Anxiety and depression are major psychiatric disorders of significant clinical and socioeconomic significance. Clinical Depression generally presents alongside Anxiety Disorders, and vise-versa. Rarely does a patient present symptoms of only one or the other.
In the general population, these disorders affect daily performance and correlate with impulse control, financial behaviors, substance abuse and organization. Anxiety is an unpleasant state that involves a complex combination of emotions that include fear, apprehension, and worry. It is often accompanied by physical sensations such as heart palpitations, nausea, chest pain, shortness of breath, or tension headache. Anxiety disorder is a blanket term covering several different forms of abnormal, pathological anxiety, fears, phobias and nervous conditions that may come on suddenly (acute anxiety) and/or gradually over a period of several years (chronic), and may impair or prevent the pursuing of normal daily routines. Anxiety disorders are often debilitating chronic conditions, which can be present from an early age or begin suddenly after a triggering event. They are prone to flare up at times of high stress.
Anxiety is often described as having cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). The cognitive component entails expectation of a diffuse and uncertain danger. Somatically the body prepares the organism to deal with threat (known as an emergency reaction): blood pressure and heart rate are increased, sweating is increased, bloodflow to the major muscle groups is increased, and immune and digestive system functions are inhibited. Externally, somatic signs of anxiety may include pale skin, sweating, trembling, and pupillary dilation. Emotionally, anxiety causes a sense of dread or panic and physically causes nausea, and chills. Behaviorally, both voluntary and involuntary behaviors may arise directed at escaping or avoiding the source of anxiety. These behaviors are frequent and often maladaptive, being most extreme in anxiety disorders. However, anxiety is not always pathological or maladaptive: it is a common emotion along with fear, anger, sadness, and happiness, and it has a very important function in relation to survival.
Neural circuitry involving the amygdala and hippocampus is thought to underlie anxiety (Rosen & Schulkin, Psychol. Rev., 105(2):325-350, 1998). When confronted with unpleasant and potentially harmful stimuli such as foul odors or tastes, PET-scans show increased bloodflow in the amygdala (Zald & Pardo, PNAS, 94(8):4119-4124, 1997; Zald, Hagen & Pardo, J. Neurophysiol., 87(2):1068-1075, 2002). In these studies, the participants also reported moderate anxiety. This might indicate that anxiety is a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors.
Conventional treatments for anxiety include behavioral therapy, lifestyle changes and/or pharmaceutical therapy (medications). Most drugs used to treat these disorders are known to have negative side effects that may limit their use, or cause habituation and dependence.
Postsynaptic density-95 protein (PSD-95) couples NMDARs to pathways mediating excitotoxicity and ischemic brain damage (Aarts et al., Science 298, 846-850 (2002)). This coupling was disrupted by transducing neurons with peptides that bind to modular domains on either side of the PSD-95/NMDAR interaction complex. This treatment attenuated downstream NMDAR signaling without blocking NMDAR activity, protected cultured cortical neurons from excitotoxic insults and reduced cerebral infarction volume in rats subjected to transient focal cerebral ischemia. This result has led to the proposal to use peptide antagonists of PSD-95/NMDAR for treating stroke and other diseases mediated by excitotoxicity. No significant side effects have been observed in phase I trials of one such antagonist.