Depression and Anxiety: The Frenemies No College Student Wants to Meet
Kaiya Bhatia
Illustrations by: Ayane Garrison
Frenemies. We all know Jim and Dwight from The Office, or Perry the Platypus and Dr. Doofenshmirtz from Phineas and Ferb. Each side of these pairs has opposing agendas, but like all good frenemies, they occasionally work together to help one another out. College students, however, deal with a different kind of frenemy relationship: one that lives inside their heads.
The most common and insidious pair of frenemies present in the lives of college students is anxiety and depression, a difficult and sometimes deadly duo. The energetic volatility of anxiety versus the dull monotony of depression ignites a fierce rivalry within the host’s mind. And yet, each condition makes us more vulnerable for the other’s attack on our neural systems. For example, imagine you get anxious about failing your upcoming test, making you question if you’re prepared enough or how you might fare. In turn, you may begin to fear that you have no chance of passing the exam at all, leading you to feel hopeless and lost. These swells of depression may then render you unmotivated to study, compounding your initial anxiety of failure [1]. This cycle repeats itself over and over, enabling anxiety and depression to feed off of each other, ultimately leaving you paralyzed. It is a self-defeating, self-fulfilling prophecy — one that can lead to fatal consequences if misunderstood.
The Diagnoses
While depression and anxiety exist in many different forms, college students are most commonly diagnosed with Generalized Anxiety Disorder (GAD) and/or Major Depressive Disorder (MDD). GAD is characterized by persistent and excessive worrying that is difficult to control, usually without apparent or rational cause for concern [2]. Experiencing these symptoms over a period of six months warrants an official diagnosis of GAD. MDD, on the other hand, is characterized by a period of at least two weeks of depressed mood or loss of interest. Related symptoms of MDD include issues with sleep, eating, energy, or concentration [3]. The “frenemy” relationship between GAD and MDD is clinically referred to as a comorbid relationship, which describes one or more additional conditions that exist with a primary condition; in this case, the primary condition can be either MDD or GAD.
The Collegiate Mental Health Crisis
GAD and MDD are the two most common mental health issues reported in college students, affecting 41.6% and 36.4% of students, respectively [5]. In fact, their presence is much more prevalent on college campuses than anywhere else in the country — a mere 2.7% of adults in the United States are estimated to have GAD, and only 7.1% are diagnosed with MDD [2, 3]. Interestingly, even with the overwhelming prevalence of both disorders in college students, this comorbidity is often overlooked in the investigation of mental health on college campuses [6]. However, this relationship actually plays a significant role in the college mental health crisis, as a recent study found an astronomical 29.8% of college females and 13.9% of college males are diagnosed with both GAD and MDD [6]. As comorbid GAD and MDD diagnoses are associated with much greater impairment compared to that of just one of the conditions alone, identifying and exploring this comorbidity is essential to providing better treatment to those affected.
A recent study has sought to address this lack of research attention on comorbidity, delving into the impact of comorbid GAD and MDD on college students’ wellbeing [6]. Researchers found that those who screened positive for both of the two psychiatric disorders showed a significant decrease in quality of life as compared to those diagnosed with either one [6]. One of the main explanations for this phenomenon lies in the cognitive impairment associated with comorbid MDD and GAD. The combination of MDD and GAD makes individuals generally more inclined to express negativity towards day-to-day problems. The overthinking and self-doubt characteristic of GAD are compounded, causing the individual to over-assess a problem, leading to increased anxiety [7]. All the while, MDD stirs up feelings of hopelessness towards the issue at hand [7]. And, even beyond these affective symptoms, researchers also found that college students with comorbid MDD and GAD show cognitive impairments, despite their constant need to harness cognitive skills. These impairments often cause students to struggle with school work and other daily tasks, likely leading to an increase in stress. This build-up of stress significantly worsens the patient’s primary condition and quality of life.
While this combination of symptoms would make it difficult for anyone to deal with arising problems, college students can become especially frustrated and burnt out, as their academic and social environments push them to confront urgent and intellectually complex issues every day. As such, to deal with this emotional distress, college students with GAD and MDD often also develop a tendency for cognitive avoidance — the process of avoiding or eliminating negative thoughts — leading to high levels of overall thought suppression [7]. This is cause for concern, as college students are expected to reflect on highly conceptual material both in and out of the classroom. The college experience of comorbid GAD and MDD is presenting major barriers to academic success and emotional well-being.
GAD & MDD Brain Chemistry
Before we consider how to treat these comorbid disorders, we first need to understand the key players involved. Brain chemistry refers to the activity of neurotransmitters and their effects on behavior or brain functioning. Neurons are a type of brain cell that communicate using neurotransmitters — chemical messengers that each serve a distinct purpose. These molecules are released by one neuron, the presynaptic neuron, and attach to the receptor of another, the postsynaptic neuron, resulting in either an inhibitory or excitatory response. This process is like receiving a letter in the mail, containing information regarding your future plans. The news could be disappointing, making you less likely to go through with your plans, or it could be exciting, preparing you to move forward. In this analogy, the letter is a neurotransmitter; inhibitory neurotransmitters render the postsynaptic neuron less likely to send a signal after the neurotransmitter binds to its receptor, while excitatory neurotransmitters make the neuron more likely to do so. Gamma-aminobutyric acid (GABA) and serotonin are the two major players in the brain chemistry of anxiety and depression.
A new focus of research regarding GAD and MDD treatment centers around GABA. Recent studies have found that increased presence of GABA can have both antidepressant and anti-anxiety effects [8]. To achieve an anxiolytic effect, GABA binds to receptors on neurons in the amygdala, a brain region responsible for our fear and stress responses, inhibiting signals of fear and stress [9]. However, patients with anxiety have a decreased abundance of GABA receptors, meaning that they are less likely to get this anti-anxiety effect in their system [10]. Benzodiazepines are one of the most common treatments for anxiety, working to correct this imbalance by helping GABA neurotransmitters inhibit the postsynaptic neuron. By doing this, the benzodiazepines work to reduce anxiety effects within an individual. This medication has been used for 50 years to treat anxiety, and, while effective, it also raises concerns for long-term dependence and sedative effects [9].
In contrast, our understanding of GABA’s role in MDD has been much more recent. Unlike in anxiety disorders, we do not see a change in GABA receptor abundance in patients suffering from MDD. However, this does not mean GABA has no role in MDD. On the contrary, there is significant evidence showing patients with MDD to have overall reduced levels of GABA in brain regions such as the amygdala [10]. Furthermore, there is evidence that those with MDD may have an altered gene expression for GABA receptors as well [10]. Our current treatments for depression do not target the GABA system, but still increase inhibitory signals [11]. Researchers have proposed that targeting GABA receptors will help reduce depression, as the inhibitory nature of GABA may help slow down the cognitive processes involved with depressive thoughts [11]. While the specific mechanisms involved with GABA in MDD are not completely understood, related research still conveys the need for future antidepressants to correct neurological chemical imbalances rather than the symptoms themselves [10].
Serotonin’s role in MDD, on the other hand, is much clearer. Serotonin is important for regulating the mood, well-being and cognition of an individual. This inhibitory neurotransmitter has been consistently implicated as a cause for MDD but has not yet been strongly linked to GAD. Despite these differences in links, selective serotonin reuptake inhibitors (SSRIs) are still the starting point for the treatment of comorbid GAD and MDD. SSRIs work to influence the concentration of serotonin in the brain [12]. When neurotransmitters are released, SSRIs enter into the space between the presynaptic and postsynaptic neuron, known as the synaptic cleft. After some time, the neurotransmitters are absorbed back into the presynaptic neuron to be recycled. SSRIs work to prevent this reuptake so that more serotonin is present in the synaptic cleft, increasing the neurotransmitter’s effectiveness in the postsynaptic neuron.
However, as mentioned earlier, despite the success SSRIs have had with treating GAD, serotonin’s role in the disorder is not very well understood. Our best inferences on the role of serotonin in GAD come from looking at how SSRIs work to treat GAD. For example, a recent study found that the use of SSRIs in anxiety and depression treatment normalizes amygdala activity in the brain, as well as a decrease in activity in the limbic system (i.e., the region responsible for emotion) [13]. These changes were seen to cause a reduction in anxiety symptoms experienced by individuals. This suggests that reduction in activity is a potential mechanism of anxiety reduction. However, that the observed effective treatment of GAD with SSRIs is more of an accidental action than an intentional action of the drugs, further understanding of the mechanisms and serotonin’s role is still needed.
Serotonin is arguably the most famous of the neurotransmitters implicated in MDD. The serotonin hypothesis was first proposed half a century ago, stating that decreased activity of serotonin pathways has a causal role in the pathophysiology of depression [14]. Like many hypotheses developed in psychiatry, the study claimed that the condition is caused by serotonin because we see that a drug involving serotonin is an effective treatment. While we cannot outright refute this hypothesis, as it does hold some truth, we need to acknowledge that MDD is not likely an issue due to the activity of a single neurotransmitter. The reason this can be said is because SSRIs do not work for everyone, suggesting that there are other neurotransmitters at play here (e.g. GABA).
Comorbid MDD & GAD Treatment
One of the biggest issues we face in the treatment of depression and anxiety is the lack of knowledge surrounding the nature of their comorbidity. Generally, researchers believe that the high prevalence of both GAD and MDD suggests there are commonalities in their causes. However, our current pharmaceutical tactic for treating GAD and MDD is to throw different drugs at the symptoms and hope that one sticks (without making any symptoms worse). The intention of this treatment is to reduce symptoms to allow the individual to improve functionality. However, the presence of one disorder often reduces the efficacy of treatment for the other, creating a tricky situation [15]. Thus, the first step towards effective treatment is being able to recognize the presence of a comorbidity, which increases chronicity and recurrence, and typically requires long-term pharmaceutical treatments [16]. Incomplete diagnoses, likely due to the symptom overlap associated with the disorders, may result in incomplete treatment. As such, the recognition of these conditions is essential in guiding treatment plans.
When considering medication to treat comorbid anxiety and depression, experts flock to SSRIs as their primary treatment option [16]. However, as we have discussed, SSRIs do not work for everyone. Furthermore, we see antidepressants improving symptoms for each disorder alone, but are such results enough to ensure that antidepressants will effectively treat both illnesses at the same time? It’s a difficult question to answer conclusively, yet it certainly highlights the need for more research concerning MDD and GAD treatment. As of now, treatment research for comorbidity is lacking, and there is no existing medication that works to treat comorbid anxiety and depression [16]. Our current void in research suggests that our attempt at treatment is a patchwork of guesses with hints of understanding. Therefore, furthering our understanding of the similarities between GAD and MDD, as well as their differences, may help us improve treatment availability for the future.
Looking Ahead
With so much uncertainty in our current understanding of comorbid depression and anxiety, it’s no wonder we are struggling to treat patients. Our tunnel-vision, symptom-based approach to treatment has blinded us to the significance of comorbidity, especially in the case of comorbid MDD and GAD. Yet, it’s also true that there is no easy fix. The collegiate mental health crisis won’t magically resolve itself with a few days off for student wellness or an email encouraging self-care. A solution relies on recognizing the importance of comorbid conditions and redefining our focus, not just pharmaceutically. There is a crisis that is leaving a significant portion of college students emotionally and cognitively impaired, and we can only alleviate the stress of their conditions by addressing the issue head-on. It may be unrealistic to implore every institution to divert resources towards funding treatment for comorbid GAD and MDD. However, it is necessary to ask schools to reconsider how they help students manage their symptoms, so that they may improve their emotional and academic well-being, and steer clear of these frenemies for good.
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