- Email: [email protected]
Psychogenic polydipsia and water intoxication—Concepts that have failed
1308
BIOL PSYCHIATRY 1985 ;20:1308-1320
Psychogenic Polydipsia and Water Intoxication Concepts that Have Failed W. V. R. Vieweg, J. J. David, W. T. Rowe, M. J. Peach, J. D. Veldhuis, D. L. Kaiser, and W. W. Spradlin
Ten patients (8 men, 2 women; mean age 38.7 +_ 8.1 years), 7 of whom had schizophrenic disorders and 3 of whom had bipolar disorder (manic-depressive illness), manifested psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). The relationship between serum sodium and urinary water excretion among the 10 PIP patients is described in detail. The success of lithium in improving serum sodium levels and in decreasing urinary water excretion among the three PIP patients with bipolar disorder and the failure of changes in urinary water excretion to explain changes in serum sodium levels among the 10 PIP patients argue against "psychogenesis" as the explanation for the polydipsia and excessive water intake as the sole explanation for hyponatremia or complications ascribed to water intoxication.
Introduction Psychogenesis is applied to a symptom or illness when "mental" or "psychic" rather than "organic" or "structural" factors are thought to be causative (APA 1980). This concept has been applied to patients drinking large daily volumes of fluids for no apparent reason, resulting in the use of the term psychogenic polydipsia. The term water intoxication is used to describe the pathological consequences resulting from the daily consumption of large volumes of fluids (Rowntree 1923). The literature has been less than rigorous in describing the polydipsic psychiatric population, resulting in the use of such terms as polydipsia, psychogenic polydipsia, hysterical polydipsia, primary polydipsia, compulsive polydipsia, compulsive water drinking, increased water ingestion, water intoxication, psychogenic water intoxication, and self-induced water intoxication (Rowntree 1923; Bauer 1925; Barahal 1938; Carter and Robbins 1947; Dingman et al. 1957; Barlow and DeWardener 1959; Dies et al. 1961; Langgard and Smith 1962; Hobson and English 1963; Bewley 1964; Sahadevan and Bayliss 1965; Leiken and Caplan 1967; Resnick and Patterson 1969; Devereaux and McCormick 1972; Dubovsky et al. 1973; Chinn 1974; Raskind 1974; Raskind et al. 1975; Mendelson and Deza 1976; Rae 1976; Noonan and
From the Clinical Evaluation Unit, Western State Hospital; the Department of Mental Health and Mental Retardation, Commonwealth of Virginia; the Department of Behavioral Medicine and Psychiatry, Department of Pharmacology, and the Division of Endocrinology and Metabolism and the Clinical Computing Laboratory, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA. Address reprint requests to Dr. W. V. R. Vieweg, Western State Hospital, Box 2500, Staunton, VA 24401. Received January 7, 1985; revised July 8, 1985.
© 1985 Society of Biological Psychiatry
0006-3223/85/$03.30
Psychogenic Polydipsia
BIOLPSYCHIATRY
1309
1985;20:1308-1320
Ananth 1977; Rendell et al. 1978; Jos and Perez-Cruet 1979; Jos et al. 1979; Rosenbaum et al. 1979; Blotcky et al. 1980; DiMaio and DiMaio 1980; Hariprasad et al. 1980; Jos and Evenson 1980; Shevitz et al. 1980; Smith and Clark 1980; Davis et al. 1981 ; Nixon et al. 1982; Saruta et al. 1982; Blum and Friedland 1983; Blum et al. 1983; Kramer and Drake 1983; Jos 1984; Roberge et al. 1984; Zubenko et al. 1984). When using these terms, the author may be simply implying that the patient drinks inordinately large amounts of water or may be implying that complications, including hyponatremia, hypoosmolality, cerebral edema, psychosis, seizures, coma, death, polyuria, bowel and bladder dilatation and hypotonicity, hydronephrosis, renal failure, and congestive heart failure, are due to the large water consumption. Despite these complications associated with polydipsia, no studies are available relating magnitude of water consumption to complications assumed to be due to water toxicity (Rowntree 1923; Bauer 1925; Barahal 1938; Carter and Robbins 1947; Dingman et al. 1957; Barlow and DeWardener 1959; Dies et al. 1961; Langgard and Smith 1962; Hobson and English 1963; Bewley 1964; Sahadevan and Bayliss 1965; Leiken and Caplan 1967; Resnick and Patterson 1969; Devereaux and McCormick 1972; Dubovsky et al. 1973; Chinn 1974; Raskind 1974; Raskind et al. 1975; Mendelson and Deza 1976; Rae 1976; Noonan and Ananth 1977; RendeU et al. 1978; Jos and PerezCruet 1979; Jos et al. 1979; Rosenbaum et al. 1979; Blotcky et al. 1980; DiMaio and DiMaio 1980; Hariprasad et al. 1980; Jos and Evenson 1980; Shevitz et al. 1980; Smith and Clark 1980; Davis et al. 1981; Nixon et al. 1982; Saruta et al. 1982; Blum and Friedland 1983; Blum et al. 1983; Kramer and Drake 1983; Jos 1984; Roberge et al. 1984; Zubenko et al. 1984). It is the purpose of this report to describe, in detail, the relationship between serum sodium and urinary water excretion among 10 patients with polydipsia, intermittent hyponatremia, and psychosis (PIP syndrome). The success of lithium in improving serum sodium levels and in decreasing urinary water excretion, and the failure of changes in urinary water excretion to explain changes in serum sodium levels among our 10 PIP patients, argue against "psychogenesis" as an explanation for the polydipsia and excessive water intake as the sole explanation for hyponatremia or complications ascribed to water intoxication. Methods Ten patients (eight men and two women) were referred consecutively to the Clinical Evaluation Unit because of complications ascribed to polydipsia that were refractory to management. These patients comprise the study population. Ages ranged from 28 to 53 years, with a mean value of 38.7 ___ 8.1 years. Each patient manifested auditory hallucinations, delusions, and distortions of thought content and progression consistent with psychosis. According to DSM-III criteria, seven patients suffered from schizophrenic disorders and three patients had bipolar disorder (manic-depressive illness). Each patient had consumed large quantities of water for many years. Complications included recurrent seizures and coma secondary to hyponatremia, gastrointestinal and bladder dilatation and hypotonicity, and mild hydronephrosis. No patients were edematous, hypotensive, or hypovolemic. Adrenal, hepatic, renal, and thyroid function studies were normal. No patient had abnormal serum glucose, lipids, or nonprotein nitrogen determinations. Studies were generally performed on Mondays, Wednesdays, and Fridays, and study periods for patients 1 through 10 were 7, 7, 7, 7, 7, 5.5, 4.5, 5.5, 5.5, and 4.5 months, respectively. During these times, patients 1, 2, 4, 8, and 10 received haloperidol (Haldol);
1310
eIOLPSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
patients 6 and 9 received trifluoperazine (Stelazine); patient 5 received chlorpromazine (Thorazine); patient 7 received thioridazine (Mellaril); and patient 3 received haloperidol (Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin) during the first one-third of the study period and no drugs thereafter. In addition to the abovementioned antipsychotic agents, patients 8 through 10 received trials of lithium for bipolar disorder. No patients received diuretics. In the case of patient 2, the dose of haloperidol (Haldol) was decreased, leading to exacerbation of psychosis, hyponatremia, and polydipsia. In the case of patient 6, trifluoperazine (Stelazine) was temporarily discontinued, yielding psychosis, increased water consumption, and the lowest serum sodium determination during the period of study. Patients 1,2, 3, 4, 7, 8, and 9 received supplemental salt by mouth (patient 3 during the first one-third of the study period), whereas the remaining three patients were given regular 8-g salt (136 meq of sodium) diets during the study periods. Serial determinations of serum sodium, urinary creatinine concentration, and urinary specific gravity were obtained between 6 and 7 AM each study day. Patients 8, 9, and 10 underwent serial determinations of serum lithium levels following initiation of treatment with that drug. Patterns of urinary excretion throughout the day were established for PIP patients by measuring urinary specific gravity at 8 AM, 4 PM, and 8 PM on 8 consecutive Thursdays. A control group of psychotic nonpolydipsic patients was also studied. For all 10 patients, the relationships between serum sodium and specific gravity, serum sodium and urinary creatinine concentration, and specific gravity and urinary creatinine concentration were sought using the Pearson correlation coefficient. Student's t-test was used to evaluate parameters of water metabolism before and during lithium administration for the three PIP patients with bipolar disorder (manic-depressive illness). Also, Student's t-test was used to compare parameters of water metabolism among the seven PIP patients with schizophrenic disorders and the three PIP patients with bipolar disorder. Multiple regression was used to identify significant associations among patient characteristics (age, sex, weight), specific gravity, serum sodium, and urinary creatinine concentration. A general linear model was used for the analysis in order to incorporate categorical variables (sex) with interval measures. Results For patients I through t0, 17.8%, 30.7%, 41.9%, 63.2%, 54.7%, 21.0%, 34.1%, 58.1%, 11.1%, and 3.7% of the serum sodium values were less than 136 meq/liter, respectively, and 125, 128, 120, 121, 125, 128, 128, 124, 122, and 109 meq/liter were the respective lowest serum sodium levels during the study periods. All patient characteristics (age, sex, weight) were found to be significant in predicting serum sodium levels (p < 0.0001). This is probably reflective of inherent differences in sodium levels from patient to patient, rather than causal links between these measures and serum sodium. For the seven PIP patients with schizophrenic disorders, mean serum sodium levels ranged between 133.63 and 139.54 meq/liter, mean specific gravity ranged between 1.00195 and 1.00712, and mean urinary creatinine concentration ranged between 11.65 and 69.81 mg/dl (Table 1). Using 17.5 mg creatinine/kg body weight for men and 12.5 creatinine/kg body weight for women to estimate 24-hr urinary excretion of creatinine and then dividing by early morning creatinine concentration, mean estimated 24-hr urinary volumes for PIP patients 1 through 7 (schizophrenic disorders) were 9330, 4286, 5123,
r = 0.016 p = 0.88
Serum sodium vs urinary
creatinine concentration
creatinine concentration Specific gravity r = 0.782 vs urinary p = 0.0001
r = 0.142
p = 0.18
vs specific gravity
13.30 ± 9.26 5.0-62.0
3.45 ± 2.36 1-14
139.19 ± 4.00 128-146
M 76.36 11/23/83 to 4/13/84 62
28
6
1.95 ± 1.14 1-8
137.39 __. 4.71 128-145
M 64.55 2/14/84 to 6/29/84 41
28
7
4.52 ± 2.78 0-17
136.55 --- 4.58 120-151
540
6M/IF 75.39 ± 9.85
39.57 ± 9 . 5 4
Group
r = 0.811 p = 0.0001
r = 0.714 p - 0.0001
r = 0.348 p = 0.001
r = 0.618 p = 0.0001
r = 0.096 p = 0.37
r = 0.727 p = 0.0001
r = 0.935 p = 0.0001
r = 0.325 p = 0.01
r = 0.844 p = 0.0001
r = -0.355 p = 0.02
r = 0.743 p ~ 0.0001
r = -0.113 p < 0.05
r = -0.162 p = 0.14
7.12 ± 2.36 2-17
134.94 ± 3.31 125-142
M 86.36 9/26/83 to 4/18/84 86
53
5
r = -0.020 p = 0.86
3.97 ± 1.60 0-8
133,63 ± 4,21 121-143
to 4/13/84 87
9/14/83
M 86.36
45
Patient 4
22.38 --+ 18.14 11.65 ± 14.20 27.35 ± 25.93 69.81 ± 29.88 15.0-185.0 8.5 ± 103.0 5.5-97.0 4.0-185.0 r = 0.027 r = 0.265 r = -0.360 r = -0.030 p = 0.81 p = 0.04 p = 0.02 p > 0.2
5.93 ___ 3.50 1-16
135.38 ± 4.44 120-147
M 80.91 9/12/83 to 4/13/84 86
46
3
18.16 ± 11.36 27.64 __. 19.68 19.88 ± 10.71 6.0-80.0 4.0-84.0 5.3~6.0 r = -0,000 r = 0.460 r = 0.196 p = 0.999 p = 0.0001 p = 0.07
5.07 ± 1.97 1-12
2.60 ± 1.63 1-9
125-151
136.84 ± 2.94 128-144
F 62.27 9/14/83 to 4/11/84 88
139.54 ± 4.97
42
M 70.91 9/12/83 to 4/13/84 90
2
35
Serum sodium
creatinine concentration (mg/dl) Mean Range
Range Specific gravity 1.00 Mean Range Urinary
(meq/liter) Mean
Number of observations Serum sodium
Age (years) Sex (M/F) Weight (kg) Study period
1
T a b l e 1. A n a l y s i s o f P a r a m e t e r s o f W a t e r M e t a b o l i s m f o r S e v e n P a t i e n t s w i t h P s y c h o s i s , I n t e r m i t t e n t H y p o n a t r e m i a , a n d P o l y d i p s i a ( P I P )
U~
~t")
1312
BIOL PSYCHIATRY 1985;20:1308-1320
W.V.R.
V i e w e g e t al.
7602, 2165, 5971, and 9696 ml, respectively, yielding a relationship of r = 0.406, p > 0.2 between mean 24-hr urinary volumes and mean serum sodium determinations. Group correlation of serum sodium versus urinary creatinine concentration yielded r = -0.113, p < 0.05, whereas group correlation of serum sodium versus specific gravity did not reach statistical significance (p > 0.2). For the three PIP patients with bipolar disorder, mean serum sodium levels ranged between 134.45 and 142.30 meq/liter, mean specific gravity ranged between 1.00358 and 1.00507, and mean urinary creatinine concentration ranged between 20.33 and 33.01 mg/dl. Mean estimated 24-hour urine volumes for PIP patients 8 through 10 were 7043, 5209, and 2806 ml, respectively. When these parameters of water regulation were separated into prelithium and lithium periods, lithium administration led to increased serum sodium values and decreased polyuria, as shown by increased urinary specific gravity and increased urinary creatinine concentration (p < 0.01) (Table 2). Furthermore, lithium administration seemed to enhance the relationship between serum sodium and specific gravity and urinary creatinine concentration (p < 0.01). Table 3 provides a comparison of the schizophrenic disorders group and the bipolar disorder group. When the seven PIP patients with schizophrenic disorders were compared with the three PIP patients with bipolar disorder prior to lithium treatment, mean serum sodium values were similar, but the bipolar patients were more polyuric. Following the administration of lithium to the bipolar patients, serum sodium was greater, whereas polyuria was similar as compared with the schizophrenic patients. PIP patients remain hyposthenuric throughout the day, although their 8 A M u r i n a r y specific gravity is slightly more concentrated than the 4 PM and 8 PM determinations (Table 4). Nonpolyuric psychotic patients receiving comparable doses of antipsychotic drugs have strikingly higher urinary specific gravities (p < 0.001).
Table 2. Analysis of Parameters of Water Metabolism for Three Patients with Psychosis, Intermittent Hyponatremia, and Polydipsia.
N u m b e r o f observations S e r u m sodium (meq/liter)
Before lithium administration
D u r i n g lithium administration
48 135.313 --- 7 . 0 3 2
48 140.479 ± 4 . 4 6 3
Specific gravity 1.00 Urinary creatinine concentration (mg/dl) S e r u m lithium (meq/liter) S e r u m sodium vs specific g r a v i t y S e r u m sodium vs urinary creatinine concentration Specific gravity vs urinary creatinine concentration
3.146 -
1.868
4 . 6 0 4 ~ 2.541
14.556 -+ 7.421
r p r p r p
= > = > = <
-0.015 0.2 0.113 0.2 0.764 0.001
28.613 ~ 23.979
r p r p r p
Student's t-test
t p t p t p
= < = < = <
-4.252 0.001 -3.169 0.01 -3.839 0.001
0.899 ~ 0.286 = 0.390 < 0.01 = 0.332 < 0.01 = 0.849 < 0.001
Parameters were determined before and during lithium administration. There were 16 determinations for each patient during each phase, See text for discussion.
Psychogenic Polydipsia
BIOL PSYCHIATRY 1985;20:1308-1320
1313
Table 3. Population Comparison Using Student's t-test of Seven PIP Patients (A) who Did Not Receive Lithium with Three PIP Patients (B) who Did Receive Lithium A
B
t-test
A compared with B before lithium treatment Serum sodium (meq/liter) Specific gravity 1.00 Urinary creatinine concentration (mg/dl)
136.55 ± 4.58 4.52 ± 2.78 27.35 ± 25.93
135.313 ± 7.032
t = 1.699, p > 0.05
3.146 ± 1.868 14.556 ± 7.421
t = 3.352, p < 0.001 t = 3.400, p < 0.001
A compared with B during lithium treatment Serum sodium (meq/liter) Specific gravity 1.00 Urinary creatinine concentration (mg/dl)
136.55 ± 4.58 4.52 ± 2.78 27.35 +_ 25.93
140.479 ± 4.463 4.604 ± 2.541 28.613 ± 23.979
t = -5.841,p
< 0.001
t = - 0 . 2 0 2 , p > 0.5 t = - 0 . 3 2 5 , p > 0.5
Discussion The association of psychosis and polydipsia was firmly established by the work of Hoskins et al. in the early 1930s, when they demonstrated that patients with schizophrenic disorders excreted almost twice (2602 ml) the daily urine volume of normal subjects (1328 ml) (Hoskins 1933; Hoskins and Sleeper 1933; Sleeper and Jellinek 1936). Our patients excreted much larger volumes than did Hoskin's patients, but we were referred only the most seriously ill PIP patients. Using 17.5 mg creatinine/kg body weight for men and
T a b l e 4. V a r i a t i o n s o f U r i n a r y S p e c i f i c G r a v i t y ( 1 . 0 0 ) T h r o u g h o u t the D a y a m o n g P I P P a t i e n t s 1-4 a n d 6. Patient
8 AM
4 PM
8 PM
1 No. of observations 2 No. of observations 3 No. of observations 4 No. of observations 6 No. of observations Group No. of observations Controls No. of observations t value PIP group vs controls
3.50 -+ 1.20 8 5.13 - 3.27 8 6.50 + 2.78 8 4.63 ± 2.83 8 3.50 ± 1.60 8 4.65 -¢- 2.60 40 18.1 ± 7.6 8 - 8.703 p < 0.00l
1.57 - 0.79 7 4.67 --_ 3.78 6 4.40 _+ 3.21 5 2.29 --- 1.25 7 2.14 __. 0.90 7 2.88 ± 2.41 32 13.1 ± 6.6 9 - 7.037 p < 0.00l
2.13 ± 0.99 8 2.33 - 1.03 6 4.63 --- 3.93 8 2.38 -'- 0.92 8 2.13 _+ 0.99 8 2.74 ± 2.14 38 I1.1 ± 3.6 8 -- 8.555 p < 0.001
Tests were run each Thursday for 8 consecutive weeks. A control group of psychotic nonpolydipsic patients is provided.
1314
aIOL PSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
12.5 mg creatinine/kg body weight for women to estimate 24-hr urinary excretion of creatinine, we divided 24-hr urinary creatinine by early morning creatinine concentration to provide a gross estimate of urinary volume. Among PIP patients, urinary flow is relatively constant throughout the day (Table 4), and thus, this method is satisfactory in estimating daily urine volume (Peters and Van Slyke 1946; Vieweg et al. 1984a,b,c; Vieweg et al. 1985a,c,d,e). Other investigators have used specific gravity of 1.008 or less as criterion for psychogenic polydipsia (Blum and Friedland 1983). There was excellent correlation between early morning urinary creatinine concentration and specific gravity (r = 0.773, p < 0.0001) among PIP patients, and so we used both these parameters as indices of polyuria (hence polydipsia). We have defined daily urine volumes of 2600 ml or greater for men and 2200 ml or greater for women or early morning specific gravity of 1.008 or less as criteria for polydipsia for our patients. Implied in the term "water intoxication" is that the pathological features are a product of water consumption. Yet nowhere in the literature is there a description of the relationship between the amount of water consumed and pathological findings (Rowntree 1923; Bauer 1925; Barahal 1938; Carter and Robbins 1947; Dingman et al. 1957; Barlow and DeWardener 1959; Dies et al. 1961; Langgard and Smith 1962; Hobson and English 1963; Bewley 1964; Sahadevan and Bayliss 1965; Leiken and Caplan 1967; Resnick and Patterson 1969; Devereaux and McCormick 1972; Dubovsky et al. 1973; Chinn 1974; Raskind 1974; Raskind et al. 1975; Mendelson and Deza 1976; Rae 1976; Noonan and Ananth 1977; Rendell et al. 1978; Jos and Perez-Cruet 1979; Jos et al. 1979; Rosenbaum et al. 1979; Blotcky et al. 1980; DiMaio and DiMaio 1980; Hariprasad et al. 1980; Jos and Evenson 1980; Shevitz et al. 1980; Smith and Clark 1980; Davis et al. 1981; Nixon et al. 1982; Saruta et al. 1982; Blum and Friedland 1983; Blum et al. 1983; Kramer and Drake 1983; Jos 1984; Roberge et al. 1984; Zubenko et al. 1984). The suggestion is that "water intoxication" occurs when solute-free water is ingested in excess of maximal free water clearance. As maximal free water clearance approaches 20 ml/min, "water intoxication" occurs when the patient consumes at least 29 liters of water per day (20 ml free water/ min × 1440 min/day = 28,800 ml water/day) (Bartter 1973). None of our patients consistently consumed such large quantities of fluids, although on very rare occasions several of our patients have excreted more than 30 liters of urine in a day. We have used serum sodium levels of less than 136 meq/liter to define hyponatremia. In such settings, one must be sure that pseudohyponatremia is not present (i.e., elevated serum glucose, lipids, or urea nitrogen). Pseudohyponatremia can be excluded by obtaining concomitant serum osmolality. The frequency of hyponatremia among PIP patients ranged between 3.7% and 63.2%. Using urinary creatinine concentration and specific gravity as indices of polyuria, we found a very poor relationship between serum sodium and polyuria (r = - 0.113, p < 0.05) (Table 1). Thus, water consumption alone cannot explain "water intoxication." Water balance studies have been used to better understand the syndrome of inappropriate antidiuresis (SIAD) (Leaf et al. 1953; Stormont and Waterhouse 1961; Kaye 1966; Cooke et al. 1979). An early model suggested that the state of hydration determined the effect the antidiuretic hormone arginine vasopressin (AVP) had on serum sodium level; that is, AVP controlled a filter that allowed water to pass by: The more water that passed by, the more sodium was carried with it, leading to hyponatremia and compounding the dilutational effect of increased plasma water (Leaf et al. 1953). A more complicated model speculated that polydipsia provokes expansion of total body water, leading to intracellular hypotonicity followed by a shift of sodium ion from extracellular to intra-
Psychogenic Polydipsia
BIOLPSYCHIATRY
1315
1985;20:1308-1320
cellular fluid (Kaye 1966). This redistribution of sodium results in serum hyponatremia and the clinical complications that follow. There have been multiple reports linking PIP and SIAD (Hobson and English 1963; Dubovsky et al. 1973; Raskind et al. 1975; Rosenbaum et al. 1979; Hariprasad et al. 1980; Jos and Evenson 1980; Smith and Clark 1980; Kramer and Drake 1983; Roberge et al. 1984). Barlow and DeWardener (1959) studied patients with psychogenic polydipsia and demonstrated that they failed to develop features of "water intoxication" until exogenous AVP was given. Despite the mounting evidence, standard textbooks of medicine continue to describe psychogenic polydipsia and complications that follow as problems of water intake (Wyngaarden and Smith 1982). Lithium has long been known to influence water regulation through such mechanisms as natriuresis, decreasing renal tubular concentrating capacity, distal renal tubular acidosis, and the induction of nephrogenic diabetes insipidus by partial blockage of AVP at the renal receptor sites (Baylis and Health 1978; Miller et al. 1979; Bucht and Wahlin 1980; Vestergaard and Amdisen 1981; Battle et al. 1982; Ramsey and Cox 1982; Gold et al. 1983). Interference with renal tubular concentrating capacity is the most common clinical renal effect yielding polyuria and secondary polydipsia. However, this is seldom a problem. Because lithium can inhibit AVP action in the kidney, it has been used effectively to treat SIAD (White and Fetner 1975; Forrest et al. 1978). The finding that lithium administration to PIP patients with bipolar disorder resulted in stabilization of serum sodium in the normal range and reduction in polyuria warrants comment. In this population, the mean serum sodium rose from 135.313 to 140.479 meq/liter following lithium administration (Table 2). Furthermore, early morning urinary creatinine concentration rose from 14.556 to 28.613 mg/dl and specific gravity rose from 1.003146 to 1.004604. As lithium acts peripherally by blocking AVP action at the distal renal tubules and collecting ducts (partial nephrogenic diabetes insipidus with the induction of polyuria), its action among our three PIP patients with bipolar disorder must have produced a central override wherein better control of the psychosis reduced polydipsia and polyuria and normalized serum sodium. Zubenko et al. (1984) described three PIP patients with recurrent affective disorders who improved clinically following control of the affective exacerbations with antipsychotic drugs. However, these investigators failed to quantitate polydipsia or polyuria or to relate improvement in polyuria to serum sodium levels. Interestingly, among our bipolar patients, lithium administration enriched the relationship between serum sodium and urinary creatinine concentration and specific gravity. Of all the psychiatric diagnoses, bipolar disorder is most readily accepted as "biological" in origin. The improvement in water homeostasis following lithium administration among PIP patients argues convincingly against the concept of "psychogenic polydipsia." The antipsychotic drugs used by our patients have been implicated in the syndrome of hyponatremia in psychiatric patients (Sandifer 1983). However, the PIP syndrome clearly antedated the antipsychotic drug era. When we reviewed the severity of polyuria among 71 chronically psychotic male patients receiving antipsychotic agents, we found the mean daily urine volume, when corrected for body weight, to be identical to the figure derived by Hoskins et al. (Hoskins 1933; Hoskins and Sleeper 1933; Sleeper and Jellinek 1936). When we decreased or eliminated antipsychotic drugs in our PIP patient population, there was exacerbation of psychosis, intermittent hyponatremia, and polydipsia. In our experience, increasing rather than decreasing antipsychotic drug administration offers a more promising course for PIP patients. Although diuretics are the drugs most likely to induce hyponatremia and SIAD (Fichman et al. 1971), none of our patients received such drugs before or during the study periods.
1316
BIOLPSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
It appears to us that patients with PIP have disturbances in both the "dipsostat" and the "osmostat" in the hypothalamus. These patients consistently drink large quantities of water as a result of thirst dysregulation. Intermittently, osmotic dysregulation occurs as AVP is inappropriately secreted from the posterior lobe of the pituitary gland (nonosmotic stimulus: Type A SIAD) (Zerbe et al. 1980), or AVP effect is enhanced at the junction of the distal renal tubule and collecting ducts due to the hypersensitivity of the AVP receptors (Type D SIAD) (Zerbe et al. 1980). The complications of PIP, broadly divided into those due to hyponatremia and those due to fluid retention, then reflect the combined influence of thirst and osmotic dysregulation. If AVP effect is great, then mild polydipsia will lead to complications, and if polydipsia is great, then mildly inappropriate AVP effect will lead to complications. The former paradigm describes the classic SIAD (Bartter and Schwartz 1967) patient, and the latter paradigm describes our experience with the PIP patient (Vieweg et al. 1984a,b; Vieweg et al. 1985b,c,e). Others have speculated upon disturbances in both the "dipsostat" and "osmostat" in PIP patients (Robertson 1980). This separation of the "dipsostat" and "osmostat" is highly arbitrary, as fluid balance derangements that stimulate thirst also stimulate the release of AVP. The enteroceptor mechanisms that govern AVP release also govern water intake, with the only difference being in enteroceptor threshold AVP release threshold being lower than thirst threshold (Andersson and Rundgren 1982). There is an anatomical and biochemical linkage between the limbic system and the hypothalamus. Forebrain afferents from the lateral septum, bed nucleus of stria terminalis, ventral subiculum, and medial amygdala join the supraoptic and paraventricular nuclei of the hypothalamus where the AVP neurons are located (Powell and Rorie 1967; Swanson and Cowan 1975; Zaborsky et al. 1975; Conrad and Pfaff 1976; Rogers et al. 1979; Silverman et al. 1981; Tribollet and Dreifuss 1981). Also, the magnocellular vasopressin neurons of the supraoptic and paraventricular hypothalamic nuclei are sensitive directly to the neurotransmitters acetylcholine, norepinephrine, dopamine, angiotensin II, and opioid peptides; in addition, substance P, thyrotropin-releasing hormone, and somatostatin terminals are found in these nuclei (Hayward 1977; Palkovits and Brownstein 1978; Poulain and Wakedy 1982). It is known that patients with psychosis have elevated AVP levels (Raskind et al. 1978) and that this can be associated with acute water intoxication (Goldberg 1981). Thus, the psychotic state may alter drinking behavior and osmotic regulation, possibly through the hormone and neurotransmitter AVP, leading to the complications associated with PIP. Use of the term "psychogenic polydipsia" arises from the psychoanalytic hypothesis used to explain compulsive behavior. Arieti describes such compulsive behavior during the third or "preterminal" stage of schizophrenic disorders (Arieti 1945). According to this author, the "preterminal" stage occurs 5-15 years after the onset of psychosis, and the compulsive behavior, which includes hoarding and self-decorating habits, is regression to the analsadistic stage. Alternately, regression to the oral-dependent stage might explain such behavior. Initially (1933), Hoskins's group thought that disturbances in water regulation among PIP patients involved the hypothalamus or posterior lobe of the pituitary gland (Hoskins 1933), but 3 years later, they claimed that the polydipsia was "psychical" rather than "physiological" or "biochemical" in origin (Sleeper and Jellinek 1936). We believe that the overall evidence suggests that biochemical changes in the hypothalamus could best explain PIP. Moreover, we have demonstrated that polydipsia alone cannot explain the complications of PIP, which thus limits both the uses and concepts of "psychogenic polydipsia" and "water intoxication." In addition to the psychoanalytic hypothesis to explain PIP, several other hypotheses have
Psychogenic Polydipsia
BIOLPSYCHIATRY
1317
1985;20:1308-1320
been offered recently. Kissileff (1973) proposed that compulsive water drinking is a "response to increased levels of transmitter substances accumulating in the limbic system during the experience of frustration." This speaks to the putative role AVP has as a neurotransmitter for memory, behavior, and learning as well as its role in water metabolism (Nemeroff and Prange 1978). Mellinger and Zafar (1983) described a patient with a diseased "dipsostat" and normal "osmostat" who manifested a lifelong pattern of polydipsia (up to 6 liters/day) without intermittent hyponatremia. When AVP was administered exogenously, hypoosmolality appeared and polydipsia stopped. The patient has been maintained on exogenously administered AVP sufficient to stabilize plasma osmolality to below 270 mosmol/kg, yielding symptomatic relief from thirst without producing complications associated with PIP. It may be that our PIP patients are secreting AVP inappropriately in an attempt to interdict thirst, i.e., compensate for disruption in the feedback mechanism between the "dipsostat" and the "osmostat." Work by Snyder has demonstrated that opiate agonists are up to 50 times stronger in the absence of sodium and that opiate receptors are highly concentrated in numerous structures of the limbic system (the site of emotional regulation in the brain), particularly the amygdala (Snyder 1984). An interesting possibility is that PIP patients seek to enhance opiate receptor effect by decreasing surrounding sodium concentration. In a sense, they may be addicted to water. References Andersson B, Rundgren M (1982): Thirst and its disorders. Annu Rev Med 33:231-239. APA (1980): A Psychiatric Glossary, 5th ed. Washington, DC: American Psychiatric Association. Arieti S (1945): Primitive habits in the preterminal stage of schizophrenia. J Nerv Ment Dis 102:367-375. Barahal HS (1938): Water intoxication in a mental case. Psychiatr Q 12:767-771. Barlow ED, DeWardener HE (1959): Compulsive water drinking. Q J Med 28:235-258. Bartter FC (1973): The syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In Disease-a-Month. Chicago: Yearbook Medical. Bartter FC, Schwartz WB (1967): The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42:790-806. Batlle D, Gaviria M, Grupp M, Arruda JAL, Wynn J, Kurtzman NA (1982): Distal nephron function in patients receiving chronic lithium therapy. Kidney lnt 21:447--485. Bauer R (1925) Zur Pathologie und Differentialdiagnose von "Diabetes insipidus" und primarer Polydipsia. Wien Arch Inn Med 11:201. Baylis PH, Health DA (1978): Water disturbances in patients treated with oral lithium carbonate. Ann Intern Med 88:607---609. Bewley TH (1964): Acute water-intoxication from compulsive water-drinking. Br Med J 2:864. Blotcky MJ, Grossman I, Looney JG (1980): Psychogenic water intoxication: A fatality. Tex Med 76:58-59. Blum A, Friedland GW (1983): Urinary tract abnormalities due to chronic psychogenic polydipsia. Am J Psychiatry 140:915-916. Blum A, Tempey FW, Lynch WJ (1983): Somatic findings in patients with psychogenic polydipsia. J Clin Psychiatry 44:55-56. Bucht G, Wahlin A (1980): Renal concentrating capacity in long-term lithium treatment and after withdrawal of lithium. Acta Med Scand 207:309-314. Carter AC, Robbins J (1947): The use of hypertonic saline infusions in the differential diagnosis of diabetes insipidus and psychogenic polydipsia. J Clin Endocrinol 7:753-766. Chinn RA (1974): Compulsive water drinking. J Nerv Ment Dis 158:78-80. Conrad LC, Pfaff DW (1976): Autoradiographic tracing of the nucleus accumbens efferents in the rat. Brain Res 113:589-596.
1318
BIOLPSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
Cooke CR, Turin MD, Walker WG (1979): The syndrome of inappropriate antidiuretic hormone secretion (SIADH): Pathophysiologic mechanisms in solute and volume regulation. Medicine 58:240-251. Davis JRE, McNeill M, Miilar JW (1981): latrogenic water intoxication in psychogenic polydipsia. Scott Med J 26:148-150. Devereaux MW, McCormick RA (1972): Psychogenic water intoxication: A case report. Am J Psychiatry 129:140-142. Dies F, Rangel S, Rivera A (1961): Differential diagnosis between diabetes insipidus and compulsive polydipsia. Ann Intern Med 54:710-725. DiMaio VJM, DiMaio SJ (1980): Fatal water intoxication in a case of psychogenic polydipsia. J Foren Sci 25:332-335. Dingman JF, Benirschke K, Thorn GW (1957): Studies of neurohypophyseal function in man. Am J Med 23:226-238. Dubovsky SL, Grabon S, Bed T, Schrier RW (1973): Syndrome of inappropriate secretion of antidiuretic hormone with exacerbated psychosis. Ann Intern Med 79:551-554. Fichman MP, Vorherr H, Kleeman CR, Telfer N (1971): Diuretic-induced hyponatremia. Ann Intern Med 75:853-863. Forrest JN, Cox M, Hong C, Morrison G, Bia M, Singer I (1978): Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 298:173-177. Gold PW, Robertson GL, Post RM, Kaye W, Ballenger J, Rubinow D, Goodwin FK (1983): The effect of lithium on the osmoregulation of arginine vasopressin secretion. J Clin Endocrinol Metab 56:295-299. Goldberg M (1981): Hyponatremia. Med Clin North Am 65:251-269. Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS, Nidus BD (1980): Hyponatremia in psychogenic polydipsia. Arch Intern Med 140:1639-1642. Hayward JN (1977)" Functional and morphological aspects of hypothalamic neurons. Physiol Rev 57:574-658. Hobson JA, English JT (1963): Self-induced water intoxication. Case study of a chronically schizophrenic patient with physiological evidence of water retention due to inappropriate release of antidiuretic hormone. Ann Intern Med 58:324-332. Hoskins RG (1933): Schizophrenia from the physiological point of view. Ann Intern Med 7:445-456. Hoskins RG, Sleeper FH (1933): Organic functions in schizophrenia. Arch Neurol Psychiatry 30:123-140. Jos CJ (1984): Generalized seizures from self-induced water intoxication. Psychosomatics 25:153-157. Jos CJ, Perez-Cruet J (1979): Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry 136:221-222. Jos CJ, Barton JL, Perez-Cruet J (1979): Hyponatremic seizures in psychiatric patients. Biol Psychiatry 14:839-843. Jos CJ, Evenson RC (1980): Antecedents of self-induced water intoxication. A preliminary report. J Nerv Ment Dis 168:498-500. Kaye M (1966): An investigation into the cause of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 41:910-926. Kissileff HR (1973): Epstein AN, Kissileff HR, Stellar E (eds), Nonhomeostatic controls of drinking. In Neuropsychology of Thirst: New Findings and Advances in Concepts. New York: Halsted Press. Kramer DS, Drake ME Jr (1983): Acute psychosis, polydipsia, and inappropriate secretion of antidiuretic hormone. Am J Med 75:712-714. Langgard H, Smith WO (1962): Self-induced water intoxication without predisposing illness. Report of two cases. N Engl J Med 266:378-381.
Psychogenic Polydipsia
BIOLPSYCHIATRY
1319
1985;20:1308-1320
Leaf A, Bartter FC, Santos RF, Wrong O (1953): Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J Clin Invest 32:868-879. Leiken SJ, Caplan H (1967): Psychogenic polydipsia. Am J Psychiatry 123:1573-1576. Mellinger RC, Zafar MS (1983): Primary polydipsia. Syndrome of inappropriate thirst. Arch Intern Med 143:1249-1251. Mendelson WB, Deza PC (1976): Polydipsia, hyponatremia, and seizures in psychotic patients. J Nerv Ment Dis 162:140-143. Miller PD, Dubovsky SL, McDonald KM, Katz FH, Robertson GL, Schrier RW (1979): Central, renal and adrenal effects of lithium in man. Am J Med 66:797-803. Nemeroff CB, Prange AJ Jr (1978): Peptides and psychoneuroendocrinology. Arch Gen Psychiatry 35:999-1010. Nixon RA, Rothman JS, Chin W (1982): Demeclocycline in the prophylaxis of self-induced water intoxication. Am J Psychiatry 139:828-830. Noonan JPA, Ananth J (1977): Compulsive water drinking and water intoxication. Compr Psychiatry 18:183-187. Palkovits M, Brownstein MJ (1978): Concentrations of the neurotransmitters in the supraoptic and the paraventricular nuclei in the rat. In Bargmann W, Oksche A, Polenov A, Scharrer B (eds), Neurosecretion and Neuroendocrine Activity. Berlin: Springer-Verlag, pp 250-255. Peters JP, Van Slyke DD (1946): Quantitative Clinical Chemistry: Interpretations vol 1. Baltimore: Williams & Wilkins. Poulain DA, Wakerly JB (1982): Electrophysiology of hypothalamic magnocellular neurons secreting oxytocin and vasopressin. Neuroscience 7:773-808. Powell EW, Rorie DK (1967): Septal projections to nuclei functioning in oxytocin release. Am J Anat 120:605-610. Rae J (1976): Self-induced water intoxication in a schizophrenic patient. Can MedAssoc J 114:438-439. Ramsey RA, Cox M (1982): Lithium and the kidney: A review. Am J Psychiatry 139:443---449. Raskind M (1974): Psychosis, polydipsia, and water intoxication. Report of a fatal case. Arch Gen Psychiatry 30:112-114. Raskind MA, Orenstein H, Christopher G (1975): Acute psychosis, increased water ingestion, and inappropriate antidiuretic hormone secretion. Am J Psychiatry 132:907-910. Raskind MA, Weitzman RE, Orenstein H, Fisher DA, Courtney N (1978): Is antidiuretic hormone elevated in psychosis: A pilot study. Biol Psychiatry 13:385-390. Rendell M, McGrane D, Cuesta M ( 1978): Fatal compulsive water drinking. JAMA 240:2557-2559. Resnick ME, Patterson C (1969): Coma and convulsions due to compulsive water drinking. Neurology 19:1125-1130. Roberge R, Gernsheimer J, Sparano R, Tartakoff R, Morgenstem MJ, Rubin K, Senekiian D, Andrade R, Matthew V (1984): Psychogenic polydipsia--an unusual cause of hyponatremic coma and seizure. Ann Emerg Med 13:274---276. Robertson GL (1980): Psychogenic polydipsia and inappropriate antidiuresis. Arch Intern Med 140:1574. Rogers RC, Talbot K, Novin D, Butcher LL (1979): Afferent projections to the supraoptic nucleus of the rat. Soc Neurosci Abstr 5:233. Rosenbaum JF, Rothman JS, Murray GB ( 1979): Psychosis and water intoxication. J Clin Psychiatry 40:287-291. Rowntree LG (1923): Water intoxication. Arch Intern Med 32:157-174. Sahadevan MG, Bayliss VD (1965): Compulsive water drinking. A report of two cases. J Assoc Physicians India 13:755-757. Sandifer MG (1983): Hyponatremia due to psychotrophic drugs. J Clin Psychiatry 44:301-304. Saruta R, Fujimaki M, Ogihara R, Saito I, Konishi K, Kondo K (1982): Evaluation of the renin-angiotensin system in diabetes insipidus and psychogenic polydipsia. Nephron 32:14-17.
1320
BIOLPSYCHIATRY !985;20:1308-1320
W.V.R. Vieweg et al.
Shevitz SA, Jameison RC, Petrie WM, Crook JE (1980): Compulsive water drinking treated with high dose propranolol. J Nerv Ment Dis 168:246-248. Silverman AJ, Hoffman DL, Zirnmerman EA (1981): The descending afferent connections of the paraventricular nucleus of the hypothalamus. Brain Res Bull 6:47-61. Sleeper FH, Jellinek EM (1936): A comparative physiologic, psychologic, and psychiatric study of polyuric and nonpolyuric schizophrenic patients. J Nerv Ment Dis 83:557-563. Smith WO, Clark ML (1980): Self-induced water intoxication in schizophrenic patients. Am J Psychiatry 137:1055-1060. Snyder SH (1984): Drug and neurotransmitter receptors in the brain. Science 224:22-31. Stormont JM, Waterhouse C (1961): The genesis of hyponatremia associated with marked overhydration and water intoxication. Circulation 14:191-203. Swanson LW, Cowan WM (1975): Hippocampal-hypothalamic connections: Origin in subicular cortex, not Ammon's horn. Science 189:303-304. Tribollet E, Dreifuss JJ (1981): Localization of neurons projecting to the hypothalarnic paraventricular nucleus area of the rat: A horseradish peroxidase study. Neuroscience 6:1315-1328. Vestergaard P, Amdisen A (1981): Lithium treatment and kidney function. A follow-up study of 237 patients in long-term treatment. Acta Psychiatr Scand 63:333-345. Vieweg WVR, Rowe WT, David JJ, Spradlin WW (1984a): Hyposthenuria as a marker for selfinduced water intoxication and schizophrenic disorders. Am J Psychiatry 141:1258-1260. Vieweg WVR, Rowe WT, David JJ, Sutker LH, Spradlin WW (1984b): Evaluation of patients with self-induced water intoxication and schizophrenic disorders (SIWIS). J Nerv Ment Dis 172:552-555. Vieweg WVR, Rowe WT, David JJ, Yank GR, Spradlin WW (1984c): The "Mini-Mental State" in the syndrome of self-induced water intoxication and schizophrenic disorders (SIWIS): A pilot study, lnt J Psychiatry Med 14:347-359. Vieweg WVR, David JJ, Rowe WT, Wampler GJ, Burns WJ, Spradlin WW (1985a): Death from self-induced water intoxication among patients with schizophrenic disorders. J Nerv Ment Dis 173:161-165. Vieweg WVR, Rowe WT, David J J, Spradlin WW (1985b): Oral sodium chloride in the management of schizophrenic patients with self-induced water intoxication. J Clin Psychiatry 46:16-19. Vieweg WVR, David JJ, Rowe WT, Canterbury ILl, Spradlin WW (1985c): Hypocalcemia: An additional complication of the syndrome of self-induced water intoxication and psychosis (SIWlP). Psych Med (in press). Vieweg WVR, Rowe WT, David JJ, Curnow RT, Spradlin WW (1985d): Patterns of urinary excretion among patients with self-induced water intoxication and psychosis (SIWIP). Psychiatry Res (in press). Vieweg WVR, Rowe WT, David JJ, Curnow RT, Spradlin WW (1985e): Self-induced water intoxication and psychosis (SIWIP): Subcategory of the syndrome of inappropriate antidiuresis (SIAD). Psych Med (in press). White MG, Fetner CD (1975): Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with lithium carbonate. N Engl J Med 292:390-392. Wyngaarden JB, Smith LH Jr (eds) (1982): Cecil's Textbook of Medicine, 16th ed. Philadelphia: W.B. Saunders. Zaborsky L, Leranth CS, Makara GB, Palkovits M (1975): Quantative studies on the supraoptic nucleus in the rat. II. Afferent fiber connections. Exp Brain Res 22:525-540. Zerbe R, Stropes L, Robertson G (1980): Vasopressin function in the syndrome of inappropriate antidiuresis. Annu Rev Med 31:315-327. Zubenko GS, Altesman RI, Cassidy JW, Barreira PJ (1984): Disturbances of thirst and water homeostasis in patients with affective illness. Am J Psychiatry 141:436---438.
BIOL PSYCHIATRY 1985 ;20:1308-1320
Psychogenic Polydipsia and Water Intoxication Concepts that Have Failed W. V. R. Vieweg, J. J. David, W. T. Rowe, M. J. Peach, J. D. Veldhuis, D. L. Kaiser, and W. W. Spradlin
Ten patients (8 men, 2 women; mean age 38.7 +_ 8.1 years), 7 of whom had schizophrenic disorders and 3 of whom had bipolar disorder (manic-depressive illness), manifested psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). The relationship between serum sodium and urinary water excretion among the 10 PIP patients is described in detail. The success of lithium in improving serum sodium levels and in decreasing urinary water excretion among the three PIP patients with bipolar disorder and the failure of changes in urinary water excretion to explain changes in serum sodium levels among the 10 PIP patients argue against "psychogenesis" as the explanation for the polydipsia and excessive water intake as the sole explanation for hyponatremia or complications ascribed to water intoxication.
Introduction Psychogenesis is applied to a symptom or illness when "mental" or "psychic" rather than "organic" or "structural" factors are thought to be causative (APA 1980). This concept has been applied to patients drinking large daily volumes of fluids for no apparent reason, resulting in the use of the term psychogenic polydipsia. The term water intoxication is used to describe the pathological consequences resulting from the daily consumption of large volumes of fluids (Rowntree 1923). The literature has been less than rigorous in describing the polydipsic psychiatric population, resulting in the use of such terms as polydipsia, psychogenic polydipsia, hysterical polydipsia, primary polydipsia, compulsive polydipsia, compulsive water drinking, increased water ingestion, water intoxication, psychogenic water intoxication, and self-induced water intoxication (Rowntree 1923; Bauer 1925; Barahal 1938; Carter and Robbins 1947; Dingman et al. 1957; Barlow and DeWardener 1959; Dies et al. 1961; Langgard and Smith 1962; Hobson and English 1963; Bewley 1964; Sahadevan and Bayliss 1965; Leiken and Caplan 1967; Resnick and Patterson 1969; Devereaux and McCormick 1972; Dubovsky et al. 1973; Chinn 1974; Raskind 1974; Raskind et al. 1975; Mendelson and Deza 1976; Rae 1976; Noonan and
From the Clinical Evaluation Unit, Western State Hospital; the Department of Mental Health and Mental Retardation, Commonwealth of Virginia; the Department of Behavioral Medicine and Psychiatry, Department of Pharmacology, and the Division of Endocrinology and Metabolism and the Clinical Computing Laboratory, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA. Address reprint requests to Dr. W. V. R. Vieweg, Western State Hospital, Box 2500, Staunton, VA 24401. Received January 7, 1985; revised July 8, 1985.
© 1985 Society of Biological Psychiatry
0006-3223/85/$03.30
Psychogenic Polydipsia
BIOLPSYCHIATRY
1309
1985;20:1308-1320
Ananth 1977; Rendell et al. 1978; Jos and Perez-Cruet 1979; Jos et al. 1979; Rosenbaum et al. 1979; Blotcky et al. 1980; DiMaio and DiMaio 1980; Hariprasad et al. 1980; Jos and Evenson 1980; Shevitz et al. 1980; Smith and Clark 1980; Davis et al. 1981 ; Nixon et al. 1982; Saruta et al. 1982; Blum and Friedland 1983; Blum et al. 1983; Kramer and Drake 1983; Jos 1984; Roberge et al. 1984; Zubenko et al. 1984). When using these terms, the author may be simply implying that the patient drinks inordinately large amounts of water or may be implying that complications, including hyponatremia, hypoosmolality, cerebral edema, psychosis, seizures, coma, death, polyuria, bowel and bladder dilatation and hypotonicity, hydronephrosis, renal failure, and congestive heart failure, are due to the large water consumption. Despite these complications associated with polydipsia, no studies are available relating magnitude of water consumption to complications assumed to be due to water toxicity (Rowntree 1923; Bauer 1925; Barahal 1938; Carter and Robbins 1947; Dingman et al. 1957; Barlow and DeWardener 1959; Dies et al. 1961; Langgard and Smith 1962; Hobson and English 1963; Bewley 1964; Sahadevan and Bayliss 1965; Leiken and Caplan 1967; Resnick and Patterson 1969; Devereaux and McCormick 1972; Dubovsky et al. 1973; Chinn 1974; Raskind 1974; Raskind et al. 1975; Mendelson and Deza 1976; Rae 1976; Noonan and Ananth 1977; RendeU et al. 1978; Jos and PerezCruet 1979; Jos et al. 1979; Rosenbaum et al. 1979; Blotcky et al. 1980; DiMaio and DiMaio 1980; Hariprasad et al. 1980; Jos and Evenson 1980; Shevitz et al. 1980; Smith and Clark 1980; Davis et al. 1981; Nixon et al. 1982; Saruta et al. 1982; Blum and Friedland 1983; Blum et al. 1983; Kramer and Drake 1983; Jos 1984; Roberge et al. 1984; Zubenko et al. 1984). It is the purpose of this report to describe, in detail, the relationship between serum sodium and urinary water excretion among 10 patients with polydipsia, intermittent hyponatremia, and psychosis (PIP syndrome). The success of lithium in improving serum sodium levels and in decreasing urinary water excretion, and the failure of changes in urinary water excretion to explain changes in serum sodium levels among our 10 PIP patients, argue against "psychogenesis" as an explanation for the polydipsia and excessive water intake as the sole explanation for hyponatremia or complications ascribed to water intoxication. Methods Ten patients (eight men and two women) were referred consecutively to the Clinical Evaluation Unit because of complications ascribed to polydipsia that were refractory to management. These patients comprise the study population. Ages ranged from 28 to 53 years, with a mean value of 38.7 ___ 8.1 years. Each patient manifested auditory hallucinations, delusions, and distortions of thought content and progression consistent with psychosis. According to DSM-III criteria, seven patients suffered from schizophrenic disorders and three patients had bipolar disorder (manic-depressive illness). Each patient had consumed large quantities of water for many years. Complications included recurrent seizures and coma secondary to hyponatremia, gastrointestinal and bladder dilatation and hypotonicity, and mild hydronephrosis. No patients were edematous, hypotensive, or hypovolemic. Adrenal, hepatic, renal, and thyroid function studies were normal. No patient had abnormal serum glucose, lipids, or nonprotein nitrogen determinations. Studies were generally performed on Mondays, Wednesdays, and Fridays, and study periods for patients 1 through 10 were 7, 7, 7, 7, 7, 5.5, 4.5, 5.5, 5.5, and 4.5 months, respectively. During these times, patients 1, 2, 4, 8, and 10 received haloperidol (Haldol);
1310
eIOLPSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
patients 6 and 9 received trifluoperazine (Stelazine); patient 5 received chlorpromazine (Thorazine); patient 7 received thioridazine (Mellaril); and patient 3 received haloperidol (Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin) during the first one-third of the study period and no drugs thereafter. In addition to the abovementioned antipsychotic agents, patients 8 through 10 received trials of lithium for bipolar disorder. No patients received diuretics. In the case of patient 2, the dose of haloperidol (Haldol) was decreased, leading to exacerbation of psychosis, hyponatremia, and polydipsia. In the case of patient 6, trifluoperazine (Stelazine) was temporarily discontinued, yielding psychosis, increased water consumption, and the lowest serum sodium determination during the period of study. Patients 1,2, 3, 4, 7, 8, and 9 received supplemental salt by mouth (patient 3 during the first one-third of the study period), whereas the remaining three patients were given regular 8-g salt (136 meq of sodium) diets during the study periods. Serial determinations of serum sodium, urinary creatinine concentration, and urinary specific gravity were obtained between 6 and 7 AM each study day. Patients 8, 9, and 10 underwent serial determinations of serum lithium levels following initiation of treatment with that drug. Patterns of urinary excretion throughout the day were established for PIP patients by measuring urinary specific gravity at 8 AM, 4 PM, and 8 PM on 8 consecutive Thursdays. A control group of psychotic nonpolydipsic patients was also studied. For all 10 patients, the relationships between serum sodium and specific gravity, serum sodium and urinary creatinine concentration, and specific gravity and urinary creatinine concentration were sought using the Pearson correlation coefficient. Student's t-test was used to evaluate parameters of water metabolism before and during lithium administration for the three PIP patients with bipolar disorder (manic-depressive illness). Also, Student's t-test was used to compare parameters of water metabolism among the seven PIP patients with schizophrenic disorders and the three PIP patients with bipolar disorder. Multiple regression was used to identify significant associations among patient characteristics (age, sex, weight), specific gravity, serum sodium, and urinary creatinine concentration. A general linear model was used for the analysis in order to incorporate categorical variables (sex) with interval measures. Results For patients I through t0, 17.8%, 30.7%, 41.9%, 63.2%, 54.7%, 21.0%, 34.1%, 58.1%, 11.1%, and 3.7% of the serum sodium values were less than 136 meq/liter, respectively, and 125, 128, 120, 121, 125, 128, 128, 124, 122, and 109 meq/liter were the respective lowest serum sodium levels during the study periods. All patient characteristics (age, sex, weight) were found to be significant in predicting serum sodium levels (p < 0.0001). This is probably reflective of inherent differences in sodium levels from patient to patient, rather than causal links between these measures and serum sodium. For the seven PIP patients with schizophrenic disorders, mean serum sodium levels ranged between 133.63 and 139.54 meq/liter, mean specific gravity ranged between 1.00195 and 1.00712, and mean urinary creatinine concentration ranged between 11.65 and 69.81 mg/dl (Table 1). Using 17.5 mg creatinine/kg body weight for men and 12.5 creatinine/kg body weight for women to estimate 24-hr urinary excretion of creatinine and then dividing by early morning creatinine concentration, mean estimated 24-hr urinary volumes for PIP patients 1 through 7 (schizophrenic disorders) were 9330, 4286, 5123,
r = 0.016 p = 0.88
Serum sodium vs urinary
creatinine concentration
creatinine concentration Specific gravity r = 0.782 vs urinary p = 0.0001
r = 0.142
p = 0.18
vs specific gravity
13.30 ± 9.26 5.0-62.0
3.45 ± 2.36 1-14
139.19 ± 4.00 128-146
M 76.36 11/23/83 to 4/13/84 62
28
6
1.95 ± 1.14 1-8
137.39 __. 4.71 128-145
M 64.55 2/14/84 to 6/29/84 41
28
7
4.52 ± 2.78 0-17
136.55 --- 4.58 120-151
540
6M/IF 75.39 ± 9.85
39.57 ± 9 . 5 4
Group
r = 0.811 p = 0.0001
r = 0.714 p - 0.0001
r = 0.348 p = 0.001
r = 0.618 p = 0.0001
r = 0.096 p = 0.37
r = 0.727 p = 0.0001
r = 0.935 p = 0.0001
r = 0.325 p = 0.01
r = 0.844 p = 0.0001
r = -0.355 p = 0.02
r = 0.743 p ~ 0.0001
r = -0.113 p < 0.05
r = -0.162 p = 0.14
7.12 ± 2.36 2-17
134.94 ± 3.31 125-142
M 86.36 9/26/83 to 4/18/84 86
53
5
r = -0.020 p = 0.86
3.97 ± 1.60 0-8
133,63 ± 4,21 121-143
to 4/13/84 87
9/14/83
M 86.36
45
Patient 4
22.38 --+ 18.14 11.65 ± 14.20 27.35 ± 25.93 69.81 ± 29.88 15.0-185.0 8.5 ± 103.0 5.5-97.0 4.0-185.0 r = 0.027 r = 0.265 r = -0.360 r = -0.030 p = 0.81 p = 0.04 p = 0.02 p > 0.2
5.93 ___ 3.50 1-16
135.38 ± 4.44 120-147
M 80.91 9/12/83 to 4/13/84 86
46
3
18.16 ± 11.36 27.64 __. 19.68 19.88 ± 10.71 6.0-80.0 4.0-84.0 5.3~6.0 r = -0,000 r = 0.460 r = 0.196 p = 0.999 p = 0.0001 p = 0.07
5.07 ± 1.97 1-12
2.60 ± 1.63 1-9
125-151
136.84 ± 2.94 128-144
F 62.27 9/14/83 to 4/11/84 88
139.54 ± 4.97
42
M 70.91 9/12/83 to 4/13/84 90
2
35
Serum sodium
creatinine concentration (mg/dl) Mean Range
Range Specific gravity 1.00 Mean Range Urinary
(meq/liter) Mean
Number of observations Serum sodium
Age (years) Sex (M/F) Weight (kg) Study period
1
T a b l e 1. A n a l y s i s o f P a r a m e t e r s o f W a t e r M e t a b o l i s m f o r S e v e n P a t i e n t s w i t h P s y c h o s i s , I n t e r m i t t e n t H y p o n a t r e m i a , a n d P o l y d i p s i a ( P I P )
U~
~t")
1312
BIOL PSYCHIATRY 1985;20:1308-1320
W.V.R.
V i e w e g e t al.
7602, 2165, 5971, and 9696 ml, respectively, yielding a relationship of r = 0.406, p > 0.2 between mean 24-hr urinary volumes and mean serum sodium determinations. Group correlation of serum sodium versus urinary creatinine concentration yielded r = -0.113, p < 0.05, whereas group correlation of serum sodium versus specific gravity did not reach statistical significance (p > 0.2). For the three PIP patients with bipolar disorder, mean serum sodium levels ranged between 134.45 and 142.30 meq/liter, mean specific gravity ranged between 1.00358 and 1.00507, and mean urinary creatinine concentration ranged between 20.33 and 33.01 mg/dl. Mean estimated 24-hour urine volumes for PIP patients 8 through 10 were 7043, 5209, and 2806 ml, respectively. When these parameters of water regulation were separated into prelithium and lithium periods, lithium administration led to increased serum sodium values and decreased polyuria, as shown by increased urinary specific gravity and increased urinary creatinine concentration (p < 0.01) (Table 2). Furthermore, lithium administration seemed to enhance the relationship between serum sodium and specific gravity and urinary creatinine concentration (p < 0.01). Table 3 provides a comparison of the schizophrenic disorders group and the bipolar disorder group. When the seven PIP patients with schizophrenic disorders were compared with the three PIP patients with bipolar disorder prior to lithium treatment, mean serum sodium values were similar, but the bipolar patients were more polyuric. Following the administration of lithium to the bipolar patients, serum sodium was greater, whereas polyuria was similar as compared with the schizophrenic patients. PIP patients remain hyposthenuric throughout the day, although their 8 A M u r i n a r y specific gravity is slightly more concentrated than the 4 PM and 8 PM determinations (Table 4). Nonpolyuric psychotic patients receiving comparable doses of antipsychotic drugs have strikingly higher urinary specific gravities (p < 0.001).
Table 2. Analysis of Parameters of Water Metabolism for Three Patients with Psychosis, Intermittent Hyponatremia, and Polydipsia.
N u m b e r o f observations S e r u m sodium (meq/liter)
Before lithium administration
D u r i n g lithium administration
48 135.313 --- 7 . 0 3 2
48 140.479 ± 4 . 4 6 3
Specific gravity 1.00 Urinary creatinine concentration (mg/dl) S e r u m lithium (meq/liter) S e r u m sodium vs specific g r a v i t y S e r u m sodium vs urinary creatinine concentration Specific gravity vs urinary creatinine concentration
3.146 -
1.868
4 . 6 0 4 ~ 2.541
14.556 -+ 7.421
r p r p r p
= > = > = <
-0.015 0.2 0.113 0.2 0.764 0.001
28.613 ~ 23.979
r p r p r p
Student's t-test
t p t p t p
= < = < = <
-4.252 0.001 -3.169 0.01 -3.839 0.001
0.899 ~ 0.286 = 0.390 < 0.01 = 0.332 < 0.01 = 0.849 < 0.001
Parameters were determined before and during lithium administration. There were 16 determinations for each patient during each phase, See text for discussion.
Psychogenic Polydipsia
BIOL PSYCHIATRY 1985;20:1308-1320
1313
Table 3. Population Comparison Using Student's t-test of Seven PIP Patients (A) who Did Not Receive Lithium with Three PIP Patients (B) who Did Receive Lithium A
B
t-test
A compared with B before lithium treatment Serum sodium (meq/liter) Specific gravity 1.00 Urinary creatinine concentration (mg/dl)
136.55 ± 4.58 4.52 ± 2.78 27.35 ± 25.93
135.313 ± 7.032
t = 1.699, p > 0.05
3.146 ± 1.868 14.556 ± 7.421
t = 3.352, p < 0.001 t = 3.400, p < 0.001
A compared with B during lithium treatment Serum sodium (meq/liter) Specific gravity 1.00 Urinary creatinine concentration (mg/dl)
136.55 ± 4.58 4.52 ± 2.78 27.35 +_ 25.93
140.479 ± 4.463 4.604 ± 2.541 28.613 ± 23.979
t = -5.841,p
< 0.001
t = - 0 . 2 0 2 , p > 0.5 t = - 0 . 3 2 5 , p > 0.5
Discussion The association of psychosis and polydipsia was firmly established by the work of Hoskins et al. in the early 1930s, when they demonstrated that patients with schizophrenic disorders excreted almost twice (2602 ml) the daily urine volume of normal subjects (1328 ml) (Hoskins 1933; Hoskins and Sleeper 1933; Sleeper and Jellinek 1936). Our patients excreted much larger volumes than did Hoskin's patients, but we were referred only the most seriously ill PIP patients. Using 17.5 mg creatinine/kg body weight for men and
T a b l e 4. V a r i a t i o n s o f U r i n a r y S p e c i f i c G r a v i t y ( 1 . 0 0 ) T h r o u g h o u t the D a y a m o n g P I P P a t i e n t s 1-4 a n d 6. Patient
8 AM
4 PM
8 PM
1 No. of observations 2 No. of observations 3 No. of observations 4 No. of observations 6 No. of observations Group No. of observations Controls No. of observations t value PIP group vs controls
3.50 -+ 1.20 8 5.13 - 3.27 8 6.50 + 2.78 8 4.63 ± 2.83 8 3.50 ± 1.60 8 4.65 -¢- 2.60 40 18.1 ± 7.6 8 - 8.703 p < 0.00l
1.57 - 0.79 7 4.67 --_ 3.78 6 4.40 _+ 3.21 5 2.29 --- 1.25 7 2.14 __. 0.90 7 2.88 ± 2.41 32 13.1 ± 6.6 9 - 7.037 p < 0.00l
2.13 ± 0.99 8 2.33 - 1.03 6 4.63 --- 3.93 8 2.38 -'- 0.92 8 2.13 _+ 0.99 8 2.74 ± 2.14 38 I1.1 ± 3.6 8 -- 8.555 p < 0.001
Tests were run each Thursday for 8 consecutive weeks. A control group of psychotic nonpolydipsic patients is provided.
1314
aIOL PSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
12.5 mg creatinine/kg body weight for women to estimate 24-hr urinary excretion of creatinine, we divided 24-hr urinary creatinine by early morning creatinine concentration to provide a gross estimate of urinary volume. Among PIP patients, urinary flow is relatively constant throughout the day (Table 4), and thus, this method is satisfactory in estimating daily urine volume (Peters and Van Slyke 1946; Vieweg et al. 1984a,b,c; Vieweg et al. 1985a,c,d,e). Other investigators have used specific gravity of 1.008 or less as criterion for psychogenic polydipsia (Blum and Friedland 1983). There was excellent correlation between early morning urinary creatinine concentration and specific gravity (r = 0.773, p < 0.0001) among PIP patients, and so we used both these parameters as indices of polyuria (hence polydipsia). We have defined daily urine volumes of 2600 ml or greater for men and 2200 ml or greater for women or early morning specific gravity of 1.008 or less as criteria for polydipsia for our patients. Implied in the term "water intoxication" is that the pathological features are a product of water consumption. Yet nowhere in the literature is there a description of the relationship between the amount of water consumed and pathological findings (Rowntree 1923; Bauer 1925; Barahal 1938; Carter and Robbins 1947; Dingman et al. 1957; Barlow and DeWardener 1959; Dies et al. 1961; Langgard and Smith 1962; Hobson and English 1963; Bewley 1964; Sahadevan and Bayliss 1965; Leiken and Caplan 1967; Resnick and Patterson 1969; Devereaux and McCormick 1972; Dubovsky et al. 1973; Chinn 1974; Raskind 1974; Raskind et al. 1975; Mendelson and Deza 1976; Rae 1976; Noonan and Ananth 1977; Rendell et al. 1978; Jos and Perez-Cruet 1979; Jos et al. 1979; Rosenbaum et al. 1979; Blotcky et al. 1980; DiMaio and DiMaio 1980; Hariprasad et al. 1980; Jos and Evenson 1980; Shevitz et al. 1980; Smith and Clark 1980; Davis et al. 1981; Nixon et al. 1982; Saruta et al. 1982; Blum and Friedland 1983; Blum et al. 1983; Kramer and Drake 1983; Jos 1984; Roberge et al. 1984; Zubenko et al. 1984). The suggestion is that "water intoxication" occurs when solute-free water is ingested in excess of maximal free water clearance. As maximal free water clearance approaches 20 ml/min, "water intoxication" occurs when the patient consumes at least 29 liters of water per day (20 ml free water/ min × 1440 min/day = 28,800 ml water/day) (Bartter 1973). None of our patients consistently consumed such large quantities of fluids, although on very rare occasions several of our patients have excreted more than 30 liters of urine in a day. We have used serum sodium levels of less than 136 meq/liter to define hyponatremia. In such settings, one must be sure that pseudohyponatremia is not present (i.e., elevated serum glucose, lipids, or urea nitrogen). Pseudohyponatremia can be excluded by obtaining concomitant serum osmolality. The frequency of hyponatremia among PIP patients ranged between 3.7% and 63.2%. Using urinary creatinine concentration and specific gravity as indices of polyuria, we found a very poor relationship between serum sodium and polyuria (r = - 0.113, p < 0.05) (Table 1). Thus, water consumption alone cannot explain "water intoxication." Water balance studies have been used to better understand the syndrome of inappropriate antidiuresis (SIAD) (Leaf et al. 1953; Stormont and Waterhouse 1961; Kaye 1966; Cooke et al. 1979). An early model suggested that the state of hydration determined the effect the antidiuretic hormone arginine vasopressin (AVP) had on serum sodium level; that is, AVP controlled a filter that allowed water to pass by: The more water that passed by, the more sodium was carried with it, leading to hyponatremia and compounding the dilutational effect of increased plasma water (Leaf et al. 1953). A more complicated model speculated that polydipsia provokes expansion of total body water, leading to intracellular hypotonicity followed by a shift of sodium ion from extracellular to intra-
Psychogenic Polydipsia
BIOLPSYCHIATRY
1315
1985;20:1308-1320
cellular fluid (Kaye 1966). This redistribution of sodium results in serum hyponatremia and the clinical complications that follow. There have been multiple reports linking PIP and SIAD (Hobson and English 1963; Dubovsky et al. 1973; Raskind et al. 1975; Rosenbaum et al. 1979; Hariprasad et al. 1980; Jos and Evenson 1980; Smith and Clark 1980; Kramer and Drake 1983; Roberge et al. 1984). Barlow and DeWardener (1959) studied patients with psychogenic polydipsia and demonstrated that they failed to develop features of "water intoxication" until exogenous AVP was given. Despite the mounting evidence, standard textbooks of medicine continue to describe psychogenic polydipsia and complications that follow as problems of water intake (Wyngaarden and Smith 1982). Lithium has long been known to influence water regulation through such mechanisms as natriuresis, decreasing renal tubular concentrating capacity, distal renal tubular acidosis, and the induction of nephrogenic diabetes insipidus by partial blockage of AVP at the renal receptor sites (Baylis and Health 1978; Miller et al. 1979; Bucht and Wahlin 1980; Vestergaard and Amdisen 1981; Battle et al. 1982; Ramsey and Cox 1982; Gold et al. 1983). Interference with renal tubular concentrating capacity is the most common clinical renal effect yielding polyuria and secondary polydipsia. However, this is seldom a problem. Because lithium can inhibit AVP action in the kidney, it has been used effectively to treat SIAD (White and Fetner 1975; Forrest et al. 1978). The finding that lithium administration to PIP patients with bipolar disorder resulted in stabilization of serum sodium in the normal range and reduction in polyuria warrants comment. In this population, the mean serum sodium rose from 135.313 to 140.479 meq/liter following lithium administration (Table 2). Furthermore, early morning urinary creatinine concentration rose from 14.556 to 28.613 mg/dl and specific gravity rose from 1.003146 to 1.004604. As lithium acts peripherally by blocking AVP action at the distal renal tubules and collecting ducts (partial nephrogenic diabetes insipidus with the induction of polyuria), its action among our three PIP patients with bipolar disorder must have produced a central override wherein better control of the psychosis reduced polydipsia and polyuria and normalized serum sodium. Zubenko et al. (1984) described three PIP patients with recurrent affective disorders who improved clinically following control of the affective exacerbations with antipsychotic drugs. However, these investigators failed to quantitate polydipsia or polyuria or to relate improvement in polyuria to serum sodium levels. Interestingly, among our bipolar patients, lithium administration enriched the relationship between serum sodium and urinary creatinine concentration and specific gravity. Of all the psychiatric diagnoses, bipolar disorder is most readily accepted as "biological" in origin. The improvement in water homeostasis following lithium administration among PIP patients argues convincingly against the concept of "psychogenic polydipsia." The antipsychotic drugs used by our patients have been implicated in the syndrome of hyponatremia in psychiatric patients (Sandifer 1983). However, the PIP syndrome clearly antedated the antipsychotic drug era. When we reviewed the severity of polyuria among 71 chronically psychotic male patients receiving antipsychotic agents, we found the mean daily urine volume, when corrected for body weight, to be identical to the figure derived by Hoskins et al. (Hoskins 1933; Hoskins and Sleeper 1933; Sleeper and Jellinek 1936). When we decreased or eliminated antipsychotic drugs in our PIP patient population, there was exacerbation of psychosis, intermittent hyponatremia, and polydipsia. In our experience, increasing rather than decreasing antipsychotic drug administration offers a more promising course for PIP patients. Although diuretics are the drugs most likely to induce hyponatremia and SIAD (Fichman et al. 1971), none of our patients received such drugs before or during the study periods.
1316
BIOLPSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
It appears to us that patients with PIP have disturbances in both the "dipsostat" and the "osmostat" in the hypothalamus. These patients consistently drink large quantities of water as a result of thirst dysregulation. Intermittently, osmotic dysregulation occurs as AVP is inappropriately secreted from the posterior lobe of the pituitary gland (nonosmotic stimulus: Type A SIAD) (Zerbe et al. 1980), or AVP effect is enhanced at the junction of the distal renal tubule and collecting ducts due to the hypersensitivity of the AVP receptors (Type D SIAD) (Zerbe et al. 1980). The complications of PIP, broadly divided into those due to hyponatremia and those due to fluid retention, then reflect the combined influence of thirst and osmotic dysregulation. If AVP effect is great, then mild polydipsia will lead to complications, and if polydipsia is great, then mildly inappropriate AVP effect will lead to complications. The former paradigm describes the classic SIAD (Bartter and Schwartz 1967) patient, and the latter paradigm describes our experience with the PIP patient (Vieweg et al. 1984a,b; Vieweg et al. 1985b,c,e). Others have speculated upon disturbances in both the "dipsostat" and "osmostat" in PIP patients (Robertson 1980). This separation of the "dipsostat" and "osmostat" is highly arbitrary, as fluid balance derangements that stimulate thirst also stimulate the release of AVP. The enteroceptor mechanisms that govern AVP release also govern water intake, with the only difference being in enteroceptor threshold AVP release threshold being lower than thirst threshold (Andersson and Rundgren 1982). There is an anatomical and biochemical linkage between the limbic system and the hypothalamus. Forebrain afferents from the lateral septum, bed nucleus of stria terminalis, ventral subiculum, and medial amygdala join the supraoptic and paraventricular nuclei of the hypothalamus where the AVP neurons are located (Powell and Rorie 1967; Swanson and Cowan 1975; Zaborsky et al. 1975; Conrad and Pfaff 1976; Rogers et al. 1979; Silverman et al. 1981; Tribollet and Dreifuss 1981). Also, the magnocellular vasopressin neurons of the supraoptic and paraventricular hypothalamic nuclei are sensitive directly to the neurotransmitters acetylcholine, norepinephrine, dopamine, angiotensin II, and opioid peptides; in addition, substance P, thyrotropin-releasing hormone, and somatostatin terminals are found in these nuclei (Hayward 1977; Palkovits and Brownstein 1978; Poulain and Wakedy 1982). It is known that patients with psychosis have elevated AVP levels (Raskind et al. 1978) and that this can be associated with acute water intoxication (Goldberg 1981). Thus, the psychotic state may alter drinking behavior and osmotic regulation, possibly through the hormone and neurotransmitter AVP, leading to the complications associated with PIP. Use of the term "psychogenic polydipsia" arises from the psychoanalytic hypothesis used to explain compulsive behavior. Arieti describes such compulsive behavior during the third or "preterminal" stage of schizophrenic disorders (Arieti 1945). According to this author, the "preterminal" stage occurs 5-15 years after the onset of psychosis, and the compulsive behavior, which includes hoarding and self-decorating habits, is regression to the analsadistic stage. Alternately, regression to the oral-dependent stage might explain such behavior. Initially (1933), Hoskins's group thought that disturbances in water regulation among PIP patients involved the hypothalamus or posterior lobe of the pituitary gland (Hoskins 1933), but 3 years later, they claimed that the polydipsia was "psychical" rather than "physiological" or "biochemical" in origin (Sleeper and Jellinek 1936). We believe that the overall evidence suggests that biochemical changes in the hypothalamus could best explain PIP. Moreover, we have demonstrated that polydipsia alone cannot explain the complications of PIP, which thus limits both the uses and concepts of "psychogenic polydipsia" and "water intoxication." In addition to the psychoanalytic hypothesis to explain PIP, several other hypotheses have
Psychogenic Polydipsia
BIOLPSYCHIATRY
1317
1985;20:1308-1320
been offered recently. Kissileff (1973) proposed that compulsive water drinking is a "response to increased levels of transmitter substances accumulating in the limbic system during the experience of frustration." This speaks to the putative role AVP has as a neurotransmitter for memory, behavior, and learning as well as its role in water metabolism (Nemeroff and Prange 1978). Mellinger and Zafar (1983) described a patient with a diseased "dipsostat" and normal "osmostat" who manifested a lifelong pattern of polydipsia (up to 6 liters/day) without intermittent hyponatremia. When AVP was administered exogenously, hypoosmolality appeared and polydipsia stopped. The patient has been maintained on exogenously administered AVP sufficient to stabilize plasma osmolality to below 270 mosmol/kg, yielding symptomatic relief from thirst without producing complications associated with PIP. It may be that our PIP patients are secreting AVP inappropriately in an attempt to interdict thirst, i.e., compensate for disruption in the feedback mechanism between the "dipsostat" and the "osmostat." Work by Snyder has demonstrated that opiate agonists are up to 50 times stronger in the absence of sodium and that opiate receptors are highly concentrated in numerous structures of the limbic system (the site of emotional regulation in the brain), particularly the amygdala (Snyder 1984). An interesting possibility is that PIP patients seek to enhance opiate receptor effect by decreasing surrounding sodium concentration. In a sense, they may be addicted to water. References Andersson B, Rundgren M (1982): Thirst and its disorders. Annu Rev Med 33:231-239. APA (1980): A Psychiatric Glossary, 5th ed. Washington, DC: American Psychiatric Association. Arieti S (1945): Primitive habits in the preterminal stage of schizophrenia. J Nerv Ment Dis 102:367-375. Barahal HS (1938): Water intoxication in a mental case. Psychiatr Q 12:767-771. Barlow ED, DeWardener HE (1959): Compulsive water drinking. Q J Med 28:235-258. Bartter FC (1973): The syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In Disease-a-Month. Chicago: Yearbook Medical. Bartter FC, Schwartz WB (1967): The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42:790-806. Batlle D, Gaviria M, Grupp M, Arruda JAL, Wynn J, Kurtzman NA (1982): Distal nephron function in patients receiving chronic lithium therapy. Kidney lnt 21:447--485. Bauer R (1925) Zur Pathologie und Differentialdiagnose von "Diabetes insipidus" und primarer Polydipsia. Wien Arch Inn Med 11:201. Baylis PH, Health DA (1978): Water disturbances in patients treated with oral lithium carbonate. Ann Intern Med 88:607---609. Bewley TH (1964): Acute water-intoxication from compulsive water-drinking. Br Med J 2:864. Blotcky MJ, Grossman I, Looney JG (1980): Psychogenic water intoxication: A fatality. Tex Med 76:58-59. Blum A, Friedland GW (1983): Urinary tract abnormalities due to chronic psychogenic polydipsia. Am J Psychiatry 140:915-916. Blum A, Tempey FW, Lynch WJ (1983): Somatic findings in patients with psychogenic polydipsia. J Clin Psychiatry 44:55-56. Bucht G, Wahlin A (1980): Renal concentrating capacity in long-term lithium treatment and after withdrawal of lithium. Acta Med Scand 207:309-314. Carter AC, Robbins J (1947): The use of hypertonic saline infusions in the differential diagnosis of diabetes insipidus and psychogenic polydipsia. J Clin Endocrinol 7:753-766. Chinn RA (1974): Compulsive water drinking. J Nerv Ment Dis 158:78-80. Conrad LC, Pfaff DW (1976): Autoradiographic tracing of the nucleus accumbens efferents in the rat. Brain Res 113:589-596.
1318
BIOLPSYCHIATRY
W.V.R. Vieweg et al.
1985;20:1308-1320
Cooke CR, Turin MD, Walker WG (1979): The syndrome of inappropriate antidiuretic hormone secretion (SIADH): Pathophysiologic mechanisms in solute and volume regulation. Medicine 58:240-251. Davis JRE, McNeill M, Miilar JW (1981): latrogenic water intoxication in psychogenic polydipsia. Scott Med J 26:148-150. Devereaux MW, McCormick RA (1972): Psychogenic water intoxication: A case report. Am J Psychiatry 129:140-142. Dies F, Rangel S, Rivera A (1961): Differential diagnosis between diabetes insipidus and compulsive polydipsia. Ann Intern Med 54:710-725. DiMaio VJM, DiMaio SJ (1980): Fatal water intoxication in a case of psychogenic polydipsia. J Foren Sci 25:332-335. Dingman JF, Benirschke K, Thorn GW (1957): Studies of neurohypophyseal function in man. Am J Med 23:226-238. Dubovsky SL, Grabon S, Bed T, Schrier RW (1973): Syndrome of inappropriate secretion of antidiuretic hormone with exacerbated psychosis. Ann Intern Med 79:551-554. Fichman MP, Vorherr H, Kleeman CR, Telfer N (1971): Diuretic-induced hyponatremia. Ann Intern Med 75:853-863. Forrest JN, Cox M, Hong C, Morrison G, Bia M, Singer I (1978): Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 298:173-177. Gold PW, Robertson GL, Post RM, Kaye W, Ballenger J, Rubinow D, Goodwin FK (1983): The effect of lithium on the osmoregulation of arginine vasopressin secretion. J Clin Endocrinol Metab 56:295-299. Goldberg M (1981): Hyponatremia. Med Clin North Am 65:251-269. Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS, Nidus BD (1980): Hyponatremia in psychogenic polydipsia. Arch Intern Med 140:1639-1642. Hayward JN (1977)" Functional and morphological aspects of hypothalamic neurons. Physiol Rev 57:574-658. Hobson JA, English JT (1963): Self-induced water intoxication. Case study of a chronically schizophrenic patient with physiological evidence of water retention due to inappropriate release of antidiuretic hormone. Ann Intern Med 58:324-332. Hoskins RG (1933): Schizophrenia from the physiological point of view. Ann Intern Med 7:445-456. Hoskins RG, Sleeper FH (1933): Organic functions in schizophrenia. Arch Neurol Psychiatry 30:123-140. Jos CJ (1984): Generalized seizures from self-induced water intoxication. Psychosomatics 25:153-157. Jos CJ, Perez-Cruet J (1979): Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry 136:221-222. Jos CJ, Barton JL, Perez-Cruet J (1979): Hyponatremic seizures in psychiatric patients. Biol Psychiatry 14:839-843. Jos CJ, Evenson RC (1980): Antecedents of self-induced water intoxication. A preliminary report. J Nerv Ment Dis 168:498-500. Kaye M (1966): An investigation into the cause of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 41:910-926. Kissileff HR (1973): Epstein AN, Kissileff HR, Stellar E (eds), Nonhomeostatic controls of drinking. In Neuropsychology of Thirst: New Findings and Advances in Concepts. New York: Halsted Press. Kramer DS, Drake ME Jr (1983): Acute psychosis, polydipsia, and inappropriate secretion of antidiuretic hormone. Am J Med 75:712-714. Langgard H, Smith WO (1962): Self-induced water intoxication without predisposing illness. Report of two cases. N Engl J Med 266:378-381.
Psychogenic Polydipsia
BIOLPSYCHIATRY
1319
1985;20:1308-1320
Leaf A, Bartter FC, Santos RF, Wrong O (1953): Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J Clin Invest 32:868-879. Leiken SJ, Caplan H (1967): Psychogenic polydipsia. Am J Psychiatry 123:1573-1576. Mellinger RC, Zafar MS (1983): Primary polydipsia. Syndrome of inappropriate thirst. Arch Intern Med 143:1249-1251. Mendelson WB, Deza PC (1976): Polydipsia, hyponatremia, and seizures in psychotic patients. J Nerv Ment Dis 162:140-143. Miller PD, Dubovsky SL, McDonald KM, Katz FH, Robertson GL, Schrier RW (1979): Central, renal and adrenal effects of lithium in man. Am J Med 66:797-803. Nemeroff CB, Prange AJ Jr (1978): Peptides and psychoneuroendocrinology. Arch Gen Psychiatry 35:999-1010. Nixon RA, Rothman JS, Chin W (1982): Demeclocycline in the prophylaxis of self-induced water intoxication. Am J Psychiatry 139:828-830. Noonan JPA, Ananth J (1977): Compulsive water drinking and water intoxication. Compr Psychiatry 18:183-187. Palkovits M, Brownstein MJ (1978): Concentrations of the neurotransmitters in the supraoptic and the paraventricular nuclei in the rat. In Bargmann W, Oksche A, Polenov A, Scharrer B (eds), Neurosecretion and Neuroendocrine Activity. Berlin: Springer-Verlag, pp 250-255. Peters JP, Van Slyke DD (1946): Quantitative Clinical Chemistry: Interpretations vol 1. Baltimore: Williams & Wilkins. Poulain DA, Wakerly JB (1982): Electrophysiology of hypothalamic magnocellular neurons secreting oxytocin and vasopressin. Neuroscience 7:773-808. Powell EW, Rorie DK (1967): Septal projections to nuclei functioning in oxytocin release. Am J Anat 120:605-610. Rae J (1976): Self-induced water intoxication in a schizophrenic patient. Can MedAssoc J 114:438-439. Ramsey RA, Cox M (1982): Lithium and the kidney: A review. Am J Psychiatry 139:443---449. Raskind M (1974): Psychosis, polydipsia, and water intoxication. Report of a fatal case. Arch Gen Psychiatry 30:112-114. Raskind MA, Orenstein H, Christopher G (1975): Acute psychosis, increased water ingestion, and inappropriate antidiuretic hormone secretion. Am J Psychiatry 132:907-910. Raskind MA, Weitzman RE, Orenstein H, Fisher DA, Courtney N (1978): Is antidiuretic hormone elevated in psychosis: A pilot study. Biol Psychiatry 13:385-390. Rendell M, McGrane D, Cuesta M ( 1978): Fatal compulsive water drinking. JAMA 240:2557-2559. Resnick ME, Patterson C (1969): Coma and convulsions due to compulsive water drinking. Neurology 19:1125-1130. Roberge R, Gernsheimer J, Sparano R, Tartakoff R, Morgenstem MJ, Rubin K, Senekiian D, Andrade R, Matthew V (1984): Psychogenic polydipsia--an unusual cause of hyponatremic coma and seizure. Ann Emerg Med 13:274---276. Robertson GL (1980): Psychogenic polydipsia and inappropriate antidiuresis. Arch Intern Med 140:1574. Rogers RC, Talbot K, Novin D, Butcher LL (1979): Afferent projections to the supraoptic nucleus of the rat. Soc Neurosci Abstr 5:233. Rosenbaum JF, Rothman JS, Murray GB ( 1979): Psychosis and water intoxication. J Clin Psychiatry 40:287-291. Rowntree LG (1923): Water intoxication. Arch Intern Med 32:157-174. Sahadevan MG, Bayliss VD (1965): Compulsive water drinking. A report of two cases. J Assoc Physicians India 13:755-757. Sandifer MG (1983): Hyponatremia due to psychotrophic drugs. J Clin Psychiatry 44:301-304. Saruta R, Fujimaki M, Ogihara R, Saito I, Konishi K, Kondo K (1982): Evaluation of the renin-angiotensin system in diabetes insipidus and psychogenic polydipsia. Nephron 32:14-17.
1320
BIOLPSYCHIATRY !985;20:1308-1320
W.V.R. Vieweg et al.
Shevitz SA, Jameison RC, Petrie WM, Crook JE (1980): Compulsive water drinking treated with high dose propranolol. J Nerv Ment Dis 168:246-248. Silverman AJ, Hoffman DL, Zirnmerman EA (1981): The descending afferent connections of the paraventricular nucleus of the hypothalamus. Brain Res Bull 6:47-61. Sleeper FH, Jellinek EM (1936): A comparative physiologic, psychologic, and psychiatric study of polyuric and nonpolyuric schizophrenic patients. J Nerv Ment Dis 83:557-563. Smith WO, Clark ML (1980): Self-induced water intoxication in schizophrenic patients. Am J Psychiatry 137:1055-1060. Snyder SH (1984): Drug and neurotransmitter receptors in the brain. Science 224:22-31. Stormont JM, Waterhouse C (1961): The genesis of hyponatremia associated with marked overhydration and water intoxication. Circulation 14:191-203. Swanson LW, Cowan WM (1975): Hippocampal-hypothalamic connections: Origin in subicular cortex, not Ammon's horn. Science 189:303-304. Tribollet E, Dreifuss JJ (1981): Localization of neurons projecting to the hypothalarnic paraventricular nucleus area of the rat: A horseradish peroxidase study. Neuroscience 6:1315-1328. Vestergaard P, Amdisen A (1981): Lithium treatment and kidney function. A follow-up study of 237 patients in long-term treatment. Acta Psychiatr Scand 63:333-345. Vieweg WVR, Rowe WT, David JJ, Spradlin WW (1984a): Hyposthenuria as a marker for selfinduced water intoxication and schizophrenic disorders. Am J Psychiatry 141:1258-1260. Vieweg WVR, Rowe WT, David JJ, Sutker LH, Spradlin WW (1984b): Evaluation of patients with self-induced water intoxication and schizophrenic disorders (SIWIS). J Nerv Ment Dis 172:552-555. Vieweg WVR, Rowe WT, David JJ, Yank GR, Spradlin WW (1984c): The "Mini-Mental State" in the syndrome of self-induced water intoxication and schizophrenic disorders (SIWIS): A pilot study, lnt J Psychiatry Med 14:347-359. Vieweg WVR, David JJ, Rowe WT, Wampler GJ, Burns WJ, Spradlin WW (1985a): Death from self-induced water intoxication among patients with schizophrenic disorders. J Nerv Ment Dis 173:161-165. Vieweg WVR, Rowe WT, David J J, Spradlin WW (1985b): Oral sodium chloride in the management of schizophrenic patients with self-induced water intoxication. J Clin Psychiatry 46:16-19. Vieweg WVR, David JJ, Rowe WT, Canterbury ILl, Spradlin WW (1985c): Hypocalcemia: An additional complication of the syndrome of self-induced water intoxication and psychosis (SIWlP). Psych Med (in press). Vieweg WVR, Rowe WT, David JJ, Curnow RT, Spradlin WW (1985d): Patterns of urinary excretion among patients with self-induced water intoxication and psychosis (SIWIP). Psychiatry Res (in press). Vieweg WVR, Rowe WT, David JJ, Curnow RT, Spradlin WW (1985e): Self-induced water intoxication and psychosis (SIWIP): Subcategory of the syndrome of inappropriate antidiuresis (SIAD). Psych Med (in press). White MG, Fetner CD (1975): Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with lithium carbonate. N Engl J Med 292:390-392. Wyngaarden JB, Smith LH Jr (eds) (1982): Cecil's Textbook of Medicine, 16th ed. Philadelphia: W.B. Saunders. Zaborsky L, Leranth CS, Makara GB, Palkovits M (1975): Quantative studies on the supraoptic nucleus in the rat. II. Afferent fiber connections. Exp Brain Res 22:525-540. Zerbe R, Stropes L, Robertson G (1980): Vasopressin function in the syndrome of inappropriate antidiuresis. Annu Rev Med 31:315-327. Zubenko GS, Altesman RI, Cassidy JW, Barreira PJ (1984): Disturbances of thirst and water homeostasis in patients with affective illness. Am J Psychiatry 141:436---438.