# Are Anxiety and Depression Actually the Same Disorder?



## David Baxter PhD (Apr 2, 2007)

Are Anxiety and Depression Actually the Same Disorder?
Norman Sussman, MD
Primary Psychiatry. 2007;14(4):15-16

The dilemmas facing clinicians who diagnose and treat psychiatric disorders are different than the issues that confront practitioners specializing in cardiology, endocrinology, hematology, gynecology, or virtually any other field of medicine. In the case of most mental disorders, causation has not been established, diagnosis is based on clusters of symptoms, and treatments have a tendency to be non-specific. For example, I have given and heard lectures over the years on the differential diagnosis of depression and anxiety. Typically, variation in the focus of these talks included distinguishing between anxiety symptoms associated with depression, coexisting anxiety and depression, and mixed anxiety-depression. Often, these disorder distinctions seemed forced, with many points of differentiation reflecting a greater degree of diagnostic certainty than appeared to exist in real-world clinical care. In both clinical and epidemiologic samples, major depressive disorder (MDD) and generalized anxiety disorder (GAD) display substantial comorbidity and/or symptom overlap.

In the March _Archives of General Psychiatry_, Wray and colleagues1 help to explain why many practitioners have difficulty defining the “correct” primary diagnosis when patients present with MDD or other depressive disorders and/or GAD. Their findings could potentially change how clinicians view the classification of psychiatric disorders and add to our understanding of etiology of depression and anxiety.

Wray and colleagues1 describe a probable genetic association between variants of gene plexinA2 and anxiety disorders. Plexins are receptors for semaphorns, which have not only been implicated in the development of the nervous system but also in neurogenesis within the adult brain. Semaphorins are a class of secreted and membrane proteins that act as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals through multimeric receptor complexes. They are usually cues to deflect axons from inappropriate regions, which is especially important in neural system development. The major class of proteins that act as their receptors are called plexins.

According to the authors, the well-known comorbidity between depression and anxiety disorders may be explained by the adult neurogenesis theory of depression. Key in understanding the neurogenesis theory of depression is the concept of apoptosis, which is programmed cell death.2 A normal cellular process involving a genetically programmed series of events, such programmed cell death leads to the elimination of cells without the release of harmful substances into the surrounding area. Thus, the brain maintains a capacity for structural plasticity and perhaps genetically based differences determine the rate and degree of which the brain sprouts new cells.

New evidence is consistent with other data suggesting that anxiety and depression share genetic risk factors. The researchers rely on the older psychoanalytic conceptualization of neuroticism. Kendler and colleagues3 have studied patients with lifetime diagnoses of MDD and GAD and found that familial environment had little or no impact on the etiology of either disorder. They did report finding that genetic factors were important for both MDD and GAD and were completely shared between the two disorders. Thus, the authors observed that the liability to MDD and GAD is influenced by the same genetic factors. Therefore, whether a vulnerable individual develops MDD or GAD is a result of environmental factors. More specifically, the findings provide support for the hypothesis that predisposition to MDD and GAD are the result of the same genetic factors, and some environmental risk factors provoke depression while others provoke anxiety. 

Consequently, there is individual variation in susceptibility due to life events. In the study, a minority of the adolescent girls experiencing life events showed depression and/or anxiety. Genetic effects on depression and anxiety, especially on their co-occurrence, were substantially and significantly greater in individuals who had experienced negative life events in the past year than in those without such experiences. The authors showed that this difference in genetic effect was due to gene/environment interaction, with there being no difference in the effects of baseline genes.3

Increasingly, the role of stressors in the presence of genetic polymorphisms is becoming the focus of psychiatric research. Apart from current interest on vulnerability to adverse effects from stress, researchers are investigating why some individuals demonstrate a capacity for resilience.4 Resilience is conceptualized as the capacity to avoid negative effects (such as psychiatric symptoms) or to recover following stress.

Neurogenesis in certain brain areas now appears to be involved in the process of the onset and persistence of depression as well as the process of recovery. Impairment of neurogenesis, most likely due to genetic factors, may underlie treatment resistance and loss of resilience over time. Perhaps, all new treatments should be screened for their impact on apoptosis and neurogenesis.

The potential impact of these findings on the development of the new _Diagnostic and Statistical Manual of Mental Disorders_ will be an interesting outcome to examine. Current classification of psychiatric disorders follows a categorical disease model, whereby major disorders are conceptualized as separate conditions. Although not explicitly stated, the psychiatric field assumes that different disorders are caused by different genetic factors and biochemical or neuranatomical abnormalities. However, this classification model is now in doubt. There is evidence of shared underlying genetic and biochemical factors in the broad therapeutic effects of the most currently used psychotropic agents. Classification of drugs as antidepressants, anxiolytics, mood stabilizers, or antipsychotics has become increasingly difficult to sustain as each class gains new indications that cross diagnostic boundaries. 

*References*
1 Wray NR, James MR, Mah SP, et al. Anxiety and comorbid measures associated with PLXNA2. Arch Gen Psychiatry. 2007;64(3):318-326.

2 Alzheimer’s Association. Available at: www.alz.org/Resources/Glossary.asp. Accessed March 13, 2006.

3 Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ. Major depression and generalized anxiety disorder. Same genes, (partly) different environments? Arch Gen Psychiatry. 1992;49(9):716-722.

4 Charney DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry. 2004;161(2):195-216.

_Dr. Sussman is editor of Primary Psychiatry and professor of psychiatry at the New York University School of Medicine in New York City.

Dr. Sussman is a consultant to and on the advisory boards of GlaxoSmithKline and Wyeth; and has received honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, and Wyeth._


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## braveheart (Apr 3, 2007)

hmmmmmmm...... interesting...


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## David Baxter PhD (Apr 3, 2007)

> I have given and heard lectures over the years on the differential diagnosis of depression and anxiety. Typically, variation in the focus of these talks included distinguishing between anxiety symptoms associated with depression, coexisting anxiety and depression, and mixed anxiety-depression.



This distinction was much more important 20 years ago than today, at least from a pharmacological point of view. In the past, whether the patient exhibited primary depression with secondary anxiety, or primary anxiety with secondary depression, was important to determine the approriate medication. With the advent of SSRIs and SNRIs and the popular use of these medications to treat both anxiety and depression, the distinction is less critical - albeit still of importance in terms of other therapies such as CBT.

That said, being aware that anxiety and depression often coexist and that they may share some common physiological or neurochemical characteristics does not, in my opinion, make them "the same disorder".


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## braveheart (Apr 3, 2007)

Except in PTSD, Complex PTSD and Borderline PD maybe? Although that's a slightly different topic.....


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## David Baxter PhD (Apr 3, 2007)

I'm not sure what you mean, braveheart.


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## Halo (Apr 3, 2007)

David Baxter said:


> ...the distinction is less critical - albeit still of importance in terms of other therapies such as CBT.



Whether depression is primary and anxiety is secondary or vice versa I was wondering if you could explain why it would still be important in terms of therapist such as CBT.  Do the techniques/exercises differ?

Thanks


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## David Baxter PhD (Apr 3, 2007)

Nancy said:


> Whether depression is primary and anxiety is secondary or vice versa I was wondering if you could explain why it would still be important in terms of therapist such as CBT.  Do the techniques/exercises differ?



No, but it may be helpful in narrowing down and identifying the specific primary cognitive distortions which trigger the cycle and addressing those first.


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## braveheart (Apr 3, 2007)

I mean where anxiety and depression are included in the same diagnosis.


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## Halo (Apr 3, 2007)

David Baxter said:


> No, but it may be helpful in narrowing down and identifying the specific primary cognitive distortions which trigger the cycle and addressing those first.



Oh, I understand...thanks


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## David Baxter PhD (Apr 3, 2007)

braveheart said:


> I mean where anxiety and depression are included in the same diagnosis.



Can PTSD include symptoms of both anxiety and depression? Certainly.


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