Alexithymia in biomedical findings

2.3.4.1 Neurological studies

The neurological base of alexithymia has been proposed to lie in dysfunctional activity of the brain hemispheres – diminished right side activity and salient left side activity with or without interhemispheric transfer deficit (Parker and Taylor 1997). However, transfer deficit has remained without proof as there are controversial results – alexithymia has been connected to facilated transcallosal inhibition (Grabe et al. 2004) and reduced transcallosal inhibition (Romei et al.

2008). The current research interest is focused more on emotion processing areas of the brain, not in differences in hemisphere functions.

Neuroimaging techniques have been used in exploring if there are morphological and/or functional differences between alexithymic and nonalexithymic individuals. Alexithymia is mainly measured by TAS-20 total score.

Several brain imaging studies have found differences between alexithymic and

nonalexithymic persons in the experimental circumstances - the usual procedure is to show pictures or films which may arouse specific emotional and/ or cognitive states and then appraise the activation in different brain areas.

The anterior cingulated cortex has an important task in affect regulation and a voxel-based morphometry study of 54 female volunteers revealed that participants with TAS-20 score > 60 (n=14), had smaller grey matter volume in the anterior cingulate cortex (Borsci et al. 2009). The same type of study of 33 high alexithymic and 31 low alexithymic (according to the TAS-20 score) healthy right-handed males did not show any morphological differences between the groups explored (Heinzel et al. 2012).

Fear is a strong feeling and the amygdala and premotor cortex are activated when a fearful stimulus is observed and these brain areas prepare for an adaptive response. In an experimental study healthy right-handed men (13 high and 12 low alexithymic participants) observed fearful body expressions and fMRI was performed. The authors found that right amygdala activity (a response to fearful stimuli) correlated negatively with DIF, activity in the anterior cingulate cortex was greater in high alexithymic participants and premotor cortex activity was connected with reduced subjective emotional reactivity. The differences were explained by overregulation of emotional state among high alexithymic individuals (Pouga et al.

2010). An emotional stimulus (sad, neutral, amusing films) administrated to alexithymic and non-alexithymic healthy women provoked different activation modes between the groups, the alexithymic participants having more activation in sensory and motor cortices (Karlsson et al. 2008). An fMRI study of emotion perception and emotion regulation in healthy participants showed that alexithymia was correlated with lower activation in emotional attention and recognition networks, but no difference from nonalexithymic participants was found in emotion regulation areas (van der Welde et al. 2015).

Kano and Fukudo (2013) proposed that the link between alexithymia and physical disorders is based on lower reactivity of emotional brain regions in alexithymic individuals, meaning a lack of adaptive emotional processes to cope with different (physiological) stimuli. Instead of that, alexithymics show pronounced activation in somatosensory brain areas. In the case of visceral pain, there was hyperactivity in the visceral perception areas but hypoactivity in pain processing areas. The authors suggested that deficiency of emotional regulation causes hypersensitivity to unpleasant painful bodily sensations and pain related distress. A study of the connectivity of the default mode network of brain areas showed differences between alexithymic and nonalexithymic healthy volunteers,

alexithymics having diminished connectivity in those brain areas suggested to be involved in emotional awareness and self-referential processing, and higher connectivity in areas associated with emotional suppression and a more action-oriented focus (Liemburg et al. 2012).

In a study using triangle animation (a theory of mind task) and neuroimaging, alexithymic individuals showed hypoactivity in the right medial prefrontal cortex which was related to impairment in taking a perspective different from self and thus, in understanding the mental states of self and others (Moriguchi et al. 2006).

A review of neuroimaging studies on alexithymia summarized that alexithymia is related to reduced neural responses to external affective stimuli in the limbic and paralimbic systems, in the posterior cingulate cortex during an imaginary task, reduced activation in the medial prefrontal cortex when engaged in cognitive processes needed for social tasks and increased neural response to stimuli having somatosensory or sensorimotor processes. The authors concluded that neuroimaging studies support the characteristics of alexithymia (Moriguchi and Komaki 2013).

2.3.4.2 Immunological studies

Stress induces immunological changes (Segerstrom and Miller 2004).

Immunological consequences have been found to be associated with early stress and possibly predispose to depression (Cattaneo et al. 2015). Emotions and immunity have a bi-directional relation (Brod et al. 2014). Poor ability to deal with negative emotions may indirectly contribute to immune dysregulation; coping styles such as denial or repression are connected with altered immunity (Kiecolt-Glaser et al. 2002). In repeated studies inflammatory markers have been associated with depression (Valkanova et al. 2013). These findings among others have given indirect evidence that alexithymia, too, may be connected with immunological alterations.

It has been proposed that immunological findings (cytokine imbalance) observed in alexithymic subjects refer to a situation similar to chronic stress (Guilbaud et al. 2003). Previously it was found that alexithymic individuals’

dexamethasone suppression tests were positive indicating dysregulation in the stress system (Lindholm et al. 1990) but the number of alexithymic test participants was low. Alexithymic men showed impaired cellular immunity when compared with nonalexithymic men (Dewaraja et al. 1997). A study with healthy females found a positive association between alexithymia and inflammatory marker

interleukin-4 (Corcos et al. 2004). Depressed cell-mediated immunity was found in alexithymic women (Guilbaud et al. 2009). In a general population study, the levels of inflammatory markers (high-sensitivity C-reactive protein and interleukin-6) were higher in alexithymic subjects, and according to logistic regression analysis, elevated hs-CRP predicted alexithymia (Honkalampi et al. 2011). However, a clinical study (patients referred for upper endoscopy), alexithymia predicted lower levels of interleukin-4 and -6 (Mandarelli et al. 2011). Alexithymic subjects have been shown to have lower levels of adiponectin (which has an anti-inflammatory effect) than their nonalexithymic controls (Honkalampi et al. 2014). Alexithymia has also been found to be associated with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematous (Vadacca et al. 2014). A review of studies on alexithymia and immunological markers concluded that the studies suggest significant relations between stress, alexithymia and immunological dysregulation (Uher 2010).

2.3.4.3 Physiological responses

Alexithymia has been found to be associated with sympathetic overactivity or inappropriate sympathetic function (Martin 1986, Fukunishi et al. 1999) and with a tendency to hypertension (Jula et al. 1999). Alexithymic individuals have been found to have higher pulse rate, higher electrodermal activity and lower oxygen consumption during normal or resting periods but during the acute stress, alexithymic individuals show unchanged sympathetic activity or at least lower state than nonalexithymic individuals (Lumley et al. 2007). However, no recent studies are available on differences in physiological responses per se between alexithymic and nonalexithymic individuals.

More recent studies have measured and compared stress responses between alexithymic and nonalexithymic subjects. An experimental study measuring cortisol release before and during social stress test found that alexithymia (especially factor DDF) was associated with higher basal anticipatory level of cortisol but not with the cortisol values during the test (de Timary et al. 2008). Another social stress study showed that both before and during the test alexithymic participants had higher cortisol values than nonalexithymic participants and that the result was mainly related to alexithymia factor DDF (Hua et al. 2014). Hyperarousal (a sign of overactivity of the sympathetic nervous system) was connected with alexithymia and its factor DIF in a clinical study on posttraumatic distress (Declercq et al.

2010).