
David S JanowskyUniversity of California San Diego · Psychiatry
David S Janowsky
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Publications (403)
Background
Cannabis use is a component risk factor for the manifestation of schizophrenia. The biological effects of cannabis include effects on epigenetic systems, immunological parameters, in addition to changes in cannabinoid receptors 1 and 2, that may be associated with this risk. However, there has been limited study of the effects of smoked...
(Reprinted with the permission American Journal of Psychiatry 1974; 131: 250-255).
Mood disorders are highly prevalent and are the leading cause of disability worldwide. The neurobiological mechanisms underlying depression remain poorly understood, although theories regarding dysfunction within various neurotransmitter systems have been postulated. Over 50 years ago, clinical studies suggested that increases in central acetylchol...
The adrenergic-cholinergic balance hypothesis of mania and depression suggests that depression may be due to an over-activity or a hypersensitivity to central acetylcholine. From this hypothesis, it is logical that scopolamine, a centrally acting antimuscarinic agent, would be useful as an antidepressant. Authors, working at the Intramural Program...
Lithium has been shown to increase serum creatinine levels in a subgroup of patients. However, lithium-induced increases in serum creatinine have not been well studied with regard to timing, trajectory, or predictability.
The medical records of 16 intellectually disabled individuals treated with lithium between 1980 and 2010 in whom serum creatinin...
The author has reviewed bipolar disorder-relevant abstracts from the July 2008 Munich CINP (Collegium Internationale Neuro-Psychopharmacologicum) meeting. Seven abstracts are summarized, focusing on the psychopharmacologic treatment of bipolar depression, the neuropsychological effects of psychotropic drugs used to treat bipolar disorder, and the r...
The author has reviewed selected bipolar disorder- and major depression-relevant abstracts from the 2009 9th World Congress of Biological Psychiatry Meeting in Paris. The seven selected abstracts, which represent a small percentage of the presentations made at the meeting, explore the relationship between bipolar and unipolar diagnoses and suicidal...
The current study evaluated the effects of chronic administration of lithium on renal functioning in an intellectually disabled population.
Fifty-seven lithium-treated individuals were compared with 24 behaviorally symptomatic controls using a retrospective chart review method. Serum creatinine levels and creatinine clearance activities were compar...
The antagonistic effects of scopolamine, methscopolamine, and a combination of methscopolamine and scopolamine were evaluated in preventing physostigmine induced lethality in Swiss Webster mice. Low dose scopolamine was found to be highly effective in reversing high dose (3 × the LD100) physostigmine induced lethality, in contrast to methscopolamin...
Severe intellectual and developmental disabilities are frequently associated with aggression toward self and others, destruction of property, and disruption. Antipsychotic medications are a mainstay of treatment of such behaviors. National and state guidelines suggest stopping these medications or decreasing their dosages when possible if patients...
It is now widely accepted that depressive disorders in humans are heterogeneous. Therefore, it is very likely that several
distinctly different animal models of depression can be useful. Because of the heterogeneity of the manifestations of depressive
disorders, it is important for developers of animal models to indicate which specific aspects of t...
For more than a century, acetylcholine has been postulated to be a factor in the regulation and etiology of affect. In 1889, Willoughby (1) reported a case in which pilocarpine, now known to be a muscarinic cholinergic agonist, was used to alleviate acute mania. Subsequently, in the late 1940s, 1950s, and early 1960s, a number of authors observed t...
This review discusses several depression-relevant abstracts of posters and talks presented at the 2005 American College of Neuropsychopharmacology Annual Meeting and the 2006 Collegium Internationale Neuro-Psychopharmacologicum Meeting. Described are several novel psychopharmacologic treatments for major depressive disorder, some predictors of effi...
Mental retardation is frequently associated with aggression toward self and others. Antipsychotic medications are frequently used as a major treatment of such aggression. However, national and state policies and guidelines are weighted toward stopping or decreasing the doses of these medications whenever possible, although exceptions are permitted....
Depression in mentally retarded individuals is not uncommon and usually is treatable. However, studies of the diagnosis and treatment of psychiatric illnesses in general and depression specifically in this population are relatively rare. Although Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria can be applied to mildly...
Reviewing abstracts of posters and presentations at scientific meetings offers a rapid overview summary of the state of the art of a given discipline and/or disorder, with data presented being available months to years before formal publication occurs. This article reviews selected abstracts of posters presented at the Sixth International Conferenc...
Animal studies exploring the antagonism of irreversible cholinesterase inhibitors (i.e. nerve agents) such as soman and sarin have shown that pretreatment with the reversible centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic drug, scopolamine, antagonizes the lethality and to...
There is a growing body of evidence that serotonergic antidepressants are useful in the treatment of maladaptive behaviours in the intellectually disabled. However, not all studies have shown positive results due to lack of efficacy, tolerance development, and troublesome side-effects. The current study consisted of a review of the treatment respon...
Retrospective review of records from 1990 to 1997 revealed unsuccessful attempts to withdraw antipsychotic medications from a total of 34 intellectually disabled individuals. The lowest dose of antipsychotic medication necessary to maintain symptom suppression and the dose at which relapse occurred were noted. Target behaviors observed indicating r...
This is a review derived from the abstracts of a group of symposia and posters presented at the International Society for Bipolar Disorders Regional Group Conference, held in Sydney, Australia, February 5-7, 2004. It consists of selected abstracts published collectively. In part due to sponsorship by the pharmaceutical industry, information present...
Studies in animals exploring the antagonism of the cholinesterase inhibitors soman and sarin have shown that pretreatment with low doses of the centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic agent, scopolamine, is effective against their lethality and toxicity. The current...
An inverse relationship exists between an individual's degree of negative affect and the interpersonal perception of friendliness, sympathy and empathy, acceptance, warmth, regard, and genuineness, and the converse relationship persists for the perception of sadness and anger. Thus, a "negative interpersonal bias" exists in those with diagnoses of...
This study reviews the treatment response to the antiepileptic drug topiramate (Topamax-mean dose 202 mg/d, range 150-350 mg/d) of a group of 22 institutionalized intellectually disabled adults (8 males, 14 females, mean age 46.5 years, age range 25-70 years). These individuals were predominantly classified as having severe or profound intellectual...
The effectiveness of olanzapine in treating challenging behaviors in the intellectually disabled and its ability to substitute for conventional antipsychotic drugs were evaluated.
A total of 20 institutionalized adults with a mean age of 42.7 years (range, 18-55 years) with intellectual disability and aggression, self-injurious behavior, destructiv...
Animal studies suggest that preference for relatively high concentrations of sweet solutions and lack of control over sweet solution consumption is related to a preference for alcohol over water. There also is evidence in humans that alcoholics prefer high concentration sweet solutions. This study was designed to determine whether patients with coc...
The biology and treatment of premenstrual tension syndrome has advanced significantly in the past 30 years. Newer research expands on earlier literature that has been accumulated before 1972. This review selectively considers this earlier literature, because it defines the nature and impact of what was then considered to be premenstrual tension syn...
The current study was designed to compare the distribution of Myers Briggs Type Indicator (MBTI) personality types in patients with Unipolar Depression compared to normative data.
The MBTI divides individuals into four dichotomous types: Extroverted and Introverted, Sensing and Intuitive, Thinking and Feeling, and Judging and Perceiving. This yield...
The current study characterized the Myers Briggs Type Indicator (MBTI) personality profiles of 64 suicidal and 30 non-suicidal psychiatric inpatients with affective disorder diagnoses. The MBTI divides individuals categorically into eight personality preferences (Extroverted and Introverted, Sensing and Intuitive, Thinking and Feeling, and Judging...
A growing body of information suggests that core or underlying personality is a significant concomitant of depression and suicidality. Introversion (ie, low extroversion) is especially promising in its relationship to the phenomenology and outcome of depression, and may represent an underlying heritable trait of etiologic significance. Furthermore,...
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were David S. Janowsky and Jan Fawcett. The presentations were (1) The tridimensional personality questionnaire: Predictor of relapse in detoxified alcoholics, by Kurt Meszaros; (2) Novelty seeking predicts clinical trial attrition in alc...
There is now more information to assimilate in clinical psychopharmacology and newer ways to acquire this information. Educational materials should be designed for and targeted to meet the diverse needs of such groups as medical students, psychiatry residents, clinical practitioners, industry and federal scientists, and clinical research organisati...
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were David S. Janowsky and Jan Fawcett. The presentations were (1) The tridimensional personality questionnaire: Predictor of relapse in detoxified alcoholics, by Kurt Meszaros; (2) Novelty seeking predicts clinical trial attrition in alc...
The purpose of this study is to profile the personalities of patients with social phobia. Sixteen patients with social phobia were compared with a normative population of 55,971, and with 24 hospitalized Major Depressive Disorder inpatients, using the Myers Briggs Type Indicator. The Myers Briggs Type Indicator, a popular personality survey, divide...
It is common to treat some diseases with more than one medication simultaneously. Since more than one neurotransmitter system is involved in alcohol-seeking behaviour, then a therapeutic approach that targets more than one system should be more effective in reducing alcohol intake than one addressing a single system. To test this hypothesis, we com...
The current study was designed to compare personality differences between bipolar patients and unipolar depressed patients, as evaluated on the Myers Briggs Type Indicator (MBTI) and the Tridimensional Personality Questionnaire (TPQ).
A group of bipolar and a group of unipolar depressed patients filled out the MBTI, the TPQ, the Beck Depression Inv...
This clinical trials review is derived from the presentations made at the Third International Conference on Bipolar Disorder, held June 17-19, 1999 in Pittsburgh, PA, published as abstracts in Bipolar Disorders: An International Journal of Psychiatry and Neurosciences, Edited by Jair C. Soares, and Samuel Gershon. In this review, abstracts reportin...
This study evaluated the role of personality in the short-term outcome of alcohol/substance-use disorder patients. Detoxifying alcohol/substance-use disorder patients were administered the Myers-Briggs Type Indicator (MBTI), the Tridimensional Personality Questionnaire (TPQ), the Michigan Alcohol Screening Test (MAST), the CAGE Questionnaire, and t...
The Myers-Briggs Type Indicator (MBTI), a popular personality test, was used to profile the personalities of in-patient alcoholics/substance-use disorder patients who had, and those who did not have, a concurrent affective disorder diagnosis. The MBTI divides individuals into eight categories: Extroverts and Introverts, Sensors and Intuitives, Thin...
The Myers–Briggs Type Indicator (MBTI), a popular personality test, was used to profile the personalities of in-patient alcoholics/substance-use disorder patients who had, and those who did not have, a concurrent affective disorder diagnosis. The MBTI divides individuals into eight categories: Extroverts and Introverts, Sensors and Intuitives, Thin...
Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals
with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an
attempt at self-medication with nicotine by these individuals. Although some animal and human studies sug...
This report reviews a series of studies demonstrating a relationship between the consumption of sweets and alcohol consumption. There is consistent evidence linking the consumption of sweets to alcohol intake in both animals and humans, and there are indications that this relationship may be at least partially genetic in nature. Alcohol-preferring...
Animal studies have shown a positive association between the consumption of high concentrations of sweet solutions and subsequent alcohol intake. In a previous clinical study, it was shown that a preference for a high (0.83 M) concentration of sucrose (sweet liking) is characteristic of alcoholics, compared with controls. The present study was desi...
This article reviews published reports and presents new evidence that support a number of commonalties between lines of rats selectively bred for differences in cholinergic (muscarinic) and serotonergic (5-HT1A) sensitivity. The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression derived for cholinergic supersensitivity, is more...
The purpose of this study was to test in humans the finding from animal studies indicating an association between preference for more concentrated sweet solutions and excessive alcohol drinking.
The hedonic response to five different concentrations of sucrose solution was evaluated in 20 detoxified alcoholic and 37 nonalcoholic Caucasian men. All s...
It was previously reported that selection for differences in the hypothermic effects to the selective 5-HT-1A agonist, 8-OH-DPAT, occurred rapidly, with very substantial differences present by the fourth generation. The present communication summarizes the findings from the next five generations of selection and from behavioral and other functional...
Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensi...
The Chinese herbal medicine, NPI-028, has been used for centuries in China to counteract alcohol intoxication. The present study used a number of different experimental conditions to determine whether NPI-028 and its derivatives might selectively influence alcohol intake in rodents that naturally exhibit high alcohol intakes. It was determined that...
It was previously reported that selection for differences in the hypothermic effects to the selective 5-HT-1A agonist, 8-OH-DPAT, occurred rapidly, with very substantial differences present by the fourth generation. The present communication summarizes the findings from the next five generations of selection and from behavioral and other functional...
Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Li...
In a situation offering a free choice between 0.1% saccharin solution and tap water, Fawn Hooded (FH) rats consumed 363.0 +/- 33.5 ml/kg/day of saccharin solution. Subsequently those animals drank 3.0 +/- 0.4 g/kg of ethanol in a free choice between water and 10% ethanol solution. Control FH rats that did not have access to saccharin consumed 5.0 +...
This study examined the relationship between saccharin intake and ethanol consumption in alcohol preferring (P) rats and Fawn Hooded (FH) rats before and after exposure to forced ethanol (10%, v/v) solution. Both groups exhibited large increases (> 2X) in daily fluid intake (DFI) when saccharin (0.1%, w/v) was present and exhibited moderate levels...
Complement proteins and fragments participate in the induction and modulation of specific and nonspecific immune reactions. We have examined the effect of 4 weeks of chronic mild stress (CMS) on complement sheep red blood cell hemolytic activity measured in CH50 units in two selectively bred lines of rats, the Flinders resistant line (FRL) and the...
The recent literature on the involvement of cholinergic muscarinic mechanisms and adrenergic/cholinergic balance in affective disorders is reviewed and integrated with the older literature. There is strong evidence supporting the presence of exaggerated responses (behavioral, neuroendocrine, sleep) to cholinergic agents in affective disorder patien...
Ca(2+) channel inhibitors suppress ethanol intake in various strains of alcohol-preferring rats. To test whether that inhibitory effect involves interference with the caloric consequences of preferred fluids, we compared the effects of two dihydropyridines, nicardipine and isradipine, and diltiazem, a benzothiazepine Ca(2+) channel inhibitor, on in...
National Institutes of Health (NIH) heterogeneous stock (HS) rats were obtained and genetically selected for either larger (HI line) or smaller (LO line) hypothermic responses to the selective serotonin-1A (5-HT1A) agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). A randomly bred (RA) control line was also bred in parallel. There was a ra...
The involvement of serotonergic mechanisms in the neuropharmacology of alcohol was appreciated before it was recognized that there were multiple subtypes of serotonin (5-hydroxytryptamine; 5-HT) receptors. Thus, it was known that manipulations of the central serotonergic system could lead to a modification of the rate of tolerance development to al...
The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression, was cross-bred with its normal control, the Flinders Resistant Line (FRL) rat, in order to investigate the relationship between cholinergic sensitivity, the selected variable, and two apparent genetically correlated variables, serotonergic sensitivity and swim test immobil...
The effects of acute and chronic stressors on saccharin intake and preference in the hypercholinergic Flinders Sensitive Line (FSL) rat, a putative genetic animal model of depression, were studied and compared to the control Flinders Resistant Line (FRL) rats. Overall, the FRL rats drank significantly less saccharin and water than the FSL rats when...
Neuronal Ca2+ channels have been shown to be involved in both alcohol drinking behavior in rats and nonhuman primates and in the manifestation of alcohol withdrawal symptoms in rodents. Experiments were performed to determine the effect of a single injection of levemopamil, a novel Ca2+ channel antagonist with antiserotonergic [5-hydroxytryptamine2...
The effect of pretreatment with (±)-verapamil (5, 10 or 15 mg/kg, i.p.) on place preference induced with d-amphetamine (1 mg/kg, i.p. 40 min after verapamil) was studied in male rats. Place preference conditioning was performed using two-compartment shuttle boxes and 8 alternating stimulant/saline sessions. Verapamil dose-dependently suppressed amp...
Saccharin and ethanol intakes were measured in seven strains of rats known to differ in their preferences for ethanol: The Fawn-Hooded (FH), alcohol-preferring (P) and Maudsley Reactive rats have been reported to drink ethanol voluntarily, whereas the alcohol-nonpreferring, Maudsley Nonreactive and Flinders Line (FSL and FRL) rats do not. Saccharin...
The behavior of Maudsley reactive and nonreactive rats, along with that of Wistar controls, was studied using three behavioral tasks which have been associated with emotionality. Consistent with the hypothesis that they are more emotional, the Maudsley reactive rats were more immobile in the forced swim test and spent less time in the open arms of...