Information process in depressives

BIOLPSYCHIATRY

Correspondence

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1992;31:~ !72-118~

Table 1. Iron Metabolisni Parameters Akathisia Serum iron (p,mol/L) TIBC (ttmoFL) Transferrin saturation (%) Erythrocytic protoporphyrin (gg/ml erythrocyts)

15.2 51.9 29.9 40.1

Control

_+ 5.0 ± 10.8 + 10.5 _ 7.9

19.6 56.1 37.4 42.0

_ _

7.2" 8.7 18.7 9.8

ap < 0.05 (Mann-~,'i,;;..,,y ,.," .r.o.~. ---,

iron level than the subjects in the control group, although there were no significant differences between akathisic patients and controls for the other iron metabolism parameters. Akathisia is a dose-dependent side effect of neuroleptics. Although its pathophysiology is not well known, the most widely accepted hypothesis relates akathisia to dopaminergic blockade of the frontal cortex meso-cortical pathway. In addition, it has been reported that a high concentration of iron is found in several areas of the extrapyramidal system, and that iron is present in the c~tfiguration of the D2 dopaminergic receptor. Good response to iron supplementafion treatment has been reported in two motor disturbances--the restlessness syndrome and the jitteriness syndrome--which are clinically similar m akathisia and which have also be~:n related to a decrease in serum iron levels. In sum, despite the fact that in all available studies with ,~mall groups of patients, it has been extremely difficult to control the many variables that may affect the analysis of serum iron levels, the involvement of iron in akathisia is indisputable, though the relationship between serum iron levels and central nervous system iron is not entirely clear. V. VallOs R. GuUlamat

Information Process in Depressives To the Editor: A biochemical heterogeneity of depression has been suggested by Van Praag et al (1970). Asberg et al (1976) assessed that dysfunction in central sero-

C. Vilaplana R. Duff6 C. Almenar C. Almenar

Clinica Mental Santa Coloma Prat de la Riba s/n 08921 Santa Coloma de Gramanet Barcelona, Spain

References 4"

Barton A, Bowie J, Ebmeier K (1990): Low plasma iron status and akathisia. J Neurol Neurosurg Psychiatry 53:671-674. Brown KE, Glen SE, White T (1987): Low serum iron status and akathisia. Lo~cet 1234-1236. Horiguchi J (1991): Low serum iron in patients with neuroleptic-indu'ced akathisia and dystonia under antipsyehotic drug treatment. Acta Psychiatr $cand 84:301303. Nemes ZC, Rotrosen J, Angrist B, Pe~low E, Schoentag R (1992): Serum iron levels and akathisia. Biol Psychiatry 29:411-413. Sachdev P, Loneragan C (1991): The present status of akathisia. J Nerv Ment Dis 179:381-391.

tonin transmission results in a greater impulsivity. Particular affective dis~urba~ices such as increased aggression and augmented anxiety correlate with signs of decreased central 5HT metabolism (Van Pra~g et al 1987). On the other hand, flat affect or emotional blunting and retardation could be explained by dif-

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BIOLPSYCHIATRY 1992;31:1172-1183

felent pathophysiological mechanisms (e.g., Swerdlow and Koob 1987). We assumed that these clinical features could be ~nked to differences in activation processes when a ~ha'.,;,er*~J inhibi',!~ !~_ required. Contingent Negative Variation (CNV), an electrophysiological index of activation (Walter et al 1964), was analyzed in two groups of depressive patients differing by their clinical expression, before (DO) and after (D21) treatment by a serotonin reuptake inhibitor. Two groups were constituted among patients (aged 20-65 years) fulfilling the DSM-III criteria for major depressive disorder and scoring 17 or more on the Hamilton (1960) Rating Scale for Depression (HRSD): (1) 8 anxious agitated impulsive patients scoring at least 2 points on the agitation item of the HRSD, at least 10 points on Tyrer's (1984) anxiety scale and presenting a clinical impulsiveness (Jouvent et al 1988); (2) 8 f ~tients with retardation and blunted affect scoring at least 15 points on the Widl6cher's (1983) retardation scale and at least 15 points on the Abrams and Taylor (1978) blunted affect scale. In a go/no-go task, subjects had either to respond or not to an imperative stimulus ($2) according to the color of a 4-see preceding warning stimulus (S 1). In this paradigm, CNV has two components: an early component that indexes orienting reaction to S l; a late component that indexes readiness for perceptual or motor processing (e.g., Rohrbaugh and Gaillard 1983). CNV was recorded on the vertex derivation (Cz) with respect to a linked-earlobes reference. Ninetysix trials were performed, the first 48 being considered as learning trials. On the last 48, the mean amplitude of the early and late CNV components were calculated between 1000 msec-2500 msec and 2500 msec-4000 msec post S l, respectively, before and after treatment, Three factor Analysis of Variance (ANOVAs) (group × situation × treatment)showed, on both components, a situation (go/no-go) effect (early CNV: F(I-14) = 4.78, p < 0.05; late CNV: F(I-14) = 7.38, p < 0.05) and a group × treatment (D0/D21) interaction (early CNV: F(I-14) = 5.28, p < 0.05; late CNV: F(I-14) = 4.58, p < 0.05). As observed in normal subjects (Irwin et al 1966), depressed patients with retardation and blunted affect show larger CNV amplitudes in the go than in the no-go situation. This differ~::ace remains after treatment. In contrast, patients with anxious agitation and impulsiveness do not depict any difference. However, this lack of differentiation is due to opposite reasons before and after treatment: before treatment, CNVs abnormalities are

Correspondence

in the no-go situation; the CNV amplitude is as large in the no-go as in the go situation. On the contrary, after treatment, abnormalities are in the go situation, CNVs being flat in both go and no-go situations. Therefore, in this group, normalization of CNVs in the no-go situation after treatment is realized at the cost of a general disactivation. The CNV amplitude decrease between DO and D21 in the go situation is statistically significant for the early CNV component (T(8) = 4, p < 0.02). In conclusion, these results show differences in activation processes according to clinical dimensions and confirm that the effect of the 5HT reuptake blocker is a cortical disactivation {-aly on depressed patients with anxious agitation and impulsivity. They illustrate the interest of a functional description of psychopathology based on hypotheses concerning the effects of specific drugs. A. Partiot ~ A. Pierson 2 V. Dodin 2 S. Ammar I R. Jouvent 2 B. Renault 2

tLaboratoire de Psychopathologie et Pharmacologie des Comportements INSERM U302 groupe COGNEM H6pital de La Sall~tri6re 2Laboratoire de Psychophysiologie Cognitive CNRS URA654 Universit6 de Paris 6 H6pital de La Sall~tri6re, Paris, France

References Abrams R, Taylor MA (197~}: A rating scale for emotional blunting. Am J Psychiatry 135:226-229. Asberg M, Traskman L, Thor~n P (1976): 5-HIAA in the cerebmspinal fluid: A biochemical suicide predictor.'? Arch Gen Psychiatry 33:1193-1197. Hamilton MA (1960): Rating scale for depression. Neurol Neurosur8 Psychiatry 23, 56-62. Irwin DA, Knott JR, McAdam DW, Rebert CS (1966): Motivational determinantsof the "Contingent Negative Variation." Electroencephalogr Clin Neurophysiol 21:538-543. Jouvent R, Vindreau C, Montreuil M, Bungener C, WidI~her D (1988): La clinique polydimensionnelle de rhumeur d6pressive. Nouvelle version de r~helle EHD. Psychiatr Psychobiol 3:245-253.

Correspondence

Rohrbaugh JW, Gaillard AWK (1983): Sensory and motor aspectsof contingentnegativevariation. In GaillardAWK, Ritter W (eds), Tutorials in ERP Research: Endogenous Components. Amsterdam: Elsevier, pp 269-31 I. SwerdlowNR, Koob GF (1987): Dopamine, schizophrenia, mania and depression: Toward a unified hypothesis of cortico-striato-pallidothalamic function. Behav Brain Sci 10:197-245.

Tyrer P, Owen RT, Cicchetti DV (1984): The brief scale for anxiety: A subdivision of the comprehensive psychopathological rating scale. J Neurol Neurosurg Psychiatry 47:970-975. Van Praag HM, Korf J, Puite J (1970): 5-Hydmxyindole-

Depression after Cyproheptadine: MAO Treatment To the Editor: Cyproheptadine has been reported to be effective in the treatment of anorgasmia induced by the administration of tricyclic antidepressants (Sovner 1984; Steele and Howell 1986), monoamine oxidase inhibitors (MAOIs) (DeCastro 1985), or fluoxetine (McCormick et al 1990). It has been postulated that cyproheptadine's efficacy in treating this symptom is caused by the blockade of serotonin receptors. The administration of cyproheptadine for the treatment of antidepressant-induced sexual dysfunction has recently been associated with a recurrence of depressive symptomatology in a series of three patients treated with fluoxetine (Feder 1991), as well as with the reversal of therapeutic benefit in two patients with bulimia nervosa, also treated with fluoxetine (Goldboom and Kennedy 1991). We report here a case of recurrence of depressive symptoms after administration of cyptoheptadine in a patient who received full therapeutic benefit from tseatment with pheneizine. Mr. C. is a 37-year-old man who presented for diagnosis and treatment of chronic depressive symptomatology. Upon evaluation, he was severely depressed, with a blunted affect, as well as mood irritability, and a history of chronic impulsive selfinjurious behavior, usually during the periods of more severe depression. A 17-item Hamilton Depression Rating Scale (HDRS) score of 38 was obtained on

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acetic acid levels in the cerebrospinalfluid of depressive patients treated with pmbenecid. Nature 225:1259-1260. Van Praag HM, Kalm RS, Asnis GM, et al (1987): Denolosization of biological psychiatry or the specificityof 5-HT disturbances in psychiatric discrders. J Affective Disord 13:1-8. Walter WG, Cooper R, AldridgeVJ, McCallumWC, Winter A (1964): Contingentnegative variation: An electric sign of ~nsori-mot.or association of expectancy in the humaii brain Nature 203:380-384. Widl6cherD (! 983): Psychomotorretardation: Clinical,theoretical and psychometric aspects. Psychiat Clin North Am 6:27-40.

initial evaluation. Although no actual suicide attempts were reported, he described almost constant suicidal ideation, which he resisted by increasing his physical activity until exhaustion. During the year prior to evaluation, he had been attending weekly outpatient psychotherapy. Concomitant with the psychotherapeutic intervention, several medication trials had been attempted, including desipramine, imipramine and nortriptyline, without relief of depressive symptoms. Trazodone was reported of limited benefit, with a mild reduction in depressive symptomatology, but severe sedation and orthostatic hypotension necessitated discontinuation of this agent. A trial of fluoxetine significantly reduced symptomatology after 6 weeks, but was also poorly tolerated due to severe agitation and anxiety. In addition to a referral for cognitive-behavioral therapy, phenelzine was initiated, to a maximum dose of 75 mg per day. After 5 weeks on this regimen, his depressive symptomatology remitted (HDRS score = 4). Suicidal ideation and self-injurious behavior, as well as the demanding, impulsive, and irritable style noted in the initial presentation, were also markedly diminished. Concomitant with the resolution of his depressive symptomatology, the patient reported difficulties in sexual activity, with delayed ejaculation that later progressed to anorgasmia. Treatment with cyproheptadine was initiated at a daily dose of 4 mg in an attempt to reduce his sexual dysfunction. Within 3 days of initiating this medication, nearly complete recurrence of depressive symptomatology was observed. No improvement of anorgasmia was reported