How does physical or mental isolation lead to despair in Macbeth?

In many ways, Shakespeare's Macbeth is a study of a character gradually isolating himself on many levels. Macbeth begins the play as a respected warrior, one of King Duncan's favorites. However, as the play progresses, Macbeth physically, mentally, and emotionally isolates himself by systematically eliminating those who threaten his power. This isolation also leads to the breakdown of Macbeth's reputation and his network of allies. We can see the desperation this situation causes in part of Macbeth's famous speech in Act V: 

Life's but a walking shadow, a poor playerThat struts and frets his hour upon the stageAnd then is heard no more. It is a taleTold by an idiot, full of sound and fury,Signifying nothing. (5.5.26-30)

In this moment, Macbeth has just learned that Lady Macbeth, his last true human connection, has just passed away, leading him utterly adrift in loneliness. This revelation leads Macbeth to conclude that life is essentially meaningless. Thus, it's possible to suggest that Macbeth's isolation causes him to realize that the power he thirsted after is, in the end, meaningless without the human connections he forfeited in the process of usurping the throne, and this realization leads to utter despair. It is here that we truly see Macbeth, for all of his evil actions, as a tragic character.