This is somewhat surprising, but we really don’t know the actual causes of anxiety. All we have are theories and preliminary neurobiological findings. Sadly, since we do not know the pathophysiology and biology of anxiety disorders, we have no objective, biological markers to diagnose anxiety. However, we do have preliminary neurobiological findings that may eventually help to uncover the causes of anxiety. The following are 13 unusual causes of anxiety to know about:
- Enlarged and hyperactive amygdala
- Increased blood flow to the amygdala and ACC
- Disruption of the corticolimbic circuit
- Abnormal brain structure and function in panic disorder
- Anxiety genes
- Environmental transmission of anxiety
- Various substances/compounds can cause panic attacks
- Hyperconnection of the orbitofrontal cortex and the basal ganglia
- Decreased hippocampal volume
- Stress hormones
- Drugs of abuse
- Medical illness causing anxiety
The amygdala activity is increased in anticipation of aversion in patients with generalized anxiety disorder. Patients with generalized anxiety disorder also have increased amygdala volume (Schienle et. al., 2011). Another study confirmed that when subjects with specific phobia were presented with phobic stimuli, there was hyperactivity in the amygdala, anterior cingulate cortex (ACC), and insula as measured on fMRI. However, after 2 weeks of exposure therapy, there was significant reduction of hyperactivity in the amygdala, ACC, and insula (Goossens et al., 2007). Functional neuroimaging findings in subjects with social phobia reveal abnormalities in the amygdala, medial prefrontal cortex, insula, hippocampus, and dorsolateral prefrontal cortex, which are also abnormal findings in all major anxiety disorders (Pietrini et al., 2010). The amygdala has been considered to be a key brain structure in fear processing; so in fear conditioning, the amygdala is implicated in fear acquisition and generating behavioral responses to that fear.
In subjects with post traumatic stress disorder (PTSD), increased blood flow occurred in the ventral anterior cingulate gyrus and right amygdala when generating mental images of combat, so re-experiencing trauma may be associated with increased blood flow in these regions of the brain (Shin et al., 1997).
From the scant research available, generalized anxiety disorder may involve the disruption of brain circuits which connect the anterior cingulate cortex (ACC) and the amygdala, and the dorsomedial prefrontal cortex (DMPFC) and the amygdala, which may be involved in negative emotion regulation (Schienle et. al., 2011). There is also preliminary evidence that the medial prefrontal cortex- limbic circuit is implicated in social phobia pathophysiology, the corticolimbic circuit (Freitas-Ferrari et al., 2010).
Subjects with panic disorder have an amygdala and hippocampus which are smaller in volume compared to healthy controls. The brainstem nuclei, mainly in the rostral pons, can have increased volume, and this is believed to be involved with autonomic arousal circuitry. And cortical areas having smaller volume in subjects with panic disorder include the anterior cingulated cortex (ACC), orbitofrontal cortex (OFC), temporal cortex, and the frontal cortex (Del Casale et al, 2013). During experimental panic attacks, functional neuroimaging has shown increased activity in the insula and upper brain stem (including the periaqueductal gray- PAG), and decreased activity in the ACC. Volumetric analysis of brain MRI has shown increased volume in the insula and upper brain stem, and decreased volume in the ACC of panic disorder subjects at rest, compared to healthy controls (Graeff and Del-Ben, 2008).
Anxiety disorders have a significant genetic component. In other words, if you have anxiety, you most likely have a family member who also has it, and passed on the anxiety gene to you. We currently do not know the exact genes involved in anxiety, but we know there is a significant genetic component from family studies. One study confirmed that generalized anxiety disorder has a mild to moderate familial aggregation. In this study, the odds ratio of developing generalized anxiety disorder for first-degree relatives of patients with generalized anxiety disorder ranged from 1.4 to 1.8, and when it was restricted to children of patients with generalized anxiety disorder, the odds ratio ranged from 2.1 to 2.8 (Newman and Bland, 2006). A meta-analysis of twin studies found that the heritability of generalized anxiety disorder was 0.32 (Hettema et al., 2001). A meta-analysis on twin studies revealed that specific phobia is moderately heritable (Van Houtem et al., 2013). In addition, social phobia, panic disorder, and PTSD run in families, and are moderately heritable (Hettema et al., 2001; Mosing et al., 2009; Smoller et al., 2008; Stein et al., 2002). Another study found that obsessive compulsive disorder (OCD) runs in families, mainly due to genetic factors, with environmental factors being at least as important (Mataix-Cols et al., 2013).
Environmental factors such as trauma, vicarious learning, and/or negative information are important for the transmission of specific phobia (Lichtenstein and Annas, 2000). Environmental factors associated with developing social phobia include parental overcontrol, parental psychopathology, adverse life events (sexual abuse, conflictual peer relationships and marital problems), low income, and different cultural values (Brook and Schmidt, 2008).
Various agents can induce panic attacks in healthy volunteers and those with panic disorder, including sodium lactate, carbon dioxide, caffeine, serotonergic agents, yohimbine, and cholecystokinin (Bourin et al., 1998).
One study showed that unmedicated subjects with OCD had a hyperconnection of the orbitofrontal cortex and the basal ganglia. On the other hand, when subjects with OCD were medicated with antidepressants, there was reduced connectivity of the ventral striatum compared to unmedicated subjects. This interesting research highlights the abnormalities in the cortico-striato-thalamo-cortical circuits in OCD, and how antidepressants may correct the abnormalities (Beucke et al., 2013).
In neuroimaging studies of subjects with post traumatic stress disorder (PTSD), the hippocampal volume was decreased (Nemeroff et al., 2006).
It is postulated that the hippocampus receives damage with traumatic stress, via glucocorticoid stress hormones (McEwen, 1997). There is also increased corticotropin-releasing factor (CRF) with low cortisol levels in subjects with PTSD (Yehuda et al., 2004).
Drugs of abuse, especially stimulants like cocaine, can induce anxiety symptoms such as panic attacks (Cox et al., 1990)
Hyperthyroidism and pheochromocytoma can present with anxiety symptoms and mimic anxiety disorders (Mackenzie and Popkin, 1983).
Experiencing life-threatening trauma can induce anxiety symptoms, and can progress to post traumatic stress disorder (PTSD).
In summary, the above neurobiological findings are preliminary. These findings are just associations, and more research is needed to determine the causes of anxiety. Unfortunately, there are no biological markers to help diagnose anxiety, but when the causes are elucidated in the coming years, then objective tests may be developed.