knut is fine."
In March Peta controversially called for Knut to be castrated to avert incest with Gianna because they share a bloodline.