Depressive disorders etiology

Explain the etiology and pathophysiology of major depressive disorder. 

In summary, many animal of models depressive disorders have been developed, each w ith relative advantages and disadvantages (Nestler et al., 2002). The validity of these models for human depressive disorders continues to be the subject of debate. Probably, this reflects the lack of comprehensive data on the molecular pathophysiology, genetic etiology, and relation to stress in human major depressive disorder. 

Bipolar disorder is characterized by episodes of mania or hypomania, which include hyperactivity, decreased need for sleep, and a euphoric or irritable mood. Additionally, persons with bipolar disorder may have episodes of depression similar to those seen in major depressive disorder. The lifetime prevalence of severe bipolar disorder is about 1% and 3-5% if milder cases are included, afflicting men and women equally. Both bipolar disorder and major depressive disorder tend to be episodic, and in the periods of time between episodes, persons may experience few or no symptoms. The etiology of bipolar disorder is predominately genetic, with a 70% concordance in monozygotic twins. The neurobiology of bipolar disorder is less well understood, and few animal models have been developed. Treatment of bipolar disorder usually involves mood stabilizer medications, including lithium, and the anticonvulsants valproate and carbamazepine. At times, antidepressant and antipsychotic medications are also used. 

In summary, the etiology of major depressive disorder suggests a genetic component, environmental influences, and other, as yet undetermined factors. 

The etiology of depressive disorders is too complex to be totally explained by a single social, developmental, or biologic theory. Several... 

HT has been implicated in the etiology of numerous disease states, including depression, anxiety, social phobia, schizophrenia, obsessive compulsive disorders,... 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

Several mechanisms exist to explain the etiology of affective disorders all based on the hypothesis that certain levels of amine neurotransmitters (e.g., norepinephrine - NE, serotonin - 5-HT) and receptor sensitivity are necessary for normal mood. There is ample evidence that depression occms if receptors are insensitive or if amine synthesis, storage or... 

Bouton ME, Mineka S, Barlow DH (2001) A modern learning theory perspective on the etiology of panic disorder. Psychol Rev 108 4-32 Braunewell KH, Manahan-Vaughan D (2001) Long-term depression a cellular basis for learning RevNeurosci 12 121-140... 

The phosphatidylinositol pathway is completed by regeneration of the phospholipid from IP3 and DG. It is remarkable that IP3 is successively dephosphorylated to mositol. The last step of this sequence is inhibited by Li ions, which block phosphatidylinositol synthesis. Li salts are used to control the symptoms of manic-depressive illness, an affective mental disorder (see section 3.5.4), and it is thus tempting to implicate the last reaction of the PI pathway in the etiology of this disorder. 

---