A functional anatomical study of unipolar depression used positron emission tomography (PET) to measure regional cerebral blood flow (BF) differences in subjects with familial pure depressive disease (FPDD). The study identified increased BF in the left ventrolateral prefrontal cortex and medial prefrontal cortex, along with increased activity in the left amygdala in depressed subjects. These findings suggest that the left prefrontal cortex may represent a state marker of FPDD, while the left amygdala may represent a trait marker. The study also found that the left amygdala showed increased activity in both depressed and remitted subjects, though this difference was significant only in the depressed group. The results indicate that a circuit involving the prefrontal cortex, amygdala, and related brain structures is involved in the functional neuroanatomy of depression. The study highlights the importance of using homogeneous subject groups to detect physiologic differences between depressed and control groups. The findings suggest that unipolar depression involves multiple neural systems and that the prefrontal cortex and amygdala play key roles in the pathophysiology of the disorder. The study also notes that the left prefrontal cortex shows a normal asymmetry in control subjects, but this asymmetry is lost in the depressed state. The results support the idea that depression is associated with altered brain function, particularly in the prefrontal cortex and amygdala. The study underscores the need for further research to confirm these findings and to better understand the underlying mechanisms of depression.A functional anatomical study of unipolar depression used positron emission tomography (PET) to measure regional cerebral blood flow (BF) differences in subjects with familial pure depressive disease (FPDD). The study identified increased BF in the left ventrolateral prefrontal cortex and medial prefrontal cortex, along with increased activity in the left amygdala in depressed subjects. These findings suggest that the left prefrontal cortex may represent a state marker of FPDD, while the left amygdala may represent a trait marker. The study also found that the left amygdala showed increased activity in both depressed and remitted subjects, though this difference was significant only in the depressed group. The results indicate that a circuit involving the prefrontal cortex, amygdala, and related brain structures is involved in the functional neuroanatomy of depression. The study highlights the importance of using homogeneous subject groups to detect physiologic differences between depressed and control groups. The findings suggest that unipolar depression involves multiple neural systems and that the prefrontal cortex and amygdala play key roles in the pathophysiology of the disorder. The study also notes that the left prefrontal cortex shows a normal asymmetry in control subjects, but this asymmetry is lost in the depressed state. The results support the idea that depression is associated with altered brain function, particularly in the prefrontal cortex and amygdala. The study underscores the need for further research to confirm these findings and to better understand the underlying mechanisms of depression.