Haim Y. Knobler

Cognitive performance in schizophrenia patients assessed before and following the first psychotic episode

BACKGROUND The purpose of this historical prospective study was to follow the cognitive impairment in schizophrenia from the premorbid period until shortly after the onset of the first psychotic episode within the same subjects. METHODS Forty-four first episode schizophrenia patients were enrolled in the study. Their cognitive performance was assessed as part of the Israeli Draft Board aptitude assessments at ages 16-17, when all were found to be in good mental health (first assessment) and again, following the manifestation of the first psychotic episode (second assessment). Forty-four healthy comparisons were also enrolled and tested twice, at the same ages as the patients. Both times, the assessments included four subtests assessing abstract reasoning (Raven Progressive Matrices-R), mental speed and concentration (Otis-R), verbal reasoning (Similarities-R), and mathematical abilities (Arithmetic-R). RESULTS A within group analysis did not reveal statistically significant changes between the first and the second assessment among the schizophrenia patients on any measure. However, a between group comparison of changes showed that relative to the healthy comparisons, schizophrenia patients deteriorated on the RPM-R (p=0.021) and Otis-R (p<0.001), but not on the Similarities-R and Arithmetic-R. Schizophrenia patients performed worse than comparisons in all four subtests on the first and second assessments (all p<0.01). CONCLUSIONS The results indicate that most of the cognitive impairment exhibited by first-episode schizophrenia patients precedes the first psychotic episode. A decline between ages 16 and 17 and the onset of psychosis is evident in some but not all cognitive functions.

Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism.

An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.

Paternal age and intelligence: implications for age-related genomic changes in male germ cells.

Background A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. Objective An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. Method We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. Results A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parents age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for ∼2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. Conclusion We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.

Premorbid Intellectual Functioning and Risk of Schizophrenia and Spectrum Disorders

Evidence from longitudinal studies indicates that lower IQ score in childhood and early adolescence increases risk of schizophrenia and schizophrenia spectrum disorders (SSD). This study investigated the association between premorbid IQ and risk of SSD in a population-based cohort of 17-year-old conscripts. Fifty four thousand males assessed by the Israeli Draft Board during two consecutive years were followed by means of the Israeli National Psychiatric Hospitalization Case Registry for up to 11 years. Tests of verbal and non-verbal reasoning, mathematical knowledge and instructions comprehension and several psychosocial variables were recorded by the Draft Board. Risk for SSD increased with decreasing IQ score. Only poorer non-verbal reasoning conferred a significant increased risk for SSD after taking into account general intellectual ability. IQ was not associated with age of onset. These results confirm the importance of low intellectual functioning as a risk factor for SSD. This is unlikely to be due to prodrome.

Hypnotherapy in the Treatment of Chronic Combat-Related PTSD Patients Suffering From Insomnia: A Randomized, Zolpidem-Controlled Clinical Trial

Abstract This study evaluated the benefits of add-on hypnotherapy in patients with chronic PTSD. Thirty-two PTSD patients treated by SSRI antidepressants and supportive psychotherapy were randomized to 2 groups: 15 patients in the first group received Zolpidem 10 mg nightly for 14 nights, and 17 patients in the hypnotherapy group were treated by symptom-oriented hypnotherapy, twice-a-week 1.5-hour sessions for 2 weeks. All patients completed the Stanford Hypnotic Susceptibility Scale, Form C, Beck Depression Inventory, Impact of Event Scale, and Visual Subjective Sleep Quality Questionnaire before and after treatment. There was a significant main effect of the hypnotherapy treatment with PTSD symptoms as measured by the Posttraumatic Disorder Scale. This effect was preserved at follow-up 1 month later. Additional benefits for the hypnotherapy group were decreases in intrusion and avoidance reactions and improvement in all sleep variables assessed.

Self-reported drug abuse in male adolescents with behavioral disturbances, and follow-up for future schizophrenia

BACKGROUND The prevalence of illicit drug abuse in persons with schizophrenia is greater then in the general population and has been attributed to self-medication of the symptoms of the illness; however, limited data indicate that drug abuse is already prevalent before the manifestation of psychosis, consistent with the possibility that drug abuse might be associated with increased risk for schizophrenia. METHODS The Israeli Draft Board screens the entire, unselected population of 16- to 17-year-old male adolescents for behavioral or personality disturbances. In a cohort of 270,000 male adolescents screened, 50,413 adolescents were suspected of having behavioral or personality disturbances and were questioned about drug use and abuse. These adolescents were followed for hospitalization for schizophrenia using a national, population-based psychiatric hospitalization registry; 268 of 50,413 (.5%) were hospitalized for schizophrenia over the following 5-11 years. RESULTS The prevalence of self-reported drug abuse in adolescents later hospitalized for schizophrenia was 12.4%, compared with 5.9% prevalence of drug abuse in adolescents not later hospitalized; adjusted RR = 2.016, 95% confidence interval: 1.309-3.104. CONCLUSIONS In this cohort of male adolescents with behavior disturbances, these results further support the hypothesis that drug abuse may be associated with increased risk for future schizophrenia.

Affective psychosis following Accutane (isotretinoin) treatment

Isotretinoin (Accutane) ranks in the top 10 of the US Food and Drug Administrations database of drugs associated with reports of depression and suicide attempts. However, this association is still controversial because up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, improvement of acne often reduces associated depression, and isotretinoin users are reportedly no more likely than those taking antibiotics for acne to have depression or commit suicide. We describe a series of cases of manic psychosis that developed in a 1-year period (2003) in association with isotretinoin treatment and resulted in suicidality and progression to long-standing psychosis. Cases were drawn from 500 soldiers who had been evaluated in a military specialists dermatology clinic for severe acne. Data were summarized from medical records of five severe acne patients treated by isotretinion during their compulsory military service. Data from their draft board examinations and service records, as well as repeated clinical assessments by certified psychiatrists at the Israel Defense Forces (IDF) Mental Health Department clinic, were evaluated. Five young adults developed manic psychosis within a mean of 7.6 months of exposure to isotretinoin. In three cases, this was accompanied by a suicide attempt, and in three cases, psychosis lasted for longer than 6 months. Either a personal history of obsessive–compulsive disorder, neurological insult or family history of a major psychiatric illness were present in all cases. The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis. Associated risk factors were both family and personal history of psychiatric morbidity. Further studies are needed to establish our findings.

Impaired Reading Comprehension and Mathematical Abilities in Male Adolescents With Average or Above General Intellectual Abilities Are Associated With Comorbid and Future Psychopathology

Research indicates that persons with learning disorders often suffer from psychopathology. We assessed current and future psychopathology in male adolescents with discrete impairments in reading comprehension (IRC) or arithmetic abilities (IAA) but with average or above-average general intellectual abilities. Subjects were a population-based cohort of 174,994 male adolescents screened by the Israeli Draft Board with average or above-average intellectual abilities but with low scores (8.6th and 10th lowest percentile respectively) on reading or arithmetic tests. They were compared with adolescents who scored in the 10th percentile and above on these tests (comparison group). Relative to the comparison group, male adolescents with IRC, IAA, or IRC and IAA (0.69%), had poorer scores on most behavioral assessments and higher prevalence of current psychopathology: 4.2% (comparison group), 8.0% (IRC), 7.0% (IAA), and 9.8% (IRC and IAA). Adolescents with IRC were also at increased risk for later hospitalization for schizophrenia (hazard ratios = 1.8, 95% confidence interval: 1.3–2.6). Male adolescents with average and above-average general intellectual abilities but with IRC or IAA are more likely to have current and future psychopathology. Impairments in intellectual functioning and abnormal behaviors leading to mental illnesses may share common neurobiological substrates. The results support screening male adolescents with learning disorders for psychopathology.

Psychological guidelines for a medical team debriefing after a stressful event.

Medical and rescue workers are at risk of developing mental syndromes including post-traumatic stress disorder after disasters and it is widely accepted that they should be offered a preventive intervention. The Israel Defense Force Medical Corps has developed psychological guidelines for the medical forces: a medical team debriefing after treating the injured as a preventive intervention for an event that may be experienced as stressful. The main purpose of the debriefing is to investigate the circumstances of the event, analyze the medical teams functioning, and draw the relevant conclusions and the manner of their implementation. The purpose of the guidelines is to enhance mental coping, possibly prevent stress reactions, and help in screening individuals in need of further professional intervention for stress reactions. These guidelines are suitable for similar interventions in other professional teams.

Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: A historical-prospective cohor study

OBJECTIVE The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. METHOD Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. RESULTS Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4-16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05-3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1-9 cigarettes/day were 1.38 times (95% CI=0.48-4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19-4.34) as likely; the latter difference was statistically significant. CONCLUSIONS Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.