Finnish adoptive family study: sample selection and adoptee DSM-III-R diagnoses.

OBJECTIVE: To evaluate the genetic contribution to schizophrenia using an adoption design that disentangles genetic and environmental factors. METHOD: Finnish hospital diagnoses of schizophrenic/paranoid psychosis in a nationwide sample of adopting-away women are compared with DSM-III-R research diagnoses for these mothers. DSM-III-R diagnoses of their index offspring are blindly compared with adopted-away offspring of epidemiologically unscreened control mothers. RESULTS: Primary sampling diagnoses of index mothers were confirmed using DSM-III-R criteria. Lifetime prevalence of typical schizophrenia in 164 index adoptees was 6.7% (age-corrected morbid risk 8.1%), significantly different from 2.0% prevalence (2.3% age-corrected morbid risk) in 197 control adoptees. When adoptees with diagnoses of schizoaffective disorder, schizophreniform disorder, schizotypal disorder and affective psychoses were added, the contrast between the index and control adoptees increased. CONCLUSION: The genetic liability to 'typical' DSM-III-R schizophrenia is decisively confirmed. Additionally, the liability also extends to a broad spectrum of other psychotic and non-psychotic disorders.

Thought disorder index of Finnish adoptees and communication deviance of their adoptive parents.

BACKGROUND: Diverse forms of thought disorder, as measured by the Thought Disorder Index (TDI), are found in many conditions other than schizophrenia. Certain thought disorder categories are primarily manifest during psychotic schizophrenic episodes. The present study examined whether forms of thought disorder qualify as trait indicators of vulnerability to schizophrenia in persons who are not clinically ill, and whether these features could be linked to genetic or environmental risk or to genotype-environment interactions. The Finnish Adoptive Study of Schizophrenia provided an opportunity to disentangle these issues. METHODS: Rorschach records of Finnish adoptees at genetic high risk but without schizophrenia-related clinical diagnoses (N = 56) and control adoptees at low genetic risk (N = 95) were blindly and reliably scored for the Thought Disorder Index (TDI). Communication deviance (CD), a measure of the rearing environment, was independently obtained from the adoptive parents. RESULTS: The differences in total TDI between high-risk and control adoptees were not statistically significant. However, TDI subscales for Fluid Thinking and Idiosyncratic Verbalization were more frequent in high-risk adoptees. When Rorschach CD of the adoptive rearing parents was introduced as a continuous predictor variable, the odds ratio for the Idiosyncratic Verbalization component of the TDI of the high-risk adoptees was significantly higher than for the control adoptees. CONCLUSIONS: Specific categories of subsyndromal thought disorder appear to qualify as vulnerability indicators for schizophrenia. Genetic risk and rearing-parent communication patterns significantly interact as a joint effect that differentiates adopted-away offspring of schizophrenic mothers from control adopted-away offspring.

Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia.

OBJECTIVE: This study assessed the interaction of genetic risk and rearing-family risk as a subsyndromal test measure of schizophrenic thought disorder in adoptees. METHOD: A group of 58 adoptees with schizophrenic biological mothers was compared with 96 comparison adoptees at ordinary genetic risk; putative adoptee vulnerability was assessed blindly and reliably by using the Rorschach Index of Primitive Thought. Environmental risk was measured by using frequency of communication deviance as a continuous variable, scored independently from Rorschach assessments of the adoptive parents. RESULTS: High genetic risk in itself was not associated with greater vulnerability to schizophrenic thought disorder in the adoptees, as indicated by the Index of Primitive Thought. Also, greater communication deviance in the adoptive parents was not associated with greater thought disorder in the comparison adoptees. However, there was a highly significant gene-environment interaction. Among the offspring of the adoptive parents with high levels of communication deviance, a higher proportion of high-risk than comparison adoptees showed evidence of thought disorder. In contrast, among the offspring of adoptive parents with low communication deviance, a lower proportion of high-risk than comparison adoptees showed evidence of thought disorder. The distribution of communication deviance scores did not differ significantly between the adoptive parents of high-risk offspring and the adoptive parents of comparison offspring. CONCLUSIONS: The findings are consistent with genetic control of sensitivity to the environment. There is no evidence that high genetic risk of schizophrenia among offspring is associated with high levels of communication problems in rearing parents.

Antidepressant efficacy and quality of life in depression: a double-blind study with moclobemide and fluoxetine.

The efficacy of moclobemide (300-450 mg/day) was compared with fluoxetine (20-40 mg/day) in a double-blind, multicentre study in 209 patients with new episodes of depression selected from 612 consecutive depressed patients representative of those consulting psychiatric services in Finland. Antidepressant efficacy was assessed with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale and Clinical Global Impression (CGI). The Medical Outcome Study Short-form General Health Survey (SF-20) and 15D Measure of Quality of Life were used to measure effectiveness in terms of health-related quality of life. Efficacy was evident with both drug treatments, with 67% in the moclobemide group and 57% in the fluoxetine group having a reduction in HDRS of more than 50%. Similarly, 77% of the patients in the moclobemide group and 67% in the fluoxetine group were assessed on the CGI as much better or very much better after 6 weeks of treatment. The most commonly reported adverse events were nausea, other gastrointestinal symptoms, nervousness, dizziness and sleep disorders. Nausea was significantly more common in the fluoxetine group and was found especially in women. Premature terminations of treatment were 18% in the moclobemide and 21% in the fluoxetine group. A significant change for the better in quality of life was found in both treatment groups, even at week 2 but especially after 6 weeks of treatment. Improvement was not only seen in dimensions measuring depression or mental health but also in other dimensions.

The Finnish adoptive family study of schizophrenia. Implications for family research.

A nationwide Finnish sample of schizophrenics' offspring given up for adoption was compared blindly with matched controls, who were adopted offspring of non-schizophrenic biological parents. The adoptive families were investigated thoroughly using joint and individual interviews and psychological tests. The biological parents were also interviewed and tested. Among the 155 index offspring, the percentage of both psychoses and other severe diagnoses (borderline syndrome and severe personality disorders) was significantly higher than in the 186 matched control adoptees. This supports a genetic hypothesis. However, notable differences between these two groups only emerged in the families which were rated as disturbed. Thus the genetic effect (i.e. the differences between high and low genetic propensity) was only manifested as a psychiatric disorder in the presence of a disturbed family environment. The impact of disturbed family relations was strongest in the presence of the appropriate genotype.

Alprazolam and oxazepam in the treatment of anxious out-patients with depressive symptoms: a double-blind multicenter study.

In a four-week double-blind study comparing alprazolam with oxazepam, 62 outpatients suffering from anxiety with depressive symptoms were evaluated. The average daily doses of alprazolam and oxazepam were 1.48 mg and 44.4 mg, respectively. According to all rating scales applied, both alprazolam and oxazepam were effective in relieving anxiety associated with mild depression (p less than 0.01). Alprazolam proved somewhat more effective than oxazepam especially with regard to overall performance (p less than 0.05). Treatment-emergent adverse effects were few and mild for both compounds tested.

Genetic and psychosocial factors in schizophrenia: the Finnish Adoptive Family Study.

A nationwide Finnish sample of schizophrenic mothers' offspring given up for adoption was compared blindly with matched controls (i.e., adopted-away offspring of nonschizophrenic biological parents). The offspring were born 1927-79. To date, a total of 247 adoptive families (112 index and 135 controls) have been investigated and rated. Of the 10 psychotic cases, 8 are offspring of schizophrenics and 2 are control offspring. However, no seriously disturbed offspring is found in a healthy or mildly disturbed adoptive family, and of those offspring who were psychotic or seriously disturbed, nearly all were reared in disturbed adoptive families. This supports the hypothesis that a possible genetic vulnerability has interacted with the adoptive rearing environment.

The Finnish adoptive family study of schizophrenia.

A nationwide Finnish sample of index offspring given up for adoption by schizophrenic women has been compared blindly with matched controls, that is, adopted-away offspring of nonschizophrenic biologic parents. The adoptive families have been investigated directly by joint and individual interviews and psychological tests. Interviewing and testing of biologic parents is in progress. In the total sample, thus far examined, of 124 index offspring, 9 (7.3%) have become psychotic; of 147 control offspring, 2 (1.4%) have become psychotic.

The Finnish adoptive family study of schizophrenia.

A nationwide Finnish sample of schizophrenic mothers' offspring given up for adoption has been compared blindly with matched controls; i.e., adopted-away offspring of non-schizophrenic biologic parents. The families have been investigated thoroughly by joint and individual interviews and psychological tests. In the 91 pairs where both the index and control families have already been investigated and rated, the total number of severe diagnoses (psychosis, borderline, character disorder) is 28.6 percent (26/91) in the index group and 16.5 percent (15/91) in the matched control group. Of the seven psychotic cases, six are offspring of schizophrenics and only one is a control offspring. However, no seriously disturbed offspring has been found in a healthy or mildly disturbed adoptive family, and those offspring who were psychotic and seriously disturbed were nearly all reared in disturbed adoptive families. This combination of findings supports the hypothesis that a possible genetic vulnerability has interacted with the adoptive rearing environment.

A double-blind group comparison of mianserin and clomipramine in the treatment of mildly depressed psychiatric out-patients.

The effects of mianserin 30-60 mg and clomipramine 75-150 mg were compared in a randomized double-blind study of 62 mildly depressed out-patients. Treatment was continued for three to four weeks, after which approximately 50% of patients left the study clinically much improved. Significant benefits for mianserin were apparent at days 7 and 21 on the Hamilton Depression Rating Scale (HDRS) total score and at day 7 on the HDRS anxiety-somatization factor score. No difference in overall antidepressant activity was found in those patients treated for four weeks. There was a significantly greater number of side-effects in the clomipramine treated group. It is suggested that mianserin is a more rational treatment than clomipramine in this group of patients because of a greater anxiolytic action and a lower incidence of side-effects.

Interaction of genetic and psychosocial factors in schizophrenia.

What the genetic and family dynamic theory have in common, is that the cause of schizophrenia could be found in the family. Usually the genetic factors and the rearing factors are confounded in the same family. In a study of adoptive children given away for adoption early enough, discrimination between these two sets of factors is possible. A nation-wide sample of offspring of schizophrenic mothers, given away for adoption, has been compared blindly with matched controls, i.e., adopted-away offspring of non-schizophrenic biologic parents. The families have been investigated thoroughly with joint and individual interviews and psychological tests. In the 91 pairs where both the index and control families have been investigated and rated so far, the total number of severe diagnoses (psychosis, borderline, character disorder) is 28.6% (26/91) in the index group and 16.5% (15/91) in the matched control group. Of the 7 psychotic cases, 6 are offspring of schizophrenics and only one a control offspring. The relation of psychopathology of adoptive families to the mental health ratings of the offspring supports the hypothesis that a possible genetic vulnerability has interacted with the adoptive rearing environment.

Maprotiline and doxepin in the treatment of depression. A double-glind multicentre comparison.

Maprotiline (Ludiomil) and doxepin were compared in the treatment of depression in a double-blind multicentre trial. Four centres and 95 in- and out-patients took part in the trial. The severity of depression was evaluated with the aid of a visual analogue scale and nine target symptoms. Both maprotiline and doxepin diminished neurotic as well as psychotic depression significantly. The mean time of onset of action was 7.0 days in the maprotiline group and 7.7 days in the doxepin group. No statistically significant differences in antidepressive effect were found between the treatments. Two patients in the maprotiline group and four patients in the doxepin group discontinued the treatment because of unwanted effects, one patient in each group because of lack of efficacy and nine patients due to reasons not related to the treatment.