Journal of Psychiatric Research 146 (2022) 210–218

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Journal of Psychiatric Research

journal homepage: www.elsevier.com/locate/jpsychires

Suicidal behaviour: What’s the brain up to?

Shubhangi Parkar a, Natasha Kate a, Karishma Rupani a, *, Gaurav Malhotra b, Trupti Upadhye b,
Ramesh Asopa b
a
Department of Psychiatry, KEM Hospital, Parel, Mumbai, 400012, India
b
Radiation Medicine Centre. Parel, Mumbai, 400012, India

A B S T R A C T

Background: Individuals with suicidal behaviours are increasingly recognized as having impairments in brain metabolism. However, these are not well delineated.
Aim: To evaluate regional cerebral glucose metabolism (rCMglu) in subjects with suicidal behaviours and assess differences in rCMglu between depressed and non-
depressed suicidal subjects.
Methods: Thirty-three subjects with suicidal behaviours were assessed using Columbia Suicide Severity Rating scale (CSSRS) and Beck’s Depression Inventory (BDI).
Brain metabolism was assessed using [18F]Fluoro,Deoxy-Glucose Positron Emission Tomography (FDG-PET).
Results: Of 33 subjects, eighteen had depression. FDG-PET findings revealed that in comparison to mean asymptomatic controls, subjects had decreased rCMglu in
right inferior frontal, left Broca’s, left inferiolateral andsuperiolateral temporal, right inferior parietal and left posterior cingulate cortex. Increased rCMglu was seen
in bilateral superior and medial frontal, right inferiolateral and posteriomedial temporal cortex, and midbrain. CSSRS total intensity inversely correlated with rCMglu
in medial frontal cortex, left Broca’s and superiolateral temporal cortex and directly correlated with rCMglu in right cerebellum. There was no significant difference
in rCMglu between depressed and non depressed group.
Conclusions: Significant differences exist in rCMglu of suicidal individuals, chiefly in frontal and temporal regions. Understanding these would help us identify in­
dividuals more at risk for suicidal behaviours.

1. Introduction
Suicide is an end point. An endpoint that results following the
culmination of suicidal behavior. Suicidal behaviour is now understood
as multidimensional in origin, resulting from a complex interaction of
several risk factors like psychiatric disorders, individual psychology, life
events, sociodemographics and so on (De Leo et al., 2006; World Health
Organization, 2014; Radhakrishnan and Andrade, 2012; Hendin et al.,
2008; Barraclough et al., 1974). Psychiatric disorders have been iden­
tified in more than 50% of individuals with suicidal behaviour, and the
most common psychiatric diagnosis is depression (Sokero, 2005). While
hopelessness and mental pain have been found to be strongly correlated
with suicidal behavior(Van Orden et al., 2010), not all individuals with
depression attempt suicide, despite the frequent occurrence of hope­
lessness in these individuals. It follows then, that there must be an
additional mental state or mental trait that differentiates those with
suicidal behaviours and those without, even in the depressed state. On a
related note, a large percentage of individuals with suicidal behaviours
do not have a major mental disorder. Suicidal behaviours in these in­
dividuals are traditionally believed to be secondary to impulsivity as a
personality trait (Verdejo-García et al., 2008). This could also explain
the increased risk of suicidal behaviours by those with personality dis­
orders (especially those with borderline personality disorder). However,
once more the conundrum presents itself. Not all individuals with
impulsivity attempt suicide. Additionally, recent literature has shown
that ‘impulsivity’ is not elevated in subjects of suicidal behaviours or is
not a major contributor to suicidal behaviours (Klonsky and May 2010).
So impulsivity can no longer be considered to be the only answer to why
some people attempt suicide. The question then arises: Are individuals
who attempt suicide different from those that do not? And as all
behaviour stems from our brain, the question we really need an answer
to is: Are the brains of individuals who attempt suicide different from
those that do not? Previous post mortem techniques and newer imaging
techniques using magnetic resonance imaging have identified brain
morphological or structural differences in persons with suicidal behav­
iours. Yet, changes in brain structure can occur before or after attempts
at suicidal behaviours, or can occur secondary to co-morbid psychiatric
disorders, substance use, treatment or other confounding factors. At the
same time, structural abnormalities need not necessarily mean func­
tional dysfunction and vice versa. As a result, functional imaging studies
are possibly the best medium for helping us understand the workings of
the brain of an individual with a suicidal attempt. Functional imaging of

* Corresponding author. Department of Psychiatry, GS Medical College and KEM Hospital, Parel, Mumbai, 400012, India
E-mail address: k.i.rupani@gmail.com (K. Rupani).

https://doi.org/10.1016/j.jpsychires.2021.12.052
Received 29 August 2021; Received in revised form 19 December 2021; Accepted 22 December 2021
Available online 28 December 2021
0022-3956/© 2021 Elsevier Ltd. All rights reserved.
S. Parkar et al.
the brain consists of functional magnetic resonance imaging (fMRI),
single photon emission tomography (SPECT) and positron emission to­
mography (PET), imaging techniques that are capable of measuring
global and regional brain function by measuring estimates of regional
brain blood flow (using 13N-ammonia) or metabolism through relative
regional cerebral metabolic rates of glucose (rCMRglu) using 18F-Flur­
odeoxyglucose (18FDG). Some evidence for the impairment in resting
regional brain metabolism in subjects with suicidal behaviours has
begun to surface. One study identified bilateral prefrontal hypo­
perfusion and a left-sided thalamic increased perfusion in subjects who
very recently had a suicide attempt in comparison to healthy volunteers
(Audenaert et al., 2006). while other researchers have shown relative
hypometabolism in the high-lethality attempters compared to
low-lethality attempters in the ventral, medial and lateral prefrontal
cortex (Oquendo et al., 2003). Most of the present day literature focuses
on functional changes in the prefrontal cortex (especially the orbito­
frontal region) and the temporal cortex. (),(Heeringen et al., 2014), ()
Yet most of this research is coloured with the background of mood
symptoms in the subjects studied. On the ot.
Unfortunately, current day literature in suicidal behaviours which
tries to understand the going-on of the brain of an individual with sui­
cidal behaviours is restricted to only a handful of studies with samples
focusing on either depressed or borderline subjects. Yet, this distinction
does not present itself in routine clinical practice. Studies have also
shown that neurobiology of suicidal behaviours is influenced by
depressive symptoms and impulsivity but these do not contribute in
entirety nor do they satisfactorily explain the entire clinical picture. And
finally, we must not generalize findings in western suicide attempters on
Indian populations as there are psychological and environmental factors
that influence the outcome and thus pose a challenge (15) along with.
Overall, suicidality can be seen to be a net effect of the dysregulation of
HPA activity, genetic load, epigenetics, cholesterol and triglyceride
profile, specific neurocognitive and neuropsychological impairments,
some personality traits and characters (16). In view of these reasons, it
was thought to be the need of the hour to map brain function through
cerebral metabolism patterns in subjects with suicidal behaviours (with
or without depression) in comparison with asymptomatic controls. Also,
we wanted to assess differences in brain metabolism between depressed
and non depressed suicidal subjects. This research would give an
impetus in the ascent towards etiological understanding, thereby help­
ing plan better treatment interventions. Given the heterogeneity of
subjects who present with suicidal behaviour, it was thought prudent
not to restrict the study to only subjects with either depressive or per­
sonality disorders (characterizing impulsive suicidal behaviors) but to
include a heterogeneous sample in an attempt to develop a more inte­
grated understanding of the biological underpinnings of suicide.
2. Materials and methods
The study, approved by the Institutional Ethics Committee, was
conducted in a tertiary care hospital in Western India. Subjects were
recruited from a specialty out-patient service “Suicide prevention clinic”
that runs weekly exclusively for patients with suicidal behaviours,
where all patients with attempted suicide who present to the medical/
emergency/surgical services are referred. For the purpose of this study,
consecutive sampling was undertaken and the study period was 6
months (from January 2014 to June 2014). Inclusion criteria for the
subjects were age group of 18–65, either gender with attempted suicide
in the last 72 h, not on psychotropic medication since atleast 1 month,
willing and cognitively stable to give consent. Written informed consent
was taken from all subjects prior to inclusion in the study. Females not
known to be pregnant/lactating and those having the last menstrual
period less than 1 month from time of assessment were included. Sub­
jects with mild to severe depressive disorder, anxiety disorders and
personality disorders were also included in the study. Subjects who were
already receiving pharmacotherapy/psychotherapy for their index
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Journal of Psychiatric Research 146 (2022) 210–218
episode, having catatonia or psychosis, severe cognitive impairment,
active suicidal ideations who clinically require medication, requiring
electroconvulsive therapy, medically unstable, having active substance
abuse (except nicotine) were excluded.
For this study, suicidal behavior was defined as a “a non habitual act
with nonfatal outcome that the individual, expecting to, or taking the risk to
die or to inflict bodily harm, initiated and carried out with the purpose of
bringing about wanted changes”.
3. Instruments and techniques
Clinical assessment by a qualified psychiatrist using International
Classification of Diseases (ICD-10) criteria to evaluate for psychiatric
disorders and to rule out severe depression with psychotic symptoms,
psychotic disorders, substance use disorders (except nicotine) and se­
vere cognitive impairment. In those subjects where a clinical diagnosis
of personality disorder was considered, the International Personality
Disorder Examination(Loranger et al., 1997)(IPDE) was administered. A
socio-demographic and clinical proforma that has been specially devised
and used in the specialty clinic was used to record the subjects’ de­
mographics, social situation and clinical details including stressors and
details regarding the attempt.
3.1. Other instruments used include
1. The Columbia Suicide Severity Rating scale (CSSRS) (Kelly et al., 2011)
This scale rates an individual’s degree of suicidal ideation and
identifies behaviours, which may be indicative of an individual’s
intent to commit suicide. The C-SSRS intensity subscale was
moderately correlated with the worst-point score on the Scale for
Suicide Ideation (r = 0.52, p < 0.001) with a reliability of 0.89(67)
2. The Beck’s Depression Inventory (BDI) (Beck, Steer, Ball, Ranieri)were
used to evaluate depressive symptoms
3. Assessment of brain metabolism was done using F-18 Fluoro-Deoxy-
Glucose Positron Emission Tomography (FDGPET): 18F-FDG, a
radio-labeled sugar analogue can be injected and the regional brain
distribution can be detected with a PET camera. Participants were
fasting for at least 6 h prior to the scan, had not consumed/smoked
tobacco for the last 8 h and had a blood glucose level of <150
mgdl− 1. During the procedure, the patient was lying quietly, with
eyes closed. An average dose of 185 MBq (111–222) of 18F, 2-fluoro,
2-deoxy-glucose (18F- FDG) was injected. Acquisition was carried out
approximately 45 min to 1 h after the injection. Emission scans of 70
slices were obtained parallel to the cantho-meatal line from vertex to
the neck. The images were reconstructed and reformatted into 35
trans-axial slices of 4.25 mm thickness. Regional glucose metabolism
was examined in predetermined Regions of Interest (ROI) – elliptical
ROIs for cortical and sub-cortical structures. During qualitative
assessment, it was observed that in majority of the subjects, the oc­
cipital lobes showed maximum 18FDG uptake. As most studies
examining neurobiology of suicidal behaviors have failed to report
any changes in the occipital lobe in these subjects(), (Heeringen
et al., 2014), () results related to the occipital regions were not re­
ported. The regional activity in a 47 clusters were expressed as
average of counts per second per pixel resulting in dynamic imaging
for rate calculation. Regions of interest considered included the
following:
• Prefrontal and frontal regions (right and left): including anterior
cingulate, medial frontal (ventromedial), super frontal (part of
dorsolateral prefrontal cortex), inferior frontal (orbitofrontal)
region,
• Temporal (right, left): including anteriomedial and posteriomedial
(including the insula, hippocampus and parahippocampal re­
gions), superiolateral and inferiolateral regions, posterior cingu­
late cortex
S. Parkar et al. Journal of Psychiatric Research 146 (2022) 210–218

• Parietal (left and right): including superior parietal regions and Table 1
parieto-temporal lobes Socio-demographic details of the sample.
• Basal ganglia and thalamus (right and left): including caudate Sociodemographic Total Depressed Non-depressed group
nucleus and lentiform nucleus parameters Sample group Mean (SD)/N(%)
• Brain stem including midbrain, pons, cerebellum (left, right lobes Mean (SD)/N
(%)
and vermis)
Total number of subjects 33 18 15
Limbic regions were subsumed in the respective lobes. Mean age (in years) 25.33 28.0 (11.72) 22.13 (6.26)
(9.94)
Mean asymptomatic controls: The rCMglu in terms of ratio of counts Gender:
per pixel normalized to the whole brain for each patient was compared Male 11 6(33.3%) 5(33.3%)
using the Neuro-Q software to a pre-existing database of rCMglu in the (33.3%)
corresponding ROI in normal standard population (generated using 50 female 22 12 (66.7%) 10 (66.7%)
(66.7%)
normal subjects), referred from here on as the Mean Asymptomatic
Marital status:
Control (MAC). single 20 10 (55.6%) 10 (66.7%)
(60.61%)
4. Statistical analysis married 13 8 (44.5%) 5 (33.3%)
(39.39%)
Religion: Hindu 31 18(100%) 13 (86.7%)
Analysis of resting cerebral glucose metabolism using F-18 FDG (93.93%)
(Fluoro-Deoxy-Glucose) PET (Positron Emission Tomography) scan of Education
the brain was done with the help of the Neuro-Q software which com­ 1. Illiterate -primary school 2 2 (11.11%) 0 (0%)
pares the brain glucose metabolism in regions) in the patient group to (06.06%)
2. Middle- high school 14 6 (33.33%) 8 (53.33%)
the Mean Asymptomatic Control (MAC) which was used as a reference
(42.42%)
for comparison. The variables generated were analyzed using the Sta­ 3. Post high school 17 10 (55.56%) 7 (46.67%)
tistical Program for Social Science (SPSS Version 16) for Windows (Inc. diploma/graduation (51.52%)
Statistics, 2009). Descriptive analysis was carried out using mean and Employment status
standard deviation with range for continuous variables and frequency Unemployed 23 13 (72.2%) 10 (66.7%)
(69.69%)
and percentages for discrete variables. Student’s T test was used to Employed 10 5 (27.8%) 5 (32.4%)
assess the differences in the quantitative data between groups and the (30.3%)
associations of the involved variables. Pearson’s Product Moment was Income
used to assess the association between the various variables. Below Rs 10,000/month 10 6 (33.33%) 4 (26.66%)
(30.3%)
Above Rs 10,000/month 23 12 (66.7%) 11 (73.33%)
5. Results (69.7%)
Family type:
For this study, 58 subjects were approached, of which 5 refused to Nuclear 20 10 (55.6%) 10 (66.7%)
participate in the study. On further evaluation on inclusion and exclu­ (60.6%)
Joint 13 8 (44.5%) 5 (33.3%)
sion criteria, 4 subjects were excluded because they were receiving (39.39%)
psychotropic medications, 6 subjects were excluded as they were
deemed to require electroconvulsive therapy as per their clinical status,
2 subjects were excluded as they had psychosis and substance use and 8 (11.1% in depressed group and 20% in non depressed group).
females were excluded as they had their menstrual period more than one The commonest stressful event/trigger immediately prior to the
month before presentation. This resulted in a sample of 33 subjects. On suicide attempt overall was interpersonal discord (66.6%) and this was
clinical evaluation 18 subjects were identified as having a depressive also the most frequent in the depressed and non depressed group. In
disorder as per ICD 10 criteria. Surprisingly, of the other 15 subjects, 13 depressed group the second most frequent trigger was stress due to ed­
did not have any diagnosable psychiatric disorder nor did they have ucation (22.2%), while in the non depressed group, the reason was
personality traits that were severe enough to warrant the diagnosis of a marital disharmony (13.3%). Surprisingly, financial stress was present
personality disorder. One male patient was diagnosed with antisocial in only one patient from our sample. Family history of mental illness was
personality disorder and one female patient was diagnosed with present in 12 subjects (36.4%), it was significantly lower in the non-
borderline personality disorder. In view of this, results have been pre­ depressed group as compared to the depressed group (Chi square 5.4,
sented for the whole sample, as well as for the depressed subjects and the p = 0.02). Also, family history of suicide was present in 5 subjects and
non depressed subjects separately. was significantly higher in the depressed group than the non depressed
(Chi square 3.57, p = 0.05). Only 3 subjects had repeated attempts. As
6. Socio-demographic and clinical profile expected, the BDI total score were more in the depressed subgroup of
subjects as compared to the total sample and the non depressed group.
As shown in table-1, the overall mean age of the sample was 25.33 This was also true regarding the intensity of suicidal ideations, the
(Standard deviation (SD):9.94), with mean age in the depressed group lethality of the suicidal attempt.
being 28 years (SD: 11.72) and for the non depressed group was 22.13
years (SD 6.26). Overall, there were 11 males and 22 females in our 7. FDG PET findings
sample and the male: female ratio in both the groups was 1:2. Around
70% of our sample was unemployed but this group includes housewives Forty regions were identified to study brain activity in the subjects
as well. Eighty percent of the subjects belonged to the upper-lower socio with suicidal behaviour. Fig. 1 provides illustrative images from each
economic class as per Kuppuswamy (Beck, Steer, Ball, Ranieri) classifi­ group demonstrating the uptake in various brain regions. These are
cation of socio economic status. images from MAC database and from single subjects of each group.
With regards to the clinical characteristics, as seen in Table 2, the Means and standard deviation of the ratio of average counts per
most common method of attempt at suicide in both the groups was pixel/whole brain counts of each region (indicative of rCMglu) with
poisoning (88.9% in depressed group and 80% in non depressed group). regards to the total sample, depressed and non depressed subjects are
Overdose of medication was the other method employed in our sample given in Table 3.

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S. Parkar et al. Journal of Psychiatric Research 146 (2022) 210–218

Table 2 of the brain. Further, the rCMglu of the MAC was compared with the
Clinical features of the suicide attempt. depressed subgroup and the non-depressed subgroup (Table 3).
Clinical features Total Depressed Non-depressed group 2. Comparison of the rCMglu between the depressed and the non-
Sample group Mean (SD)/N(%) depressed subgroup:Between the depressed and the non depressed
Mean (SD)/ group, significant differences were identified in the left medial
N (%)
frontal region (t value − 2.36, p = 0.024), right Broca’s region (t
Method of attempt value − 2.71, p = 0.03) and the left superiolateral temporal region (t
Poisoning 28 16 (88.9%) 12 (80%) value − 2.61, p = 0.014). These differences were however not sig­
(84.84%)
Drug Overdose 5 2 (11.1%) 3 (30%)
nificant at p values of <0.01.
(15.15%) 3. Correlation between the rCMglu and CSSRS intensity score: In order to
Psychosocial Triggers further understand the neurobiological correlates, correlation anal­
Education 5 4 (22.2%) 1 (6.7%) ysis was undertaken between the regions of brain metabolism and
(15.15%)
the CSSRS total score (Table 4).
Interpersonal discord 22 11 (61.1%) 11 (73.3%)
(66.67%) As can be seen in Table 4, the CSSRS total intensity score was
Marital disharmony 4 2 (11.1%) 2 (13.3%) inversely correlated with the rCMglu in the left medial frontal cortex,
(12.12%) the left Broca’s region, the left superior lateral temporal regions and
Financial 1 (3.03%) 0 (0%) 1 (6.7%) directly correlated with rCMglu in the right cerebellum. Of note, there
Others 1 (3.03%) 1 (5.6%) 0 (0%)
Family history
was no significant correlation between the CSSRS intensity score and the
Mental Illness 12 9 (50%) 3 (20%) rCMglu in the inferior frontal cortex.
(36.36%)
Completed Suicide 5 5 (38%) 0 (0%) 8. Discussion
(15.15%)
CSSRS ideation
-Active suicidal ideation 4 1 (5.55%) 3 (20%) We conducted the FDG PET while the participant was lying quietly,
(without plan or intent) (12.12%) unengaged in specific cognitive tasks. As a result, the rCMglu measured
-Active suicidal ideation with 23 11 (61.11%) 12 (80%) provided information about the default mode network (DMN) of the
intent (without plan) (69.69%) brain, a group of brain regions that are activated during self-referential
-Active suicidal ideation with 6 6 (33.33%) 0 (0%)
mentation. The functions of this network include baseline thinking or
specific plan and intent (18.18%)
CSSRS intensity 11.91 14.50 (2.68) 8.80 (2.00) rumination through remembering the past, envisioning future events,
(3.72) and considering the perspectives of others(Buckner and Carroll, 2006),
CSSRS lethality 1.878 2.22 (0.64) 1.47 (0.63) which have been identified as having a significant impact of suicidal
(0.73)
thoughts and behaviours (Morrison and O’Connor, 2008). Additionally,
BDI total 15.39 20.50 (5.23) 9.26 (4.04)
(7.34) as psychotropic medications are known to affect cerebral metabolism,
we included only a drug naive population to decrease the confounding of
results.
1.Comparative differences between rCMglu of MAC and total sample, The socio-demographic characteristics of our sample of 33 adults
depressed and non-depressed subjects: Comparison using Student’s t- were in keeping with other Indian studies on subjects with suicidal at­
test was done between the sample’s mean rCMglu and that of tempts. (), (Das et al., 2008), (Latha et al., 1996), (Srivastava et al.,
asymptomatic normal controls whose data was already present in the 2004), (Narang et al., 2000), (Sharma, 1998), (Sarkar et al., 2006), () All
software database. Given the number of variables, a p value of <0.01 our subjects attempted suicide by consuming poison or overdosing on
was considered to be significant so as to decrease the alpha error. As medication, a method frequently used in other Indian studies on
can be seen in Table 3, brains of individuals with suicidal behaviours attempted suicide. (), [ 29] Family history of mental illness and suicide
have differences in their rCMglu. Most of these differences were seen was significantly more in the depressed group in comparison to the non
in the frontal and temporal cortices, in comparison to other regions depressed group, indicating a possible genetic contribution to mental
illness and suicidal behavior (Lemonde et al., 2003). The total score on

Fig. 1. Representative PET images from single subjects illustrating differences in regional resting glucose uptakes among various brain regions.

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S. Parkar et al.
Fig. 2. Possible effects of changes in brain metabolism on its function in relation to suicidal behaviours.
the BDI was higher for the depressed group (20.50 ± 5.3) indicating the
presence of moderate depression, while it was lower in the non
depressed group (9.26 ± 4.04), indicating that this group had minimal
depressive symptoms. (Beck et al., 1996) On evaluation on the CSSRS
ideation domain, only 6 subjects had suicidal ideations with plans to end
their life, yet around 88% of the sample had active suicidal ideation with
intent to die at the time of assessment. This indicates that our sample
was at high degree suicidal ideation with an intent to die, and were also
at risk of repeating the suicidal act (Posner et al., 2007). Additionally,
the score on the CSSRS intensity was 11.81 ± 3.72 indicating moderate
intensity (Posner et al., 2007) of suicidal ideation in the sample, though
this was greater in the depressed subgroup. Further, the mean lethality
score of the sample was 1.87 ± 0.73 indicating minor to moderate
lethality of the act. Again, this was more in the depressed group as
compared to the non depressed subgroup.
The ratio of counts per pixel to the whole brain of the different brain
regions on the 18FDG PET revealed the differences in rCMglu in subjects
with suicidal behaviours compared with asymptomatic controls. When
compared to asymptomatic controls, the whole sample demonstrated
relative decreased rCMglu in the right inferior frontal regions, the left
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Journal of Psychiatric Research 146 (2022) 210–218
Broca’s region, the left inferiolateral temporal region, the left superio­
lateral temporal region, the right inferior parietal and parietotemporal
region and the bilateral posterior cingulate region. The depressed group
showed additional regions of low rCMglu in left anterior cingulate cor­
tex. The non depressed group did not have significantly reduced rCMR in
the right inferior frontal region, left Broca’s region or right parietal
cortex, although there was a trend towards significance in all these re­
gions. Current day neuroimaging studies have shown varied results and
some of our findings are in concordance to them while others have
contradictory evidence. In FDG PET study on subjects with suicidal
behaviours and major depression, Sublette et alfound rCMRglu was
lower in a right inferior prefrontal cortical region, but found increased
activity in the left anterior cingulate cortex (Sublette et al., 2013).
However, as we looked at the ratio of brain activity to normalized brain
activity, these findings cannot be appropriately compared. Another FDG
PET study that looked at borderline subjects found that after placebo
administration, borderline patents had lower cerebral perfusion in the
inferior frontal regions bilaterally and left superior temporal gyrus
(Soloff et al., 2000). In a SPECT study that looked at subjects with
completed suicide with major depression, Willeumier et al.
S. Parkar et al. Journal of Psychiatric Research 146 (2022) 210–218

Table 3
Average counts per pixel normalized to the whole brain in ROIs in subjects with suicidal behavior: total sample, depressed and non depressed subgroup.
Brain region Mean asymptotic Total MAC vs Total sample Depressed MAC vs Non depressed MAC vs Not depressed
controls (MAC) sample t value, (p) group Depressed group t value, (p)
t value, (p)

Prefrontal and frontal regions

Superior frontal cortex left 0.977 (0.048) 1.030 5.27, p < 0.0001 1.025 (0.029) 3.977, p = 1.037 (0.033) 4.51, p < 0.0001
(0.032) 0.0002
Superior frontal cortex right 1.009 (0.053) 1.053 4.2, p<0.0001 1.045 (0.033) 4.53, 1.062 (0.034) 3.33, p ¼ 0.009
(0.035) p<0.0001
Mid frontal cortex left 1.123 (0.025) 1.125 0.21, p = 0.83 1.126 (0.033) 0.39, p = 0.69 1.122 (0.064) − 0.09, p = 0.9
(0.049)
Mid frontal cortex right 1.123 (0.031) 1.141 1.81, p = 0.07 1.136 (0.049) 1.04, p = 0.19 1.148 (0.070) 1.97, p = 0.05
(0.059)
Inferior frontal cortex left 1.120 (0.036) 1.108 − 1.31, p = 0.19 1.099 (0.053) − 1.05, p = 1.117 (0.036) − 0.28, p = 0.77
(0.047) 0.06
Inferior frontal cortex right 1.159 (0.032) 1.111 ¡2.75, p ¼ 0.007 1.123 (0.062) ¡3.13, p ¼ 1.096 (0.257) − 1.72, p = 0.09
(0.177) 0.002
Medial frontal cortex left 1.055 (0.034) 1.102 5.34, p<0.0001 1.085 (0.043) 2.99, p ¼ 1.121 (0.041) 5.68, p<0.0001
(0.046) 0.004
Medial frontal cortex right 1.066 (0.037) 1.118 2.65, p ¼ 0.009 1.089 (0.034) 2.30, p = 0.02 1.153 (0.188) 3.13, p ¼ 0.002
(0.131)
Anterior cingulate cortex left 1.123 (0.36) 1.122 − 0.13, p = 0.89 1.062 (0.031) ¡6.37, 1.126 (0.033) 0.287, p = 0.77
(0.030) p<0.0001
Anterior cingulate cortex right 1.047 (0.032) 1.006 − 0.77, p = 0.44 1.120 (0.027) 8.62, 0.926 (0.55) − 1.5, p = 0.1
(0.375) p<0.0001
Broca’s area left 1.195 (0.03) 1.160 ¡4.8, p<0.0001 1.150 (0.036) ¡5.16, 1.172 (0.032) − 2.56, p = 0.012
(0.036) p<0.0001
Broca’s area right 1.111 (0.031) 1.114 0.30, p = 0.7 1.095 (0.065) − 1.37, p = 0.1 1.137 (0.039) 2.86, p ¼ 0.009
(0.058)
Temporal regions
Inferiolateral anterior 0.928 (0.047) 0.908 − 1.61, p = 0.10 0.899 (0.028) − 2.02, p = 0.921 (0.088) − 0.40, p = 0.6
temporal cortex left (0.063) 0.02
Inferiolateral anterior 0.897 (0.03) 0.932 5.17, p<0.0001 0.931 (0.029) 5.19, 0.934 (0.026) 5.2, p<0.0001
temporal cortex right (0.028) p<0.0001
Inferiolateral posterior 0.98 (0.03) 0.950 ¡4.69, p<0.0001 0.959 (0.026) ¡3.10, p ¼ 0.940 (0.074) ¡2.63, p ¼ 0.01
temporal cortex left (0.052) 0.002
Inferiolateral posterior 0.988 (0.03) 1.003 1.81, p = 0.07 1.005 (0.027) 1.67, p = 0.2 1.000 (0.026) 1.37 p = 0.3
temporal cortex right (0.027)
Posteriomedial temporal 0.895 (0.03) 0.900 0.59 p = 0.7 0.911 (0.025) 2.02, p = 0.04 0.887 (0.059) 0.73, p = 0.4
cortex left (0.045)
Posteriomedial temporal 0.857 (0.02) 0.893 7.39, p<0.0001 0.895 (0.026) 6.37, 0.892 (0.020) 5.94, p<0.0001
cortex right (0.024) p<0.0001
Anteriomedial temporal cortex 0.734 (0.033) 0.736 0.26, p = 0.7 0.741 (0.039) 0.73, p = 0.9 0.730 (0.030) − 0.45, p = 0.6
left (0.036)
Anteriomedial temporal cortex 0.720 (0.35) 0.722 0.26, p = 0.7 0.724 (0.028) 0.4, p = 0.6 0.720 (0.030) 0.00
right (0.029)
Posterior cingulate left 1.274 (0.038) 1.202 ¡7.92, p<0.0001 1.194 (0.052) ¡6.91, 1.211 (0.031) ¡5.84, p<0.0001
(0.044) p<0.0001
Posterior cingulate right 1.197 (0.033) 1.167 ¡3.76, p ¼ 0.003 1.159 (0.043) ¡3.86, p ¼ 1.177 (0.032) − 2.07, p = 0.04
(0.039) 0.002
Superior lateral temporal 1.108 (0.023) 1.070 ¡6.04, p<0.0001 1.058 (0.022) ¡8.01, 1.085 (0.037) ¡2.91, p ¼ 0.005
cortex left (0.033) p<0.0001
Superior lateral temporal 1.076 (0.024) 1.068 − 1.43, p = 0.15 1.065 (0.026) − 1.63, p = 0.1 1.071 (0.026) 0.69, p = 0.4
cortex right (0.026)
Parietal cortex
Parietal cortex left 0.920 (0.047) 0.899 − 2.02, p = 0.04 0.897 (0.043) − 1.9, p = 0.07 0.901 (0.047) − 1.47, p = 0.14
(0.045)
Parietal cortex right 0.969 (0.046) 0.927 ¡3.90, p ¼ 0.0002 0.922 (0.037) ¡3.89, p ¼ 0.934 (0.065) − 2.34, p = 0.02
(0.051) 0.0002
Parietotemporal left 1.0872 (0.033) 1.068 − 2.21, p = 0.02 1.060 (0.053) − 1.81, p = 1.077 (0.032) − 1.37, p = 0.17
(0.045) 0.07
Parietotemporal cortex right 1.103 (0.031) 1.063 ¡4.47, p<0.0001 1.057 (0.052) ¡4.46, 1.070 (0.043) ¡3.91, p ¼ 0.001
(0.049) p<0.0001
Basal ganglia and thalamus
Caudate nucleus left 0.967 (0.07) 0.986 1.36, p = 0.1 0.979 (0.042) 0.68, p = 0.4 0.995 (0.052) 1.67, p = 0.1
(0.048)
Caudate nucleus right 0.969 (0.09) 1.002 1.95, 0.993 (0.033) 1.67, p = 0.2 1.013 (0.052) 2.57, p = 0.07
(0.044) = 0.05
Lentiform nucleus left 1.20(0.08) 1.168 1.9, p = 0.4 1.171 (0.052) − 1.47, p = 0.1 1.164 (0.060) − 1.60 p = 0.11
(0.056)
Lentiform nucleus right 1.161 (0.07) 1.151 − 0.69, p = 0.4 1.157 (0.051) − 0.22, p = 0.8 1.143 (0.055) − 0.91, p = 0.3
(0.053)
Thalamus left 1.012 (0.07) 1.032 1.35, p = 0.17 1.030 (0.049) 0.01, p = 0.3 1.033 (0.069) 1.06, p = 0.2
(0.059)
Thalamus right 1.038 (0.07) 1.038 0.00 1.040 (0.044) 0.11, p = 0.9 1.036 (0.060) − 0.12, p = 0.9
(0.052)
(continued on next page)

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S. Parkar et al. Journal of Psychiatric Research 146 (2022) 210–218

Table 3 (continued )
Brain region Mean asymptotic Total MAC vs Total sample Depressed MAC vs Non depressed MAC vs Not depressed
controls (MAC) sample t value, (p) group Depressed group t value, (p)
t value, (p)

Midbrain and brainstem

Midbrain 0.711 (0.04) 0.739 2.91, p ¼ 0.004 0.745 (0.038) 3.13, p ¼ 0.732 (0.056) 1.61, p = 0.1
(0.047) 0.002
Cerebellum left 0.895 (0.029) 0.860 − 1.49, p = 0.13 0.895 (0.057) 0.00 0.819 (0.229) − 2.32, p = 0.02
(0.162)
Cerebellum right 0.886 (0.035) 0.897 1.22, p = 0.2 0.909 (0.050) 2.12, p = 0.03 0.883 (0.037) 0.28, p = 0.7
(0.047)
Vermis 0.895 (0.042) 0.910 1.09, p = 0.2 0.927 (0.057) 2.51, p = 0.013 0.890 (0.103) − 0.27, p = 0.78
(0.082)
Pons 0.641 (0.02) 0.661 0.63 p = 0.2 0.660 (0.060) 1.93, p = 0.05 0.662 (0.105) 1.48, p = 0.1
(0.083)

temporal cortex, right posteriomedial temporal cortex (which includes

Table 4
Relationship between rCMglu and CSSRS intensity score.
Brain region Correlation coeffecient
Medial frontal cortex left − 0.562 (0.001)
Broca’s area left − 0.454 (0.009)
Superior lateral temporal cortex left − 0.461 (0.007)
Cerebellum right 0.431 (0.01)
Data is shown as correlation coefficients: Pearson’s r, p value.
demonstrated hypoperfusion in the inferior frontal cortex, subgenual
frontal cortex (including the anterior cingulate cortex), the right
supraparietal cortex, the inferiolateral temporal lobe, the left superior
temporal cortex and the left superior parietal cortex, findings which are
similar to our study (Willeumier et al., 2011). Our findings can be better
understood in light of the functions of the involved brain regions. The
posterior cingulate cortex is part of the limbic system and is associated
with discriminative learning and affective response as well as recall of
autobiographical memories (Maddock et al., 2001). Along with the pa­
rietal cortex, the posterior cingulate cortex forms an essential part of the
default mode network. Impairments in metabolism in this region may
thus affect the baseline ‘state’ of the entire brain. The inferior frontal
cortex is essentially modulates stimulus reward association and rein­
forcement of behaviour as per reward and punishment (AlexopoulosGS
et al., 2008). The Broca’s region (left more than right) is involved in
verbal fluency (Dronkers et al., 2007), and impaired metabolism in this
region may affect the patient’s ability to verbalize his/her underlying
mental state. In addition to verbal fluency, the left Broca’s region is also
involved in discrimination of ambiguous verbal content, while the right
Broca’s region is involved in identifying ambiguous facial expressions
and inhibition of learnt responses (Rodd et al., 2010; Nishitani et al.,
2005). The left inferiolateral temporal cortex heavily influences visual
processing, connects visual objects with appropriate autobiographical
memories (Maddock et al., 2001) and discriminates ambiguous verbal
stimuli, while the left superiolateral temporal region affects social
cognition and including the identification of facial emotions (Gross,
2007), which has been found to be impaired in subjects with suicidal
behaviours (Jou et al., 2010). The right temporoparietal region is a key
node of the social brain, whose tasks include mentalizing and self
perspective (Szanto et al., 2012). The anterior cingulate cortex is
involved in conflict detection, emotional evaluation of error, and it is
connected to brain structures that regulate mood, emotional valence of
thought and autonomic responses. Hypo metabolism of left anterior
cingulate cortex is well documented in depression(Jean and Lamm,
2007) and this explains the presence of reduced rCMglu in our depressed
subgroup. The impact of hypo metabolism in these regions is summar­
ised in Fig. 1. Specifically, due to these changes, patient would have
more problems in the social domain. Most of our subjects had inter­
personal stressors as triggers for their attempt illustrates this.
Our sample also showed increased rCMglu in bilateral superior
frontal cortex, bilateral medial frontal cortex, right inferiolateral
the parahippoccampus) and the midbrain. In addition to this, there was
an increase in the rCMglu in the right anterior cingulate cortex in
depressed group and right Broca’s region in the non depressed group.
Other studies have reported have reported increased brain metabolism
in the medial frontal cortex(Sublette et al., 2013), the hippocampus and
right parahippocampus (Soloff et al., 2000). Increased cerebral meta­
bolism int the right anterior cingulate cortex has been seen in studies
that look at depression and sadness (Hamani et al., 2011), self generated
emotional states (Mayberg et al., 1999) and in depressed subjects with
suicidality (Damasio et al., 2000). Increased cerebral metabolism in the
midbrain has also been seen in subjects with similar samples (Amen
et al., 2009). Again, to understand our findings, we must first look at
functional neuroanatomy. The parahippocampal cortex which is part of
the limbic system, which plays a major role in modulation of negative
affective states and experienced mental pain (Reisch et al., 2010). The
midbrain includes the dorsal raphe nucleus, locus coeruleus and the
tegmentum, and projections from these structures play a major role in
affective modulation. The superior frontal gyrus includes the dorsolat­
eral prefrontal cortex which is involved in planning, executive function
and also in behavioural inhibition, which is thought to reflect variation
in the sensitivity of a distributed neural system responsible for gener­
ating anxiety and organizing defensive responses to threat and punish­
ment. Individuals with greater tonic resting activity in the dorsolateral
prefrontal cortex have greater behavioural inhibition, including
threat-induced negative affect (Shackman et al., 2009). Increased ac­
tivity in the dorsolateral prefrontal cortex may also occur as a result of
the brain trying to find a ‘way out’. At the end, attempted suicide is still a
goal directed behaviour, maladaptive though it may be. Evidence has
shown that planning and acting out suicidal impulses in response to
mental pain, was associated with increased activity in the frontal cortex
(Reisch et al., 2010). The medial frontal cortex is involved in cognitive
processes including detection of unfavourable outcomes, response er­
rors, response conflict, and decision uncertainty (Ridderinkhof et al.,
2004). Given the underlying deficits delineated previously in the dis­
cussion, these impairments would further destabilize an already tenuous
mental state (See Fig. 2).
Of note, our study found no statistically significant difference be­
tween the rCMglu of brain regions between the depressed and non
depressed groups indicates that the clinical differences between these
two subgroups does not hold true at the neurobiological level, at least in
the resting state of the brain. This becomes important as no studies (that
we are aware of) have directly compared the brain metabolism of these
two groups. Non depressed individuals who attempt suicide are
frequently given less clinical priority and their attempts are often
interpreted as manipulative or impulsive. Our results question this
previously held notion, as the non depressed brain seems to have a
significant number of changes in brain metabolism, most of which are
similar to depressed individuals.
Correlational analysis revealed that increased intensity of the sui­
cidal attempt correlated with decreased rCMglu in the left medial frontal

216
S. Parkar et al.
cortex, Broca’s region, superiolateral temporal cortex and with
increased rCMglu in the right cerebellum. In addition to its motor
functions, the cerebellum also has a role in the cognitive and affective
state of the individual[53] (Schmahmann and Sherman, 1998),with some
evidence that indicates a greater role of the right side.[55]Similarly,
reduced perfusion of the left medial frontal cortex, Broca’s region and
superiolateral temporal regions may also increase severity of the suicidal
attempt due to reasons mentioned previously.
While interpreting the results of this study, the following
IMPLICATIONS.
The implications of our study are manifold. It brings into sharp focus
that individuals with suicidal behaviours have impairment in the brain
functioning especially in the default mode network. No longer can sui­
cidal behaviour be viewed solely as a psychological event, the role of
biological changes cannot be ignored. Additionally, there isn’t just one
abnormality; there are a number of brain functional changes, all of
whom have downstream repercussions leading to the suicidal attempt.
Understanding and quantifying these abnormalities would help us
further identify individuals more at risk for suicidal behaviours, thereby
initiating the era of preventive medicine in psychiatry. Willeumier et al.
(2011) have already shown that changes in brain perfusion can predate
suicidal behaviours by as much as 3 years, making a case for the use of
functional neuroimaging for predicting suicidal behavior. Finally, given
that depressed and non depressed subjects’ brains have so many func­
tional changes that are common, that clinicians should realize the
distinction between these groups is arbitrary, and not well supported by
literature. Non depressed subjects who attempt suicide deserve as much
and as serious clinical attention as other groups.
Limitations
While we included consecutive subjects, we did not have a large
representation of subjects with personality disorders or anxiety disor­
ders. Also, since our sample had low to moderate lethality of their at­
tempts, the correlation between brain metabolism and lethality of the
attempt could not be assessed. Additionally, we studied subjects within
72 h of their attempted suicide. Hence, it would not be possible for us to
comment if the changes in brain metabolism are due to the mental state
of the individual or are more inherent ‘biological traits’ of the
individual.
Declaration of competing interest
None to declare.
References
AlexopoulosGS, Gunning FM., Latoussakis, V., Kanellopoulos, D., Murphy, C.F., 2008.
Anterior cingulate dysfunction in geriatric depression. Int. J. Geriatr. Psychiatr. 23
(4), 347–355.
Amen, D.G., Prunella, J.R., Fallon, J.H., Amen, B., Hanks, C., 2009. A comparative
analysis of completed suicide using high resolution brain SPECT imaging.
J. Neuropsychiatry Clin. Neurosci. 21, 430–439.
Audenaert, K., Peremans, K., Goethals, I., Van Heeringen, C., 2006. Functional imaging,
serotonin and the suicidal brain. Acta Neurol. Belg. 106, 125–131.
Barraclough, B., Bunch, J., Nelson, B., Sainsbury, P., 1974. A hundred cases of suicide:
clinical aspects. Br. J. Psychiatry 125, 355–373.
Beck, A.T., Steer, R.A., Ball, R., Ranieri, W., 1996. Comparison of Beck depression
inventories -IA and -II in psychiatric outpatients. J. Pers. Assess. 67, 588–597.
Buckner, R.L., Carroll, D.C., 2006. Self-projection and the brain. Trends Cognit. Sci. 11
(2), 1364–6613.
Damasio, A.R., Grabowski, T.J., Bechara, A., Damasio, H., Ponto, L.B., Parvizi, J., 2000.
Subcortical and cortical brain activity during the feeling of self-generated emotions.
Nat. Neurosci. 3, 1049–1056.
Das, P.P., Grover, S., Avasthi, A., Chakrabarti, S., Malhotra, S., Kumar, S., 2008.
Intentional self-harm seen in psychiatric referrals in a tertiary care hospital. Indian J.
Psychiatr. 50, 187–191.
De Leo, D., Burgis, S., Bertolote, J., Kerkhof, A., Bille-Brahe, U., 2006. Definitions of
suicidal behavior lessons learned from the WHO/EURO multicentre study. Crisis 27,
4–15.
217
Journal of Psychiatric Research 146 (2022) 210–218
Dronkers, N.F., Plaisant, O., Iba-Zizen, M.T., Cabanis, E.A., 2007. Paul Broca’s historic
cases: high resolution MR imaging of the brains of Leborgne and Lelong. Brain 130
(5), 1432–1441.
Gross, C.G., 2007. Single neuron studies of inferior temporal cortex. Neuropsychologia
46, 841–852.
Hamani, C., Mayberg, H., Stone, S., Laxton, A., Haber, S., Lozano, A.M., 2011. The
subcallosal cingulate gyrus in the context of major depression. Biol. Psychiatr. 69
(4), 301–308.
Heeringen, K.V., Bijttebier, S., Desmyter, S., Vervaet, M., Baeken, C., 2014. Is there a
neuroanatomical basis of the vulnerability to suicidal behavior? A coordinate-based
meta-analysis of structural and functional MRI studies. Front. Hum. Neurosci. 8, 824.
Hendin, H., Phillips, M., Vijayakumar, M., Pirkis, J., Wang, H., Yip, P., 2008. Suicide and
Suicide Prevention in Asia. World Health Organization.
SPSS Inc, 2009. PASW Statistics for Windows. SPSS Inc, Chicago, Version 18.0.
Jean, D., Lamm, C., 2007. The role of the right temporoparietal junction in social
interaction: how low-level computational processes contribute to meta-cognition.
Neuroscientist 13 (6), 580–593.
Jou, R.J., Minshew, N.J., Keshavan, M.S., Vitale, M.P., Hardan, A.Y., 2010. Enlarged
right superior temporal gyrus in children and adolescents with autism. Brain Res.
1360, 205–212.
Kelly, P., Gregory, B., Barbara, S., David, B., Kseniya, Y., Maria, O., 2011. The
Columbia–suicide severity rating scale: initial validity and internal consistency
findings from three multisite studies with adolescents and adults. Am. J. Psychiatr.
168 (12), 1266–1277.
Klonsky, E.D., May, A., 2010. Rethinking impulsivity in suicide. Suicide Life-Threatening
Behav. 40, 612–619.
Latha, K.S., Bhat, S.M., D’Souza, P., 1996. Suicide attempters in a general hospital unit in
India: their sociodemographic and clinical profile-emphasis on cross-cultural
aspects. Acta Psychiatr. Scand. 94, 26–30.
Lemonde, S., Turecki, G., Bakish, D., Lisheng, D., Hrdina, P., Bown, C., et al., 2003.
Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism
associated with major depression and suicide. J. Neurosci. 23 (25), 8788–8799.
Loranger, A.W., Janca, A., Sartorius, N., 1997. Assessment and Diagnosis of Personality
Disorders: the ICD-10 International Personality Disorder Examination (IPDE).
Cambridge University Press.
Maddock, R.J., Garrett, A.S., Buonocore, M.H., 2001. Remembering familiar people: the
posterior cingulate cortex and autobiographical memory retrieval. Neuroscience 104
(3), 667–676.
Mayberg, H.S., Liotti, M., Brannan, S.K., McGinnis, S., Mahurin, R.K., Jerabek, P.A.,
et al., 1999. Reciprocal limbic-cortical function and negative mood: converging PET
findings in depression and normal sadness. Am. J. Psychiatr. 156 (5), 675–682.
Morrison, B.A., O’Connor, R.C., 2008. A systematic review of the relationship between
rumination and suicidality. Suicide Life-Threatening Behav. 38 (5), 385–523.
Narang, R.L., Mishra, B.P., Nitesh, M., 2000. Attempted suicide in Ludhiana. Indian J.
Psychiatr. 42, 83–87.
Nishitani, N., Schürmann, M., Amunts, K., Hari, R., 2005. Broca’s region: from action to
language. Physiology 20, 60–69.
Oquendo, M.A., Placidi, G.P.A., Malone, K.M., Campbell, C., Keilp, J., Brodsky, B., et al.,
2003. Positron emission tomography of regional brain metabolic responses to
serotonergic challenge and lethality of suicide attempts in major depression. Arch.
Gen. Psychiatr. 60, 14–22.
Posner, K., Oquendo, M.A., Gould, M., Stanley, B., Davies, M., 2007. Columbia
Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal
events in the FDA’s pediatric suicidal risk analysis of antidepressants. Am. J.
Psychiatr. 164 (7), 1035–1043.
Radhakrishnan, R., Andrade, C., 2012. Suicide: an Indian perspective. Indian J.
Psychiatr. 54 (4), 304–319.
Reisch, T., Seifritz, E., Esposito, F., Wiest, R., Valach, L., Michel, K., 2010. An fMRI study
on mental pain and suicidal behavior. J. Affect. Disord. 126 (1–2), 321–325.
Ridderinkhof, K.R., Ullsperger, M., Crone, E.A., Nieuwenhuis, S., 2004. The role of the
medial frontal cortex in cognitive control. Science 306, 443–447.
Rodd, J.M., Johnsrude, I.S., Davis, M.H., 2010. The role of domain-general frontal
systems in language comprehension: evidence from dual-task interference and
semantic ambiguity. Brain Lang. 115 (3), 182–188.
Sarkar, P., Sattar, F.A., Gode, N., Basannar, D.R., 2006. Failed suicide and deliberate self-
harm: a need for specific nomenclature. Indian J. Psychiatr. 48, 78–83.
Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome.
Brain 121, 561–579.
Shackman, A.J., McMenamin, B.W., Maxwell, J.S., Greischar, L.L., Davidson, R.J., 2009.
Right dorsolateral prefrontal cortical activity and behavioral inhibition. Psychol. Sci.
20 (12), 1500–1506.
Sharma, R.C., 1998. Attempted suicide in Himachal Pradesh. Indian J. Psychiatr. 40,
50–54.
Sokero, P., 2005. Prospective study of risk factors for attempted suicide among patients
with DSM-IV major depressive disorder. Br. J. Psychiatry 186, 314–318.
Soloff, P.H., Meltzer, C.C., Greer, P.J., Constantine, D., Kelly, T.M., 2000. A fenfluramine-
activated FDG-PET study of borderline personality disorder. Biol. Psychiatr. 47 (6),
540–547.
Srivastava, M.K., Sahoo, R.N., Ghotekar, L.H., Dutta, S., Danabalan, M., Dutta, T.K.,
et al., 2004. Risk factors associated with attempted suicide: a case control study.
Indian J. Psychiatr. 46, 33–38.
Sublette, M.E., Milak, M.S., Galfalvy, H.C., Oquendo, M.A., Malone, K.M., Mann, J.J.,
2013. Regional brain glucose uptake distinguishes suicide attempters from non-
attempters in major depression. Arch. Suicide Res. 17 (4).
S. Parkar et al.
Szanto, K., Dombrovski, A.Y., Sahakian, B.J., Mulsant, B.H., Houck, P.R., Reynolds, C.F.,
et al., 2012. Social emotion recognition, social functioning, and attempted suicide in
late-life depression. Am. J. Geriatr. Psychiatr. 20 (3), 257–265.
Van Orden, K., Witte, T., Kelly, C., Braithwaite, S., Selby, E., Thomas, E., 2010. The
interpersonal theory of suicide. Psychol. Rev. 117 (2), 575–600.
Verdejo-García, A., Lawrence, A.J., Clark, L., 2008. Impulsivity as a vulnerability marker
for substance-use disorders: review of findings from high-risk research, problem
gamblers and genetic association studies. Neurosci. Biobehav. Rev. 32 (4), 777–810.
218
Journal of Psychiatric Research 146 (2022) 210–218
Willeumier, K., Taylor, D.V., Amen, D.G., 2011. Decreased cerebral blood flow in the
limbic and prefrontal cortex using SPECT imaging in a cohort of completed suicides.
Transl. Psychiatry 1, e28.
World Health Organization, 2014. Preventing Suicide: a Global Imperative. WHO Press,
Luxembourg.