Cerebral hemodynamic response to generalized anxiety disorder

Anxiety disorders, as the most prevalent mental disorders, create a massive economic burden due to the harmful effect of anxiety on people's psychological and physical well-being (Kessler and Greenberg, 2002). Anxiety disorders are associated with developing or exacerbating other mental and physical disorders. Many studies have shown a strong relationship between generalized anxiety disorder and medical illnesses, especially cardiovascular events (Roy-Byrne et al., 2008, Allgulander, 2016, Muller et al., 2005, Culpepper, 2009, Tully et al., 2016).

Neurocognitive impairments in psychiatric disorders seem to be associated with alterations in cerebral blood flow (Gur et al., 1985, Risberg and Gustafson, 1988). A wide range of cerebral blood flow (CBF) impairments and noticeable changes in blood flow velocities have been observed in patients with schizophrenia, depression, and bipolar disorder (Liddle et al., 1992, Ingvar and Franzen, 1974, Bench et al., 1993, Mathew et al., 1980, Lesser et al., 1994, Toma et al., 2018). Similar studies investigated vascular and blood flow changes, mostly regional CBF (rCBF), in anxiety disorders (Mathew et al., 1980, Hasler et al., 2007, Fredrikson and Furmark, 2003). Few studies performed on global CBF showed both decreased and increased CBF in patients with anxiety (Van den Bergh et al., 2013). This complicated relationship between anxiety and CBF may be caused by interactions among different physiological pathways, including increased cortical arousal (Estevez and Phillis, 1997), different anxiety-induced changes in breathing patterns in mild and severe anxiety (Mathew et al., 1997), and reinforcement of sympathetic activation in acute anxiety (Lambert and Lambert, 2011, Roth et al., 2008).

Increased blood flow velocity of extracranial internal carotid artery (ICA) during resting baseline was shown in patients with panic attack compared to healthy controls (Gecici et al., 2005). In another study increase in the mean flow velocity of bilateral intracranial middle cerebral arteries (MCA) in patients with acute untreated panic attacks was demonstrated. Therefore, it is possible that alterations in cerebral perfusion may have a role in the clinical features and clinical time course of the panic disorder (Owega et al., 2001).

Such measurements are limited in chronic GAD which are necessary to elucidate conflicting findings in anxiety-related neuroscience research. Since some neurobiological mechanisms overlap in induced and pathological anxiety, few studies have investigated rCBF changes in GAD with an induced anxiety model (Makovac et al., 2016). Nevertheless, GAD, with the least similarity to induced anxiety (Chavanne and Robinson, 2021), is still the least studied and understood among anxiety disorders (Lenze and Wetherell, 2009). In a study by Andreescu et al., although GAD patients exhibited increased CBF in the posterior associative temporo-occipital areas relative to their resting state, no significant differences were observed between GAD patients and healthy controls regarding CBF during worry induction (Andreescu et al., 2011). In comparison, such between-group differences in CBF at the inferior parietal lobule and the postcentral and precentral gyrus were found in another study (Karim et al., 2017).

A better understanding of CBF hemodynamic in GAD may provide essential information to explore its possible diagnostic and therapeutic role. Color doppler ultrasonography is a fast, safe and feasible method to measure blood flow parameters and allows continuous and bilateral monitoring of the main cerebral arteries (Gecici et al., 2005, Fiedler et al., 2021). Several studies have used it numerously to evaluate changes in hemodynamic patterns and pathologies to better interpret psychological and neurological impairments (Siragusa et al., 2020). Although there are limited data about vascular changes in GAD patients (Guo et al., 2017), there is no study regarding their cervical vessels. Consequently, we aimed to investigate the extracranial (cervical) blood flow velocities in the resting state of chronic GAD patients, without worry induction, using doppler ultrasonography.

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