Psychology, 2010, 1: 17-21
doi:10.4236/psych.2010.11003 Published Online April 2010 (http://www.SciRP.org/journal/psych)
Copyright © 2010 SciRes PSYCH
17
Beta Thalassemia Minor as a Risk Factor for
Suicide and Violence: A Failure to Replicate
Alireza Fotouhi Ghiam2, Alireza Hashemi1, Samira Taban1, Mohammad Reza Bordbar1,
Mehran Karimi1
1Hematology Research Center, Nemazee Hospital, Shiraz University of Medical Science, Shiraz, Iran; 2Mental Health University
Institute, Douglas Hospital, McGill University, Montreal, Canada.
Email: karimim@sums.ac.ir
Received January 13th, 2010; revised February 22nd, 2010; accepted February 23rd, 2010.
ABSTRACT
The aim of present study was to evaluate the association of thalassemia minor with suicide, impulsivity and aggression.
The study group consisted of 293 suicidal subjects, 300 violent criminals and 300 control subjects. Thalassemia trait
was slightly more common in criminals (7.3%) than in contro ls (6.67%), this difference was not statistically sig nificant
(p = 0.75). Similarly, carrier trait was observed more in suicidal subjects (8.87%) though this difference was not sta tis-
tically significant (p = 0.3). Despite a plausible biological hypo thesis, our study results do not support tha t thalassemia
minor could be a risk factor for suicidal, impulsivity and aggressive behaviors.
Keywords: Thalassemia Minor, Aggression, Suicide
1. Introduction
Beta-thalassemia is among the most common genetic disor-
ders worldwide. The clinical spectrum of β-thalassemia
ranges from the severe transfusion-dependent β-thalassemia
major to the asymptomatic β-thalassemia carriers [1].
Showing geographical differences in prevalence, het-
erozygote β-thalassemia minor is frequent particularly in
Mediterranean area and amongst people of Greek, Italian,
Middle Eastern, Southeast Asian, Southern Chinese and
African descent [2]. The significant clinical manifesta-
tions and complications commonly associated with
β-thalassemia major are not seen in β-thalassemia minor.
That is, most affected individuals are asymptomatic or
characterized clinically by mild anemia with persistent
microcytosis that usually goes unnoticed [1,3]. Consid-
ering the high prevalence of β-thalassemia minor in Iran
(7-10 %), the National Thalassamia Program has been
launched since 1997 for screening and genetic counseling
in attempt to reduce the birth rate of β-thalassemia major
[4-6].
Abnormal lipid profile has been repeatedly reported in
all clinical phenotypes of β-thalassemia including thalas-
semia major, thalassemia intermedia and thalassemia
minor [7-11]. Patients with β-thalassemia trait have been
found to have lower plasma concentrations of total cho-
lesterol (TC) and low-density lipoprotein cholesterol
(LDL-C), but unmodified plasma levels of high-density
lipoprotein cholesterol (HDL-C) and triglycerides (TG)
[12,13]. The most suggested underlying mechanism for
hypocholesterolemia observed in heterozygous β-thalasse-
mia is the higher erythroid bone marrow activity with the
enhanced cholesterol requirement [14]. To date, the
clinical implications of this associated hypocholestro-
lemia are still unknown.
Over the past years, many epidemical and clinical
studies have shown the substantial evidences for low
serum cholesterol concentrations in people with suicidal,
aggressive and violent behaviors meaning that low cho-
lesterol level is significantly related to physical aggres-
sion and violence towards self or others [15-23]. The
severity of a suicide attempt as well as the degree of sui-
cidal ideation was found to be inversely correlated with
serum cholesterol levels. Low levels of cholesterol are
associated with a more violent pattern of suicidal behav-
ior [24,25]. There is also a report of low cholesterol lev-
els in parasuicidal patients [24]. Impulsivity is closely
associated with suicide and aggression or hostility [26].
The replication of these findings with different study
designs across diverse populations has validated such
associations. A reduced central serotonergic neurotrans-
mission through decreased serotonergic (5HT) receptor
function is a biochemical mechanism responsible for
association between low cholesterol level and psycho-
pathological processes involved in suicidal, aggressive
Beta Thalassemia Minor As a Risk Factor for Suicide and Violence: A Failure to Replicate
Copyright © 2010 SciRes PSYCH
18
and violent behaviors [27-31].
Taking these separate associations together, one may
expect that suicidal, aggressive and violent behaviors
would be more observed in thalassemia minor, at a
population level. Therefore, the attention is called to the
psychosocial problems that this thought could emerge in
a society where thalassemia trait is common. Without
appropriate validation, over the years, this premise could
bring the false impression of facing unstable relation-
ships and interpersonal difficulties with β-thalassemia
carriers and thus put them in considerable distress. To the
best of our knowledge, no study exists that clinically
challenges the correlation of β-thalassemia minor pheno-
type with suicide, aggression and violence. This study
was conducted to test this hypothesis.
2. Method
2.1 Subjects
This cross-sectional, case-controlled study was con-
ducted in Shiraz, south of Iran, from April 2007 to June
2008. The study sample included three separate groups of
subjects: Group (A): subjects with attempted suicide (n =
293, mean age = 25.15 ± 10.94 y/o) who had been ad-
mitted to Nemazee University Hospital following a sui-
cide attempt. Group (B): violent criminals were the pris-
oners sentenced to Adelabad jail (main jail of Fars prov-
ince, southern of Iran) by court because of proven crimes
linked to violence against life or health of others (n = 300,
mean age = 33.29 ± 11.47 y/o). Violent crimes com-
prised of murder and/or attempted murder, infanticide,
stabbing or wounding or other act endangering life, rape,
sexual assault, child abuse, vandalism, arson, criminal
damage to a dwelling or vehicle, burglary equipped by
weapons, possession of and trafficking in drugs and/or
firearms. None of the individuals were the subject of
false arrest or self-defense. Only male subjects were in-
vestigated because we were not able to identify enough
females with the same criteria of recruitment. Group (C):
control subjects (n = 300, mean age = 28.15 ± 10.3 y/o)
normal healthy volunteers and recruited from couples
screened by Iranian National Thalassemia Screening
Program as part of mandatory premarital blood tests
[5-31]. A detailed medical history was taken from and a
complete physical examination was performed on all
subjects. Any subject with a history of or current definite
physical diseases that could possibly influence the find-
ings was excluded from the study. They were screened
not to have personal and familial psychiatric histories as
well. None used psychotropic medications or abused
substances. Before recruitment, the purpose of the study
was explained to each participant. Participants signed an
informed consent form, which in case of group B was
countersigned by a member of the prison staff. The study
was preapproved by medical ethical committee of Shiraz
University of Medical Sciences.
2.2 Methods
Blood samples were taken from all studied subjects. The
diagnosis of β-thalassemia trait was established based on
basic hematological criteria: anisocytosis, poikilocytosis,
hypochromia and microcytosis (mean corpuscular hemo-
globin (MCH) < 27 pg, mean corpuscular volume (MCV)
< 80 fL), and the quantity of HbA2 3.5% and 2% < Hb
F < 10%, performed by high performance liquid chro-
matography (HPLC)) [31]. Complete blood count was
performed by Coulter counter machine, and hemoglobin
electrophoresis by Citrate Agar. Suspected results were
then confirmed by direct DNA sequencing using poly-
merase chain reaction (PCR)-based techniques. Subjects
with normal hemoglobin, normal MCV, normal MCH,
normal morphology, HbA2 < 3.5%, HbF < 2% and nor-
mal hemoglobin electrophoresis were regarded as
non-β-thalassemia trait. To rule out iron deficiency ane-
mia, individuals with HbA2 < 3.5% and anemia were
treated with oral iron (one ferrous sulfate tablet equiva-
lent with 50 mg elemental iron, three times daily) for 2
months. The tests were repeated after this period and a
decision was reached using the same laboratory values as
above. Alpha and beta-thalassemia trait was differenti-
ated by fresh blood incubated with Leucin H3 method.
2.3 Statistical Analysis
The data were analyzed using SPSS software (version
13.0.0; SPSS, Chicago, IL, USA).
Pearson’s χ2-test and Fisher’s exact probability test
were used, when appropriate. Findings were deemed to
be statistically significant at a p-value of less than < 0.05.
3. Results
The prevalence of thalassemia trait in all of three groups
is shown in Table 1. Thalassemia trait was slightly more
common in prisoners (22 (7.3%)) than in controls (20
(6.7%)), but this higher frequency was not statistically
significant (p = 0.75). Similarly, carrier trait was ob-
served more in suicidal subjects (26 (8.9%)), but this
difference was not statistically significant (p = 0.3). More
significantly, the prevalence of Thalassemia minor, in all
three groups of studied subjects, was consistent with pre-
vious studies reporting the prevalence of β-thalassemia
trait to be as 7-10% of Iranian population [5].
4. Discussion
Thalassemia is in one of the most prevalent genetic dis-
eases and approximately 7-10% of Iranian population are
carriers for this disease [4,5].
Previous studies have consistently shown a higher rate
of aggression, violence and impulsivity as well as suici-
dal behaviors in individuals with low cholesterol level
Beta Thalassemia Minor As a Risk Factor for Suicide and Violence: A Failure to Replicate
Copyright © 2010 SciRes PSYCH
19
Table 1. Prevalence of thalassemia-minor in patients with
suicidal attempts and violence criminals
Patients Healthy
(n)(%)
Thalassemia
trait (n)(%)
Total
(n)(%) p-Value
Patients with sui-
cidal attempt
(Group A)
267
(91.1%) 26 (8.9%) 293
(100%) 0.3*
Prisoners with
violence crime
(Group B)
278
(92.7%) 22 (7.3%) 300
(100%) 0.75*
Controls (Group C) 280
(93.3%) 20 (6.7%) 300
(100%)
n = number, NS = Non-significant
[15-23], due to reduction of serotonergic activity in the
brain [27-30]. Given that thalassemia patients (major,
minor and intermedia) have lower cholesterol levels
[7-13,32-36] one may assume that carrier state may rep-
resent a risk factor for these behaviors [37]. Considering
the high prevalence of carrier individuals in our popula-
tion, we were concerned about the emerging problem of
the increase of emotional distress, unstable interpersonal
relationships and marriage difficulties. These psychoso-
cial concerns brought us to conduct the present study and
assess the accuracy of this hypothesis for the first time in
literature. We studied a large sample size and designed a
reverse approach to evaluate the prevalence of thalas-
semia trait in individuals with suicidal attempts and in
those with extreme aggressive behaviors as violent
criminals.
Our findings failed to show significant correlation
between being a thalassemia carrier and an increased rate
of violence and suicide, that is to say thalassemia trait is
unlikely to serve as a risk factor for future suicide and/or
violence when considered in isolation. Although, a rela-
tion of low cholesterol to suicide and violence is con-
firmed to be causal, other factors could manipulate the
behavioral impact of low cholesterol in thalassemia car-
riers. Suicide and violence are complex behaviors with
multiple causes in nature and any single factor is likely to
account for only a relatively small effect [38].
There were limitations in the present study. We used
convenience samples consisting of accessible couples
screened by National Thalassemia Screening Program,
patients admitted to our university hospital and prisoners
sentenced to local jail. Also, we only recruited male sub-
jects with proven crimes linked to violence. Due to its
selective nature, the sample may not entirely represent
the general population. Nevertheless, the findings gener-
ated from this large sample may provide valuable infor-
mation about the psychopathologies; suicide, aggression
and violence, that were studied in thalassemia trait. We
used a one-time blood sampling, potentially remote from
the time of the violent crime. However, the measurement
of HbA2 and HbF by HPLC is reproducible and precise.
It is a reliable method for rapid screening in population
surveys for beta thalassaemia. Moreover, the suspected
results were confirmed by direct DNA sequencing tech-
niques.
The importance of these findings is that the individuals
with thalassemia trait would not be rejected by the rest of
society due to fear of impulsive behaviors. The extent
and significance of these findings should be evaluated
through further epidemiological studies on greater sam-
ples with follow-up periods, after controlling for poten-
tial confounding variables.
5. Acknowledgements
The authors thank the thalassaemic patients as well as
Cooley’s Centre staff for their contributions to this study.
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