To our knowledge, it is the first study, which compared volumetric brain parameters in acute suicidal patients after first and repeated suicidal attempts to healthy subjects without a history of suicidal attempt and mental disorder. The main finding of this research that already after the first suicide attempt in comparison to healthy controls lower cortical thickness was observed in temporal and frontal areas; smaller size of some parts of hippocampus structure was found in suicidal patients.
Volumetric brain analysis in our study revealed that frontal cortex thickness was reduced in rostral middle frontal region on the left hemisphere and superior frontal regions on both hemispheres. Moreover, these differences in cortical thickness were significantly higher in the assessment of patients after repeated suicide attempts: the significant difference in cortical thinning of almost all frontal regions was found.
Many studies investigated frontal cortex role in suicidality. It is known that DL, VL areas of PFC and ACC regulate behaviour and emotions [15]. The aforementioned changes lead to impaired behavioural control and impulsive behaviour. It is thought that in an emotionally unstable person the frontal cortex limbic system inhibition is not sufficient enough, which causes impulsive, irrational decision making and emotional liability in individuals [16, 17]. Serotonin also plays an important role in emotion regulation and behavioural control. People with serotonin deficiency can succumb to strong emotions like suicidal thoughts and aggressive actions that ultimately lead to suicide [18]. In the findings of other researchers, cortex thinning in PFC and OFC areas was linked with suicidality [19, 20]. Atrophy in prefrontal cortex ventrolateral, dorsolateral and anterior cingulate parts was also discovered in MDD, bipolar depression and schizophrenia patients who attempted suicide [4, 5, 21]. Study of Wang et al. found that MDD patients with a history of SA had a reduced volume in the right and left amygdala and ventral, medial, dorsal PFC. These demonstrate the role of the amygdala and PFC in the pathogenesis of suicidal behavior and imply the amygdala-PFC circuit as a probable target for detection and prevention of suicidal behavior [22].
Our study has also revealed significant differences in superior frontal gyrus, rostral middle frontal gyrus, pars triangularis and precentral gyrus and other areas of frontal cortex. It has been investigated that pars triangularis is associated with cognitive control of memory and may contribute to suicidal behaviour through a connection with hippocampus [23]. Prefrontal cortex is also linked to suicidality because of its role in executive functions [24]. Other frontal cortex regions involved in suicide have not yet been investigated.
Furthermore, our investigation of temporal lobe structures revealed reduced cortical thickness in inferior, middle and superior regions in patients with first suicidal attempt and nearly all TC regions - in patients with repeated suicidal attempts. It is known about the association of TC with limbic structures and the PFC: these interfaces are important in recognizing and controlling mood and emotion [25]. Superior temporal gyrus is related to emotional intelligence, the ability of following own and others’ emotions to make decisions and perform actions [15]. Superior temporal gyrus and sulcus are the components of the face recognition system [26]. This gyrus becomes active upon seeing scared faces [27]. Superior temporal sulcus, amygdala and insula analyse movements of other objects, providing information about their intentions [28]. In addition, these structures regulate a sudden, reflexive response to negative visual stimuli [29]. In other studies, the role of TC in suicidality has been mainly linked to degradation in medial and superior cortices [5, 20, 27, 30, 31]. This could be due to the fact that temporal lobe contributes to emotion responding [32]. Our research has demonstrated significant volumetric results in the previously mentioned middle, superior TC and also in inferior, left fusiform and left temporal pole. Similar findings were reported in other studies that investigated fusiform relation to borderline personality disorder, while smaller temporal pole is associated with psychotic disorders and suicide attempts [27, 33].
One of the aims of our study was to examine hippocampus structure differences in suicide attempted patients. When comparing all study patients and healthy controls, we have found significant volume differences in some left and right parts of hippocampus structures. However, some hippocampus regions were found as reduced only in patients after repeated SA, without significant differences in patients after first suicidal attempt in comparison to controls.
The hippocampus is associated with the pathophysiology of mental disorders; the main function of the hippocampus is memory processing. Changes in this cognitive function are associated with suicidal behaviour and lower hippocampal volume in individuals who have attempted suicide [34]. It also modulates the activity of the hypothalamic–pituitary–adrenal axis which is impaired in people who have attempted suicide, not to mention the prefrontal cortex which perform executing functions and is regulated by the hippocampus [35, 36]. An acute stressing event and high levels of cortisol also could associate with decreased volume of the hippocampus [37]. However, hippocampus volume changes in suicidal behavior remained contradictory [38].
Our findings support the Colle et al. study in which depressed suicide patients had smaller right and total hippocampus volume than non-suicidal attempters. In addition, researchers have suggested that hippocampal volume could be a suicidal state marker in depressive disorder [39]. Hippocampal volumes were negatively associated with impulsivity in individuals; high lethality attempts were associated with smaller volumes of the hippocampus and parahippocampal gyrus in adult suicidal attempters [27, 40]. Other study of Gosnell and colleagues has found smaller hippocampus in depressed suicidal patients in comparison to healthy controls. However, they did not find differences in hippocampus of suicidal and not suicidal depressive patients. Researchers hypothesized that hippocampus difference could be due to a characteristic other than suicidality [19].
It is known that mental disorder, especially MDD and schizophrenia, are related to suicide behaviors [41, 42]; affective disorders comprise more than half of all suicide deaths [43]. Most of the volumetric studies evaluating suicidal patients provided observations when comparing suicidal vs. non-suicidal patients with an affective or psychotic disorder. In our study only one-third of patients were diagnosed with MDD, other patients had adjustment disorder, anxiety disorders and personality disorders. However, our study results revealed that reduced brain volume in suicidal patients is completely unrelated to neither age, gender, method of suicide attempt or diagnosis of MDD. Hence, at this stage of understanding, we hypothesized that the model of suicidal behavior is related to the reduction of brain volume in specific brain regions - frontal, temporal cortex and hippocampal structures. Moreover, these changes become express with repeated suicidal attempts.
Our study has a few limitations. For brain structure visualization we used 1,5T tomography imaging. 3T computer tomography has a better resolution because of the ability to better visualize the boundaries between grey matter, white matter, and cerebrospinal fluid. However, the 1.5T tomography imaging provides a more accurate measurement of realistically small brain structures such as the hippocampus, amygdala, and nuclei [44]. An apparent limitation of the method is a cross-sectional design. This bears importance because differentiating the cause and effect becomes impossible – we are unable to tell whether reduced brain volume contributes to suicidal behaviour or the opposite. The prospective analysis of structural brain changes after each repeated SA could provide more clear information about neuroimaging markers of the suicidal brain.