Psychophysiological Study of Pain Perception in Depressed Patients With Suicidal Risk
Psychophysiological Study of Pain Perception in Depressed Patients With Suicidal Risk
Joiner's interpersonal theory of suicide postulates that the wish of death comes from
 feelings of perceived burdensomeness and thwarted belongingness. But, only people who have
 acquired the capability to kill themselves will attempt suicide. The acquired capability
 refers to a reduction of fear to death, and a higher pain tolerance. Indeed, to commit
 suicide involves to endure pain during the act. Thus, higher pain tolerance seems to be a
 necessary feature for suicidal act.

 Past studies have shown higher pain threshold and tolerance in suicidal patients, whatever
 the stimulus was (electric, thermic or mechanical), compared to patients without suicide
 history. Moreover, Caceda and colleagues demonstrated higher pain threshold in recent suicide
 attempters (suicidal act within 72h) compared with depressed patients. Five days after the
 initial evaluation, pain threshold of recent suicide attempters decreased to be similar to
 depressed patients with suicidal ideation. Therefore, it may exist a specific state during
 which the pain tolerance is increased. During this "hypoalgesic state" patients with suicidal
 ideation could attempt suicide to get relief from suffering.

 However, little is known about the specific mechanisms that are responsible for the higher
 pain threshold and tolerance in suicide attempters. Pain is a dynamic system that results
 from excitatory and inhibitory messages. The modification of one of these mechanisms could
 explain the higher tolerance in recent suicide attempters. Three of them are of particular
 interest:

 1. The conditioned pain modulation (CPM) is a modulatory pain mechanism. CPM works through
 descending pathway that reaches the spinal cord and modulates pain processing from the
 first nociceptive synapse.In recent suicidal patients, an increase of the CPM could
 explain higher pain tolerance.

 2. The "wind-up" mechanism is defined as the highest excitability of the second order
 nerve. Even if the stimulus remains stable, pain continuously raises. In recent suicide
 attempters, a reduction of this mechanism could explain higher pain tolerance.

 3. The threshold of Aδ and C nociceptors. If a nociceptive fiber is less excitable than the
 other, it would explain higher pain threshold.
Aim: The first objective of this project is to test different pain mechanisms that could be
 involved in the increase of pain thresholds and tolerance in suicidal patients. The second
 objective is to test whether there's a loss of pleasantness during social touch in suicidal
 patients.

 The main aim is to compare the efficacity of CPM between three groups of depressed patients:
 recent or former suicide attempters and non-attempters. The secondary aims are 1) to compare
 the wind-up mechanism between groups, 2) to compare the difference of excitability of Aδ and
 C fibers between groups, 3) to correlate these physiological results to clinical variables
 (emotional reactivity and emotional regulation, dissociation and body perception), and 4) to
 compare the pleasantness associated with social touch between groups.

 Target population: 153 depressed women will be enrolled and divided into three groups. I)
 Women having recently attempted suicide (less than 72 hours) - II) women having a past
 suicide attempt (more than 72 hours) - III) Women without lifetime history of suicidal
 behaviour (affective control group).

 Materials: The heat test stimuli are performed by a thermode (TCS II, QST Lab) which produces
 ramping heat pulses from 32°C to 52°C. For the conditioning stimulus (cold pressor task),
 participants will insert their arm (up to the elbow) in circulating cold water (8°C). Pain
 intensity is rated by a CoVAS (computer visual analog scale). This scale is similar to a
 classic visual analog scale (VAS) ranging from "no pain" to the "most intense pain
 tolerable". The participant has just to move a cursor, thanks to the computer mouse. The
 stroking is performed thanks to a Natural hair Blush Brush (No. 7, The Boots Company).

 Clinical assessment: A clinical assessment will be made by a trained researcher. This
 assessment will evaluate psychiatric diagnosis by the DSM-V (Diagnostic and Statistical
 Manual of Mental Disorders), the severity of depression by the IDS-C30 (Inventory of
 Depressive Symptomatology), the intensity of suicidal thoughts by the CSSRS (Columbia Suicide
 Severity Rating Scale), and the suicidal life history by the RRRS (Risk-Rescue Rating Scale)
 and SIS (Suicidal Intent Scales). It will also gather information about socio-demographic
 variables, the number of depressed episodes, the number of psychiatric hospitalizations, the
 hormonal status, and the current medications. All psychotropics medications taken by the
 patient will be collected for the last 72 hours, as well as the dose and the date of the
 beginning of the treatment. The patients will also have to complete some self-report measures
 about the severity of their depression (BDI-II), their level of anxiety (STAI), their
 physical and psychological pain (EVA current and past), their childhood trauma (CTQ), their
 emotional state (PANAS), their difficulty in emotional regulation (DERS), their emotional
 reactivity (ERS), their body perception (BIS), their dissociative experiences, their
 borderline symptomatology (BSL-23) and the kind of non-suicidal self-injuries practiced
 (SHI).

 Blood tests: The blood test is made between 2 and 24 hours before the experimental procedure.
 The biological collection is made to measure medications' concentration if the patient takes
 antiepileptics and/or lithium, and to measure complete blood count (CBC).

 Experimental design: All three pain mechanisms and social touch will be tested in one session
 lasting 1h approximately.

 1. To distinguish the threshold of Aδ and C, a thermal stimulus will be used to provoke
 painful and non-painful sensations (Thermode QST lab). Successive and alternate phases
 of painful (hot) and non-painful (warm) stimulations will be used. The warm phase will
 remain stable at 38°C for 5 seconds whereas the hot phase will consist of ascending heat
 pulses from 39°C to 52°C for 1 second each. At every phase, the participant will be
 asked if she feels pain or not to determine the pain threshold. The Aδ fiber threshold
 will be the first time when the participant will report pain during the hot phase. The C
 fiber threshold will be the first time when the participant will report pain during the
 warm phase. These measures will be repeated five times.

 2. Wind-up and CPM will be evaluated successively in three steps:

 1. To measure the activity of the wind-up, a constant temperature (individually
 determined) will be applied during 2 minutes on the left forearm (stimulus test).
 This temperature will correspond to a painful sensation of 40/100 on the CoVAS for
 each patient previously evaluated. During the test, the participant will report the
 intensity of pain on the CoVAS in a continuous manner. The patient will move the
 cursor along the continuous line to indicate the pain she feels and every change.

 2. The CPM activation will be produced by a counter nociceptive stimulation (cold
 pressor task). The right forearm of the participant will be placed during 2 minutes
 in a cold water maintained at 8°C (conditioning stimulus).

 3. To measure the efficiency of the CPM, the hot constant temperature (corresponding
 to CoVAS= 40/100) will be re-applied, during 2 minutes on the left forearm
 (conditioned stimulus). As previously, participant will report her pain on the
 CoVAS.

 Before and after the painful tests, the participant will have to complete two self-report
 measures. The PANAS to evaluate their emotional state and the STAI state to evaluate their
 anxiety.

 In a final step, the pleasure associated with social touch will be tested. The experimenter
 stroked the participant's marked skin areas for 70 seconds with a soft brush in either
 CT-optimal speed (3 cm/s; slow touch group associated with pleasantness) or non-CT-optimal
 speed (18 cm/s; fast touch group associated with a neutral feeling). The pleasure associated
 with the stroke is then assessed on a 10-point Likert scale (from really unpleasant to really
 pleasant). In this within design, the reaped measures (slow touch vs fast touch) will be
 counterbalanced between participants.

 Pairing: A pairing will be made on age and antidepressant class (none, selective serotonin
 reuptake inhibitor (SSRI), Serotonin-norepinephrine reuptake inhibitor (SNRI), tricyclic,
 others). For each category of antidepressant, a 1 will be attributed if the patient takes one
 medication of this category and a 0 if not. In each group, the sum of every classes of
 medication will have to be equal. As a reminder, class of antidepressant are exclusive
 between them.

 Medical load: To control medication, a medication load index will be calculated as described
 in Olié and al., 2018. Antiepileptics and lithium medications will be dosed in plasma.
Inclusion Criteria for all patients:

 -  Woman;

 -  Being aged between 18 and 65 years;

 -  Currently meeting the DSM-5 major depressive episode criteria;

 -  Being able to understand the nature, purpose and methodology of the study and agreeing
 to cooperate during the assessments;

 -  Having signed informed consent;

 -  Being affiliated with a social security or equivalent.

 Inclusion Criteria specific to each group:

 -  Recent attempters: women having recently attempted suicide (less than 72 hours)

 -  Past attempters: women having a past suicide attempt (more than 72 hours)

 -  Affective control: women without lifetime history of suicidal behaviour (affective
 control group).

 Exclusion Criteria for all patients:

 -  Existence of current psychotic or mixed characteristics;

 -  Lifetime history of schizoaffective disorder or schizophrenia;

 -  Current substance dependence (within the last 6 months);

 -  Existence of mental retardation or serious medical comorbidity interfering with
 measures (HIV, diabetes, cancer, chronic inflammatory pathology, neurological
 disorder);

 -  Having taken painkillers within the last 24 hours preceding the evaluation;

 -  Existence of a usual or current treatment with analgesics or NSAIDs (daily analgesic
 treatment more than 3 months);

 -  Existence of a sensory or cognitive handicap;

 -  Pregnant or lactating woman.