I sourced Eyes of the Eighth which tells us that 6th March 1944 was the first time that a USAAF Spitfire completed a recon sortie over Berlin. The mission was originally scheduled for 4th March but delayed by poor weather. Capt. Walter Weitner flew Spitfire PA892 and some of his post-strike photos are published in this book.
Many Americans served in RAF and RCAF squadrons, so it is possible that Weitner was not the first Yankee to fly a Spitfire over Berlin.
Can you imagine the tension of flying alone deep within enemy territory (to their actual lair)? Granted the danger might not compare with the bombers, but at least they had the feeling of the relative safety in numbers.