Life may begin at 40, but research suggests that 44 is the age at which we are most vulnerable to depression.
Realistic aspirations may be the key to happiness
Data analysis on two million people from 80 countries found a remarkably consistent pattern around the world.
The risk of depression was lowest in younger and older people, with the middle-aged years associated with the highest risk for both men and women.
The study, by the University of Warwick and Dartmouth College in the US, will feature in Social Science & Medicine.
The only country which recorded a significant gender difference was the US, where unhappiness reached a peak around the age of 40 for women, and 50 for men.
Previous research has suggested that the risk of unhappiness and depression stays relatively constant throughout life.
However, the latest finding - of a peak risk in middle age - was consistent around the globe, and in all types of people.
Researcher Professor Andrew Oswald, an economist at the University of Warwick, said: "It happens to men and women, to single and married people, to rich and poor, and to those with and without children."
He said the reason why middle age was a universally vulnerable time was unclear.
Count your blessings
However, he said: "One possibility is that individuals learn to adapt to their strengths and weaknesses, and in mid-life quell their infeasible aspirations.
"Another possibility is that a kind of comparison process is at work in which people have seen similar-aged peers die and value more their own remaining years. Perhaps people somehow learn to count their blessings."
Professor Oswald said for the average person, the dip in mental health and happiness comes on slowly, not suddenly in a single year.
Only in their 50s do most people emerge from the low period.
"But encouragingly, by the time you are 70, if you are still physically fit then on average you are as happy and mentally healthy as a 20-year-old.
"Perhaps realizing that such feelings are completely normal in midlife might even help individuals survive this phase better."
Marjorie Wallace, chief executive of the mental health charity Sane, said: "This study raises intriguing questions about the processes that lead to depression in mid-life, as well as indicating what a common experience it is worldwide.
"Depression is a complex and challenging condition that remains poorly understood, with as many as one in ten people with severe depression taking their own life.
"We welcome any scientific contribution to our understanding of this illness, particularly if the research can aid the development of better treatments, both therapeutic and pharmaceutical."
Andy Bell, of the Sainsbury Centre for Mental Health, said mental health problems were extremely common - but he stressed they could occur at any time in life.