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Research has described the differences in illness onset, outcome and the type of symptoms experienced between schizophrenic males and females. Studies have shown that schizophrenia began at an earlier age for men (Evenson, Meier, & Hagan, 1993; Goldstein, Tsuang, & Faraone, 1989; Troisi, Pasini, & Spalletta, 2001). As a result of their earlier onset, men show less developed premorbid functioning with poorer treatment outcome, such as persistent social withdrawal and speech disturbances (Salokangas & Stengard, 1990). Men also experience more severe negative symptoms and display more structural brain abnormalities (Salokangas & Stengard, 1990; Troisi et al., 2001).
Since structural brain abnormalities are significant in men, research has investigated the feature of hypofrontality. In one study, the MRI scans of schizophrenic males demonstrated hypofrontality particularly in decreased metabolic activity of the dorsolateral prefrontal cortex compared with non-schizophrenics (Molina et al., 2005). In this case, the drug treatment given did not help the subjects’ negative symptoms. Another study discovered lowered whole brain volume, cortical and temporal lobe gray matter volume, noticeably the left temporal lobe, which is exhibited in the schizophrenics’ poor language and verbal ability, and their significantly greater lateral and third ventricular volumes (Fannon et al., 2000). With their focus on the relationship between frontal size and symptoms, Andreasen et al. (1986) observed smaller frontal areas of schizophrenics in about 40% of the male subjects, which are likely due to reduced dorsolateral and orbital regions. Despite the weak association between low frontal sizes and negative symptoms, they found that smaller cerebral and cranial sizes were strongly related to such symptoms. Perhaps the relationship between hypofrontality and negative symptoms cannot be more strongly emphasised than in the comparison of these symptoms with those of behavioural variant frontotemporal dementia(bv-FTD) (Ziauddeen, Dibben, Kipps, Hodges, & McKenna, 2011). Based on the proposal that “negative symptoms are a manifestation of impaired frontal lobe function”, a study produced similar pattern of scores between the schizophrenic and bv-FTD subjects on measurements of negative symptoms. Schizophrenic symptoms like affective flattening and avolition-apathy were scored by bv-FTD subjects which might closely relate with their emotional inexpressiveness. Schizophrenics also scored on bv-FTD’s Frontal Systems Behaviour Scale for apathy. Speech deficits shared between both groups could be possibly attributed to reduced frontal lobe function. As for sex differences in brain processes, one MRI study looked into the cerebral gray matter volumes of healthy young girls and boys during their period of brain maturation of synaptic pruning. The rate of decrease in gray matter volume in boys is faster than that of girls (De Bellis et al., 2001). An explanation is that estradiol in girls could have delayed such pruning process and played a part in neurodevelopment with its receptor distribution in the brain.
While the differences in severity of illness are more pronounced between young men and women, such contrast is not for post-menopausal women. In fact, research has suggested the protective effect of oestrogen for women since the late 70s (Häfner, 2003). Fink (as cited in Häfner, 2003) found out from animal experiments that the stimulation of the serotonin transporter gene by oestrogen has a protective, antipsychotic function similar to decreased D2-receptor sensitivity. Such receptor density was reported by Kaasinen et al. (as cited in Rao & Kölsch, 2003) to be higher in post-menopausal women. Riecher-Rossler et al. (as cited in Häfner, 2003) discovered increasing oestrogen plasma levels correlated negatively with schizophrenic symptom scores of women with regular menstrual cycles. Oestrogen also appears to enhance the effectiveness of neuroleptics taken by schizophrenic women. Frisch and Gur et al. (as cited in Rao & Kölsch, 2003) reported that increased cerebral blood flow and more body fat in women also aid in more efficient bodily distribution of lipophilic antipsychotic medication. Pozzo-Miller et al. (as cited in Rao & Kölsch, 2003) mentioned that a female sex hormone, estradiol – 17β, which indirectly prevents neuronal cell loss by controlling intracellular calcium concentrations, is presumed to interact with NMDA and AMPA receptors. Javitt (as cited in Rao & Kölsch, 2003) stated that drugs which reduce negative symptoms also work by enhancing these receptors’ functions.
Brain atrophy and low oestrogen level aside, studies have shown less promising pharmacological treatment of negative symptoms which are more prevalent with men despite hopes with second-generation antipsychotics(SGA) (Erhart, Marder, & Carpenter, 2006). Adjunct treatments do not have well-grounded efficacy and are not widely used. Overall, the effectiveness of SGAs and available adjunct medication in treating negative symptoms is questionable and explains poorer prognosis of schizophrenic men.
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