Psychopharmacology of maternal separation anxiety in vervet monkeys.

Maternal separation in non-human primates has been proposed as a model of early adversity. The symptoms of separation anxiety were studied in vervet monkeys, during the weaning period, when psychotropic medications were administered. The control group received a normal diet and treatment groups received citalopram, reboxetine or lamotrigine in their food daily. Treatment was given for 7 weeks starting 1 month prior to weaning. Behavior was recorded twice weekly for 8 weeks, and was rated for anxiety and depression. Cerebrospinal fluid was collected at the beginning and end of the trial and analyzed for monoamines and metabolites using High Performance Liquid Chromatography. Citalopram pretreatment prevented the reduction of affiliation behavior and reduced stereotypies after weaning, and both citalopram and reboxetine abolished the increase in activity seen in control monkeys after weaning, but no statistically significant differences were found between groups. Citalopram pretreatment also significantly increased noradrenaline and 5-hydroxyindolacetic acid (5-HIAA) levels and reboxetine significantly decreased dopamine levels over time. The 5-HIAA levels of reboxetine and lamotrigine treated monkeys were significantly lower than that of the control group at the end of the trial. Although limited by a small sample size, this study demonstrates the possibility of investigating the psychopharmacology of early adversity in a non-human primate model.

Pharmacological challenge with a serotonin 1D agonist in alcohol dependence.

BACKGROUND: Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink. METHODS: Fifteen patients with alcohol dependence who had undergone detoxification were recruited. Sumatriptan (100 mg) and placebo was administered in cross-over fashion on 2 separate days 72 hours apart. Both patients and raters were blind to all treatments. Patients were assessed on the following scales at -30, 0, 30, 90, 150 and 210 minutes: A 6-item scale designed to rate the patient's intention to drink; The Sensation Scale; a 13-item affect analog scale designed to rate the pattern and extent of emotional changes; and an 8-item scale designed to rate the patient's craving for alcohol. RESULTS: No significant differences were found between the placebo and sumatriptan groups and no significant cross over effects were found. CONCLUSION: The general lack of efficacy of sumatriptan in producing alcohol-like symptoms or a desire to drink alcohol may suggest that the 5HT1D receptor plays little role in the pathophysiology of alcoholism.

Single photon emission computed tomography in posttraumatic stress disorder before and after treatment with a selective serotonin reuptake inhibitor.

BACKGROUND: Posttraumatic stress disorder (PTSD) is recognized as a disorder mediated by specific neurobiological circuits. Functional imaging studies using script-driven trauma imagery and pharmacological challenges have documented altered cerebral function (activation and deactivation) in several brain regions, including the amygdala, hippocampus, prefrontal cortex and anterior cingulate. However, the neural substrates of PTSD remain poorly understood and the effect of selective serotonin reuptake inhibition on regional cerebral activity is deserving of further investigation. METHODS: Eleven adult patients (seven men, four women) (mean age+S.D.=33.6+/-9.2 years) with a DSM-IV diagnosis of PTSD, as determined by the Structured Clinical Interview for DSM-IV (SCID-I) and the Clinician-Administered PTSD Scale (CAPS), underwent single photon emission computed tomography (SPECT) with Tc-99m HMPAO pre- and post-8 weeks of treatment with the selective serotonin reuptake inhibitor, citalopram. Symptoms were assessed at baseline and at 2-week intervals with the Clinician-Administered PTSD Scale (CAPS), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis of baseline and post-treatment scans was performed using Statistical Parametric Mapping (SPM). RESULTS: Treatment with citalopram resulted in significant deactivation in the left medial temporal cortex irrespective of clinical response. On covariate analysis, a significant correlation between CAPS score reduction and activation in the left paracingulate region (medial prefrontal cortex) was observed post-treatment. No significant pre-treatment differences were observed between responders and non-responders in anterior cingulate perfusion. CONCLUSIONS: These preliminary findings are consistent with clinical data indicating temporal and prefrontal cortical dysfunction in PTSD and preclinical data demonstrating serotonergic innervation of these regions. However, further studies, in particular in vivo receptor imaging studies, are needed to confirm whether these regional abnormalities correlate with clinical features and treatment response.

Community attitudes toward and knowledge of mental illness in South Africa.

BACKGROUND: Although recent advances in psychiatry have increased our understanding of psychiatric disorders,many people with chronic or severe psychiatric disorders may be unaware that effective treatment is available. It is possible that ignorance and stigma prevent such persons from seeking appropriate help, and that community attitudes and beliefs play a role in determining the help-seeking behaviour and successful treatment of the mentally ill. Nevertheless, there is little research on the attitudes of lay persons toward mental illness within the South African community. OBJECTIVES: The aim of this study was to investigate the knowledge and attitudes of the general South African public toward mental illness, specifically regarding the causes of illness and treatment options. METHOD: The study design employed a questionnaire survey. Structured interviews (n = 667) were conducted with members of the general public. One of eight vignettes, portraying depression, schizophrenia, panic disorder or substance abuse, with subtle or obvious symptoms, was presented to each respondent. RESULTS: The main findings were that cases were most often conceptualised as stress-related or due to a lack of willpower rather than as medical disorders. Treatment advocated was more often to talk the problem over than to consult professional medical help. Psychotherapy was the preferred treatment option, particularly in vignettes where symptom presentation was subtle, and in cases of substance abuse. CONCLUSIONS: These data suggest that stigma and misinformation regarding mental illness exist, influencing preferred treatment modality and help-seeking behaviour. More work needs to be done to educate the public about the psychobiological underpinnings of psychiatric disorders and about the value of effective treatments. A better understanding of these disorders amongst the public would presumably lessen stigmatisation and encourage the use of currently available and effective interventions.

Fluoxetine decreases stereotypic behavior in primates.

BACKGROUND: Primates reared in captivity may display stereotypic behaviors. These behaviors are arguably reminiscent of human obsessive-compulsive or posttraumatic symptoms, which respond to selective serotonin reuptake inhibitors (SSRIs). Captive primates with marked stereotypic behaviors were entered into a randomized controlled study of the SSRI, fluoxetine. METHODS: A sample of 10 vervet monkeys with behaviors such as marked saluting, somersaulting, weaving, or head tossing was selected. Subjects were randomized to receive fluoxetine 1 mg/kg for 6 weeks (n=5) or no treatment (n=5). A rater blind to the medication status of subjects noted the frequency of the stereotypic behaviors. RESULTS: Repeated-measures analysis of variance (RM-ANOVA) demonstrated a significant GroupxTime difference with significantly fewer stereotypic symptoms in the fluoxetine group by endpoint. At this time, three of the five fluoxetine-treated subjects (but none of the no-treatment subjects) were responders on the Clinical Global Impressions (CGI) change item (CGI < or =2). CONCLUSIONS: Stereotypic behaviors in captive vervets gradually and partially decrease in response to administration of an SSRI, paralleling research on human anxiety symptoms. Further research on animal stereotypies may be useful in providing appropriate veterinary care, and in exploring the underlying neurobiology of certain psychiatric disorders.

Functional brain imaging and pharmacotherapy in trichotillomania. Single photon emission computed tomography before and after treatment with the selective serotonin reuptake inhibitor citalopram.

The neurobiology and pharmacotherapy of trichotillomania has received increasing attention in recent years. Parallels have been drawn between findings in this disorder and those in obsessive-compulsive disorder (OCD). To date, however, there has been little work on the effect of a pharmacotherapeutic intervention on functional brain imaging in trichotillomania. Female patients (n = 10) with DMS-IV diagnostic criteria for trichotillomania were subjected to single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI), citalopram. Pharmacotherapy led to significantly reduced activity in inferior-posterior and other frontal regions. Correlates of hair-pulling symptoms with regional brain activity differed before and after pharmacotherapy. These data are to some extent consistent with work suggesting that trichotillomania, like OCD, is mediated by corticostriatal circuits. Pharmacotherapeutic response to SSRIs in trichotillomania may not be as robust as in OCD. Further research is necessary to determine the neurobiological underpinnings of these differences.

SPECT scans in identical twins with trichotillomania.

SPECT scans of a set of twins with trichotillomania showed that the twin with more severe disease had larger perfusion defects, involving more areas on the scan. Prospective brain imaging studies of twins may provide useful information about the neurobiology of trichotillomania and other obsessive-compulsive spectrum disorders.