DEPRESSION AND THE MONOAMINES:

       DOPAMINE:

            Tightly linked to reward, euphoria

            Depressives self-administer drugs which enhance
               dopamine

            Rebound from dopaminergic over-stimulation often
               involves depression AND down-regulation of dopamine receptors.

            Bupropion and nomifensine are both specific
               dopamine reuptake inhibitors, both have good antidepressive effects

            Some recent PET scans suggest dopamine receptor
               abnormalities in depressed non-medicated patients

  MORE ON THE EPIDEMIOLOGY OF DEPRESSION

       SEX DIFFERENCES


            Females 1.7 times as likely to be depressed as
               males world-wide

            Differences seem to lessen after menopause

            Post-partum depression also suggests some sort
               of endocrine role

       AGE: Depression of the elderly, often involving agitation,
          is a common and perhaps distinctive form of depression

       GENETIC FACTORS

            Monozygotic twins have about a 50% concordance
               for major depression: dizygotic twins about 20%

            Children with depressive siblings or parents are also
               about three times as likely to be depressive as are controls

            This shows a clear genetic predisposition, but leaves
               ample room for environmental effects

       ENVIRONMENTAL INFLUENCES ON DEPRESSION


            Major stressors have a 10-fold likelihood of
               triggering a major depressive disorder within 30 days.  These include:

               1. Death of a close relative

               2.  Assault

               3.  Serious marital problems

               4.  Divorce/breakup


            AND people with a genetic predisposition to
               depression are more likely to experience major stressors, including:

               1. Assault

               2. Serious marital problems

               3. Divorce/breakup

               4. Job loss

               5. Serious illness

               6. Major financial problems

               7. Trouble getting along with relatives/friends

            Depression and divorce or death of a parent:

               1. Children of divorce are more likely to be
                    depressive

               2. This finding is multiply confounded:

                    a. Parents who divorce are more likely to
                         carry genes for depression

                    b. Children of divorce are more likely to
                         divorce and to have money problems, both of which predispose to depression

       GENE BY ENVIRONMENT INTERACTIONS

          In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively

  IMAGING STUDIES OF DEPRESSION

       FOCUS ON THE PREFRONTAL SYSTEM

            Prefrontal role in emotion:

               1. Normal subjects show prefrontal activity during
                    emotional experiences

               2. Prefrontal brain damage causes a host of
                    emotional changes, including depression


               3. There seems to be lateralization, in that right
                    prefrontal damage can cause euphoria, left can cause depression

               4. Orbital prefrontal cortex and cingulate cortex
                    seem particularly involved