Bipolar Disorder complicated by Selfmutilation: neurofunctional changes demonstrated by Tc99mHMPAO Neuro SPECT. AJ38-1

Abstract

We report neurofunctional changes in patients with selfmutilation and bipolar disorder. We compared a sample of 29 patients with selfmutilation and bipolar disorder with a group of 20 patients with bipolar disorder without selfmutilation. Furthermore we had an additional control of 22 patients with Major Depression without selfmutilation. Among the findings in selfmutilation, increased anterior dorsal-ventral thalamic perfusion stands out, this is associated with decreased perfusion in the perilimbic area (areas 24, 32 and 23 of Brodmann). There are multiple reports relating in animals and humans selfmutilation with hypoalgesia, anesthesia and disestesias; an hypothesis can be formulated relating self mutilation phenomena with a dysfunction of thalamus and perilimbic circuits associated with nosoceptive circuits and somato-psychic conscience.

Key words: NeuroSPECT, Thalamus, Selfmutilation, Bipolar Affective Disorder.

Introduction

Selfmutilation is defined as a clinical phenomenon of complex order: concept and general features.

Selfmutilation can be understood in its clinical presentation as a spectrum of heterogenic conducts with common psychopathologic features.  Modern psychiatry describes it like symptom present in many syndromes of different etiologies ^{[2, 3]} Table1. It is described also like a normal behavior of development if it is presented as a minor clinical manifestation (Head banging, onicophagia and skin pinching). Clinically, selfmutilation can present as Tics, stereotypias, rituals, Selfstimulation, compulsions and as a mean of communications.

Table 1. Clinical Syndromes presenting with Selfmutilation

A phenomenological description of selfmutilation has to consider two complementary psycho-pathological perspectives: namely, depersonalization and  abnormalities in control of impulses. We will concentrate this time on Depersonalization in order to better understand the hypothesis we will formulate.

Depersonalization.

It has been described  as “an impairment in perception or in the experience of one self, in such a way that the individual feels foreign to him self, distant as if he were  an external observer of his mental processes or his body.”

Since the early descriptions of depersonalization it has been proposed that there is an impairment in the perception of pain in these patients. It has been reported that there is an increased threshold to pain  in subjects with depersonalization ^[5]. However, from a neuro-psyquiatric perspective the response to pain in patients with depersonalization resembles more the definition of “pain asymbolia”. In this neurological condition patients experience pain but do not react to it neither emotionally nor motorly ^[6]. This relates the altered experience to pain in depersonalization with selfmutilation phenomena that occur in many patients in these dissociative states.

Clinical Aspects of Selfmutilation

Clinical and epidemiological description.

Approximated a 4% of hospitalized patients in Psyquiatric Hospitals self mutilate, more frequently among women in a ratio to men of 3:1. This type of self-inflicting damage does not carry a desire to commit suicide. Thus, this phenomenon is more frequently observed in drug addicts (10 to 30%), as in patients with borderline and antisocial personality disorder. However, if selfmutilation becomes a condition for the diagnosis of borderline personality disorder, then considering this as a tautologic condition, we should exclude selfmutilation among the pathognomonic symptoms of borderline personality disorder in order to avoid an incorrect use of the DSM criteria.

Repetitive selfmutilation is included among the category of impairment of control of impulses. These clinical entities share the characteristic of impossibility of resistance to control impulse or tendency of self inflicting lesions or also to damage other individuals (Volitional impairment). During selfmutilation there is a release of tension or increasing excitation as a manner of getting immediate gratification ^[7].

Types of Selfmutilation.

Hawton (1989) classified different types of selfmutilation based on clinical observation. Monique Ernst defined 10 dimensions in selfmutilation with their clinical correlations in different syndromes ^{8]. One of the dimensions described by this author is the sensation to pain, presenting clinical situation where selfmutilation evolves without perception of pain. She includes in this group selfmutilation due to self stimulation such as head banging, autism, borderline personality disorder and learned behavior.

Etiology of Selfmutilation

General Models.

The models more frequently applied are: theoretical (Psychoanalytical, cognitive, abnormal development, reflex model, self stimulation and seizure like model). There are also Pharmacologic models using induction or control of symptoms by different pharmacologic molecules: stimulants, Clonidine, GABA, Morphine, Caffeine, alcohol, teophiline and Muscinol. Experimental lesions such as Posterior Ryzotomy in rats, bitemporal lesions in monkeys, use of agonists D1 and D2 and glycerol induced lesions and finally, social models (Isolation animal models).

Correlation between selfmutilation and altered pain perception.

Animal models have been reported demonstrating that hypoestesias, disestesias and analgesia are related to selfmutilation conducts. The techniques used are vascular lesions, neural, chemical and electrolytic lesions. These have been induced in the extremities and have resulted in repetitive selfmutilation conducts ^{[11, 12]}.

There are four clinical syndromes related to selfmutilation, namely:

1) Congenital anhidrosis (CIPA), evolving with insensitivity. This is an infrequent autosomic recessive abnormality characterized by absence of response to nosoceptive stimuli, mental retardation, selfmutilation, repetitive fever, and prolonged healing time of dermal wounds. Impairment of nosoception is due to absence of ganglia in the dorsal spinal roots associated with self mutilation ^[13].

2) Reports of selfmutilation in patients presenting with deaferentation due to entrapment of spinal medulla due to malformations in this segment ^{[14, 15]}.

3) Reports of nosoceptive deficits in borderline patients with selfmutilation behavior ^[16].

4) Compulsive selfmutilation in the Lesch-Nyhan Syndrome might be due to thalamic dysfunction responsible for loss of consciousness of corporal sensations (somato-psychic conscience) ^[17].

Description of the Study

Objective

1.) Describe neurofunctional changes in a group of patients presenting with selfmutilation and affective disorders in a bipolar spectrum.

2.) Define regions of interest (ROIS) that present a statistical neuro-functional distinction comparing a group of patients having bipolar affective disorder and selfmutilation with a control group constituted by patients that presents with affective bipolar disorder but without selfmutilation.

3.) Suggestion of an explanatory model of selfmutilation phenomena.

Hypothesis.

1.- Self mutilation phenomena have a characteristique neurofunctional expression.

2.- Neurofunctional changes will be observed in areas of the brain related to nosoception, affective assessment of it or somato-psiquic conscience in depersonalization phenomena.

Method.

We studied 29 patients with selfmutilation and affective bipolar disorder comparing them to 20 patients with affective bipolar disorder without selfmutilation. All patients comply with the DSM-IV criteria for bipolar disorder, we have not differentiated the sample for type of bipolarity. Patients were clinically compensated and ambulatory at the time of testing. Mean age of bipolar and selfmutilation patients was 19.6 years (20 females and 9 men) while the mean age of the bipolar patients without self mutilation was 35.2 years (8 females and 12 men).

We compared also our Neuro-Spect results of bipolar with selfmutilation versus a group of 22 patients with major Depression and without selfmutilation as further control.

NeuroSPECT Imaging.

Full methodological description of NeuroSPECT and Image Reconstruction techniques can be read at previous publications by the authors ^{[19, 20]}.

Statistical Analysis.

Cortical and subcortical perfusion values were reported as Maximum, (upper 2.5% of pixel values in Brodmann area), Minimum (lower 2.5% of pixel values in Brodmann areas), Average and Standard Deviation of each Brodmann area evaluated. Maximum and Minimums were used in order to evaluate sub regions in the different Brodmann areas. For the 58 Brodmann areas studied we report the Mean of the study. Considering that the absolute values of the sample is a continuous variable, we applied a t Student test for comparison for ipsilateral pares of results in both groups. We analyzed also subcortical structures and we analyzed Maxima in Basal Ganglia.

Results

Cerebral Cortex.

BPDS presented increased cortical perfusion larger than 2 Standard Deviations (S.D.) in comparison to standard age matched normal data base in frontal and pre-frontal areas 9, 10 and 46 of Brodmann, also in associative visual area 17 and superior temporal gyrus, area 22 of Brodmann. Figures 1 and 3.

Figure 1. 3D representation of cortical perfusion in patient with Bipolar Disorder and selfmutilation. Gray color denotes normal perfusion (mean + 2 S.D.). There is increased perfusion +2 to + 4 S.D. above the normal mean (colors red to white) in frontal executive cortex,( areas 10,9,8, 46 and 44 of Brodmann), there is hypoperfusion in areas 24 and 25 of Brodmann, anterior cingulate and subgenual area.

Figure 2. Sub cortical structures in patient with Bipolar Disorder and selfmutilation. There is increased perfusion (above 2 SD deviations) in both thalami in dorso-ventral anterior region and in inferior aspects of both lentiform nuclei. (color white)

Figure 3. Cortical perfusion in Selfmutilation. Increased perfusion (> 2 SD) in areas 9,10 and 46 of Brodmann in the frontal cortex, also in area 22 of Brodmann in temporal lobes, and 17 in visual associative cortex.. Furthermore, there is very significative hypoperfusion in the limbic system, namely areas 24, 23 and 32 of Brodmann and also in areas 4 and 20.

This group of patients presented with Minimums larger than -4 SD in cortex, perilimbic area (areas 32, 24 and 23 of Brodmann) in inferior temporal gyrus and in premotor cortex (area 4 of Brodmann ) (Table 2 ). These findings were not statistically different from the results published by our group in Bipolar patients without Selfmutilation ^{[19 , 20 ]} Figure 4. Table 2.

Figure 4. Cortical Perfusion in Bipolar Disorder without Selfmutilation. Cortical perfusion results are similar to Selfmutilation patients.

Subcortical Structures.

BPDS patients presented increased thalamic perfusion bilaterally and this result was statistically significant when compared with the Non mutilation group (BPD) and the normal database. In 64% of BPDS studied, increased perfusion was observed in anterior dorsal-ventral segment of the thalami. Patients without selfmutilation did not have an anatomical distribution of increased thalamic perfusion, if it existed. (Figure2 Table 2 and 4 ).

There was also increased perfusion in the lower aspects of the lentiform nucleus in the left hemisphere in patients with BPDS versus BPD.

Table 2. Mean regional cerebral uptake HMPAO in Brodmann areas. Maximums and Minimums.

BPDS Bipolar Disorder associated with self mutilation
BPD Bipolar Disorder without self mutilation
Roi Regions of Interest in Brodmann areas.

BPDS versus Major depression without selfmutilation.

Cortical findings reproduce a previous report by one of the authors. ^[18] . Figure 5.

Figure 5. Cortical perfusion in patients with Unipolar Major Depression, ( N= 22) Minimal perfusion in limbic and subgenual areas (areas 24 and 25 of Brodmann), also inlateral and mesia; temporal lobes. There is absence of increased frontal perfusion.

 

SubCortical Structures.

In the group of 22 patients with Major Depression and without Selfmutilation there was a significant markedly increased perfusion on the anterior dorsal-ventral aspects of both thalami in comparison to the BPDS group. In the depression patients there was also increased perfusion in the head of the left caudate nucleus. Table 3.

Table 3.  Mean regional cerebral uptake HMPAO Subcortical Maximums. Comparison between Bipolar Patients with selfmutilation and Depression Patients without Selfmutilation.

Table 4.  Anterior Dorsal-Ventral thalamic perfusion (D-V-A) bilateral in 64% of patient with selfmutilation studied versus 17% bipolar patients without selfmutilation.. There was also significative increased perfusion in the left lentiform nucleus in the selfmutilation group.

 

Discussion

Progress in functional and structural studies of the thalamus are pointing out that this organelle is not limited to being a connection and modulation step of sensory afferent fibers. It appears currently as a filtering and integrating structure that integrates multisensorial signals to the brain cortex ^[21]. Its close to 50 nuclei interact among themselves and with different cortical structures. Its participation in pain circuits, namely spinothalamic fibers, spinoreticular fibers and cervico-thalamic fibers, appears to be mediated by the thalamic internal and external nuclei. Within the external nuclei we must consider ventral and posterior nucleus that we have demonstrated hyperperfused in patients with Bipolar Disorder and selfmutilation conducts ^[22]. On the other hand, PET studies have demonstrated cortical structures involved with nosoceptive responses namely, corpus callosum and the insular cortex.

Our results correlate selfmutilation conducts in the three groups of patients studied with neurofunctional changes in the thalamus and peri limbic structures, this is corroborated also by phenomena of hypoalgesia or anesthesia in selfmutilation processes in animals and human reports. Furthermore, similar mechanisms can be postulated for selfmutilation in other pathological processes. Therefore, it is hypothesize that anterior dorsal-ventral thalamic hyperperfusion accompanied by perilimbic hypoperfusion (areas 23, 24 and 32 of Brodmann) constitute the neuro-biological substrate of selfmutilation. It is possible that both thalamus and perilimbic cortex participate in the modulation of self being sensation, namely perceptive, subjective perception of constancy and familiarity with self and surrounding environment. Dysfunction of theses structures could lead or facilitate experie nces of depersonalization/ derealization and the development of self mutilation as a strategy for coping against this egodystonic experience. Thalamus would have a rol in integration and filtering of aferences and also in modulation of nosoceptive information. Perilimbic structures would participate in the modulation of affective component and both would participate in the experience of a somato-psychic conscience. Present information mediates these phenomena with a gabaergic and glutamatergic thalamic dysregulation located in the anterior dorsal-ventral area and possible the reticular nucleus. The thalamus would therefore activate inhibitory circuits that would depress anterior cingulate and perilimbic structures, expressed as hypoperfusion. We are not aware of previous publications relating selfmutilation from a multilevel strategy connecting clinical expressions with elements of cognitive neurosciences and functional Neuroimaging.

The finding of marked increased anterior thalamic perfusion in major depression can be explained by three possible hypotheses:

1. Thalamic hyperperfusion secondary to dysfunction of frontal-subcortical circuits, particularly in orbito-frontalcircuits and anterior cingulate described by Cummings ^[23]. Thalamic dysfunction would be a new element playing in the neurofunctional expression of unipolar depression or depressive phase of bipolar disorder and would represent increased inhibitory thalamic function expressed a diminished limbic function (areas 24,23 and 32 of Brodmann).
2. Presence of thalamic dysfunction secondary to depression with pain as a central clinical manifestation. There is currently bibliographic reference to somatic pain as a depression symptom mediated by serotonine, norepinephrine, substance P or Gonadotrophine realeasing factor (GRF). Of particular relevance are the effects of serotonine as anti-nocioceptive molecule with effect on 5HT1A and 5HT2 receptors located centrally in antinocioceptive descending fibers, also , norepinephrine alfa-2 receptors reduction effect on sensitivity affecting dorsal roots of the spinal medulla ^{[24, 25, 26, 27]}. Reports of ambulatory cohorts demonstrate that up to 80% of depressive episodes present with somatic pain as a central affective manifestation.
3. Presence of subtle impairment of somato-psychic conscience of the depressive patient expressed clinically depersonalization/derealization/ dissociative conducts with or without selfmutilation behavior associated.

These hypothesis are alternatives not necessarily mutually excluyent on the contrary they can coexist and explain fully the neuro-functional changes reported.

References