Almost every researcher who works in this field has some favorite hypothesis that explains better the current non-quite-satisfactory simple explanations based on one neutrotrasmitter or antoher, e.g. a 2008 review in Nature by Krishnan and Nestler said:
I doubt that's the ultimate word on the topic (all such narrative reviews have their biases when it comes to the less investigated aspects, no matter how prestigious the venue or the author), but it's clear that the "brighter bulbs" keep looking for more satisfying answers than the monoamine hypothesis (this what's called in the mass media "chemical imbalance"). I think any ultimately useful answer has to account for how the current antidepressants work... which is by acting on neurotransmitters, which in turn does alleviate depression (better than placebo) in some people but alas does not in quite a few others.
What Krishnan and Nestler favor is another fairly circulated notion (but not so much in the mass media!) that a final common pathway for depression exists. But alas, the case is far from being closed on that. Here are a few textbook paragraphs that contrast diabetes (another heterogeneous disease) with depression, which also gets to this final-common-pathway issue, as well as the difficulty in distinguishing cause from effect with individual neurotransmitter systems:
Researchers have compared MDD [major depressive disorder] to other chronic, heterogeneous diseases such as diabetes mellitus (Krishnan & Nestler, 2008), which, like MDD, is projected to increase in prevalence in the coming decades. [...] Like depression, diabetes can present with a variety of symptoms, such as polyuria, polydipsia, polyphagia, as well as with cardiovascular, digestive, and nervous system dysfunction. Unlike MDD, however, these symptoms are a product of a known molecular basis of the disease: a deficit in the production or utilization of insulin. The involvement of insulin—due to the lack of the hormone or to failure of its intended signaling—represents a final common molecular pathway (FCMP) in diabetes that unites the involvement of disparate physiological systems. This FCMP has allowed researchers to begin to use powerful animal models to understand the symptoms, risk factors, and complications of this disorder. In addition, the identification of insulin and the pancreatic ß-cells involved in insulin production have led to dramatic improvements in the prevention and treatment of diabetes. At this point, however, an FCMP is absent in the study of MDD; presently, there is no neurobiological equivalent in depression of insulin from ß-cells.
Over the past few decades, many molecular systems have been implicated in depression. [...] Because of the wide array of molecular systems that are disrupted in MDD, or in which disruption leads to depression, it has been difficult for researchers and clinicians to cleanly link molecular and behavioral systems. Investigators have noted limitations with all these single-system theories of MDD; indeed, to date, there is no known single molecule that is both necessary and sufficient to explain all the varied combinations of symptoms that can be present in individuals diagnosed with MDD. Genetic studies of MDD, too, have not been definitive in determining consistent risk loci, due to heterogeneity, environmental factors, and nosological limitations (Shyn & Hamilton, 2010). Even evidence of successful antidepressant action is not sufficient to demonstrate the primacy of the targetted molecular system in the pathophysiology of MDD. In fact, some researchers have argued that anomalies in traditional molecules implicated in the pathophysiology of MDD, like monoamines or glutamate, are unlikely to be at the etiological core of depression (Krishnan & Nestler, 2010). This difficulty disentangling the causal links between symptoms profiles and molecular systems has historically led to simplifications and misconceptions of the neurobiology of depression (Lacasse & Leo, 2005).
A primary challenge for investigators is differentiating between molecules that are disrupted as a consequence of depression and molecules that, when disrupted, are involved in the etiology of MDD. Demonstrating that a particular molecule—for example, a metabolite of a neurotransmitter— is up- or down-regulated in MDD is not sufficient to claim that disruption in this molecule causes MDD. Even when molecules can be causally linked to depression, the heterogeneity of this disorder prevents researchers from linking that molecule to all forms of MDD. For example, showing that interferon alpha (IFN-) can cause MDD is not equivalent to proving that IFN- underlies all cases of the disorder. Indeed, whereas some molecular systems may be strongly associated with one particular domain of impairment (e.g., dopamine and deficits in motivation and behavior), the effects of other molecular systems, like norepinephrine, may be less specific. Adding to this complexity is the fact that MDD is a moderately heritable disorder (Levinson, 2009) in which preexisting vulnerabilities interact with stressful life events to increase risk for initial and recurrent depressive episodes in a manner similar to the kindling model of epileptogenesis (Kendler, Thornton, & Gardner, 2000). Moreover, different symptoms and symptom clusters in MDD are inherited at different rates. For example, sleep and appetite disruption have higher heritability estimates than does psychomotor retardation (Jang, Livesley, Taylor, Stein, & Moon, 2004).
Reproduced from Chen and Gotlib "Molecular Foundations of the Symptoms of Major Depressive Disorder" in The Oxford Handbook of Molecular Psychology, OUP 2015