EEG coherence in post-LSD visual hallucinations.

LSD use in certain individuals may result in chronic visual hallucinations, a DSM-IV syndrome known as hallucinogen persisting perception disorder (HPPD). We studied 38 HPPD subjects with a mean of 9.7 years of persistent visual hallucinations and 33 control subjects. Measures of local and medium distance EEG spectral coherence were calculated from all subjects. Coherence, a measure of spectral similarity over time, may estimate cortical coupling. In the eyes-open state in HPPD subjects, widespread reduction of coherence was noted. However, upon eye closure, the occipital region demonstrated augmented regional coherence over many frequencies but with reduced coherence of the occipital region to more distant regions. This occipital coherence increase correlated with previously reported shortened occipital visual evoked potential latency for HPPD subjects. We speculate from coherence and known clinical and psychophysical data that, in HPPD, there is widespread cortical inhibition in the eyes-opened state, but localized and isolated occipital disinhibition upon eye closure, a state known to facilitate hallucinatory experiences. An analogy is drawn to findings in the interictal and ictal epileptic focus. In HPPD, we speculate that occipital EEG hypersynchrony resulting from increased regional coherence, when coupled with relative isolation of visual cortex, especially upon eye closure, facilitates hallucinations and illusions.

A longitudinal study of the order of onset of alcohol dependence and major depression.

Alcohol dependence and major depression commonly occur together; however, few studies have assessed prospectively the magnitude of the risk that one disorder imparts on the subsequent occurrence of the other. We used data from the first two waves of the Epidemiologic Catchment Area community survey (n=14480) to estimate the odds of either major depression or alcohol dependence being followed by the other disorder after 1 year of follow-up. The odds of developing major depression associated with low, medium, and high levels of alcoholic symptoms at baseline were 1.66, 3.98, and 4.32 for females (P<0.001), and 1.19, 2.49, and 2.12 for males (P=0.026). Conversely, odds ratios indicating the 1-year follow-up risk of incident alcohol dependence within low, medium, and high categories of baseline depressive symptomatology were 2.75, 3.52, and 7.88 for females (P<0.001) and 1.50, 1.41, and 1.05 for males (P=0.091). Individuals with alcohol dependence appeared more likely to meet lifetime diagnostic criteria for both disorders after 1 year than individuals with depression. These results suggest that both alcohol dependence and major depression pose a significant risk for the development of the other disorder at 1 year.

Order of onset of substance abuse and depression in a sample of depressed outpatients.

Drug abuse has been thought to cause depression, or to serve as a form of self-medication for depression. Our objective was to examine whether specific types of drug abuse preceded or followed the onset of depression. A retrospective, blinded case-controlled assessment of the drug and depressive history of depressed outpatients was conducted. Three hundred seventy-five patients with major depressive disorder were evaluated for comorbid drug dependence using the Structured Clinical Interview for DSM-III-R (SCID). They were selected from the psychiatric outpatient department of a metropolitan teaching hospital and grouped into homogeneous classes of drug dependence including alcohol, cannabis, cocaine, amphetamine, LSD, hypnosedative, opiate, and polysubstance use. We determined the percent of depressed patients with each specific type of drug abuse, their age of onset of depression and onset of specific drug abuse, and the mean number of lifetime depressive episodes for each patient. We found that alcohol dependence followed the onset of first life depression by 4.7 years (P = .02, two-tailed). Among polydrug-dependent patients, each drug abused followed the onset of depression, except for LSD, which coincided with the onset of depression. Among polydrug users, cocaine dependence occurred 6.8 years after the first major depressive episode (P = .007) and alcohol dependence 4.5 years after the onset of depression (P = .007). Opiate and sedative users had the least number of lifetime depressive episodes (3.7), and LSD and cocaine users had the greatest number (12.2). We conclude that alcohol and cocaine use in this sample of depressed outpatients conformed to a pattern of self-medication.

Seroprevalence of hepatitis C in a sample of middle class substance abusers.

Hepatitis C (HCV) is an indolent and often fatal disease affecting four million Americans commonly associated with low socioeconomic status. We assessed its prevalence in a sample of 334 consecutively admitted middle class substance abusers in a private urban hospital, and ascertained risk factors for its transmission. We found that the point prevalence rate for HCV was 27.7% among all substance abusers, and 76.7% among intravenous drug users. Using logistic regression, we found risk factors associated with HCV were intravenous drug use, needle sharing, prior liver disease, opioid dependence, HIV infection, and benzodiazepine dependence. Not found to increase infective risk were lower social class, male gender, African-American race, male homosexuality, unemployment, and the absence of private health insurance. Multiple viral genotype types were identified in this sample, suggesting diverse sources of transmission in the sample. This study documents an epidemic of HCV in an American middle class sample.

Somatization disorder in sphincter of Oddi dysfunction.

OBJECTIVE: Sphincter of Oddi dysfunction (SOD) is a biliary disorder with a recognized pathophysiology and demonstrated surgical treatment. We sought to examine whether women with SOD were overrepresented on measures of somatization, sexual and physical abuse, socially compliant attitudes, and familial psychiatric illness. METHOD: We matched 33 women with SOD to 33 normal controls by age, sex, and race, and, with a case-controlled cross-sectional questionnaire, compared the groups on the study variables. Statistics included a chi 2 for categorical variables, t tests for scores of somatization and attitudes of social desirability, and Pearson correlation coefficients for post hoc associations of variables. Bonferroni corrections were used with chi 2 values to reduce capitalization by chance. RESULTS: SOD patients exhibited excessive nongastroenterological somatic complaints compared with controls (p < .0001). There was a statistical increase in reports of childhood sexual, but not physical, abuse in the SOD women (p < .02) compared with controls. The severity of the abuse correlated strongly with the severity of somatic complaints. There were no differences in social desirability attitudes or family psychiatric histories of the two groups. CONCLUSIONS: We conclude that SOD is associated with a high degree of somatization in adulthood, and a mean rate more than four times that of controls in self-reports of sexual abuse in childhood. The severity of childhood sexual abuse is correlated with the severity of somatization in later life. A psychological model for this disorder is suggested by the data. Increased psychiatric attention is indicated in the treatment of women with this disorder.

Stable quantitative EEG difference in post-LSD visual disorder by split-half analysis: evidence for disinhibition.

Hallucinogen persisting perceptual disorder (HPPD) may follow the ingestion of LSD or other hallucinogens in a subset of users. It is characterized by chronic, intermittent or constant visual hallucinations of many sorts persisting beyond the period of acute drug effects. We studied 44 LSD-induced HPPD subjects and 88 matched controls to search for spectral and evoked potential differences using quantitative EEG (qEEG). HPPD subjects demonstrated faster alpha frequency and shorter VER (visual evoked response) latency, consistent with prior animal and human data on response to acute LSD administration which suggest LSD-induced cortical disinhibition. AER (auditory evoked response) latency was prolonged consistent with a differential LSD effect upon visual and auditory systems. The exploratory T-statistic significance probability mapping (T-SPM) technique demonstrated HPPD-control differences mostly involving temporal and left parietal scalp regions, confirmed by a split-half analysis. Significant variables were all derived from the long latency flash VER and click AER. None were derived from spectral analyzed EEG data. Canonical correlation between SPM-derived measures and variables reflecting disease severity was highly significant. A between-group stepwise discriminant analysis based upon a full set of qEEG measures demonstrated 87% prospective classification success by jackknifing and 88% success in a separate split-half analysis.

LSD-like panic from risperidone in post-LSD visual disorder.

Risperidone, a novel antipsychotic agent, is an antagonist of postsynaptic serotonin-2 and dopamine D2 receptors. In certain individuals, the hallucinogenic drug lysergic acid diethylamide (LSD) is associated with apparently lifelong continuous visual disturbances, characterized in DSM-IV as hallucinogen-persisting perception disorder (HPPD). Because the hallucinogenic mechanism of LSD is known to act in part at postsynaptic serotonin-2 receptors, it is noteworthy that three HPPD patients treated with risperidone reported an exacerbation of LSD-like panic and visual symptoms. We conclude that HPPD may be a relative contraindication for the use of risperidone.

The psychopharmacology of hallucinogens.

Hallucinogenic drugs have been inhaled, ingested, worshipped, and reviled since prehistory. With the purification and synthesis of bontanical preparations and the ensuing discovery of chemically unique agents, hope was raised regarding their therapeutic potential, but this hope has been clouded by an epidemic of abuse and an inventory of adverse effects. This review examines aspects of that controversy, including the history of hallucinogens, epidemiology of current hallucinogen abuse, the association of LSD use with prolonged psychoses and hallucinogen persisting perception disorder, and the efforts to demonstrate the drug's therapeutic efficacy. Human subject ramifications in hallucinogen experimentation are discussed. Future lines of research are suggested in human, animal, and tissue culture paradigms.

Neuroleptic malignant syndrome in the elderly.

Four cases of neuroleptic malignant syndrome (NMS) were identified in a general hospital over a 5-year period. Two cases presented to the psychiatric consultation liaison service, and two were found by a computerized review of discharge diagnoses. Cases were examined for age, sex, administered neuroleptic potency and dose, premorbid history, prodromal symptoms, methods of treatment, and clinical outcome. The mean age of cases was found to be 14 years greater than the age of the non-NMS patient population. All NMS cases had premorbid neuropsychiatric disorders and recognizable prodromal symptoms. The mean neuroleptic dose was significantly lower than in previously reported cases. A systems model integrating premorbid factors, intercurrent illness, and drug effects in pathogenesis is presented.

Adverse consequences of lysergic acid diethylamide.

The continued endemic use of hallucinogenic drugs, and of LSD in particular, raises concern regarding their short and long term adverse consequences. The epidemiology of LSD abuse is reviewed suggesting an increase in LSD use among the young as the prevalence rates for other substances continues to fall. Evidence supports the association of LSD use with panic reactions, prolonged schizoaffective psychoses and post-hallucinogen perceptual disorder, the latter being present continually for as long as 5 years. Evidence does not support claims of genetic disorders arising from hallucinogens. In light of the foregoing, current data confirm earlier findings of long lasting psychopathology arising in vulnerable individuals from the use of LSD. A hypothetical long term molecular mechanism of adverse effects is proposed.

Length of stay in a general hospital psychiatric unit.

Fifty psychiatric inpatients with a prolonged length of stay were compared to 50 control admissions for factors associated with prolonged hospitalizations in a general hospital. Seven variables were found to be significantly overrepresented among the long stayers, including treatment with electroconvulsive therapy, medical consultations, underemployment, dementia, disposition to a place other than home, absence of alcohol or drug abuse, and presence of psychosis without affective symptoms. The clinical and policy implications of these finding are discussed.

Bulimic vomiting alters pain tolerance and mood.

Bulimia, a disorder of episodic binging and purging, remains without a known etiology. A case report is presented of a patient who attributed bulimic episodes to efforts at inducing euphoria. Experimental pain tolerance was increased by bulimic vomiting, blocked by naloxone, but not by saline. Vomiting was also associated with falls in depression and anxiety. Plasma ACTH and cortisol, putative markers for beta-endorphin, also rose following vomiting. It is hypothesized that in some bulimics, the disorder arises by virtue of an addiction to one's own internally released endogenous opioid peptides.

Visual phenomenology of the LSD flashback.

One hundred twenty-three persons with a history of LSD use were studied for the presence of the LSD flashback phenomenon and compared with 40 control subjects. A syndrome emerged that included ten distance visual disturbances. It had lasted for five years in half of the population, was treatable with benzodiazepines, exacerbated by phenothiazines, and precipitated by 19 different stimuli, most commonly emergence into a dark environment. Sensitivity to LSD as determined by flashbacks appears to divide the study sample into three discrete subgroups. There may be a genetic basis to LSD sensitivity.

L-5-hydroxytryptophan for LSD-induced psychosis.

The serotonin precursor L-5-hydroxytryptophan reversed the symptoms of a 23-year-old man suffering from LSD-induced psychosis who participated in a randomized, double-blind crossover study of the drug and a placebo. This finding is compatible with the speculation that some LSD-induced psychotic disorders may be caused by a relative deficiency of CNS serotonin.

Inching toward Armageddon: a psychiatric view.

The existence of thermonuclear arsenals capable of destroying much of humanity takes its origins from, and has an influence on, processes that are largely psychological. The threat to use a single nuclear bomb to resolve contemporary conflict is an anathema in part because complex nation-states did not evolve with surviving a nuclear war in mind. The atomic arms race has proceeded apace because of maladaptive psychological mechanism including denial, distortion, projection, and, most relevantly, the need to enhance bonding within groups by creating stereotypes. One consequence of the arms race is a climate of fear and hopelessness, and especially destructive effect of which is seen in children. The physician's role in the prevention of nuclear war is critical, but divided between contradictory roles. On one hand, the physician is traditionally identified as a non-political advocate of the sick; on the other, as an advocate for the public health. It is this second model that enables physicians most legitimately to work for the prevention of nuclear war and to deal with the psychiatric concomitants of a planet drifting toward disaster.