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Diminished nocturnal penile tumescence in depression: A replication study
1 ! 36
BIOL PSYCHIATRY I.o92;31.1130- t 142
Diminished Nocturnal Penile Tumescence in Depression: A Replication Study Michael E. Thase, Charles F. Reynolds III, J. Richard Jennings, Ellen Frank, Gregory L. Garamoni, Eric A. Nofzinger, Amy L. Fascizka, and David J. Kupfer
A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic criteria (RDC) major depression in order to replicate earlier observations that measure~ of nocturnal penile tumescence (NPT) and penile rigidity are disturbed in depressive s:~ztes. When compared to both the age-equated patient (n = 34) and normal control (n = 28) groups reported in our 1988 study, the new sample manifested significant abnormalities ~,f NPT and diminished penile rigidity. Such distuPbances were not, however, significantly correlated with psychobiological indicators oJ severe or endogenous depression.
Introduction Although the libidinal disturbances associated with depressive syndromes have been longrecognized (Small and Small 1930), more recent work suggests that some depressed patients also manifest abnormalities of underlying sexual neurophysiology (Roose et al 1982); Thase et al 1987). In an initial study we demonstrated a reduction in nocturnal penile tumescence (NPT) and decreased penile rigidity in a sample of 34 depressed men (Thase et al i988a). Such disturbances were of sufficient degree to lead to false positive diagnoses of presumably irreversible erectile dysfunction in about 15% of depressed men (Thase et al 1988b). These findings have significant clink:al implications for two groups of patients: depressed patients (i.e., with respect to further illuminating the mechanisms and/or correlates of apparently state-dependent sexual difficulties); and patients seeking evaluation for sexual dysfunctior~ (i.e., for whom an abnormal NPT study may be incorrectly presumed to be caused by an irreversible organic pathglogy rather than depression). More specifically, NPT studies may not be valid in the evaluation of erectile dysfunction until a man has been assessed for and, if pertinent, treated foc ~ depressive episode (Thase et al 1987). In the current report, we provide additional evidence of altered NPT in depression by
From the Western Psychiatric Institute and Clinic, Department of Psychiatry, Unive~.ity of Pittsburgh Scho'q of Medicine, Pittsburg, Pennsylvania. Address reprint requests to Dr. Michael E. Thase, Western Psychiatric Institute and Clinic, Departmet L., t'sychiatry, University of Pittsburgh School of Medicine, 3811 C'Hara Street, Pittsburgh, PA 15213. Received July 27, 1991; revised March 30, 1~)2. © 1992 Society of Biological Psychiatry
0006-3223/92/$05.00
Nocturnal Penile Tumescence in Depression
BIOLPSYCHIATRY 1992;3 ~: 1136-1142
1137
presenting results of an internal replication study, conducted in a nonoverlapping sample of 51 depressed men. We have compared this new sample with both the control and depression groups from an original study (Thase et al 1988b) in order to determine if the finding of diminished NIT is present in a new sample of depressed men. We also examined potential psychobiological correlates of diminished NIT in this new patient sample. Methods The methods for recruitment, inclusion, exclusion, and assessment of patients and controls, as well as those for performance of NPT studies are virtually identical to those described in our earlier reports (Thase et al 1988a, 1988b). To briefly summarize, physically healthy men meeting the criteria of both DSM-HI-R (APA 1987) and researcia diagnostic criteria (RDC) (Spitzer et a11987) for a unipolar, nonpsychotic major depressive episode were. enrolled in the study if they scored >- 14 points on the first 17 items of the Hamilton Rating Scale for Depression (HRSD; Hamilton 1960). Diagnoses were based on at~ initial interview conducted by a clinical evaluator and faculty psychiatrist and confirmed by a second, semistructured interview using the Schedule for Affective Disorders and Schizoprhenia (Endicott and Spitzer 1978). Patients were representative of men seeking outpatient treatment at our hospital and they w e r e n o t selected on the basis of clinical reports of sexual dysfunction. After patients provided written informed consent they began a minimum 14-day drug- a~d alcohol-free, supc~wised wash out. During the first week of wash out, potential patients were further evaluated with physical and urological examinations, including Doppler assessment of penile arterial blood flow. Laboratory screening included complete blood count, chemistry profile, syphilis and acquired immune deficiency syndrome (AIDS) serology, thyroid function studies, and electrocardiogram. Sixty men with major depression were initially enrolled in the replication series, with two subsequently withdrawing consent for research participation ~,rior to sleep/NPT assessment and seven excluded on the basis of identification of medical factors that might affect sleep and/or sexual function (such as diabetes, hypertension, prior lumbosacral spinal surgery, and/or urological disorders). The remaining sample of 51 patients began all-night electroencephalographic (EEG) sleep and NPT studies in our Sleep Evaluation Center upon completion of the wash out. Sample chat~acteristics are described in Table 1. Nocturnal penile tumescence recoldings (Karacan et al 1978; Wasserman et al 1980) were performed in conjunction with all-night polysomnographic studies on at least 3 consecutive nights. The methods for scoring these measures and their rdiability have been reported previously (Campbell et al 1987; Thase et al 1988a, 1988b). In our NPT protocol, Night 1 is used for adaptation to the laboratory ~nd procedures. Night 2 is utilized to collect polygraphic r~easures of tumescence (Le., minutes of NIT, number of NPT episodes, NPT time divided by rapid eye movement (REM) time, and NIT time divided by total sleep time). On Night 3, visua~ inspection procedures are performed, which include technologists' and patients' ratings of erectile fullness and measurement of penile buckling force (Wein et al 1983). Consistent with the preliminary report of Karacan et al (1985) and the findings from our initial study of depressed men (Thase et al 1988a, 1988b), we selected a maximum buckling force value of ~500 g force as the criterion for dimir~ished penile rigidity. Two sets of between-group comparisons were conducted on these measures. First,
1138
M.E. Thase et al
BIOL PSYCHIATRY 1992;31:1136-1142
Table 1. Clinical Characteristics of Depressed and Healthy Control Subjects° Group t-tests or X2
Age (yr) Race (white/other) Education (yr) Partner status (yes/no) ° HRSD (17-item) Number of depressive episodes Duration of current episode (wk) Median Range Diagnostic subtype
Controls
Study i depressed
Study 2 depressed
(n = 28)
(n = 34)
(n = 51)
34.8 (13.0) 26/2 16.3 (2.3) 18/10 0.8 (1.5)
35.3 (10.2) 31/3 14.8 (2.3) 18/16 18.6 (3.5) 2 . 4 (1.5)
37.5 (9.6) 49/2 15.7 (2.6) 38/13 19.2 (3.8) 1. I (2.6)
4 5 . 5 (48.7)
43.3 (49.7)
24 3-156
26 3-260
13/5/14
7,14/30
~d3C endogenous
(No/probable/definite) Pretreatmeat EEG sleep Sleep efficiency (%) Slow-wave sleep (%) REM sleep (%) REM Latency (min)
89.6 14.5 21.0 81.8
(6.8) (10.3) (5.4) (41.6)
87.1 14.1 20.9 75.2
(9.0) (10.7) (5.4) (42.6)
89.8 10.1 24.3 60.2
(7.8) (8.1) (4.6) (16.2)
Study l depressed vs study 2 depressed t X2 t X2 t t
= = = = =
- 1.01 0.89 - 1.64 4.22 b -0.74 2.64 c
Study 1 controls vs study 2 depressed t = - 1.05 X2 = 0 . 3 9 t = 1.02 X2 - 0.92 t = -24.54 a
t = 0.20
)~z _ 7.95 c
t t t t
= --
- 1.45 1.94 -3.13 ~ 2.28 b
t t t t
- - 1. I 1 - 2.0cYs = -2.87 c - 3.29 d
*Mean( -.+ SD) unless otherwise noted. Partnerstatus "yes" includesmarriage,cohabitation, and/oran ongoing monogamousrelationship.
~t,< 0,05. ~p < o.oI. ~j, < o.ool.
two-tailed t-tests or, when appropriate for nonparametric comparisons, 7(2 tests were performed, comparing the new samples of 51 depressed men against the 28 controls from the earlier series (Thase et al 1988a). Second, the new sample was similarly compared to the previous sample of 34 depressed men. We predicted a full replication, thus it was hypothesized that a comparable level of abnormality would be observed in the two depressed samples, whereas the new depressive sample would show reduced measures of tumescence time and diminished maximum penile rigidity when compared to controls. Next, potential clinical and sleep EEG correlates of diminished NPT were examined in the new sample of 51 depressed men. The following univariate measures were correlated with NPT time (divided by REM time) and buckling force: age, pretreatment HRSD severity, percentage of sleep maintenance, percentage of slow-wave sleep, REM density (units), and REM latency (min). Pearson correlation coefficients were computed for the comparisons with NPT/REM time, whereas nonparametric Spearman correlations were used for comparisons with maximum buckling force. A nonparametric statistic was used in the latter correlational analyses because buckling force scores were not normally distributed (see Figure 1). We also compared these NPT parameters in patients diagnosed as meeting the criteria of RDC for nonendogenous (n = 7), probable endogenous (n = 14), or definite endogenous (n - 30) subtype of major depression. A one factor analysis of variance (ANOVA) was used for the polygraphic measure (NPT time divided by REM
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time) and a KruskaI-Wallace nonparametric ANOVA was used for comparing maximum buckling force. Based on our earlier findings (Thase et al 1988), we predicted that diminished NIT in depression would be associated with older age, increased HRSD severity, and poorer sleep m.':intenance. Results
The two sets of comparisons between these samples are summarized in Table 2 and illustrated in Figures 1 and 2. When compared to nondepressed controls, the new sample of 51 depressed men had highly significant reductions of all polygraphic measures of NIT (Ps < 0.001), including decreased tumescence time when considered in relation to the amount of total sleep time and the amount of REM time. Depressed men also averaged about one fewer episode of tumescence per night than controls (p - 0.002). Each of these differences remained significant when the analyses were recomputed as one factor analyses of covariance, using age as the covariate. A significantly greater proportion of depressed men in the new sample also had maximum buckling force values in the impaired range (i.e., < 500 g force): 29/51 (57%) versus 4/28 (16%), X2 = 4.2, df = 1, p = 0.04.
1140
M.E. Thase et al
BIOL PSYCHIATRY 1992;31:1136-1142
Table 2. Comparison of Sleep-Related Tumescence in Depressed and Healthy Control Subjects (Means _+ SD) Group t-tests or X2
Study 1 depressed (n = 34)
Study 2 depressed (n = 51)
Study 1 depressed vs study 2 depressed
144.9 (49.7)
98.7 (46.8)
105.2 (49.0)
t = -0.6
t = 3.4`"
0.37 (0.14)
0.26 (0.11)
0.27 (0.12)
t = -0.4
t = 3.4"
1.87 (0.93)
1.34 (0.74)
1.16 (0.54)
t = 1.3
t = 3.8`"
4.3 (1.4) 4 (16)
3.9 (1.3) 12 (38)
3.3 (1.3) 29 (57)
t = 2.2* X2 = 2.9
Controls (n = 28) Total tumescence time (rain) Total tumescence time/time spent asleep Total tumescence time/REM time Number of episodes Maximum buckling force: Number of cases <500 g
Study I controls vs study 2 depressed
t = 3.2 b X2 = 4.2*
(%) °p < 0.05.
~p< o.ol. Cp < 0.001.
Comparisons of the two depression samples demonstrated no differences on the three polygraphic measures of NPT (see Figure 2 and Table 2). The new sample, however, had a lower mean number of episodes of tumescence (p = I).03) and tended to have a higher proportion of patients with impaired penile rigidity (p = 0.09) when compared to the original sample. In the series of correlational analyses, the tumescence time/REM time measure was not significantly associated with age (r = 0.02, HRSD severity (r = 0.12), sleep maintenance (r = -0.08), percentage of slow wave sleep (r = 0.09), REM density (r = 0.10), and REM latency (r = -0.07). Similarly, maximum buckling force was not significantly associated (Spearman correlation coefficients) with HRSD severity (rs = - 0.01), sleep maintenance (rs = 0.15), percentage of slow-wave sleep (rs = -0.04), and REM latency (rs = - 0 . 0 7 ) . Only age was weakly associated in the predicted direction with reduced buckling force (rs = - 0 . 2 4 , p = 0.09). With respect to categorical subtype diagnoses of depression, there was no evidence that the ratio of tumescence time to REM time was lower in definite RDC endogenous depression when compared to probable or nonendogenous depression cases (ANOVA; F2,49 = 0 . 6 5 , p --': 0 . 5 4 ) . In fact, there was a trend for RDC definite endogenous cases to have significantly higher buckling force scores when compared to the other cases (Kruskal-Wallis X2 = 5.08, df = 2, p = 0.08). Discussion The results of this internal replication study provide further evidence that depressed men manifest alterations of erectile neurophysiology. The current sample had somewhat more abnormal NPT profiles than the patient~ described in the 1988 report. In this regard, the patients in the first and second studies did not differ with respect to either age or ratings
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Figure 2. Distribution of polygraphic measures of nocturnal penile tumescence for depressed patients from study I (Din; n -- 34), study 2 (D2; n - 51), and normal controls (n - 28).
of depressive severity. However, patients in the second series were significantly more likely to meet criteria for RDC definite endogenous depression subtype and they had significantly more abnormal EEG sleep profiles, including significantly reduced REM latency, significantly increased REM time, and a trend for a reduced percentage of slowwave sleep. In both of our outpatient studies, the level of reduction in polygraphic measures of tumescence and penile rigidity generally reflect a relative decrease rather than an absence of tumescence as r~,iginally described by Roose et al (1982) in two older, severely depressed hospitalized patients. The significant abnormalities noted in this second series again point to a pathological process adversely affecting NPT in depression. This is particularly striking because episodes of nocturnal penile tumescence typically accompany REM sleep periods (Karacan et al 1978) and, in the new sample, REM time was significantly increased, whereas measures of NPT remained significantly decreased. Depression thus appears to belong to a group of disorders in which there is an apparent uncoupling cf REM sleep and NPT (Nofzinger et al 1992; Wasserman et al 1980; Wein et al 1983). Although independent confirmation of these results is still desirable, the findings of our replication study strengthen the likelihood that diminished NPT is a neurophysiological correlate of depression. The question of the reversibility (i.e., state dependence) of NFT
1142
BIOL PSYCHIATRY 1992;31:i 136-1142
M.E. Thase etal
disturbances will be addressed in a subsequent report (Nofzinger et al in press). However, in this replication study, we were unable to confirm any substantial relationship between disturbances of NPT and psychobiological indicators of severe or endogenous depression. Therefore, it seems possible that the neurophysiologicai processes that are linked to disturbed NPT in depressed patients may not be specific to affective illness. Nevertheless, we wish to reemphasize that, in a some cases, depression can be associated with an NPT profile that is indistinguishable from that seen in organic impotence. This work was supported in part by NIMH grants MH-40023, MH-00295, and MH-30915, and a grant from the John D. and Catherine T. MacArthur Foundation Research Network on the Psychobiologyof Depression. We wish to thank the faculty and staff of the Sleep Evaluation Center and the Cognitive Therapy Clinic of the Western Psychiatric Institute and Clinic and Ms. Lisa Stupar for their assistance in this research.
References Ame~can Psychiatric Association (1987): Diagnostic and Statistical Manual of Mental Disorders, 3~d ed. rev). Washington, DC: American Psychiatric Press. Campbell P!, Reynolds CF, Jennings JR, et al (1987): Laboratory note: Reliability of NPT scoring and visual estimates or erectile fullness. Sleep 10:480--485. Endicott J, Spitzer RL (1978): A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry 35:837-844. Hamilton M (1960): A rating scale for depression. J Neurol Neurosurg Psychiatry 12:56--62. Karacan I, Salis PJ, Williams RL (1978): The role of the sleep laboratory in diagnosis and treatment of impotence. In Williams RL, Karacan l (eds), Sleep Disorders: Diagnosis and Treatmert. New York: John Wiley & Sons. Karacan I, Moore C, Sahmay S (1985): Me~surement of pressure necessary for vaginal penetration. Sleep Res 14:269. Nofzinger EA, Reynolds CF 111, Jennings JR, et al (1992): Results of nocturnal penile tumescence studies are abnormal in sexually functional diabetic men. Arch Intern Med 152:114-118. Nofzinger EA, Thane ME, Frank E, et al Sexual function in depresst~d men: Assessment using self-report, behavioral and nocturnal penile tumescence measures before and after treatment with cognitive behavior therapy. Arch Gen Psychiatry in press. Roose SP, Glassman AH, Walsh BT, Cullen K (1982): Reversible loss of nocturnal penile tumescence during depression: A preliminary report. Neuropsychobiology 8:284-288. Small IF, Small JG (1980): Sex and mental illness. In Kaplan HI, Freedman AM, Saddock BJ (eds), Comprehensive Textbook of Psychiatry, 3rd ed, vol 2. Baltimore: Williams & Wilkins. Spitzer RL, Endicott J, Robit:s E (1978). Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 35:773-782. Thase ME, Reynolds CF III, Glanz LM, et al (1987). Nocturnal penile tumescence in depressed men. Am J Psychiatry 144:89-92. Thase ME, Reynolds CF III, Jennings JR, et al (1988a): Nocturnal penile tumescence is diminished in depressed men. Biol Psychiatry 24:33-46. Thase ME, Reynolds CF III, Jennings JR, et al (1988b): Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men. Psychiatry Res 26:79-87. Wasserman MD, Pollack CP, Spielman AJ, Weitzman ED (1980): The differential diagnosis of impotence: The measurement of nocturnal penile tumescence. JAMA 243:2038-2042. Wein AJ, Van Arsdalen K, Malloy TR (1983): Nocturnal penile tumescence. In Ktane RJ, Siroky MB, Goldstein I (eds), Male Sexual Dysfunction. Boston: Little, Brown.
BIOL PSYCHIATRY I.o92;31.1130- t 142
Diminished Nocturnal Penile Tumescence in Depression: A Replication Study Michael E. Thase, Charles F. Reynolds III, J. Richard Jennings, Ellen Frank, Gregory L. Garamoni, Eric A. Nofzinger, Amy L. Fascizka, and David J. Kupfer
A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic criteria (RDC) major depression in order to replicate earlier observations that measure~ of nocturnal penile tumescence (NPT) and penile rigidity are disturbed in depressive s:~ztes. When compared to both the age-equated patient (n = 34) and normal control (n = 28) groups reported in our 1988 study, the new sample manifested significant abnormalities ~,f NPT and diminished penile rigidity. Such distuPbances were not, however, significantly correlated with psychobiological indicators oJ severe or endogenous depression.
Introduction Although the libidinal disturbances associated with depressive syndromes have been longrecognized (Small and Small 1930), more recent work suggests that some depressed patients also manifest abnormalities of underlying sexual neurophysiology (Roose et al 1982); Thase et al 1987). In an initial study we demonstrated a reduction in nocturnal penile tumescence (NPT) and decreased penile rigidity in a sample of 34 depressed men (Thase et al i988a). Such disturbances were of sufficient degree to lead to false positive diagnoses of presumably irreversible erectile dysfunction in about 15% of depressed men (Thase et al 1988b). These findings have significant clink:al implications for two groups of patients: depressed patients (i.e., with respect to further illuminating the mechanisms and/or correlates of apparently state-dependent sexual difficulties); and patients seeking evaluation for sexual dysfunctior~ (i.e., for whom an abnormal NPT study may be incorrectly presumed to be caused by an irreversible organic pathglogy rather than depression). More specifically, NPT studies may not be valid in the evaluation of erectile dysfunction until a man has been assessed for and, if pertinent, treated foc ~ depressive episode (Thase et al 1987). In the current report, we provide additional evidence of altered NPT in depression by
From the Western Psychiatric Institute and Clinic, Department of Psychiatry, Unive~.ity of Pittsburgh Scho'q of Medicine, Pittsburg, Pennsylvania. Address reprint requests to Dr. Michael E. Thase, Western Psychiatric Institute and Clinic, Departmet L., t'sychiatry, University of Pittsburgh School of Medicine, 3811 C'Hara Street, Pittsburgh, PA 15213. Received July 27, 1991; revised March 30, 1~)2. © 1992 Society of Biological Psychiatry
0006-3223/92/$05.00
Nocturnal Penile Tumescence in Depression
BIOLPSYCHIATRY 1992;3 ~: 1136-1142
1137
presenting results of an internal replication study, conducted in a nonoverlapping sample of 51 depressed men. We have compared this new sample with both the control and depression groups from an original study (Thase et al 1988b) in order to determine if the finding of diminished NIT is present in a new sample of depressed men. We also examined potential psychobiological correlates of diminished NIT in this new patient sample. Methods The methods for recruitment, inclusion, exclusion, and assessment of patients and controls, as well as those for performance of NPT studies are virtually identical to those described in our earlier reports (Thase et al 1988a, 1988b). To briefly summarize, physically healthy men meeting the criteria of both DSM-HI-R (APA 1987) and researcia diagnostic criteria (RDC) (Spitzer et a11987) for a unipolar, nonpsychotic major depressive episode were. enrolled in the study if they scored >- 14 points on the first 17 items of the Hamilton Rating Scale for Depression (HRSD; Hamilton 1960). Diagnoses were based on at~ initial interview conducted by a clinical evaluator and faculty psychiatrist and confirmed by a second, semistructured interview using the Schedule for Affective Disorders and Schizoprhenia (Endicott and Spitzer 1978). Patients were representative of men seeking outpatient treatment at our hospital and they w e r e n o t selected on the basis of clinical reports of sexual dysfunction. After patients provided written informed consent they began a minimum 14-day drug- a~d alcohol-free, supc~wised wash out. During the first week of wash out, potential patients were further evaluated with physical and urological examinations, including Doppler assessment of penile arterial blood flow. Laboratory screening included complete blood count, chemistry profile, syphilis and acquired immune deficiency syndrome (AIDS) serology, thyroid function studies, and electrocardiogram. Sixty men with major depression were initially enrolled in the replication series, with two subsequently withdrawing consent for research participation ~,rior to sleep/NPT assessment and seven excluded on the basis of identification of medical factors that might affect sleep and/or sexual function (such as diabetes, hypertension, prior lumbosacral spinal surgery, and/or urological disorders). The remaining sample of 51 patients began all-night electroencephalographic (EEG) sleep and NPT studies in our Sleep Evaluation Center upon completion of the wash out. Sample chat~acteristics are described in Table 1. Nocturnal penile tumescence recoldings (Karacan et al 1978; Wasserman et al 1980) were performed in conjunction with all-night polysomnographic studies on at least 3 consecutive nights. The methods for scoring these measures and their rdiability have been reported previously (Campbell et al 1987; Thase et al 1988a, 1988b). In our NPT protocol, Night 1 is used for adaptation to the laboratory ~nd procedures. Night 2 is utilized to collect polygraphic r~easures of tumescence (Le., minutes of NIT, number of NPT episodes, NPT time divided by rapid eye movement (REM) time, and NIT time divided by total sleep time). On Night 3, visua~ inspection procedures are performed, which include technologists' and patients' ratings of erectile fullness and measurement of penile buckling force (Wein et al 1983). Consistent with the preliminary report of Karacan et al (1985) and the findings from our initial study of depressed men (Thase et al 1988a, 1988b), we selected a maximum buckling force value of ~500 g force as the criterion for dimir~ished penile rigidity. Two sets of between-group comparisons were conducted on these measures. First,
1138
M.E. Thase et al
BIOL PSYCHIATRY 1992;31:1136-1142
Table 1. Clinical Characteristics of Depressed and Healthy Control Subjects° Group t-tests or X2
Age (yr) Race (white/other) Education (yr) Partner status (yes/no) ° HRSD (17-item) Number of depressive episodes Duration of current episode (wk) Median Range Diagnostic subtype
Controls
Study i depressed
Study 2 depressed
(n = 28)
(n = 34)
(n = 51)
34.8 (13.0) 26/2 16.3 (2.3) 18/10 0.8 (1.5)
35.3 (10.2) 31/3 14.8 (2.3) 18/16 18.6 (3.5) 2 . 4 (1.5)
37.5 (9.6) 49/2 15.7 (2.6) 38/13 19.2 (3.8) 1. I (2.6)
4 5 . 5 (48.7)
43.3 (49.7)
24 3-156
26 3-260
13/5/14
7,14/30
~d3C endogenous
(No/probable/definite) Pretreatmeat EEG sleep Sleep efficiency (%) Slow-wave sleep (%) REM sleep (%) REM Latency (min)
89.6 14.5 21.0 81.8
(6.8) (10.3) (5.4) (41.6)
87.1 14.1 20.9 75.2
(9.0) (10.7) (5.4) (42.6)
89.8 10.1 24.3 60.2
(7.8) (8.1) (4.6) (16.2)
Study l depressed vs study 2 depressed t X2 t X2 t t
= = = = =
- 1.01 0.89 - 1.64 4.22 b -0.74 2.64 c
Study 1 controls vs study 2 depressed t = - 1.05 X2 = 0 . 3 9 t = 1.02 X2 - 0.92 t = -24.54 a
t = 0.20
)~z _ 7.95 c
t t t t
= --
- 1.45 1.94 -3.13 ~ 2.28 b
t t t t
- - 1. I 1 - 2.0cYs = -2.87 c - 3.29 d
*Mean( -.+ SD) unless otherwise noted. Partnerstatus "yes" includesmarriage,cohabitation, and/oran ongoing monogamousrelationship.
~t,< 0,05. ~p < o.oI. ~j, < o.ool.
two-tailed t-tests or, when appropriate for nonparametric comparisons, 7(2 tests were performed, comparing the new samples of 51 depressed men against the 28 controls from the earlier series (Thase et al 1988a). Second, the new sample was similarly compared to the previous sample of 34 depressed men. We predicted a full replication, thus it was hypothesized that a comparable level of abnormality would be observed in the two depressed samples, whereas the new depressive sample would show reduced measures of tumescence time and diminished maximum penile rigidity when compared to controls. Next, potential clinical and sleep EEG correlates of diminished NPT were examined in the new sample of 51 depressed men. The following univariate measures were correlated with NPT time (divided by REM time) and buckling force: age, pretreatment HRSD severity, percentage of sleep maintenance, percentage of slow-wave sleep, REM density (units), and REM latency (min). Pearson correlation coefficients were computed for the comparisons with NPT/REM time, whereas nonparametric Spearman correlations were used for comparisons with maximum buckling force. A nonparametric statistic was used in the latter correlational analyses because buckling force scores were not normally distributed (see Figure 1). We also compared these NPT parameters in patients diagnosed as meeting the criteria of RDC for nonendogenous (n = 7), probable endogenous (n = 14), or definite endogenous (n - 30) subtype of major depression. A one factor analysis of variance (ANOVA) was used for the polygraphic measure (NPT time divided by REM
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Figure 1. Distribution of maximum buckling force in depressed patients from study 1, study 2, and normal controls.
time) and a KruskaI-Wallace nonparametric ANOVA was used for comparing maximum buckling force. Based on our earlier findings (Thase et al 1988), we predicted that diminished NIT in depression would be associated with older age, increased HRSD severity, and poorer sleep m.':intenance. Results
The two sets of comparisons between these samples are summarized in Table 2 and illustrated in Figures 1 and 2. When compared to nondepressed controls, the new sample of 51 depressed men had highly significant reductions of all polygraphic measures of NIT (Ps < 0.001), including decreased tumescence time when considered in relation to the amount of total sleep time and the amount of REM time. Depressed men also averaged about one fewer episode of tumescence per night than controls (p - 0.002). Each of these differences remained significant when the analyses were recomputed as one factor analyses of covariance, using age as the covariate. A significantly greater proportion of depressed men in the new sample also had maximum buckling force values in the impaired range (i.e., < 500 g force): 29/51 (57%) versus 4/28 (16%), X2 = 4.2, df = 1, p = 0.04.
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M.E. Thase et al
BIOL PSYCHIATRY 1992;31:1136-1142
Table 2. Comparison of Sleep-Related Tumescence in Depressed and Healthy Control Subjects (Means _+ SD) Group t-tests or X2
Study 1 depressed (n = 34)
Study 2 depressed (n = 51)
Study 1 depressed vs study 2 depressed
144.9 (49.7)
98.7 (46.8)
105.2 (49.0)
t = -0.6
t = 3.4`"
0.37 (0.14)
0.26 (0.11)
0.27 (0.12)
t = -0.4
t = 3.4"
1.87 (0.93)
1.34 (0.74)
1.16 (0.54)
t = 1.3
t = 3.8`"
4.3 (1.4) 4 (16)
3.9 (1.3) 12 (38)
3.3 (1.3) 29 (57)
t = 2.2* X2 = 2.9
Controls (n = 28) Total tumescence time (rain) Total tumescence time/time spent asleep Total tumescence time/REM time Number of episodes Maximum buckling force: Number of cases <500 g
Study I controls vs study 2 depressed
t = 3.2 b X2 = 4.2*
(%) °p < 0.05.
~p< o.ol. Cp < 0.001.
Comparisons of the two depression samples demonstrated no differences on the three polygraphic measures of NPT (see Figure 2 and Table 2). The new sample, however, had a lower mean number of episodes of tumescence (p = I).03) and tended to have a higher proportion of patients with impaired penile rigidity (p = 0.09) when compared to the original sample. In the series of correlational analyses, the tumescence time/REM time measure was not significantly associated with age (r = 0.02, HRSD severity (r = 0.12), sleep maintenance (r = -0.08), percentage of slow wave sleep (r = 0.09), REM density (r = 0.10), and REM latency (r = -0.07). Similarly, maximum buckling force was not significantly associated (Spearman correlation coefficients) with HRSD severity (rs = - 0.01), sleep maintenance (rs = 0.15), percentage of slow-wave sleep (rs = -0.04), and REM latency (rs = - 0 . 0 7 ) . Only age was weakly associated in the predicted direction with reduced buckling force (rs = - 0 . 2 4 , p = 0.09). With respect to categorical subtype diagnoses of depression, there was no evidence that the ratio of tumescence time to REM time was lower in definite RDC endogenous depression when compared to probable or nonendogenous depression cases (ANOVA; F2,49 = 0 . 6 5 , p --': 0 . 5 4 ) . In fact, there was a trend for RDC definite endogenous cases to have significantly higher buckling force scores when compared to the other cases (Kruskal-Wallis X2 = 5.08, df = 2, p = 0.08). Discussion The results of this internal replication study provide further evidence that depressed men manifest alterations of erectile neurophysiology. The current sample had somewhat more abnormal NPT profiles than the patient~ described in the 1988 report. In this regard, the patients in the first and second studies did not differ with respect to either age or ratings
Nocturnal Penile Tumt~scence in Depression
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BIOL PSYCH[ATRY ]992;3]:1136-1142
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1141
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Figure 2. Distribution of polygraphic measures of nocturnal penile tumescence for depressed patients from study I (Din; n -- 34), study 2 (D2; n - 51), and normal controls (n - 28).
of depressive severity. However, patients in the second series were significantly more likely to meet criteria for RDC definite endogenous depression subtype and they had significantly more abnormal EEG sleep profiles, including significantly reduced REM latency, significantly increased REM time, and a trend for a reduced percentage of slowwave sleep. In both of our outpatient studies, the level of reduction in polygraphic measures of tumescence and penile rigidity generally reflect a relative decrease rather than an absence of tumescence as r~,iginally described by Roose et al (1982) in two older, severely depressed hospitalized patients. The significant abnormalities noted in this second series again point to a pathological process adversely affecting NPT in depression. This is particularly striking because episodes of nocturnal penile tumescence typically accompany REM sleep periods (Karacan et al 1978) and, in the new sample, REM time was significantly increased, whereas measures of NPT remained significantly decreased. Depression thus appears to belong to a group of disorders in which there is an apparent uncoupling cf REM sleep and NPT (Nofzinger et al 1992; Wasserman et al 1980; Wein et al 1983). Although independent confirmation of these results is still desirable, the findings of our replication study strengthen the likelihood that diminished NPT is a neurophysiological correlate of depression. The question of the reversibility (i.e., state dependence) of NFT
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BIOL PSYCHIATRY 1992;31:i 136-1142
M.E. Thase etal
disturbances will be addressed in a subsequent report (Nofzinger et al in press). However, in this replication study, we were unable to confirm any substantial relationship between disturbances of NPT and psychobiological indicators of severe or endogenous depression. Therefore, it seems possible that the neurophysiologicai processes that are linked to disturbed NPT in depressed patients may not be specific to affective illness. Nevertheless, we wish to reemphasize that, in a some cases, depression can be associated with an NPT profile that is indistinguishable from that seen in organic impotence. This work was supported in part by NIMH grants MH-40023, MH-00295, and MH-30915, and a grant from the John D. and Catherine T. MacArthur Foundation Research Network on the Psychobiologyof Depression. We wish to thank the faculty and staff of the Sleep Evaluation Center and the Cognitive Therapy Clinic of the Western Psychiatric Institute and Clinic and Ms. Lisa Stupar for their assistance in this research.
References Ame~can Psychiatric Association (1987): Diagnostic and Statistical Manual of Mental Disorders, 3~d ed. rev). Washington, DC: American Psychiatric Press. Campbell P!, Reynolds CF, Jennings JR, et al (1987): Laboratory note: Reliability of NPT scoring and visual estimates or erectile fullness. Sleep 10:480--485. Endicott J, Spitzer RL (1978): A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry 35:837-844. Hamilton M (1960): A rating scale for depression. J Neurol Neurosurg Psychiatry 12:56--62. Karacan I, Salis PJ, Williams RL (1978): The role of the sleep laboratory in diagnosis and treatment of impotence. In Williams RL, Karacan l (eds), Sleep Disorders: Diagnosis and Treatmert. New York: John Wiley & Sons. Karacan I, Moore C, Sahmay S (1985): Me~surement of pressure necessary for vaginal penetration. Sleep Res 14:269. Nofzinger EA, Reynolds CF 111, Jennings JR, et al (1992): Results of nocturnal penile tumescence studies are abnormal in sexually functional diabetic men. Arch Intern Med 152:114-118. Nofzinger EA, Thane ME, Frank E, et al Sexual function in depresst~d men: Assessment using self-report, behavioral and nocturnal penile tumescence measures before and after treatment with cognitive behavior therapy. Arch Gen Psychiatry in press. Roose SP, Glassman AH, Walsh BT, Cullen K (1982): Reversible loss of nocturnal penile tumescence during depression: A preliminary report. Neuropsychobiology 8:284-288. Small IF, Small JG (1980): Sex and mental illness. In Kaplan HI, Freedman AM, Saddock BJ (eds), Comprehensive Textbook of Psychiatry, 3rd ed, vol 2. Baltimore: Williams & Wilkins. Spitzer RL, Endicott J, Robit:s E (1978). Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 35:773-782. Thase ME, Reynolds CF III, Glanz LM, et al (1987). Nocturnal penile tumescence in depressed men. Am J Psychiatry 144:89-92. Thase ME, Reynolds CF III, Jennings JR, et al (1988a): Nocturnal penile tumescence is diminished in depressed men. Biol Psychiatry 24:33-46. Thase ME, Reynolds CF III, Jennings JR, et al (1988b): Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men. Psychiatry Res 26:79-87. Wasserman MD, Pollack CP, Spielman AJ, Weitzman ED (1980): The differential diagnosis of impotence: The measurement of nocturnal penile tumescence. JAMA 243:2038-2042. Wein AJ, Van Arsdalen K, Malloy TR (1983): Nocturnal penile tumescence. In Ktane RJ, Siroky MB, Goldstein I (eds), Male Sexual Dysfunction. Boston: Little, Brown.